Ultrastructural changes associated with the inhibition of monocyte chemotaxis caused by products of axenically grown Entamoeba histolytica

The supernatant fluid of axenically grown Entamoeba histolytica-HM1 significantly modifies the ultrastructural features associated with monocyte chemotaxis as assayed in Boyden chambers. This morphological evidence supports the existence of a factor, monocyte locomotion inhibitory factor (MLIF), produced by E. histolytica that inhibits the in vitro locomotion of human monocytes. None of the leucocyte-locomotion modifying drugs included in this study (i.e., cytochalasin-B, colchicine, vinblastine, and hydrocortisone) caused changes totally comparable with those induced by MLIF. The most striking feature was the increase of centriole-associated microtubules induced by MLIF and by cytochalasin-B. MLIF may inhibit monocyte locomotion by directly inducing excessive microtubule assembly, although a direct, if somewhat weak effect upon microfilaments cannot be excluded. The increase in microtubules could then represent a perhaps futile attempt of the microtubule organizing center to overcome the locomotion blockade that has occurred elsewhere in the cell. If active in vivo, MLIF may contribute to the paucity of inflammation in the advanced stages of invasive amebiasis, and consequently to the lack of scar tissue formation upon recovery from such lesions, as monocytes constitute an essential link to the healing process.     

Inverse association between skin response to aeroallergens and Schistosoma mansoni infection

BACKGROUND: Helminthic infections and allergic disease are highly prevalent in many areas of the world. It is known that IgE antibodies are involved in the pathogenesis of both helminthiasis and atopy. However, the consequences of the presence of helminthic infections in atopic patients are still not completely understood. METHODS: Subjects infected by Schistosoma mansoni with more than 200 eggs/g of feces (n = 42) and uninfected subjects (n = 133) were selected from an endemic area of schistosomiasis. The history of allergy and results of the immediate hypersensitivity prick tests with inhalant allergen extracts were registered. Total IgE and IgE specific to S. mansoni and aeroallergens were measured in serum by ELISA. RESULTS: The proportion of individuals with a positive skin test to allergens was higher in the uninfected group (24.3%) than in the group with more than 200 eggs/g of feces (4.8%). The odds of atopy (defined as a positive test for at least one of the antigens) were 5 times higher (odds ratio = 7.0; 95% confidence interval = 1.6-31.1%; p = 0.01) in the uninfected group, after taking into account the potential influence of gender and age. While there was a tendency for higher total and S. mansoni-specific IgE levels in infected patients, an opposite trend, that is higher aeroallergen-specific IgE, was observed in uninfected subjects. CONCLUSIONS: There was a strong and statistically significant inverse association between the immediate skin test response to common aeroallergens and infection by S. mansoni. The results indicate that immediate hypersensitivity reactions may be suppressed in S. mansoni-infected individuals.     

Suprabasal p53 immunoexpression is strongly associated with high grade dysplasia and risk for malignant transformation in potentially malignant oral lesions from Northern Ireland

AIMS: No good predictive marker for the malignant transformation of potentially malignant oral lesions (PMOLs) is currently available. This study re-evaluated the value of p53 immunoexpression to predict malignant transformation of PMOLs after discounting possible confounding factors. METHODS: PMOLs from 18 patients who showed progression to carcinoma, 16 of the respective carcinomas, and PMOLs from 18 matched controls were evaluated by immunohistochemistry (IHC) for p53 expression. A mouse monoclonal antibody that detects wild-type and mutant forms of human p53 was used. The p53 immunostaining pattern was also correlated with the degree of dysplasia. RESULTS: Suprabasal p53 staining was significantly associated with high grades of dysplasia (p < 0.01). The specificity and positive predictive value (PPV) for malignant transformation of suprabasal p53 staining were superior to the assessment of dysplasia, but sensitivity was inferior. All carcinomas derived from PMOLs with suprabasal p53 showed strong p53 immunostaining. However, the absence of suprabasal p53 staining and/or dysplastic changes did not preclude malignant transformation in a considerable proportion of PMOLs. CONCLUSIONS: This study confirms and extends previous findings that suprabasal p53 immunoexpression has a high PPV for malignant transformation of PMOLs and can be used as a specific marker for lesions that are at high risk for malignant transformation. The absence of suprabasal p53 staining (that is, absence of, or basal, p53 staining) is non-informative for prognostic purposes. Because of its limited sensitivity, p53 IHC is not a substitute for the assessment of dysplasia in the evaluation of PMOLs. Instead, p53 IHC emerges as a clinically useful supplement of histopathological assessment in the prognosis of PMOLs.     

