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51.
In this investigation, we studied the importance of cellular glutathione (GSH) in the hexose monophosphate shunt (HMPS) activity of unstimulated human erythrocytes and the mechanism by which pyruvate stimulates the HMPS. The rate of HMPS activity was measured by the production of radioactive CO2 from 14C-1-glucose or 14C-1-ribose using a vibrating reed electrometer and ionization chamber. HMPS activity was not significantly impaired by N-ethylmaleimide (NEM) in concentrations which bound all red cell GSH. Red cells incubated under carbon monoxide (CO), an experimental condition which eliminates peroxide production, still had HMPS activity which was 44% of the value under air. Pyruvate stimulation of the HMPS was unaffected by doses of NEM which bound all cellular GSH or by incubation under CO. These data indicated that pyruvate stimulation of the HMPS occurs by pathways which do not involve peroxide formation, GSH, or oxygen. This study indicates that sulfhydryl blockade of GSH does not necessarily inhibit HMPS activity and that HMPS activity in red cells may respond to reactions not linked directly to glutathione reduction. 相似文献
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The biochemical and clinical consequences of 2'-deoxycoformycin in refractory lymphoproliferative malignancy 总被引:4,自引:1,他引:4
Grever MR; Siaw MF; Jacob WF; Neidhart JA; Miser JS; Coleman MS; Hutton JJ; Balcerzak SP 《Blood》1981,57(3):406-417
A deficiency of adenosine deaminase, an enzyme important in purine nucleoside catabolism, is associated with a severe combined immunodeficiency disease in children. Inhibition of this enzyme in vitro and in vivo results in an impairment in lymphoblast proliferation. We have investigated the pharmacologic inhibition of this enzyme by 2'-deoxycoformycin in 15 patients with hematologic malignancies. Biochemical consequences of the administration of this agent were closely monitored in erythrocytes, nucleated peripheral blood and bone marrow cells, serum, and urine. A marked rise in erythrocyte dATP was accompanied by a depletion of ATP in those patients exhibiting toxicity. Most patients excreted large amounts of deoxyadenosine but not adenosine in the urine. Serum deoxyadenosine rose in patients demonstrating a marked decrease in cell mass. The biochemical disturbances and clinical toxicity, including hepatic, renal, and conjunctival abnormalities, were usually reversible. Central nervous system toxicity, which potentially was the most serious consequence, was associated with high erythrocyte dATP/ATP ratios and high levels of cerebrospinal fluid deoxyadenosine. In patients with lymphoma and leukemia, objective responses were observed but were short- lived. Patients with chronic lymphocytic leukemia receiving weekly low doses of the drug demonstrated minimal toxicity and some efficacy. The chemotherapeutic potential o 2'-deoxycoformycin, as either a single agent or in combination with Ara-A, merits further exploration. 相似文献
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SP Attard-Montalto C Camacho-Hübner AM Cotterill L D'Souza-Li S Daley K Bartlett D Halliday OB Eden 《Acta paediatrica (Oslo, Norway : 1992)》1998,87(1):54-60
Changes in insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding proteins (IGFBPs) were correlated with protein synthesis and breakdown using [1- 13C]leucine before chemotherapy and during subsequent febrile neutropenia (FN) in eight children with cancer, aged 6.3–17.5 y. IGF-I levels were similar to age-matched controls before chemotherapy (mean ±SEM: 250 ±28 and 228 ±22 μg l-1, respectively). During FN, IGF-I fell to 156 ±22 /ng l -1(p= 0:02), and rose to 276 ±27 μ g l -1 with recovery at 6 months (p = 0:004). Similarly, IGFBP-3 decreased from 4.0 ±0.2mgl-1 before chemotherapy to 3.0 ±0.3 mgl-1 during FN (p= 0:01), and returned to 4.1 ±0.2mgl -1 at 6 months (p= 0:01). IGF-I correlated with IGFBP-3 (r=+0:7, p <0:001). Scanning densitometry showed a decrease in IGFBP-3 from 94 to 54% during FN, when the presence of IGFBP-3 protease activity was observed. Compared with normal human serum, IGFBP-2 was elevated throughout the study. IGFBP-1 increased from 14.6 ±3.5 to 30.6 ±2.8/ngl-1 (p = 0:004), whereas serum insulin decreased from 26.5 ±6.8 to 7.8 ±0.8 mUl-1 (p= 0:03) before and during FN, respectively. Whilst IGF-I and IGFBP-3 fell, daytime growth hormone increased from 3.3 ±0.6 to 6.7±0.8mUl -1 (p= 0:01), and cortisol from 197 ±48 to 594±98nmoll -1 (p = 0:005). Albumin decreased from 47 ±2 to 38 ±2gl-1 (p= 0:004) and improved to 47 ±2gl-1 with recovery (p= 0:003). Protein synthesis increased from 4.5 ±0.4 to 5.0 ±0.6gkg-1 d-1 before chemotherapy and during FN, while protein breakdown rose from 5.4 ±0.4 to 6.3 ±0.4kg-1d-1. Increasing protein breakdown was related to falling IGF-I and IGFBP-3 levels. Modification of IGFBP-3 by circulating proteolytic activity may alter IGF bioavailability, allowing protein synthesis to increase during periods of severe catabolic stress. 相似文献
56.
