Gamma rays in 148Sm from the decay of 148Eu and the 146Nd( alpha,2n gamma ) reaction.
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Biomedical subjects
Publications and source records attributed to B Singh.
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Nineteen women were studied before, during and after labour by assessment of their mood using a variety of psychological tests and by measurement of their plasma concentrations of beta-endorphin and cortisol. Beta-endorphin and cortisol concentrations rose markedly during labour and were influenced by the type of analgesia used. A deterioration in cognitive performance between days 2 and 4 postpartum correlated positively with the fall in beta-endorphin concentrations from those in labour to those on the fourth day postpartum. The women were more anxious and depressed at 38 weeks' gestation than on days 1-4 postpartum and the elevation of mood on day 2 postpartum correlated with a measure of depression 8 weeks later. It is postulated that the phenomenon of postpartum blues is a reaction to the euphoria of delivery which in turn is a response to endorphin release during labour. Whilst these changes may have a role in promoting maternal-infant attachment it is at the expense of maternal depression some weeks later.
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Certain preparations of rabbit gamma-globulins (Cohn Fraction II) contain an activity which, if administered intravenously to pregnant mice, causes either complete fetal resorption in virtually 100% of cases when given during the second trimester equivalent or abortions when given later in pregnancy. All mouse strains tested are sensitive to the activity with slight differences in dosages and kinetics. Unlike vaccines raised xenogeneically against rodent placenta, the activity does not cross-react with kidney or result in any maternal pathology; it can be adsorbed on mouse placental and testicular tissue. Within 1 hr of injection, there is massive venous congestion of the basal decidua and placenta associated with fetal death. There is, however, no evidence of an acute inflammatory reaction or of vascular thrombosis. Expression of the activity can be blocked by pretreatment of the animal with heparin; antihistamines, anticholinergics, and anti-inflammatory agents are without effect. The activity is heat-labile and sensitive to reduction-alkylation and periodation. Virtually all treated females can be successfully remated at a later time.
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The B10.A T cell proliferative response to pigeon cytochrome c is mainly directed against a single antigenic determinant located at the carboxy-terminal end of the molecule. In the present experiments, we used synthetic peptide analogs of the carboxy-terminal sequence of moth cytochrome c to explore the structural requirements for antigenic potency. The minimum-sized peptide capable of stimulating a full response varied with the T cell clone, but within the limits of the biological systems studied, was shown to be moth fragment 97-103. Addition of more amino acids at the amino terminal end increased the antigenic potency in uneven increments, with a large contribution being made at residue 95. Analysis of amino acid substitutions at this position provided no evidence that it contained a residue that directly contacted the T cell receptor. Instead, good agreement with an analysis that made use of helix-coil transition theory suggested that this residue, as well as others, increased antigenic potency by contributing to the stabilization of the secondary structure of the molecule in an alpha-helical configuration. The maximum effect of chain length on antigenic potency appeared to stop at residue 93, in agreement with the theoretical analysis. However, addition of several more amino-terminal residues to residue 93 showed one additional significant increment of increased potency. This was almost entirely accounted for by a single lysine located four amino acids beyond the glutamic acid at residue 93 (approximately one turn of an alpha-helix away). To experimentally test whether alpha-helix-forming tendencies could account for the increased potency of the larger analogs, the degree of helix formation in trifluoroethanol was assessed by circular dichroism measurements. A good correlation was found between antigenic potency and percentage of alpha-helix for peptides of increasing chain length from moth 95-103 up to moth 86-90; 94-103. These results suggest that secondary structure may play an important role in determining the potency of antigenic determinants involved in the activation of T lymphocytes.
Antigen-specific T cell blasts to poly-18, a polypeptide antigen of defined sequence and conformation, were generated from lymph nodes of antigen-primed BALB/cCr mice. These blasts were fused with the BW5147 thymoma to obtain anti-poly-18-reactive T cell hybridomas. All of the hybridomas were IAd-restricted and secreted IL2 in the presence of IAd/poly-18. On the basis of fine specificity analysis, these hybridomas were classified into two groups. Group A hybridomas recognized a minimal peptide sequence of Glu-Tyr-Lys-(Glu-Tyr-Ala)3-Glu-Tyr-Lys, whereas Group B needed the sequence Glu-Tyr-Ala-(Glu-Tyr-Ala)3-Glu-Tyr-Lys/Ala for activation. Three critical residues were identified in Group A hybridomas: the alanine residue at position 9, the carboxy terminal lysine, and the lysine at position 3. In Group B hybridomas, the alanine at position 3 was found to be the critical residue. We suggest that the amino acid residue at position 3 (lysine/alanine) is the T cell receptor contact residue on the poly-18 antigen in BALB/cCr mice.
