UC blood infection with clinical strains of Mycobacterium tuberculosis: a novel model.

BACKGROUND: Use of unrelated cord blood transplantation (UCBT) is increasing, yet high rates of mortality secondary to infection remain a problem. We investigated the utility of using umbilical cord blood (UCB) as a model to study a naive cell population challenged by Mycobacterium tuberculosis. METHODS: Mononuclear cells were isolated from nine UCB samples and infected with each of four distinct strains of M. tuberculosis. The isolates used were two highly transmissible clinical strains, the virulent laboratory strain H37Rv and a unique strain isolated from only one case (i.e. non-virulent). CFU were assessed at 3 h post-infection (day 0) and at day 7 to generate growth curves. Viability of the mononuclear cells was assessed prior to infection, 3 h post-infection and at days 3, 5 and 7 post-infection. IFN-gamma and TNF-alpha levels were determined at 24 h post-infection. RESULTS: All three of the virulent strains demonstrated rapid growth in UCB cells that was significantly faster than the growth rate observed for the non-virulent unique isolate. There was no significant decrease in UCB cell viability after the 7-day incubation period regardless of infecting isolate. UCB cells secreted IFN-gamma in response to infection, with no significant difference related to infection with different isolates. However, there was a significant increase in the amount of TNF-alpha elicited following infection with the non-virulent isolate compared with the virulent isolates. DISCUSSION: These results show that UCB can be used as a model to study infection, hopefully leading to new therapies for neonates and UCBT recipients.

Influence of allogeneic blood transfusion on clinical outcome during radiotherapy for cancer of the uterine cervix.

Anemia has long been reported to adversely affect the efficacy of radiation treatment in cervical cancer. On the basis of these findings, many radiation oncologists routinely use blood transfusions with the intent to maintain hemoglobin above specified levels during radiation therapy. However, allogeneic blood transfusions have been previously linked with biological and clinical phenomena correlated with immune suppression. In this study we have analyzed the effects of blood transfusion on the outcome of 130 patients with stage-IIB and -III cervical carcinomas treated with external radiation and intracavitary brachytherapy with or without concomitant platinum administration at the University of Arkansas for Medical Sciences between 1990 and 1999. With the exception of hemoglobin and hematocrit levels at the onset of treatment between the transfused and untransfused groups (p < 0.001), the distribution of age, histology, total radiation dose and duration of treatment were not significantly different between the 2 groups of stage-IIB and -III patients. Among the 45 stage-IIB patients who received blood during radiation treatment, there were 31 deaths (68.8%), compared with 14 (31.8%) among the 44 patients who did not receive blood (p > 0.05). Among the 30 stage-III patients who received blood during radiation treatment, there were 27 deaths (90%), compared with 6 (54%) among the 11 patients who did not receive blood (p > 0.11). In multivariate analysis of survival, there was a significant difference due to transfusion with a risk ratio (RR) of 2.6 (95% CI 1.6, 4.2; p < 0.001) after adjusting for no chemotherapy (RR = 2.2, 95% CI 1.4, 3.5; p < 0.001), considering all patients collectively, stage-IIB patients only (RR = 1.9, 95% CI 1.1, 3.3; p < 0.01), and stage-III patients only (RR = 3.2, 95% CI 1.2, 8.7; p < 0.02). These results suggest that routine blood transfusion of anemic cervical cancer patients does not improve outcome and may represent an independent variable predictive of diminished survival during primary radiation treatment for cervical cancer. Prospective randomized studies are strongly warranted to confirm this hypothesis.

Effects of irradiation on the expression of major histocompatibility complex class I antigen and adhesion costimulation molecules ICAM-1 in human cervical cancer.

PURPOSE: We initiated studies to analyze the effects of high doses of gamma irradiation on the surface antigen expression of MHC Class I, Class II, and ICAM-1 on human cervical carcinoma cell lines. METHODS AND MATERIALS: The expression of surface antigens (MHC Class I, Class II, and ICAM-1) was evaluated by FACS analysis on two cervical cell lines at different time points, following their exposure to high doses of gamma irradiation (i.e., 25.00, 50.00, and 100.00 Gy). RESULTS: The CaSki and SiHa cervical cancer cells we analyzed in this study expressed variable levels of MHC Class I and ICAM-1 antigens, while Class II surface antigens were not detectable. Whereas irradiation doses of 25.00 Gy were not sufficient to totally block cell replication in both cell lines, exposure to 50.00 or 100.00 Gy was able to completely inhibit cell replication. Range doses from 25.00 to 100.00 Gy significantly and consistently increased the expression of all surface antigens present on the cells prior to irradiation but were unable to induce neoexpression of antigens previously not expressed by these cells (i.e., MHC Class II). Importantly, such upregulation was shown to be dose dependent, with higher radiation doses associated with increased antigen expression. Moreover, when the kinetic of this upregulation was studied after 2 and 6 days after irradiation, it was shown to be persistent and lasted until all the cells died. CONCLUSIONS: These findings may partially explain the increased immunogenicity of tumor cells following irradiation and may suggest enhanced immune recognition in tumor tissue in patients receiving radiation therapy.