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61.
S Kozlowski M Corr M Shirai LF Boyd CD Pendleton JA Berzofsky DH Margulies 《Canadian Metallurgical Quarterly》1993,151(8):4033-4044
T cell stimulation by certain class I-restricted antigenic peptides, such as the HIV 1 gp160-derived peptide, P18, requires peptide processing by angiotensin-1 converting enzyme (ACE) in FCS. We observed that longer versions of P18 and the murine cytomegalovirus pp89-derived core peptide, pMCMV, which could stimulate T cell hybridomas in FCS, were not as sensitive to the ACE inhibitor captopril as P18. Using cell-free soluble murine class I MHC molecules and protease inhibitors, we found that there are pathways of differing efficiency that use enzymes other than ACE for the proteolytic processing of peptides in serum. The kinetics of the generation of T cell stimulatory activity among P18 variant peptides in serum differed with peptide length, and with the nature of amino and COOH-terminal extensions. Such processing occurs in human plasma as well as in FCS. The understanding of this processing, its kinetics, and its inhibitors can lead to better design of peptide-based therapies, including vaccines. 相似文献
62.
Amplification of a 340 bp sequence of the 38 kDa protein gene of Mycobacterium tuberculosis by the polymerase chain reaction has been developed. The sensitivity of this PCR was shown to be 10 fg both by agarose gel electrophoresis and Southern blot hybridisation being equivalent to 2-3 organisms and highly specific to M. tuberculosis and excluding even M. tuberculosis H37Ra and Mycobacterium bovis BCG. Sputum samples from patients with pulmonary tuberculosis gave a positivity rate of 45%. PCR was also performed using pt8 and pt9 primers which amplified a 541 bp sequence of IS6110. 41% of the above samples gave positive amplification. Three samples that were positive for 38 kDa sequence were negative for IS6110. 相似文献
63.
Mitomycin C and hyperthermia are both toxic to chronically hypoxic EMT6 tumor cells. Combinations of this drug and heat were tested in vitro in normally aerated and chronically hypoxic EMT6 mouse mammary tumor cells to establish whether greater than additive cytotoxicity could be achieved by combined treatment. Cell survival was measured at four concentrations of mitomycin C (0.01, 0.1, 1.0, and 10 microM) at 37 degrees or at elevated temperatures (41, 42, and 43 degrees) for durations of 1, 2, 3, and 6 hr. At 42 degrees, exposure to mitomycin C for 3 and 6 hr produced a 2- to 3-fold increase in hypoxic tumor cell kill at all drug concentrations over that expected for strict additivity. A 15-fold enhancement in the kill of hypoxic tumor cells was obtained at 1.0 and 10 microM mitomycin C at 43 degrees for 6 hr of exposure. Under most conditions, additivity was observed for the antibiotic and heat in oxygenated cells, except at 43 degrees with 0.01 and 0.1 microM mitomycin C following 3 and 6 hr of treatment, conditions under which a 5- to 10-fold potentiation of tumor cell kill was obtained. The rate of formation of reactive metabolites from mitomycin C under anaerobic conditions in EMT6 cell-free preparations was measured. A 30 to 50% increase in alkylating activity was observed at elevated temperatures, suggesting that the enhanced cytotoxicity of mitomycin C with heat toward hypoxic cells may, in part, be due to an increase in activation of the drug. 相似文献
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65.
F Espa?a M Martínez J Sánchez-Cuenca CD Vera A Estellés JF Jiménez-Cruz 《Canadian Metallurgical Quarterly》1996,30(4):512-518
OBJECTIVE: To improve the specificity and sensitivity of the prostate-specific-antigen (PSA) assay for the distinction between prostate cancer and benign prostate hyperplasia (BPH). METHODS: Two sensitive immunoassays, one that measures free PSA and PSA complexed to alpha 1-antichymotrypsin (alpha 1-ACT) with the same efficiency (PSAag assay) and another that specifically measures the complex between PSA and alpha 1-ACT, have been designed to measure the PSA forms in the plasma of 84 patients with prostate disease and in the seminal plasma from 60 healthy individuals. RESULTS: The proportion of plasma PSA in complex with alpha 1-ACT was significantly higher in the 34 patients with prostate cancer (89 +/- 12%, mean +/- SD; median, 91%) than in the 50 patients with BPH (71 +/- 12%; 73%) and did not correlate with the total amount of PSA. Normal seminal plasma (n = 60) had 2.1 +/- 0.6 mg/ml PSA, 175 +/- 62 microns/ml alpha 1-ACT and 9.6 +/- 3.4 micrograms/ml PSA: alpha 1-ACT complex. CONCLUSION: These results confirm that PSA: alpha 1-ACT may be a good marker for a differential diagnosis of carcinoma of the prostate and BPH. 相似文献
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WI Bensinger KS Schiffman L Holmberg FR Appelbaum R Maziarz P Montgomery E Ellis S Rivkin P Weiden K Lilleby S Rowley S Petersdorf JP Klarnet W Nichols A Hertler R McCroskey CH Weaver CD Buckner 《Canadian Metallurgical Quarterly》1997,19(12):1183-1189
