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311.
Kaufmann SH; Karp JE; Jones RJ; Miller CB; Schneider E; Zwelling LA; Cowan K; Wendel K; Burke PJ 《Blood》1994,83(2):517-530
The topoisomerase (topo) II-directed agents etoposide, daunorubicin (DNR), and amsacrine (m-AMSA) are widely used in the treatment of acute myelogenous leukemia (AML). In the present study, multiple aspects of topo II-mediated drug action were examined in marrows from adult AML patients. Colony-forming assays revealed that the dose of etoposide, DNR, or m-AMSA required to diminish leukemic colony formation by 90% (LD90) varied over a greater than 20-fold range between different pretreatment marrows. Measurement of nuclear DNR accumulation in the absence and presence of quinidine revealed evidence of P-glycoprotein (Pgp) function in 8 of 82 samples at diagnosis and 5 of 36 samples at first relapse, but the largest quinidine-induced increment in DNR accumulation (< 2-fold) was too small to explain the variations in drug sensitivity. Restriction enzyme-based assays and sequencing of partial topo II alpha and topo II beta cDNAs from the most highly resistant specimens failed to demonstrate topo II gene mutations that could account for resistance. Western blotting of marrow samples containing greater than 80% blasts revealed that the content of the two topo II isoenzymes varied over a greater than 20-fold range, but did not correlate with drug sensitivity in vitro or in vivo. In addition, levels of topo II alpha and topo II beta in 46 of 47 clinical samples were lower than in human AML cell lines. Immunoperoxidase staining showed that these low topo II levels were accompanied by marked cell-to- cell heterogeneity, with topo II alpha being abundant in some blasts and diminished or absent from others. There was a trend toward increasing percentages of topo II alpha-positive cells in pretreatment marrows that contained more S-phase cells. Consistent with this observation, treatment of patients with granulocyte-macrophage colony- stimulating factor for 3 days before chemotherapy resulted in increases in topo II alpha-positive cells concomitant with increases in the number of cells traversing the cell cycle. These observations have implications for the regulation of topo II in AML, for the use of topo II-directed chemotherapy, and for future attempts to relate drug sensitivity to topo II levels in clinical material. 相似文献
312.
Antibody-dependent cytolysis of the human leukemia cell line K-562 in the absence of effector cells or complement 总被引:2,自引:0,他引:2
K-562 human leukemia cells grown in the presence of specific goat anti- K-562 gamma globulin, F(ab)'2, Fab', or Fab showed a decrease in DNA and protein syntheses and a loss of cell viability within several hours. Eventually all cells died and lysed within 2-5 days. These events occurred in the absence of added effector cells or complement. The effect on the cell was not due to proteolytic or other external lytic activity generated at the cell surface, since 51Cr-labeled bystander cells or antibody-sensitized bystander cells (chicken erythrocytes or K-562 cells) were not lysed when added to cultures of K- 562 cells incubated with immune globulin. The anti-K-562 gamma globulin was not observed to patch or cap on K-562 cells, but the ability of bound immunoglobulin to fix complement decreased markedly (50% in 60 min), so that no complement-mediated cytolysis could be observed at 2 hr. However, the immunoglobulin, at least portions of it, reacted with fluorescein--labeled rabbit anti-goat gamma globulin for about 16 hr. 125I-labeled immune globulin appeared to be internalized and released into the medium as small degradation products. 125I-labeled Fab did not appear to be internalized, since it was released intact and more rapidly from cells than the intact globulin. 相似文献
313.
Activation of the CD95 (APO-1/Fas) system in T cells from human immunodeficiency virus type-1-infected children 总被引:8,自引:2,他引:8
Increased apoptosis of CD4+ T cells is considered to be involved in CD4+ T-cell depletion in human immunodeficiency virus type-1 (HIV-1)- infected individuals progressing toward acquired immunodeficiency syndrome (AIDS). We have recently shown that CD95 (APO-1/Fas) expression is strongly increased in T cells of HIV-1-infected children. In this report we provide further evidence for a deregulated CD95 system in AIDS. CD95 expression in HIV-1+ children is not restricted to previously activated CD45RO+ T cells but is also increased on freshly isolated naive CD45RA+ T cells. In addition, specific CD95-mediated apoptosis is enhanced in both CD4+ and CD8+ T cells. Furthermore, levels of CD95 ligand mRNA are profoundly increased. Specific T-cell receptor/CD3-triggered apoptosis in HIV-1+ children is more enhanced in CD8+ than in CD4+ T cells. Accelerated activation induced cell death of T cells could partially be inhibited by blocking anti-CD95 antibody fragments. These data suggest an involvement of the CD95 receptor/ligand system in T-cell depletion and apoptosis in AIDS and may open new avenues of rational intervention strategies. 相似文献
314.
315.
Adriana?MA?De TommasoEmail author Paula?D?Andrade Sandra?CB?Costa Cecília?AF?Escanhoela Gabriel?Hessel 《BMC infectious diseases》2005,5(1):108
Background
Biliary atresia (BA) is the most severe hepatic disorder in newborns and its etiopathogenesis remains unknown. Viral involvement has been proposed, including the human cytomegalovirus (HCMV). The aims of the study were to use the polymerase chain reaction (PCR) to screen the liver tissue of infants with extrahepatic cholestasis for HCMV and to correlate the results with serological antibodies against HCMV and histological findings. 相似文献316.
