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31.
Enhancement of erythrocyte superoxide dismutase activity: effects on cellular oxidant defense 总被引:3,自引:0,他引:3
To delineate further the role of superoxide dismutase (SOD) in red blood cell (RBC) oxidant defense, normal human erythrocytes were osmotically lysed and resealed in the presence of varying concentrations of exogenous SOD. This resulted in a dose-dependent increase in SOD activity in the resealed erythrocytes while maintaining nearly normal RBC hemoglobin concentration (less than 10% decrease from the control value), cell volume, and cellular deformability. Surprisingly, a five- or ninefold increase in SOD activity yielded no additional protection against superoxide-generating drugs (phenazine methosulfate or menadione sodium bisulfite). No significant differences were observed between the control and SOD-loaded RBCs in O2-driven methemoglobin formation or generation of thiobarbituric acid-reactive substances. In contrast, RBCs with elevated SOD activity pretreated with sodium azide (to block catalase activity) or 1-chloro-2,4- dinitrobenzene (to deplete reduced glutathione, GSH) showed significantly enhanced methemoglobin generation in response to superoxide generating drugs. No differential response was noted between the control, control-resealed, and SOD-loaded RBCs to oxidants other than superoxide. Based on our results and other data, we conclude that elevated SOD activity may imbalance cellular oxidant defense, resulting in enhanced oxidation due to the accelerated generation of H2O2, the product of O2- dismutation. This effect is significantly exacerbated under conditions in which H2O2 catabolism is altered. 相似文献
32.
Mackinnon S; Papadopoulos EB; Carabasi MH; Reich L; Collins NH; Boulad F; Castro-Malaspina H; Childs BH; Gillio AP; Kernan NA 《Blood》1995,86(4):1261-1268
Infusions of large numbers (> 10(8)/kg) of donor leukocytes can induce remissions in patients with chronic myeloid leukemia (CML) who relapse after marrow transplantation. We wanted to determine if substantially lower numbers of donor leukocytes could induce remissions and, if so, whether this would reduce the 90% incidence of graft-versus-host disease (GVHD) associated with this therapy. Twenty-two patients with relapsed CML were studied: 2 in molecular relapse, 6 in cytogenetic relapse, 10 in chronic phase, and 4 in accelerated phase. Each patient received escalating doses of donor leukocytes at 4- to 33-week intervals. Leukocyte doses were calculated as T cells per kilogram of recipient weight. There were 8 dose levels between 1 x 10(5) and 5 x 10(8). Lineage-specific chimerism and residual leukemia detection were assessed using sensitive polymerase chain reaction (PCR) methodologies. Nineteen of the 22 patients achieved remission. Remissions were achieved at the following T-cell doses: 1 x 10(7) (n = 8), 5 x 10(7) (n = 4), 1 x 10(8) (n = 3), and 5 x 10(8) (n = 4). To date, 15 of the 17 evaluable patients have become BCR-ABL negative by PCR. The incidence of GVHD was correlated with the dose of T cells administered. Only 1 of the 8 patients who achieved remission at a T-cell dose of 1 x 10(7)/kg developed GVHD, whereas this complication developed in 8 of the 11 responders who received a T-cell dose of > or = 5 x 10(7)/kg. Three patients died in remission, 1 secondary to marrow aplasia, 1 of respiratory failure and 1 of complications of chronic GVHD. Sixteen patients who were mixed T-cell chimeras before treatment became full donor T-cell chimeras at the time of remission. Donor leukocytes with a T-cell content as low as 1 x 10(7)/kg can result in complete donor chimerism together with a potent graft-versus-leukemia (GVL) effect. The dose of donor leukocytes or T cells used may be important in determining both the GVL response and the incidence of GVHD. In many patients, this potent GVL effect can occur in the absence of clinical GVHD. 相似文献
33.
P-selectin is a 140-kD protein found in the alpha-granules of platelets and the Weibel-Palade bodies of endothelial cells that on cell activation is expressed on the cell surface and also secreted into the plasma. The secreted form of P-selectin, like plasma P-selectin, differed from platelet membrane P-selectin in that its molecular mass was approximately 3 kD lower under reducing conditions. Both the secreted and plasma forms of P-selectin contained cytoplasmic sequence as determined by Western blot analysis with an affinity-purified rabbit anti-P-selectin cytoplasmic peptide antibody. We have measured plasma P- selectin and beta-thromboglobulin (beta TG) concurrently in (1) patients with consumptive thrombotic disorders, including disseminated intravascular coagulation (DIC), heparin-induced thrombocytopenia (HIT), and thrombotic thrombocytopenic purpura (TTP)/haemolytic uremic syndrome (HUS); (2) patients with idiopathic thrombocytopenic purpura (ITP); and (3) healthy controls. Patients with DIC, HIT, and TTP/HUS, but not ITP, had significantly elevated plasma P-selectin and beta TG levels when compared with their age-matched healthy controls. The increased plasma P-selectin and beta TG in patients with thrombotic disorders were likely to be the result of in vivo platelet and endothelial cell damage or activation. We also found that avoidance of veno-occlusion and other tedious measures customarily taken during blood collection and sample preparation to prevent in vitro platelet activation did not affect plasma P-selectin assay results. In addition, plasma P-selectin levels were not influenced by the presence of renal failure or heparin administration. These results indicate that plasma P- selectin may be a useful new marker for thrombotic diseases. 相似文献
34.