Objective: To identify risk factors for development of dehydration in under five year olds with acute watery diarrhoea.Design: Hospital based unmatched case-control study.Setting: Diarrhoea Treatment Unit, Government Medical College Hospital, Nagpur, India.Participants: The study included 387 cases of diarrhoea having severe or moderate dehydration and 387 controls suffering from diarrhoea with mild or no dehydration.Risk factors: The study included infancy, female sex, religion, residing in urban slums or rural area, under nutrition, cessation of breast feeding during diarrhoeal episode, fluid intake decreased/stopped during diarrhoea, ORS not received, home available fluids (HAF) not received, both ORS and HAF not received, non-washing of hands by mother before preparation of food, after defaecation, after disposal of faeces, history of measles in the previous six months, frequency of stools >8/d, frequency of vomiting more than twice per day and temperature more than 99°F, as risk factors for development of dehydration.Statistical analysis: Univariate analysis included OR, 95% CI for OR and Chi-square test. Multivariate analysis was carried out by unconditional multiple logistic regression (MLR).Results: This study identified the significance of infancy, religion, severe undernutrition, non-washing of hands by mother before preparation of food, frequency of stool >8/d, frequency of vomiting >2/d, history of measles in previous six months, withdrawal of breast feeding during diarrhoea, withdrawal of fluids during diarrhoea and not giving ORS, HAF or both during diarrhoea, in the outcome of development of moderate or severe dehydration.Conclusions: Timely intervention in the preventable risk factors included in this study may prevent the development of moderate or severe dehydration in the children suffering form acute watery diarrhoea. 相似文献
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SP Cannavò† F Borgia† M Vaccaro† F Guarneri† E Magliolo‡ B Guarneri† 《Journal of the European Academy of Dermatology and Venereology》2002,16(6):625-627
Pretibial myxoedema is a cutaneous mucinosis typically associated with Graves' disease, although it may also develop in subjects with non-thyrotoxic thyroid pathologies. This report presents a rare case of pretibial myxoedema occurring in a 58-year-old woman with biopsy-proven Hashimoto's thyroiditis. The hypothetical pathogenetic link between the two disorders is discussed with particular attention to the role of thyroid stimulating hormone receptor antibodies. 相似文献
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Inhibition of tissue factor/factor VIIa activity in plasma requires factor X and an additional plasma component 总被引:10,自引:0,他引:10
A study was carried out to explore requirements for the inhibition of tissue factor-factor VIIa enzymatic activity in plasma. Reaction mixtures contained plasma, 3H-factor IX or 3H-factor X, tissue factor (vol/vol 2.4% to 24%), and calcium. Tissue factor-factor VIIa activity was evaluated from progress curves of activation of factor IX or factor X, plotted from tritiated activation peptide release data. With normal plasma, progress curves exhibited initial limited activation followed by a plateau indicative of loss of tissue factor-factor VIIa activity. With hereditary factor X-deficient plasma treated with factor X antibodies, progress curves revealed full factor IX activation. Adding only 0.4 micrograms/mL factor X (final concentration) could restore inhibition. Inhibition was not observed in purified systems containing 6% to 24% tissue factor, factor VII, 0.5 micrograms/mL, factor IX, 13 micrograms/mL, and factor X up to 0.8 micrograms/mL, but could be induced by adding barium-absorbed plasma to the reaction mixture. Thus, both factor X and an additional material in plasma were required for inhibition. The amount of factor X needed appeared related to the concentration of tissue factor; adding more tissue factor at the plateau of a progress curve induced further activation. These results also indicate that inhibited reaction mixtures contained active free factor VII(a). Preliminary data suggest that inhibition may stem from loss of activity of the tissue factor component of the tissue factor- factor VII(a) complex. 相似文献