BsmI, TaqI, ApaI and FokI polymorphisms in the vitamin D receptor (VDR) gene and the risk of osteoporosis: a meta-analysis

A meta-analysis regarding BsmI, TaqI, ApaI and FokI polymorphisms in the vitamin D receptor (VDR) gene and their associations with osteoporosis in females is reported. The meta-analysis involved 14, seven, seven and three studies for BsmI, TaqI, ApaI and FokI polymorphisms, respectively. The studies were association studies with osteoporotic cases and controls free of osteoporosis that provided the genotype distribution of individual cases and controls. For the BsmI polymorphism, the allele contrast b vs. B showed heterogeneity among studies (p< 0.01, I2> 50%) and the random effects (RE) pooled odds ratio (OR) was non-significant: 0.94 [95% confidence interval (CI) 0.63-1.38]. Caucasians, postmenopausal cases and studies with WHO diagnostic criteria showed no association under any genetic contrast. However, in East Asians, the OR for the dominant model [fixed effects OR=0.14 (95% CI 0.04-0.50) and RE OR=0.16 (95% CI 0.03-0.84)] was significant, indicating prevention. Overall, for the TaqI, ApaI and FokI polymorphisms, the allele contrast showed heterogeneity and the pooled RE ORs were non-significant [OR=1.06 (95% CI 0.71-1.60), OR=0.99 (95% CI 0.72-1.37) and OR=1.17 (95% CI 0.76-1.80), respectively]. The allele contrast for Caucasians, East Asians, postmenopausal cases and studies with WHO diagnostic criteria showed no association for TaqI, ApaI, and FokI. The allele contrast of homozygotes, and the recessive and dominant models the results followed the same pattern as the allele contrast. Therefore, the relationship between the VDR polymorphisms and osteoporosis remains an unresolved issue and other probable genetic-environmental risk factors interacting with the above polymorphisms should be investigated.     

Immunohistochemical Evaluation of 95 Bone Marrow Reactive Plasmacytoses

We histologically and immunohistochemically studied 95 bone marrow (BM) reactive plasmacytoses. Ten biopsies from plasma cell myeloma (PCM) patients served as a control group. In addition, we studied 10 monoclonal gammopathy of undetermined significance (MGUS) cases. Histologically, plasmacytosis varied between 5% and 25% with an interstitial pattern of plasma cell (PC) distribution being characteristically displayed. Immunohistochemically, we did not find any CD56/NCAM nor cyclin D1 expression in all biopsies (95 of 95, 100%), not even a weak, doubtful one; PCs were all polyclonal and CD138 positive. On the contrary, myeloma-associated PCs showed monoclonality for κ- or λ- light chain and strong CD56/NCAM immunoreactivity (8 of 10, 80%); four of them were cyclin D1 positive. Osteoblasts exhibited similar CD56/NCAM expression in both groups. Our data confirm the diagnostic utility of CD56/NCAM in the phenotypic characterization of polyclonal plasma cells, suggesting an important role of this particular immunomarker in the BM trephine study of polyclonal versus neoplastic plasmacytic infiltrations.     

Prognostic significance of Hypoxia-Inducible Factor 1 alpha(HIF-1alpha) expression in serous ovarian cancer: an immunohistochemical study

Background  

The hypoxia-inducible factor (HIF) has emerged as an attractive target for cancer therapy. The few publications addressing the prognostic significance of Hypoxia-Inducible Factor 1α (HIF-1α) cellular expression in ovarian cancer produced contradictory findings which are not permissible to widely acceptable conclusions and clinical applications. Our study was designed to investigate this by including a comparatively large number of cases and by using a combination of antibodies to analyze immunohistochemically the expression of HIF-1α.     

The occipitoparietal pathway of the macaque monkey: comparison of pyramidal cell morphology in layer III of functionally related cortical visual areas

