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141.
Michael S. Boosalis Tohru Ikuta Betty S. Pace Silvana da Fonseca Gary L. White Douglas V. Faller Susan P. Perrine 《Blood cells, molecules & diseases》1997,23(3):434-442
ABSTRACT: Short-chain fatty acids, such as butyrate and propionate, induce fetal globin gene expression and are under clinical investigation in the β-hemoglobinopathies. Limitations of the short-chain fatty acids as therapeutics include their rapid metabolism and a tendency to induce cell growth arrest if administered for prolonged periods. In studies described here, the cellular effects of other inducers of fetal globin, phenoxyacetic acid and derivatives of short-chain fatty acids and cinnamic acids, were investigated in the human erythroid cell line K562, the IL-3 dependent multi-lineage cell line (32D), and in mice and primates. Several test compounds supported 32D cell proliferation despite a 50-fold depletion of IL-3, which resulted in growth arrest and apoptotic death in control cells. The degree of proliferation induced by certain test compounds was similar to the degree of proliferation induced by Erythropoietin and G-CSF in the cells. Eight of ten compounds induced γ globin mRNA in K562 cells. A 2.5 to 6-fold increase in reticulocytosis was observedin vivoin mice treated with two prototype compounds. Pharmacokinetic studies of three prototype compounds demonstrated millimolar plasma concentrations after single oral doses for many hours in primates. These findings identify orally bioavailable compounds which induce γ globin gene expression and hematopoietic cell proliferation through an activity which partially abrogates requirements for IL-3. Such compounds provide potential for oral therapeutics which stimulate proliferation of hematopoietic cells of multiple lineages, as well as inducing fetal globin. 相似文献
142.
F. Grisoli M.D. Th. Brue N. Graziani R. Costa J. Trouillas D. Begou Ph. Jaquet 《Acta neurochirurgica》1990,103(3-4):92-98
Summary Preliminary results obtained from 26 cases of prolactinomas less than 20 mm in diameter after treatment by enlarged adenomectomy are described.The operation consisted in removal of the adenoma, a layer of normal pituitary at the outer edge of the tumour and the pituitary capsule in contact with the sellar meninges. 24 women and 2 men were involved whose prolactin levels (PRL) were less than 200 ng/ ml. All presented abnormal PRL responses to Thyrotropin releasing hormone (TRH) and Metoclopramide (MCP) tests and an absence of a nocturnal rise in the sleep cycle study. Postoperatively, three patients developed transitory diabetes insipidus and five transitory adrenal insufficiency. Gonadotropin reserve was always found normal. All 24 women resumed normal menstrual cycles and two became pregnant within one year. From a serological viewpoint, after surgery 100% of patients were found to be normal for levels of prolactin but only 85% turned to normal dynamic tests. The results of this small series of enlarged adenomectomies seem better than those obtained using selective adenomectomy, but must be confirmed with time. 相似文献
143.
A correlation between apoptosis and proliferation in astrocytomas and oligodendrogliomas, but not in glioblastomas, has been previously reported. An index for apoptosis and proliferation was established for each tumor in a series of 20 brain metastases, and its correlation was studied using the Spearman rank correlation test. Apoptosis index (AI) ranged between 1 and 78% (mean ± SD: 11.48 ± 16.4). Proliferation index (PI) ranged between 2.4 and 21% (mean ± SD: 8.23 ± 4.8). When the relationship between AI and PI was studied, a clear correlation was found (r: 0.8965, 95% CI: 0.74–0.95; P < 0.0001). Therefore, it is concluded that a clear correlation exists between proliferation and apoptosis in secondary tumors of the brain. 相似文献
144.
A Richieri-Costa I Ferrareto D Masiero C R da Silva 《American journal of medical genetics》1987,27(4):867-884
We report on 37 patients belonging to different families, who have the tibial hemimelia-split hand/foot syndrome. Genetic aspects and phenotypic manifestations are compared with previous reports of tibial hemimelia. An attempt to clinical and genetical approach is suggested. 相似文献
145.
