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991.
The lethal effects of 4-(3-(2-chloroethyl)-3-nitrosoureido)-cis-cyclohexanecarboxylic acid (cis-acid), a water-soluble nitrosourea derivative, were investigated on a human lymphoma cell line. The survival of asynchronous cells exposed to increasing concentrations of the drug was characterized by a threshold exponential curve (Do = 20 microgram/ml; Dq = 20 microgram/ml, 1 hour) similar to that of other nitrosourea derivatives. cis-Acid exerted its main killing effect on cells in early S and in late G2 phase. Cells in mid S and early G1 phase were tenfold more resistant. Changes in survival response as a function of cell cycle stage were reflected primarily by changes in the extent of the shoulder region of the survival curve. In contrast to other nitrosoureas, the lethal effectiveness of cis-acid in solution was stable and the drug could sterilize large numbers of cells in short periods of time. Another important major difference observed for cis-acid with respect to classic nitrosourea derivatives was the capacity of treated cells to recover from sublethal and potentially lethal damage. Our studies have shown that cis-acid is as effective in killing cultured human lymphoma cells as other nitrosoureas, but possibly with a mechanism different from that of these compounds. The major shortcoming noted for cis-acid, namely the capacity of treated cells to recover from drug-induced damage, is offset by the relatively long stability of its killing effect. This, and the fact that cis-acid can be administered in an aqueous solution, make this agent an appealing compound for clinical trials. 相似文献
992.
993.
IP Smirnov TL Tsilevich SV Kochetkova GV Vladyko LV Korobchenko EI Boreko BP Gottikh VL Florent'ev 《Canadian Metallurgical Quarterly》1993,19(1):95-102
The (R/S)-5-hydroxy-4-hydroxymethyl-3-oxapent-2-yl derivatives of the uracil, thymidine, cytosine, adenine, guanine and 1,2,4-triazol-3-carboxamide were synthesized using 1,3-diacetoxy-2-(1-acetoxy)propane and 1,3-dichloro-2-(1-chlorethoxy)propane as alkylating agents. The guanine derivatives exhibited activity against HSV-1 (chemotherapeutic index 32). 相似文献
994.
995.
996.
JG Deville JD Cherry PD Christenson E Pineda CT Leach TL Kuhls S Viker 《Canadian Metallurgical Quarterly》1995,21(3):639-642
To investigate the frequency of unrecognized Bordetella pertussis infections in adults, we performed IgA and IgG ELISA antibody studies with four B. pertussis antigens--i.e., lymphocytosis-promoting factor, filamentous hemagglutinin, pertactin, and fimbriae-2--in 51 health care workers from whom six consecutive yearly serum samples (from 1984 to 1989) were available. Overall, 90% of the subjects had a significant increase in antibody (IgA or IgG) to one or more antigens between 2 consecutive years during the 5-year study period; 55% of subjects had evidence of two infections, 17% had three infections, and 4% had four infections. Infections occurred in all study years, with the following rates: 1984-1985, 32%; 1985-1986, 24%; 1986-1987, 40%; 1987-1988, 29%; and 1988-1989, 43% (P = .12). Some antibody rises may have been due to responses to cross-reacting antigens (Bordetella parapertussis, nontypable Haemophilus influenzae), but overall these data suggest that B. pertussis infections in adults are common, endemic, and usually unrecognized. 相似文献
997.
