Analysis of fibronectin expression in the bilharzial granulomas and of laminin in the transformed urothelium in schistosoma haematobium infested patients.

UNLABELLED: The bilharzial granulomas and urothelial transformation are common findings in Schistosoma haematobium infested patients. We hypothesize that the distribution of extrinsic (fibronectin, FN) and intrinsic basement membrane (BM) proteins (laminin, LN) is altered during the evolution of these lesions. METHODS: To test this hypothesis, 70 cystectomy specimens, entailing variable associations of normal and dysplastic urothelium (all cases), and bilharzial granulomas were examined for FN and LN protein expression. RESULTS: The biharzial granulomas were formed of admixture of CD3+T cells, CD68+histiocytes and CD220B cells. The CD3+T cells and and CD68+histiocytes were the predominant cell populations. Increased deposition of FN occurred with the evolution from cellular (loose fibrillary network, 20 cases) to fibrocellualr (dense fibrillary network, 30 cases) to fibrotic (tight conglomerates, 20 cases) granulomas. Alternatively, BM staining for LN was linear and continuous underlying normal and metaplastic urothelium. In dysplastic urothelium (20 cases), it showed breaks in continuity. CONCLUSIONS: Alterations of FN and LN occur during the development of the bilharzial granuloma and urothelial transformation.

Expression of CD44 protein in bilharzial and non-bilharzial bladder cancers.

OBJECTIVES: To investigate the expression of CD44 protein in bilharzial and non-bilharzial bladder carcinomas, and to relate the results of immunohistochemistry to the established prognostic factors, as studies clearly show that altered adhesive function of tumour cells is important in the metastatic process and CD44 is assumed to be critical in the malignant progression of many human tumours. PATIENTS AND METHODS: The study included 55 patients with bladder carcinoma confirmed by cystoscopy and biopsy. Of the 33 patients with transitional cell carcinoma (TCC), 19 were bilharzial and 14 non-bilharzial, and of 22 with squamous cell carcinoma (SCC), 12 were bilharzial and 10 non-bilharzial. CD44 expression was measured by immunohistochemical analysis of paraffin-embedded tissue obtained from these patients after appropriate treatment (transurethral resection, partial or radical cystectomy). RESULTS: There was significantly less CD44 expression in invasive TCC than in normal urothelium and pre-invasive TCC (P = 0.05). The expression of CD44 was inversely related to the tumour grade and depth of invasion (P = 0.05). However, there was no such relation for SCC; there was no significant difference between CD44 expression in metaplastic squamous epithelium, pre-invasive and invasive SCC. The presence or absence of bilharzial ova had no apparent effect on the expression of CD44, with no significant difference between CD44 expression in bilharzial and non-bilharzial bladder carcinomas. CONCLUSIONS: These data confirm that there is a reduction in CD44 expression with increasing tumour grade and stage of TCC, and may provide an additional aid in predicting the progression of this tumour. There was no such relationship with SCC, and no difference between CD44 expression in bilharzial and non-bilharzial bladder carcinomas.

Cytokines in leprosy, I. Serum cytokine profile in leprosy.

BACKGROUND: Leprosy is a chronic infectious disease characterized by a broad spectrum of clinical forms depending on the patient's immune response, in particular cell-mediated immune response. METHODS: Cytokines can play a role in the cell-mediated immune response. Serum levels of interferon-gamma (IFN-gamma), interleukin-2 (IL-2), interleukin-2 receptor (IL-2R), interleukin-10 (IL-10), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta) were measured by enzyme-linked immunosorbent assay (ELISA) in 55 untreated leprosy patients and 35 reactional leprosy patients, in addition to 20 age- and sex-matched healthy controls. RESULTS: Leprosy patients showed significantly higher serum levels of the studied cytokines (except IL-2) compared with healthy controls. When the two poles were compared, tuberculoid leprosy (TT) patients showed significantly higher levels of IFN-gamma and TNF-alpha with significant negative correlations with the bacterial index (BI), whereas lepromatous leprosy (LL) patients showed significantly higher serum levels of IL-2R, IL-10, and IL-1beta with significant positive correlations with the BI. Both type I and type II reactional patients showed significantly higher serum IFN-gamma, IL-2R, and IL-1beta, in addition to IL-10 in type II reactional patients, compared with nonreactional leprosy patients. When compared with each other, type I reactional patients showed increased levels of IFN-gamma, whereas type II reactional patients showed increased levels of IL-10. CONCLUSIONS: In leprosy patients, both IFN-gamma and TNF-alpha are immunoprotective, whereas IL-2R, IL-10, and IL-1beta are immunosuppressive. Our results indicate that type I reaction, with increased levels of IFN-gamma, is a cell-mediated immune response, whereas type II reaction, with increased levels of IL-10, is essentially an immune complex disease.

Cytokines in leprosy, II. Effect of treatment on serum cytokines in leprosy.