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36.
9-(2-膦酰甲氧乙基)腺嘌呤及其位置异构体3-(2-膦酰甲氧乙基)腺嘌呤的合成和抗病毒活性研究 总被引:1,自引:0,他引:1
Phosphonylmethoxyethyl)adenine (1),PMEA,an acyclic nucleotide withbroad-spectrum antiviral activity was synthesized with some modifications of Holy's procedure.Simutaneously,an N-3 regioisomer(2)of PMEA and a by-preduct, formaldehyde di-[2-(9-adenyl)ethyl] acetal(7)were seperated by silica gel chromatography in the ratio of 50:10:1.Compound(2)and(7) are new compounds that we have not yet found in literatures. The structure of them weredetermined with 1HNMR,2DNMR, MS and Spot test.Antiviral test showed that N-3 isomer(2)completely lost activity against both HIV-1 and HSV-1 in vitro. It seems that regiospecificity of theacyclic nucleotide structure is important for antiviral activity. 相似文献
37.
Hoos A. D'Incan C. Gissmann L. Altmann A. Momburg F. Nindl I. Osen W. Schönning BH. Jochmus I. 《Archives of virology》1996,141(3-4):449-458
Archives of Virology - The low expression of major histocompatibility complex (MHC) class I antigens on human papillomavirus (HPV)-infected cervical carcinoma cells may be responsible for an... 相似文献
38.
39.
Quantitative liver function in patients with rheumatoid arthritis treated with low-dose methotrexate: a longitudinal study 总被引:4,自引:0,他引:4
Beyeler C; Reichen J; Thomann SR; Lauterburg BH; Gerber NJ 《Rheumatology (Oxford, England)》1997,36(3):338-344
The objectives were to determine quantitative liver function prospectively
in patients with rheumatoid arthritis (RA) treated with low-dose
methotrexate (MTX), to search for risk factors for a loss of quantitative
liver function and to assess the relationship between quantitative liver
function and histological staging. A total of 117 patients with RA (ACR
criteria, 85 women, mean age 59 yr) had measurements of galactose
elimination capacity (GEC), aminopyrine breath test (ABT) and liver enzymes
[aspartate amino transferase (AST), alanine amino transferase (ALT),
alkaline phosphatase (AP), 7-glutamyl transferase (GGT), bile acids,
bilirubin, albumin] before treatment with weekly i.m. MTX injections and
every year thereafter. In 16 patients, liver biopsies were performed.
Before the introduction of MTX, mean GEC was 6.6 mg/min/kg [5th to 95th
percentile (5-95 PC) 5.1- 8.5; reference range 6.0-9.1] and mean ABT was
0.80% kg/mmol (5-95 PC 0.42-1.30: reference range 0.6-1.0). During
treatment with MTX [mean weekly dose 11.8 mg (5-95 PC 5.4-20.2), mean
observation period 3.8 yr (5-95 PC 0.4-6.9)], significant declines of GEC
(-0.12 mg/min/kg per year. t = 3.30, P < 0.002) and ABT (-0.06% kg/mmol
per year, t = 4.81, P < 0.001) were observed. Negative correlations were
found between the annual change in GEC and GEC at baseline (Rs = -0.40, P
< 0.0001), and the annual change in ABT and ABT at baseline (Rs = -0.43,
P < 0.0001). No correlations were found between the annual change in GEC
or ABT and weekly MTX dose, age or percentage of increased liver enzymes,
and no effect of a history of alcohol consumption > 30 g/week became
evident. Two patients with Roenigk grade III had impaired quantitative
liver function, while 14 patients with Roenigk grades I and II exhibited a
high variability of GEC and ABT from normal to abnormal values. The
continuous declines in GEC and ABT observed deserve attention in patients
with prolonged treatment. Patients with a low GEC or ABT at baseline seem
not to be at increased risk for a further loss of quantitative liver
function. An impaired GEC or ABT does not necessarily concur with hepatic
fibrosis on histological examination.
相似文献
40.
W B Ershler J A Stewart M P Hacker A L Moore B H Tindle 《Journal of the National Cancer Institute》1984,72(1):161-164
The growth characteristics and colonization potential of a transplantable melanoma administered to young (3 mo) and old (24 mo) C57BL/6 mice were investigated. After sc injection of B16-F10 melanoma cells, tumor growth was slower, and final tumor volume was less in the older mice. Furthermore, after iv injection of B16-F1 melanoma cells, the number of pulmonary colonies was also less, and the survival was greater in the older mice. These findings indicate an age advantage in this experimental tumor model that may be attributed to either physical or immunologic factors. 相似文献