PA Holme NO Solum F Brosstad N Egberg TL Lindahl 《Canadian Metallurgical Quarterly》1995,74(6):1533-1540
The mechanism of formation of platelet-derived microvesicles remains controversial. The aim of the present work was to study the formation of microvesicles in view of a possible involvement of the GPIIb-IIIa complex, and of exposure of negatively charged phospholipids as procoagulant material on the platelet surface. This was studied in blood from three Glanzmann's thrombasthenia patients lacking GPIIb-IIIa and healthy blood donors. MAb FN52 against CD9 which activates the complement system and produces microvesicles due to a membrane permeabilization, ADP (9.37 microM), and the thrombin receptor agonist peptide SFLLRN (100 microM) that activates platelets via G-proteins were used as inducers. In a series of experiments platelets were also preincubated with PGE1 (20 microM). The number of liberated microvesicles, as per cent of the total number of particles (including platelets), was measured using flow cytometry with FITC conjugated antibodies against GPIIIa or GPIb. Activation of GPIIb-IIIa was detected as binding of PAC-1, and exposure of aminophospholipids as binding of annexin V. With normal donors, activation of the complement system induced a reversible PAC-1 binding during shape change. A massive binding of annexin V was seen during shape change as an irreversible process, as well as formation of large numbers of microvesicles (60.6 +/- 2.7%) which continued after reversal of the PAC-1 binding. Preincubation with PGE1 did not prevent binding of annexin V, nor formation of microvesicles (49.5 +/- 2.7%), but abolished shape change and PAC-1 binding after complement activation. Thrombasthenic platelets behaved like normal platelets after activation of complement except for lack of PAC-1 binding (also with regard to the effect of PGE1 and microvesicle formation). Stimulation of normal platelets with 100 microM SFLLRN gave 16.3 +/- 1.2% microvesicles, and strong PAC-1 and annexin V binding. After preincubation with PGE1 neither PAC-1 nor annexin V binding, nor any significant amount of microvesicles could be detected. SFLLRN activation of the thrombasthenic platelets produced a small but significant number of microvesicles (6.4 +/- 0.8%). Incubation of thrombasthenic platelets with SFLLRN after preincubation with PGE1, gave results identical to those of normal platelets. ADP activation of normal platelets gave PAC-1 binding, but no significant annexin V labelling, nor production of microvesicles. Thus, different inducers of the shedding of microvesicles seem to act by different mechanisms. For all inducers there was a strong correlation between the exposure of procoagulant surface and formation of microvesicles, suggesting that the mechanism of microvesicle formation is linked to the exposure of aminophospholipids. The results also show that the GPIIb-IIIa complex is not required for formation of microvesicles after activation of the complement system, but seems to be of importance, but not absolutely required, after stimulation with SFLLRN. 相似文献
998.
MV Teplova BI Kurganov IA Gorskaia IN Topchieva NV Efremova TL Bushueva 《Canadian Metallurgical Quarterly》1993,58(12):1929-1935
A fluorescent study of some structural and functional properties of conjugates of a number of proteins (bovine serum albumin, pyruvate kinase, alpha-chymotrypsin, and the two toxic proteins of plant origin--ricin and viscumin) with polyalkylene oxides (polyethylene glycol and pluronic) has been carried out. Analysis of the intrinsic protein fluorescence showed that the structure and stability of various protein conjugates to denaturing agents change only slightly: the conformational mobility of tryptophan residues accessible to the solvent decreases, whereas that of tryptophan residues localized in the protein regions of low polarity remains unchanged. Besides, the conjugates display a higher thermal stability in comparison with their native proteins. The fluorescence of 1-anilinonaphthalene-8-sulfonic acid and water insoluble 2',3',4',5'-tetrabenzoylriboflavin bound to the native and modified proteins indicated that modification of the proteins with polyalkylene oxides decreased the polarity and increased the viscosity of the microenvironment. Hence, this modification makes it possible to change some functional characteristics of the protein without causing any significant changes in its structure. 相似文献
999.
Five patients on chronic hemodialysis regimens were hospitalized with six episodes of Staphylococcus aureus septicemia. Three of the patents acquired the infection during home dialysis, and it was related to the hemodialysis circulatory-access site in four. Initial therapy was methicillin sodium. Vanomycin hydrochloride was given in a 1-gm, single, weekly dose as the sole antibiotic after a short interval (mean, three days). Five of the six episodes were treated successfully. Staphylococcus epidermidis grew in blood cultures obtained during one of the treatments. The advantages of this regimen included a more prompt ambulation and the discontuation of constant infusions in patients with no peripheral veins available. 相似文献
1000.
Severe stenosis of main-stem and segmental bronchi occurred in a 79-year-old woman with previously and adequately treated endobronchial tuberculosis. Symptoms and physiologic abnormalities did not occur until more than three years after diagnosis and initiation of therapy. 相似文献