Interrupted versus continuous chemotherapy in patients with metastatic breast cancer. The Piedmont Oncology Association

BACKGROUND. Chemotherapy for metastatic breast cancer is palliative, and the optimal duration of therapy is unknown. We designed a trial to determine whether continuous treatment is superior to stopping treatment after a brief induction period and resuming treatment when the disease progresses. METHODS. We treated 250 women with metastatic breast cancer with six courses of cyclophosphamide, doxorubicin, and fluorouracil given every three weeks. At the completion of this induction period, women whose disease either regressed or remained stable were randomly assigned to receive either continued treatment with cyclophosphamide, methotrexate, and fluorouracil (maintenance therapy) or no further treatment (observation) followed by treatment with cyclophosphamide, methotrexate, and fluorouracil when disease progression became evident (reinduction). RESULTS. The combined rate of complete and partial responses after initial therapy was 30 percent (71 of 233 patients who could be evaluated; 95 percent confidence interval, 25 percent to 37 percent). In another 42 percent (98 patients), the disease remained stable. A total of 145 patients were randomized. Seventy-one were randomly assigned to the maintenance-therapy group, and 74 to the observation group. The median time to progression was 9.4 months for patients in the maintenance-therapy group and 3.2 months for patients in the observation group (P less than 0.001). After reinduction therapy, the median time to progression was 3.5 months. The median length of survival from the time of initial therapy was 14.8 months for all 250 patients; it was 21.1 months for the 71 patients in the maintenance-therapy group and 19.6 months for the 74 patients in the observation group (P = 0.67). Maintenance therapy was the most important determinant of the time before progression (P less than 0.001), but it was not associated with prolonged survival. The changes in performance status were similar in the patients in both groups, but nausea, vomiting, and mucositis were significantly more frequent in the maintenance-therapy group. CONCLUSIONS. In patients with breast cancer who received induction chemotherapy for 18 weeks, subsequent continuous chemotherapy was associated with a significant prolongation of the time before progression as compared with those receiving no further therapy; overall survival, however, was not significantly different in the two groups.     

Secular trend in age at menarche for women born between 1920 and 1979 in Rio de Janeiro, Brazil

PRIMARY OBJECTIVE: This article presents data on the secular trend in age at menarche for 1955 women from 16 to 76 years of age born between 1920 and 1979 and studied under the Nutrition and Health Survey conducted in the municipality of Rio de Janeiro, Brazil, in 1996. METHODS AND PROCEDURES: Age at menarche was defined by the retrospective method. Women were grouped according to decade of birth, and the trend was estimated using simple linear regression between age at menarche and year of birth for the following specific periods: 1920-1940, 1920-1960, 1960-1979 and 1920-1979. MAIN OUTCOMES AND RESULTS: Mean age at menarche decreased from 13.07 to 12.40 years when comparing the group of women born in the 1920s with the 1970s birth cohort, corresponding to a mean rate of -0.0123 years per year (p < 0.001). The downward trend was -0.0120 years per year (p > 0.05) for the 1920s, 30s and 40s, -0.0093 years per year (p < 0.05) for the period from 1920 to 1960, and -0.0224 years per year (p < 0.01) for the 1960s/70s. CONCLUSIONS: The results suggest a secular trend in age at menarche. The literature points to such environmental variables as improved living conditions and expanded access to health services. Within this context, age at menarche could be used as a marker for social development.     

HL-A Antigens in Leprosy

HL—A phenotype frequencies were studied in 30 patients with leprosy and in 149 healthy controls. Leprosy patients had a significantly higher frequency of HL—A14. In addition, a majority of the HL—A14 patients gave a negative response to leproma antigen using the Mitsuda test.     

Novel polymorphisms and the definition of promoter 'alleles' of the tumor necrosis factor and lymphotoxin alpha loci: inclusion in HLA haplotypes

Tumor necrosis factor (TNF) and lymphotoxin alpha (LTA) influence a variety of cellular responses and play a complex role in the immune response. Several single nucleotide polymorphisms (SNPs) have been reported in these major histocompatibility complex (MHC)-linked loci; however, a comprehensive examination of polymorphisms in the promoter regions of TNF and LTA has not been carried out and was undertaken here. Seven novel SNPs in LTA were identified by sequence analysis of 69 samples. Eight novel TNF alleles and 16 novel LTA alleles were designated. The TNF alleles clustered into two closely related groups, while the LTA alleles clustered into three distinct groups using phylogenetic and percentage difference analyses. A total of 52 unique TNF-LTA-HLA haplotypes are reported. There appear to be some associations between TNF/LTA alleles and HLA haplotypes, but not with specific HLA alleles. The majority of the SNPs appear to be randomly associated within and between the two loci except for the LTA SNPs at -293, +81 and +369. These observations may provide an explanation for the oftentimes contradictory results of studies associating individual cytokine gene SNPs with expression level phenotypes, HLA and disease.