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Three structurally related anticancer drugs, mithramycin, chromomycin A3, and olivomycin, exhibited large differences (greater than 100-fold) in their toxicity towards cultured cells from various species. These differences are species related, as all cell lines from any one species showed similar sensitivity to the three drugs. Of the three species examined, namely, human, mouse, and Chinese hamster, human cells were found to be most sensitive to these drugs. However, no significant difference in toxicity was observed between normal human diploid fibroblasts and heteroploid cell lines established from tumors. The above drugs were found to induce mutants at the hypoxanthine-guanine phosphoribosyl-transferase locus (i.e., resistance to 6-thioguanine) and produced DNA strand breaks, in a dose-dependent manner, in cells from all three species. However, the concentrations of these drugs which produced similar mutagenic or DNA strand break responses differed greatly for cells from the three species, and a good correlation was observed between the toxic and the mutagenic concentrations of these drugs for cells from the three species examined. These studies provide strong evidence that the toxic and mutagenic concentrations of different substances could differ greatly between cells from human and other species and indicate that the results of such studies cannot always be extrapolated from animal to human situations. It is suggested that a knowledge of the relative toxicity of any chemical towards cultured cells from human versus test animal should prove of value in extrapolating the results from animal systems to humans.
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The study makes an attempt to find out the action of norepinephrine (NE) and phenoxybenzamine (PB), applied at medial preoptic area (mPOA), in altering the sleep-awake responses, in free moving rats, which has not yet been reported. Effects of application of NE during day and PB during night, at mPOA, on sleep-awake responses, were compared with application of saline during identical periods. Application of NE produced arousal, whereas, PB produced the opposite effect. The findings are suggestive of the involvement of NE terminals at mPOA in normal arousal.
Several carrier systems and targeting agents have been considered as means of delivering enzymes and drugs to specific tissues or cells. In this report insulin is shown to be effective in delivering enzyme-albumin conjugates to cells and tissues rich in insulin receptors. The complex is transported into cells by a process that resembles receptor-mediated endocytosis and can be identified in a lysosomal fraction. The enzyme-albumin-insulin complex retains its enzymatic activity and its ability to bind antibodies to insulin. It also has a hypoglycemic effect; however, plasma glucose concentrations can be maintained by glucose administration.
The malonyl-CoA assay was nonlinear at low malonyl-CoA concentrations when labeled acetyl-CoA was used as fatty acid synthase primer. Linearity was obtained with low concentrations of both fatty acid synthase and labeled acetyl-CoA, but then the assay was disturbed by the diluting effect of endogenous acetyl-CoA. The problems of nonlinearity and dilution of radioactivity by endogenous compounds were absent when labeled butyryl-CoA was used as primer. The levels of malonyl-CoA in rat heart, kidney, and liver were determined. The use of butyryl-CoA gave higher values of malonyl-CoA.
The purpose of this study was to find a barrier contraceptive agent capable of controlling infections and sexual transmission of Ureaplasma urealyticum from the female genital tract, especially to help reduce nongonococcal urethritis in males caused by this organism. Therefore, the in vitro antimicrobial activity of six intravaginal contraceptives and BetadineR against the eight serotypes of the organism was investigated. The results indicate that some of these contraceptives produce partial inhibition of the Ureaplasma at low dilutions, while BetadineR produces a ureaplasmacidal effect up to dilutions of 1:64. These effects appear not to be due primarily to the pH of these agents. Thus, some of these agents may have a potential role in controlling transmission of Ureaplasma urealyticum.
There is evidence to suggest that the reticular activating system may have an influence on the neurons of the preoptic area (POA). We studied the responses of POA neurons and their relation to the cortical EEG, on stimulation of the midbrain reticular formation (MRF) at various frequencies, in unanesthetized, encéphale isolé cats. Stimulation of the MRF at high frequency produced inhibition of the firing rate in a majority of the responsive neurons of the POA. Stimulation of the MRF with lower frequencies, on the other hand, induced excitation in a majority of the responsive POA neurons. The possibility exists of a summation of stimuli and an involvement of structures bringing about changes in the EEG in causing the shift in the POA neuronal excitability.
Isolated mitochondria from rat liver were incubated in the presence of [U-14C]palmitate, ATP, CoA, carnitine, EGTA (ethylene glycol bis (beta-aminoethyl ether) N,N'-tetraacetic acid) and varying amounts of calcium. When a KC1-based incubation medium was used, the oxidation of palmitate was inhibited when the concentration of free calcium was increased from about 0.1-10 microM. When a sucrose-based incubation medium was used, the basal rate of palmitate oxidation was about half of that observed with the KC1-medium and calcium had a stimulatory effect. With the KC1-medium the rate of oxygen consumption was inhibited by calcium with alpha-ketoglutarate as well as palmitate as the respiratory substrate. No inhibitory effect of calcium was observed with succinate or beta-hydroxybutyrate. With the KC1-medium and with alpha-ketoglutarate as the respiratory substrate, state 3 respiration but not state 4 respiration was inhibited by calcium. When the sucrose-medium was used, state 3 respiration was first inhibited by calcium, but this inhibition was gradually relieved and the respiratory rate finally became higher than it was before calcium addition.
Glucagon induced a rapid (within 3 min) increase in glucose radioactivity and a decrease in the labeling of ketone bodies when isolated hepatocytes were incubated in the presence of [1-14C]palmitate. Simultaneously, the hormone induced a decrease in the levels of pyruvate and Krebs cycle intermediates and an increase in the level of phosphoenolpyruvate (PEP). The glucagon-induced increase in glucose radioactivity was much larger than the simultaneous decrease in lactate labeling. A comparison of the incorporation of labeled carbon from [1-14C]palmitate and [U-14C]palmitate into glucose and CO2 indicates a selective stimulatory action of glucagon on the flux through the phosphoenolpyruvate carboxykinase (PEPCK) reaction.