Effective granulocyte transfusion (GT) therapy has been hampered by the low yield of neutrophil granulocytes (PMN) obtainable from normal donors even by use of corticosteroid prestimulation, hydroxyethyl starch (HES), and modern leukapheresis (LA) techniques. To increase the PMN yield we performed LA in 22 healthy volunteer donors after a single subcutaneous administration of 300 micrograms of granulocyte colony- stimulating factor (G-CSF) 12 to 16 hours before LA. Five to 7 L of blood was processed within 1.9 to 3 hours using the standard CS- 3000Plus (Baxter, Deerfield, IL) LA protocol including HES. The mean number of PMN harvested was 44.32 +/- 15.5 x 10(9), corresponding to 6.88 +/- 2.1 x 10(9)/L of blood processed. In the final product PMN functions (in vitro: chemotaxis, phagocytosis, chemiluminescence, superoxide anion production; in vivo: chemiluminescence, half-life) were at least normal. In all donors G-CSF induced a consistent increase of white blood cell (mean 16.46 +/- 3.8 x 10(9)/L) and PMN counts (15.94 +/- 3.6 x 10(9)/L). No G-CSF-related side effects were observed and LA was well tolerated. G-CSF prestimulation allows to harvest three to five times higher numbers of functionally normal PMN by LA compared with corticosteroid pretreatment. This may help to overcome one of the major limitations of an effective PMN support. 相似文献
317.
Long-term treatment of lupus nephritis with cyclosporin A 总被引:9,自引:0,他引:9
Tam LS; Li EK; Leung CB; Wong KC; Lai FM; Wang A; Szeto CC; Lui SF 《QJM : monthly journal of the Association of Physicians》1998,91(8):573-580
We evaluated the efficacy and safety of long-term treatment with
cyclosporin A (CSA) in type IV lupus nephritis. Seventeen patients with
biopsy-proven WHO type IV lupus nephritis were enrolled in a prospective,
open study. Twelve of the 17 completed 48 months of treatment with CSA and
prednisolone. Three patients required the addition of azathioprine, at 12,
38 and 47 months, respectively, for cutaneous disease flare with refractory
rashes. One patient was lost to follow-up at 40 months. The mean +/- SD
duration of treatment was 43.2 +/- 10.1 months (range 15.7-48 months). A
significant reduction of proteinuria and a significant rise in serum
albumin were noted 1 month after initiation of treatment. Improvement was
maintained throughout the study except for three patients who relapsed with
recurrence of nephrotic syndrome. There were no significant changes in
serum creatinine level or creatinine clearances throughout the study.
Repeat renal biopsy at 12 months following treatment with CSA showed
histological improvement, with WHO type II changes in all 17 patients
accompanying significant reduction in activity indices. Patients with
baseline haemoglobin (Hgb) levels < 12 g/dl showed significant
improvement. Serum C3 and C4 levels were not changed significantly.
Corticosteroid-sparing effects were noted. Side-effects included
hypertension, gum hypertrophy and mild hirsuitism, but were not serious.
Combination therapy using CSA and prednisone is effective and safe for
long-term treatment in lupus patients with WHO type IV nephritis.
相似文献
318.
R Silvis ; WH Steup ; A Brand ; KA Zwinderman ; CB Lamers ; G Griffioen ; HG Gooszen 《Transfusion》1994,34(3):242-247
BACKGROUND: Perioperative blood transfusion (BT) appeared to have adverse effects on survival after surgery for malignant tumors while pretransplantation BT suppressed allograft rejection. Interest grew in the effect of BT on postoperative recurrence of Crohn's disease. STUDY DESIGN AND METHODS: To determine the effect of perioperative BT on the recurrence of Crohn's disease after primary surgery, the medical histories of 148 patients with Crohn's disease, 62 males and 86 females (49 nonparous and 37 parous), were reviewed. Eighty-seven patients received perioperative BT. RESULTS: Overall, perioperative BT showed no effect on recurrence. Patients with Crohn's disease limited to the ileum had a better prognosis with regard to recurrence than did patients with Crohn's disease located in the colon or located in both ileum and colon, but the difference was not significant. Perioperative transfusion seemed to protect against recurrent disease after colon resection, which might be explained by the fact that colon resections, which often necessitate perioperative BT, generally result in a shorter bowel segment at risk for recurrent disease. Overall, parous women showed a worse prognosis than nonparous females and men (p = 0.022). Transfusions had a beneficial effect in parous women (p = 0.068) and, after correction for type of operation, this beneficial effect was significant (p = 0.026). After perioperative BT, parous women had a similar prognosis with respect to recurrent Crohn's disease as nonparous females and men. CONCLUSION: Perioperative BT has a beneficial effect on the postoperative recurrence of Crohn's disease in parous women. 相似文献
319.
Distal ureteral calculi: detection with vaginal US 总被引:2,自引:0,他引:2
320.
The assessment of new radiologic tests can be seriously hampered by the presence of systematic bias. Biases can arise from incomplete verification of the sample population; omission of uninterpretable tests; absence of a definitive reference test; extraneous factors affecting interpretation; and extrapolation factors including variations in test efficacy among patients, hospitals, and the radiologists who interpret the tests. The authors review these biases that affect the results of efficacy studies and provide guidelines to avoid these problems. 相似文献