The purpose of this study was to determine the outcome of patients with metastatic breast cancer treated with high-dose busulfan (Bu), melphalan (Mel) and thiotepa (TT) followed by peripheral blood stem cell (PBSC) infusion. Fifty-one patients with chemotherapy refractory (n = 32) or responsive (n = 19) metastatic breast cancer received Bu (12 mg/kg), Mel (100 mg/m2) and TT (500 mg/m2) followed by PBSC collected after chemotherapy and growth factor (n = 43) or growth factor alone (n = 8). The 100 day treatment-related mortality was 8% including one death from cytomegalovirus pneumonia, one from aspiration pneumonia and two from regimen-related toxicity (RRT). Seven of 28 refractory (25%) and 5/7 (71%) responsive patients with evaluable disease achieved a complete response of all measurable disease or all soft tissue disease with at least improvement in bone lesions (PR*). Fifteen of 51 patients (29%) are alive and progression-free a median of 423 days (range 353-934) after treatment, 5/32 (16%) with refractory disease and 10/19 (53%) with responsive disease. The probabilities of progression-free survival (PFS) at 1.5 years for the patients with refractory (n = 32) and responsive (n = 19) disease were 0.24 and 0.53, respectively. These preliminary data suggest that high-dose Bu/Mel/TT has significant activity in patients with advanced breast cancer and may be superior to some previously published regimens. 相似文献
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69.
Rectal ischemia is rare because of excellent collateral supply. Although rectosigmoid ischemia is usually accompanied by more proximal colonic involvement, it may occur alone. METHODS: A retrospective review of all patients diagnosed as having colonic ischemia at the Mayo Clinic from 1976 to 1991 was performed. Clinical, endoscopic, radiological, and pathological data were obtained from patient charts. Patients with involvement of the rectosigmoid colon extending to no more than 30 cm above the dentate line on endoscopy were included in the study. A single radiologist reviewed CT scans and aortograms, and a single pathologist reviewed tissue specimens. RESULTS: Ten of 328 patients with ischemic colitis had isolated ischemic proctosigmoiditis. Six patients had acute ischemia (i.e., symptom duration of less than 4 wk), and four had chronic ischemia (symptoms for 4 wk or longer). Ischemic proctosigmoiditis affects elderly patients with atherosclerosis. An identifiable precipitating factor, such as a major illness or hemodynamic disturbance, was identified in four of six patients with acute ischemic proctosigmoiditis and in one of four patients with chronic ischemic proctosigmoiditis. CT revealed rectal wall thickening and/or perirectal stranding. Angiography may demonstrate atheromatous disease of the aortoiliac vessels. Acute and "chronic" presentations had similar histopathological changes. CONCLUSIONS: Ischemic proctosigmoiditis is rare. In contrast to generalized colonic ischemia, patients with acute rectal ischemia often have clearly identifiable precipitating factors. Conservative management is appropriate for uncomplicated acute ischemic proctosigmoiditis. Patients with chronic ischemic proctosigmoiditis. Patients with chronic ischemic proctosigmoiditis may develop bowel perforation necessitating a proctectomy or colonic diversion. Recognition of this entity and differentiation from idiopathic inflammatory bowel disease is important to determine appropriate therapy. 相似文献
70.
BACKGROUND & AIMS: The molecular mechanisms underlying pancreatitis are largely unknown. The goal of this study was to identify an early genetic event that correlated with pancreatitis. METHODS: Differential display of messenger RNAs (mRNAs) was conducted on normal pancreas vs. those of animals with secretagogue-induced pancreatitis. Northern blots from normal animals and animals with experimental acute pancreatitis were probed with cloned complementary DNAs for chemokines. Pancreatitis was induced with cerulein and by retrograde injection of bile salts. Immunocytochemistry was used to identify the source of chemokine expression. Pyrrolidine dithiocarbamate was tested for effects on chemokine expression and pancreatitis. RESULTS: A differentially amplified band was consistently observed early after cerulein hyperstimulation. This band was identified as a portion of the mob-1 gene, an alpha-chemokine. Northern analysis indicated that mRNAs for mob-1 and another chemokine, mcp-1, were induced after cerulein hyperstimulation in vivo. mob-1 mRNA was also induced by retrograde injection of bile salts and by cerulein in acinar cells in vitro. mob-1 protein was localized to exocrine cells in pancreata of diseased animals. Pyrrolidine dithiocarbamate inhibited both chemokine gene expression and early inflammatory characteristics of pancreatitis. CONCLUSIONS: Chemokines are induced in acinar cells by treatments that induce pancreatitis and may play an important role in the early stages of the disease. 相似文献