Michael P. Savage M.D. Santiago J. Munoz M.D. Walter M. Herman M.D. Victoria M. Kusiak M.D. 《The American journal of gastroenterology》1987,82(10):1088-1090
Chylous ascites is an uncommon clinical entity associated with lymphatic obstruction usually caused by underlying malignancy. The authors describe a patient with chylous ascites caused by constrictive pericarditis in the absence of mechanical lymphatic obstruction. Pathophysiological mechanisms for the development of chylous ascites in constrictive pericarditis include augmented lymph production and high impedance to lymph drainage caused by central venous hypertension. After pericardiectomy, the patient's ascites and edema resolved. Constrictive pericarditis should be considered a rare but potentially curable cause of chylous ascites. 相似文献
146.
Teresa Coccini Luciano Maestri Francesco S. Robustelli della Cuna L. Bin Lucio G. Costa Luigi Manzo 《Archives of toxicology》1996,70(11):736-741
Styrene is stereoselectively oxidized by cytochrome P450 to its reactive metabolite, styrene oxide. The (R)- and (S)-enantiomers
of styrene oxide can be conjugated with glutathione (GSH) to both (R)- and (S)-diastereoisomers of the specific mercapturic
acids, N-acetyl-S-(1-phenyl-2-hydroxyethyl)-L-cysteine (M1) and N-acetyl-S-(2-phenyl-2-hydroxyethyl)-L-cysteine (M2). Several investigations have indicated different toxic potential of the (R)- and (S)-configurations of styrene
oxide and its GSH- and N-acetyl-conjugates. In this study the mercapturic acid diastereoisomers were measured in the urine
of rats exposed to styrene in combination with ethanol, a good inducer of styrene metabolism. Male Sprague-Dawley rats were
given an isocaloric liquid diet containing ethanol (5% w/v) for 3 weeks. Starting from the 2nd week, the animals were also
exposed to styrene vapours (300 ppm, 6 h/day, 5 days/week) in a dynamic exposure chamber. Both the (R)- and (S)-diastereoisomers
of the M1 and M2 as well as the conventional biomarkers, mandelic acid (MA) and phenylglyoxylic acid (PGA) were measured in
urinary samples. Approximately 30 and 25% reduction of the levels of brain non-protein sulfhydryls (NPS) was observed in the
animals given styrene and ethanol, respectively, while the combined ethanol and styrene treatment resulted in a 60% decrease.
Ethanol consumption also resulted in higher urinary levels of the M1-R, M1-S and M2 metabolites associated with increased
M1-R/S ratio and higher urinary MA excretion compared to animals treated with styrene. These results suggest that the urinary
mercapturic acid diastereoisomers may be used as a noninvasive tool to examine stereoselective patterns of styrene metabolism
in vivo, as well as their alterations caused by ethanol. These compound-specific mercapturic acids may also be valuable indicators
of styrene-induced disorders of GSH homeostasis in nonaccessible organs.
Received: 19 December 1995/Accepted: 10 May 1996 相似文献
147.
Bongertz Costa Guimarães Grinsztejn The Hec/fiocruz Aids Clinical Research Group João Filho Galvão-Castro & Morgado 《Scandinavian journal of immunology》1998,47(6):603-608
Susceptibility to autologous and heterologous neutralization of primary human immunodeficiency virus (HIV)-1 isolates belonging to subtype B, to the B'-variant of subtype B or to subtype F from infected individuals residing in Rio de Janeiro was assayed. A lower infectivity of the B'- and F isolates when compared to the classical B-subtype HIV-1 isolates was observed. Comparisons of neutralization susceptibilities were carried out for 19 B-subtype, 11 B'-variant and two F-subtype HIV-1 isolates with plasma from autologous and heterologous samples. Frequency of autologous neutralization was slightly lower for B-subtype isolates in comparison to B'-variant isolates. Heterologous intra-subtype neutralization was significantly lower for B-subtype than for the B'-variant or the F-subtype isolates. While B-subtype isolates were neutralized by most anti-F-subtype plasma, F-subtype isolates, although most susceptible to F-subtype antibodies, were highly susceptible to neutralization by anti-B-subtype antibodies. Cross-neutralization for B'-variant and B-subtype isolates was not as extensive as observed for B- and F-subtype isolates. However, the results presented indicate a quite extensive cross-neutralization between Brazilian HIV-1 isolates. 相似文献
148.