The dendritic morphology of pyramidal cells located at the base of layer III in the primary visual area (V1), the second visual area (V2), the middle temporal area (MT), the ventral portion of the lateral intraparietal area (LIPv) and in the portion of cytoarchitectonic area 7a within the anterior bank of the superior temporal sulcus was revealed by injecting neurons with Lucifer Yellow in fixed, flattened slices of macaque monkey visual cortex. These areas correspond to different levels of the occipitoparietal cortical 'stream', which processes information related to motion and spatial relationships in the visual field. The tissue was immunocytochemically processed to obtain a light-stable diaminobenzidine reaction product, revealing the dendritic morphology in fine detail. Retrogradely labelled MT- projecting neurons in supragranular V1 (layer IIIc of Hassler's nomenclature, corresponding to Brodmann's layer IVb) were predominantly pyramidal, although many spiny multipolar (stellate) cells were also found. The average basal dendritic field area of pyramidal neurons in sublamina IIIc of V1 was significantly smaller than that in the homologous layer of V2, within the cytochrome oxidase-rich thick stripes. Furthermore, the average basal dendritic field areas of V1 and V2 pyramidal neurons were significantly smaller than those of neurons in MT, LIPv and area 7a. There was no difference in basal dendritic field area between layer III pyramidal neurons in areas MT, LIPv and 7a. While the shape of most basal dendritic fields was circularly symmetrical in the dimension tangential to the cortical layers, there were significant biases in complexity, with dendritic branches tending to cluster along particular axes. Sholl analysis revealed that the dendritic fields of neurons in areas MT, LIPv and 7a were significantly more complex (i.e. had a larger number of branches) than those of V1 or V2 neurons. Analysis of basal dendritic spine densities revealed regional variations along the dendrites, with peak densities being observed 40-130 microns from the cell body, depending on the visual area. The peak spine density of layer III pyramidal neurons in V1 was lower than that observed in V2, MT or LIPv, which were all similar. Pyramidal neurons in area 7a had the greatest peak spine density, which was on average 1.7 times that found in V1. Calculations based on the average spine density and number of dendritic branches at different distances from the cell body demonstrated a serial increase in the total number of basal dendritic spines per neuron at successive stations of the occipitoparietal pathway. Our observations, comparing dendritic fields of neurons in the homologous cortical layer at different levels of a physiologically defined 'stream', indicate changes in pyramidal cell morphology between functionally related areas. The relatively large, complex, spine-dense dendritic fields of layer III pyramidal cells in rostral areas of the occipitoparietal pathway allow these cells to sample a greater number of more diverse inputs in comparison with cells in 'lower' areas of the proposed hierarchy.      

Prevalence of antibodies to human T-lymphotropic virus types I and II in volunteer blood donors and high-risk groups in northwestern Greece

BACKGROUND: In addition to human immunodeficiency virus, human T- lymphotropic virus types I and II (HTLV-I/II) is prevalent among blood donors in the United States. In Greece, there are no epidemiologic data regarding the prevalence of HTLV-I/II among volunteer blood donors and high-risk groups. STUDY DESIGN AND METHODS: To determine the prevalence of HTLV-I/II infections in northwestern Greece, a seroepidemiologic study was conducted among volunteer blood donors, multiply transfused patients, heroin addicts, and chronic hemodialysis patients. The subjects were tested for serologic evidence of HTLV-I/II infection by enzyme immunoassays and specific protein immunoblot confirmatory test. RESULTS: None of the volunteer blood donors and heroin addicts had detectable antibodies to HTLV-I/II. Only 1 (1.45%) of the 69 multiply transfused patients had indeterminate results, while 2 (1.2%) of 163 hemodialysis patients were positive. CONCLUSION: In northwestern Greece, routine screening for HTLV-I and HTLV-II infections does not appear to be required. However, the finding of seropositivity among hemodialysis patients requires further evaluation of the origin of the infection, as its zero prevalence in this population seems to exclude transfusion transmission.     

Immunocytochemical evaluation of neoplastic and non-neoplastic breast diseases with Mab A-80

Five hundred breast tissue samples from 404 cases were immunostained with A-80, a murine IgM Mab that recognizes a mucinous glycoprotein associated with exocrine differentiation. Samples included 196 primary breast carcinomas, 30 breast carcinoma metastases, 118 fibrocystic disease (FCD), and a further group of 84 samples of FCD from cases known to have breast carcinoma. These samples represented a broad spectrum of common and rare variants of carcinoma and FCD. Samples of fibroadenomas, lactating adenomas, cystosarcoma phylloides, gynecomastia, and normal breasts were similarly studied. The vast majority of carcinomas, 203/212 (95.7%) were immunoreactive; staining varied in extent and intensity, and was virtually unrelated to histologic type and to the presence or absence of recognizable glands. In samples including in-situ and infiltrating ductal or lobular carcinoma, reactivity was frequently stronger in the infiltrating components. No significant difference in reactivity between primary and metastatic carcinomas was noted. Of the group of 118 FCD, 27 were negative whereas 91 showed focal and weak staining. Seventy-two/84 FCD with associated carcinoma were immunostained; in 13 of those 72, staining was strong and extensive. Fibroadenomas, lactating adenomas, gynecomastia, and normal "resting" and lactating breast samples stained focally or not at all. Our findings indicate that Mab A-80 is an excellent immunohistochemical marker for the overwhelming majority of breast carcinomas whereas it marks weakly or not at all the majority of benign neoplasms and normal breast. Moreover, Mab A-80 recognizes a subset of FCD that includes proliferative variants associated with an increased incidence of carcinoma, and FCD in association with carcinoma. Questions regarding rare breast carcinomas that do not react with Mab A-80 remain unclear; yet, we believe that Mab A-80 is a highly promising marker of malignant and dysplastic breast epithelium.