Biomedical subjects
Publications and source records attributed to D Gilbert.
Neurotubules and neurofilaments are homologous with cytoplasmic microtubules and microfilaments which are seen with the electron microscope in most plant and animal cells. Their subunits are transported to the growth cone of the outgrowing axon, where the subunits are added to the distal ends of the neurotubules.
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HLA-A and B phenotypes of 105 patients suffering from malignant melanomas were determined, with special regard for metastatic form or relapse. A highly significant increase of the HLA-A9 antigen is seen (X2 = 17.47); such data had already been shown by van Wijek [2], but other authors did not find this abnormality when studying melanomas whose histologic form was not specified.
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Experiments were carried out on 4 day cyclic rats or immature rats induced to ovulate by administration of pregnant mare serum gonadotrophin. Removal of the ovaries and adrenal glands at 17.00 h of pro-oestrus, i.e. after the critical period, prevented the appearance of the surge of LH. Sham-operation or removal of only one of the sets of glands had no effect. This indicates that the preovulatory increase in the concentration of oestradiol is not solely responsible for the surge of LH; the presence of a steroid, secreted by the ovaries and adrenal glands in the late afternoon of pro-oestrus, is also required. Attempts were made to reinstate the surge of LH in ovariectomized, adrenalectomized rats by administration of one of the steroids normally secreted in late pro-oestrus. Corticosterone, 20alpha- and 20beta-hydroxy-4-pregnen-3-one and 17alpha-hydroxyprogesterone all had no effect. Progesterone injected at the time of the operation stimulated the release of LH but only after the plasma concentration had reached its maximum 3--5 hr after injection. Testosterone also stimulated the release of LH some hours after administration.
Fischer 344 rats were treated with tobramycin or gentamicin, 40 mg/kg/day, for up to 10 days or with tobramycin, 120 mg/kg/day, for up to 14 days. Serum creatinine and BUN at the time of sacrifice were determined, and kidney tissues were examined by light and electron microscopy. Rats receiving gentamicin demonstrated progressive renal proximal tubular necrosis which was nearly universal at the end of 10 days. Their BUN and creatinine levels rose progressively over the same period. Even at the higher dosage, tobramycin therapy resulted in only rare foci of proximal tubular necrosis and minimal elevation of BUN and creatinine. Although they occurred later and were substantially less severe, the ultrastructural changes induced by tobramycin were the same as those seen following gentamicin administration. These results indicate that the mechanism of tobramycin-induced renal injury is probably similar to that of gentamicin and that tobramycin is significantly less nephrotoxic in this experimental model.
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A technique is described for the continuous perifusion of rat adenophypophyses. Exposure of the perifused glands to repeated equal 5 min stimuli with hypothalamic extract resulted in a series of equal peaks of corticotrophin secretion, the response was proportional to log dose over the range 0 - 25-2 - 0 rat hypothalamic equivalents/ml. Repeated equal stimuli with hypothalamic extract, or with luteinizing hormone releasing hormone (LH-RH) at concentrations of 2 or 10 ng/ml, resulted in a progressively increasing series of peaks of LH secretion, i.e. a self-potentiating or priming effect. The effect took between 30 min and 1 h to develop. A delayed increase in the responsiveness of the glands was also seen with continuous incubation of anterior pituitaries with LH-RH. The relevance of these observations to the physiological control of LH secretion is discussed.
Gentamicin nephrotoxicity was examined in rats on normal, high, and low sodium diets. Low sodium diet markedly potentiated nephrotoxic effects of the drug as evidenced by animal mortality, renal failure, pathological changes, and increased renal cortical concentration of the drug. High sodium intake reduced the cortical concentration of gentamicin but renal function and ultrastructure were similar to normally fed rats given in the same dose.
A procedure of EA rosette formation inhibition is used to show an effect of anti-HL-A alloantisera on human lymphocyte Fc receptors. IgG and F(ab')2 fragments also inhibit EA rosette formation. A relationship between Fc receptors and antigens recognized by these antibodies is suggested.
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Pseudosymmetry in the LH-RH structure is described. Eleven analogs of LH-RH (SMALLER THAN Glu-His-Trp-Ser-Tyr-Gly-Leu-Arg-Pro-Gly-NH2) have been synthesized by the fragment condensation method and the repetitive excess mixed anhydride method. Multiple substitutions have been made in the LH-RH sequence, which retain the pseudosymmetry of the LH-RH molecule, while presenting fewer problems of synthesis than the corresponding residues in the natural decapeptide. Thus Trp3, Ser4, Tyr5, Gly6, Leu7, and Arg8 residues were replaced by amino acids having similar properties to the residues that they replace. In all but one of the peptides the Gly10-NH2 residue was replaced by ethylamide, while in the remaining peptide, 1-methyl-5-aminomethyltetrazole (AMT-Me) was substituted at position 10. The compounds were assayed in vitro and in vivo. The following analogs had in vivo and in vitro activities in the range 1-28 percent relative to LH-RH: I, smaller than Glu-His-Phe-Ala-Tyr-Gly-Leu-Arg-Pro-NHEt; II, smaller than Glu-His-Phe-Gly-Tyr-Gly-Leu-Arg-Pro-NHEt; VII, smaller than Glu-His-Phe-Ala-Tyr-Gly-Phe-Arg-Pro-NHEt; IX, smaller than Glu-His-Phe-Ala-Tyr-D-Ala-Leu-Arg-Pro-NHEt; XI, smaller than Glu-His-Phe-Gly-Tyr-Gly-Leu-Arg-Pro-AMT-Me.
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1 The octanol : water partition coefficient (PC), protein binding coefficients to albumin (Ba) and haemoglobin (Bh), proton magnetic resonance (PMR) chemical shifts and pKa of 8 arylamidinoureas have been measured. 2 There were statistically significant correlations for 7 of the 8 compounds between the predicted lipophilicity parameter eta and log PC, Ba and Bh, and also between Hammett's electronic parameter sigma and the PMR and pKa observations. 3 3-Chloro,4-nitrophenylamidinourea showed a larger deviation from these correlations than any other compound. Geometric calculations based on the covalent radii and bond angles of the molecule suggested that the neighbouring chloro and nitro substituents were interacting sterically. 4 Molecular orbital calculations and the observed ultra-violet spectrum provided further evidence for such an interaction, and suggested that the nitro group is twisted out of the plane of the benzene ring in this molecule. 5 Such steric interactions can introduce an additional source of error when attempts are made to correlate the biological and predicted physicochemical properties of compounds. 6 Generalized parameters such as eta and sigma cannot be used with confidence to predict the properties of compounds in which such steric interactions occur.
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