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MA Steller KJ Gurski M Murakami RW Daniel KV Shah E Celis A Sette EL Trimble RC Park FM Marincola 《Canadian Metallurgical Quarterly》1998,4(9):2103-2109
Human papillomavirus (HPV) infection has been causally associated with cervical cancer. We tested the effectiveness of an HLA-A*0201-restricted, HPV-16 E7 lipopeptide vaccine in eliciting cellular immune responses in vivo in women with refractory cervical cancer. In a nonrandomized Phase I clinical trial, 12 women expressing the HLA-A2 allele with refractory cervical or vaginal cancer were vaccinated with four E786-93 lipopeptide inoculations at 3-week intervals. HLA-A2 subtyping was also performed, and HPV typing was assessed on tumor specimens. Induction of epitope-specific CD8+ T-lymphocyte (CTL) responses was analyzed using peripheral blood leukapheresis specimens obtained before and after vaccination. CTL specificity was measured by IFN-gamma release assay using HLA-A*0201 matched target cells. Clinical responses were assessed by physical examination and radiographic images. All HLA-A*0201 patients were able to mount a cellular immune response to a control peptide. E786-93-specific CTLs were elicited in 4 of 10 evaluable HLA-A*0201 subjects before vaccination, 5 of 7 evaluable HLA-A*0201 patients after two vaccinations, and 2 of 3 evaluable HLA-A*0201 cultures after all four inoculations. Two of three evaluable patients' CTLs converted from unreactive to reactive after administration of all four inoculations. There were no clinical responses or treatment toxicities. The ability to generate specific cellular immune responses is retained in patients with advanced cervical cancer. Vaccination with a lipidated HPV peptide epitope appears capable of safely augmenting CTL reactivity. Although enhancements of cellular immune responses are needed to achieve therapeutic utility in advanced cervical cancer, this approach might prove useful in treating preinvasive disease. 相似文献
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FM Loehrer CP Angst FP Brunner WE Haefeli B Fowler 《Canadian Metallurgical Quarterly》1998,13(3):656-661
BACKGROUND: Elevated homocysteine concentrations have been associated with premature arteriosclerosis and with impairment of key methylation reactions through accumulation of the homocysteine metabolite S-adenosylhomocysteine. In end-stage renal failure high homocysteine concentrations are commonly found but thus far the concentrations of related adenosylated metabolites in plasma have not been assessed. METHODS: In this prospective study we determined plasma homocysteine and related metabolites in 25 patients on regular haemodialysis, and in 40 healthy volunteers. Blood samples from patients were drawn immediately before and in 10 patients additionally after the dialysis session. RESULTS: Folic acid and vitamin B12 in plasma were similar in patients (mean +/- SEM 25+/-2 nmol/l and 400+/-41 pmol/l respectively) and controls (24+/-3 and 324+/-23 respectively). In patients plasma homocysteine, S-adenosylmethionine and S-adenosylhomocysteine were markedly elevated (36.6+/-3.6 micromol/l, 381+/-32nmol/l and 1074+/-55 nmol/l respectively) compared to the control values (6.8+/-0.4 micromol/l, 60+/-3 nmol/l and 24.4+/-1.1 nmol/l respectively) whereas the molar ratio of plasma S-adenosylmethionine and S-adenosylhomocysteine was significantly decreased (0.36+/-0.02 and 2.7+/-0.2 in patients and controls respectively). Haemodialysis failed to normalize the abnormal levels of these metabolites. CONCLUSION: Since the ratio of S-adenosylmethionine : S-adenosylhomocysteine is closely linked to the activity of numerous enzymatic methylation reactions, these results suggest that methylation may be impaired in these patients. 相似文献
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Virtual instruments for an extracorporeal circulation (ECC) process were developed to simulate the reactions of a patient to different artificial perfusion conditions. The computer simulation of the patient takes into account the hydraulic, volume, thermal and biochemical phenomena and their interaction with the devices involved in ECC (cannulae dimensions, oxygenator and filter types, pulsatile or continuous pump and thermal exchangers). On the basis of the patient's initialisation data (height, weight, Ht) and perfusion variables (pump flow rate, water temperature, gas flow rate and composition) imposed by the operator, the virtual ECC monitors simulated arterial and venous pressure tracings in real time, along with arterial and venous flow rate tracings, urine production tracing and temperature levels. Oxyhemoglobin arterial and venous blood saturation together with other related variables (pO2, pCO2, pH, HCO3 are also monitored. A drug model which allows the simulation of the effect of vasodilator and diuretic drugs is also implemented. Alarms are provided in order to check which variables (pressure, saturation, pH, urine flow) are out of the expected ranges during the ECC simulation. Consequently the possibility of modifying the control parameters of the virtual devices of the ECC in run-time mode offers an interaction mode between the operator and the virtual environment. 相似文献
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Ambient, biological, and biological effect monitoring of exposure to polycyclic aromatic hydrocarbons (PAHs) 总被引:1,自引:0,他引:1
BA Hatjian JW Edwards J Harrison FM Williams PG Blain 《Canadian Metallurgical Quarterly》1995,77(1-3):271-279
A novel strategy was utilised to assess the risk to health from exposure to polycyclic aromatic hydrocarbons (PAHs). Ambient monitoring was carried out by personal sampling. Urinary thioethers (UTh) and urinary 1-hydroxypyrene (1-HP) were utilised for biological monitoring. Urinary d-glucaric acid (UDGA) and sister chromatid exchange (SCE) in peripheral blood lymphocytes were used as biological effect markers. The population was categorised into exposed and control groups according to the external dose of PAHs. The excretion of 1-HP in the controls over the 3-day period showed a relatively stable baseline, while the exposed showed a significant increase over the same period of time. SCE frequency in the exposed population was significantly different from controls. 相似文献
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BACKGROUND: Serum creatinine has been reported in previous studies to be a prognostic indicator for overall mortality, in particular in a hypertensive population. METHODS: The Program on the Surgical Control of the Hyperlipidemias (POSCH) was a randomized, controlled clinical trial. All patients had survived a single myocardial infarction, were normotensive, were not obese, were not having heart failure, and were free of diabetes mellitus and renal disease at entry into the study. POSCH had followed its control group patients (N = 417) for a minimum of 7.0 years. In this group, a prospective post hoc analysis of the relationship of baseline serum creatinine with subsequent overall and atherosclerotic coronary heart disease mortality was performed. RESULTS: The baseline serum creatinine values in the control group patients ranged from 0.7 to 1.9 mg/dL (60 to 170 mumol/L), and were found to be independent predictors (P < .01) of both overall mortality and atherosclerotic coronary heart disease mortality. Each 0.1 mg/dL (9 mumol/L) increment in the baseline serum creatinine increased the relative risk for subsequent overall mortality by 36% and the relative risk for subsequent atherosclerotic coronary heart disease mortality by 47%. CONCLUSIONS: These results demonstrate that a serum creatinine value, obtained in normotensive, nonobese, normoglycemic survivors of a myocardial infarction without preexistent renal disease or heart failure, provides independent prognostic information regarding subsequent overall and atherosclerotic coronary heart disease mortality. 相似文献