BACKGROUND: Multidrug therapy (MDT) causes a decrease in the bacterial burden in leprosy patients. Does the decrease in the antigenic stimulation of the immune system have an effect on cytokine production? METHODS: The effect of treatment on serum cytokines was evaluated in 36 leprosy patients and 35 reactional leprosy patients and compared with that in 20 age- and sex-matched healthy individuals. The enzyme-linked immunosorbent assay (ELISA) technique was used to measure serum levels of interleukin-2 receptor (IL-2R), interleukin-10 (IL-10), and interleukin-1beta (IL-1beta) before and after treatment. These cytokines represent T-helper 1 (TH1), T-helper 2 (TH2), and macrophage cytokines, respectively. RESULTS: The studied serum cytokines were significantly reduced after 1 year of treatment in leprosy patients. The degrees of reduction were significantly positively correlated with a reduction in the bacterial index (BI) and morphologic index (MI). After 1 year of MDT (but not 6 months), paucibacillary (PB) patients showed a significant reduction in all the studied serum cytokines to levels comparable with those of healthy controls. Multibacillary (MB) patients also showed a significant reduction in all the studied serum cytokines, but the levels were still significantly higher than those of healthy controls. Leprosy patients with high levels of serum IL-1beta were more susceptible to the development of reactions after the initiation of treatment. Corticosteroid therapy of reactional patients resulted in a significant reduction in the studied serum cytokines to levels similar or lower than those of nonreactional leprosy patients. The dose of steroids showed a significant positive correlation with the amount of decrease in IL-1beta. CONCLUSIONS: MDT caused a reduction in serum cytokines correlated with a reduction in the bacterial burden. It is advisable to continue MDT for PB patients for 1 year. Serum IL-1beta levels may have a prognostic value for the susceptibility of leprosy patients to the development of reactions.

Prognostic significance of p53 immunostaining in epithelial ovarian cancer.

PURPOSE: To evaluate the prognostic significance of p53 expression in epithelial ovarian cancer, including a subset of stage I patients, and to look for correlations between p53 expression and other disease parameters, including stage, grade, age, histologic subtype, second-look results, ploidy, and percent S phase. PATIENTS AND METHODS: We analyzed p53 expression in 284 patients with epithelial ovarian cancer using immunohistochemical techniques in paraffin-embedded specimens. There were 36 patients with stage I disease, 20 with stage II disease, 186 with stage III disease, and 42 with stage IV disease. RESULTS: p53 immunoreactivity was present in 177 cases (62%). p53 expression was associated with grade 3 to 4 disease (P = .003). The following factors were associated with a decrease in overall survival in a univarate analysis: stage III or IV disease (P = .0001), grade 3 or 4 disease (P = .0001), age above the median (P = .0002), and p53 reactivity (P = .04). In a multivariate analysis, stage, grade, and age retained independent prognostic significance. In the subset of 36 stage I patients, p53 positively approached statistical significance (P = .10) as a negative prognostic factor in a univariate analysis. CONCLUSION: Abnormalities of p53 expression occur commonly in epithelial ovarian cancer. Although associated with decreased survival in a univariate analysis, this biologic marker did not retain independent prognostic significance in a multivariate analysis. p53 expression should be studied in a larger cohort of early-stage patients, where accurate prognostic information is needed to direct therapy.

Proliferating cell nuclear antigen in epithelial ovarian cancer: relation to results at second-look laparotomy and survival.

We determined the proliferative index (PI) of 92 previously untreated advanced epithelial ovarian cancers using PCNA/cyclin immunostaining and image analysis quantitation. In this retrospective study, there was a relationship between tumor PI and 5-year survival. For patients with a tumor PI greater than the median, the estimated 5-year survival was 44%; for patients with a tumor PI below the median, the estimated 5-year survival was 15% (P = 0.003). This may partly reflect sensitivity to chemotherapy, as those patients with more rapidly proliferating tumors were more likely to achieve a pathologic complete response to platinum-based therapy.

Family planning studies the teachers' survey. Part 2: fertility differentials and practice of family planning.

PIP: This study deals with biologic and socioeconomic fertility differentials of married female teachers in the Alexandria Governorate who were surveyed via questionnaire from October 1966 to February 1967. It also shows fertility patterns of educated working women, their opinions about family planning, their use of contraceptives, and their knowledge and use of family planning services. Of the 3893 teachers who responded, 65%, or 2626, were married and 92.5% were of childbearing age. The average age was 32.70 years; the average duration of marriage was 7.18 years. Half had just 1 or 2 children, with an inverse relationship between educational attainment and number of children. The number of children increased with the age of the teacher, but there was an inverse relationship between age at marriage and number of children. Just over 25% of the pregnancies ended in abortion, with an average of .64 abortions per teacher. There was a direct relationship between age of teacher and frequency of abortion. Teachers who married when they were under 20 were the most likely to abort. 13% of the teachers were pregnant at the time of the study. An inverse relationship existed between the desire to be pregnant and the number of surviving children. Statistics for married teachers over 45 who had completed their fertility indicate that the average teacher is likely to have 1.02 abortions, 3.1 deliveries, and 2.6 living children. All teachers favored family planning. 77.3% were currently practicing it, most in the 30-44 age group. 42% had consulted private doctors; 44.3% were prac ticing without medical advice; and only 14.8% went to a family planning center. The pill and the IUD were the most popular method, being used by 59.7%. Among those with children, those with no boys were the least likely to use contraceptives. Teachers, with their frequent contact with young people and parents, are seen as a good conduit for information about family planning. However, most teachers themselves got their initial information about family planning from the mass media.^ieng