R E Ostlund Jr J B McGill I Herskowitz D M Kipnis J V Santiago W R Sherman 《Proceedings of the National Academy of Sciences of the United States of America》1993,90(21):9988-9992
D-chiro-inositol is a rare inositol isomer present in inositol phosphoglycans which are proposed mediators of insulin action. To study D-chiro-inositol metabolism in diabetes mellitus, a sensitive and specific assay was developed using negative-ion chemical ionization gas chromatography/mass spectrometry. Median urinary D-chiro-inositol excretion, which was 2.1 mumol/day in nondiabetics, was substantially increased to 12 mumol/day in non-insulin-dependent diabetes (P < 0.0001) and to 74 mumol/day in insulin-dependent diabetes (P < 0.0001). Urinary D-chiro-inositol was strongly correlated with fasting plasma glucose (r = 0.568, P < 0.0001), glycated hemoglobin (r = 0.529, P < 0.0001), and urinary glucose (r = 0.368, P = 0.01). The renal clearance of D-chiro-inositol was selectively elevated in both non-insulin-dependent and insulin-dependent diabetes when compared with the clearances of L-chiro-inositol or myo-inositol and exceeded the glomerular filtration rate in 71% of the diabetics but in none of the nondiabetics. In poorly controlled diabetic patients insulin treatment reduced urinary D-chiro-inositol losses by 63% and increased plasma levels by 8.8-fold. The metabolism of D-chiro-inositol is abnormal in diabetes and appears to be influenced by short- and long-term metabolic control. 相似文献
149.
R B Rothman V Bykov A Reid B R De Costa A H Newman A E Jacobson K C Rice 《Neuropeptides》1988,12(3):181-187
Norbinaltorphimine (nor-BNI) is a bifunctional reagent developed as a selective antagonist of the kappa opioid receptor. In this paper we examined the in vitro selectivity of nor-BNI, 6-desoxy-6 beta-fluoronaltrexone (cycloFOXY), and the enantiomer of cycloFOXY, among opioid receptor subtypes. Nor BNI exhibited the highest affinity for kappa binding sites labeled by 3H-U69593 (Ki = 1.8nM), and was 27- to 29-fold less potent at mu and delta binding sites. In contrast, cycloFOXY had the highest affinity for mu binding sites (Ki = 2.62 nM), and bound to kappa and delta binding sites with Ki's of 9.3 nM and 89 nM, respectively. The enantiomer of cycloFOXY, did not inhibit binding even at concentrations greater than 10 microM, validating in part the use of 18F-labeled (+)-cycloFOXY to estimate "non-specific binding" in positron emission tomography. Additionally, we report that (S,S)-U50 488 and (R.R)-U50 488 bind to kappa binding sites labeled by 3H-U69 593 with Ki's of 0.89 nM and 299 nM, respectively. 相似文献
150.
Rats were fed "3% casein" or a "calorie deficient" diet, in the form of commercial pellet diet (SDS) at 50% of the amount consumed by the control group, which was fed SDS pellets ad libitum. Both of the deficient groups showed failure of weight gain in comparison with the control group. Blood levels of ethanol were measured for 3 hr after intraperitoneal injection of 1 or 1.5 g/kg at 15, 29 and 36 days after commencement of the diet. In addition the calorie deficient group was studied immediately after feeding as well as in the fasting state. Blood levels of ethanol were measured and the apparent volume of distribution and rate of removal of ethanol from the blood were calculated. A rate of ethanol metabolism/g of liver was derived. The rate of removal of ethanol was markedly decreased in the 3% casein group to less than half of control values. Three hours after injection of ethanol circulating levels were less than 50 mg/100 ml in the control and calorie deficient groups but over 200 mg/100 ml in the group fed protein deficient diets. There were no major changes in volume of distribution and the only explanation for the finding is that there is a failure of ethanol metabolism in the rats fed the low protein diet. The implication is that protein deficient human populations who often consume considerable quantities of ethanol may have a high level of tissue exposure to ethanol though the rate of metabolite formation may be low. 相似文献