Structural analysis of the venom glands of the armed spider Phoneutria nigriventer (Keyserling, 1891): microanatomy, fine structure and confocal observations

Spiders belonging to the genus Phoneutria (Perty, 1833), most commonly known as 'armed' spiders, are among the most dangerous species in Brazil due to high toxicity of their venom, associated with their habit of invading domestic or specific areas such as banana plantations. The venom of Phoneutria spiders is secreted by a pair of venom glands located inside their cephalothoraxes and connected to the chelicerae by two independent ducts. In the present study, the microanatomy and histological structure of the venom glands of Phoneutria nigriventer (Keyserling, 1891) were examined in detail by histochemical and conventional stains with laser confocal, scanning and transmission electron microscopies. The analysis confirmed the bulbous-shaped organ previously observed by others. The venom glands of P. nigriventer are covered externally by a double layer of striated muscles, which are arranged in a spiral fashion. This disposition of the external muscle fibers might provide the contraction movement of the venom gland to release their contents during a sting aggression. The presence of pore-like openings between the muscle fibers that cover the venom glands of P. nigriventer was considered quite remarkable. The presence of axon-like structures between the muscle fibers seen in the gland surface was also quite remarkable. The secretory epithelium of P. nigriventer invaginates into the gland lumen, contributing to the increase of the secretory surface area and also accommodating a higher number of secretory cells. Our observation of histological sections and SEM showed that the secretory cells in the venom gland of P. nigriventer form complex structures, secretory units, which originate at the base near the muscular layer and that extend into the central area until the gland lumen. Our study also identified a possible holocrine secretory mechanism of P. nigriventer venom gland, at least in the first venom milking, since we were able to see nuclei stained on confocal laser microscopy. However, our observation cannot disregard other possible types of secretory pathways in subsequent milkings, since we found no nuclei in the second and in the third venom secretions.     

Pediatric norovirus diarrhea in Nicaragua

Information about norovirus (NoV) infections in Central America is limited. Through a passive community and hospital pediatric diarrhea surveillance program, a total of 542 stool samples were collected between March 2005 and February 2006 in León, Nicaragua. NoV was detected in 12% (65/542) of the children; of these, 11% (45/409) were in the community and 15% (20/133) were in the hospital, with most strains (88%) belonging to genogroup II. NoV infections were age and gender associated, with children of <2 years of age (P < 0.05) and girls (P < 0.05) being most affected. Breast-feeding did not reduce the number of NoV infections. An important proportion (57%) of NoV-infected children were coinfected with diarrheagenic Escherichia coli. A significant proportion (18/31) of NoV-positive children with dehydration required intravenous rehydration. Nucleotide sequence analysis (38/65) of the N-terminal and shell region in the capsid gene revealed that at least six genotypes (GI.4, GII.2, GII.4, GII.7, GII.17, and a potentially novel cluster termed “GII.18-Nica”) circulated during the study period, with GII.4 virus being predominant (26/38). The majority (20/26) of those GII.4 strains shared high nucleotide homology (99%) with the globally emerging Hunter strain. The mean viral load was approximately 15-fold higher in children infected with GII.4 virus than in those infected with other G.II viruses, with the highest viral load observed for the group of children infected with GII.4 and requiring intravenous rehydration. This study, the first of its type from a Central American country, suggests that NoV is an important etiological agent of acute diarrhea among children of <2 years of age in Nicaragua.     

A priori prediction of response in multicentre locally advanced breast cancer (LABC) patients using quantitative ultrasound and derivative texture methods

Purpose: We develop a multi-centric response predictive model using QUS spectral parametric imaging and novel texture-derivate methods for determining tumour responses to neoadjuvant chemotherapy (NAC) prior to therapy initiation.Materials and Methods: QUS Spectroscopy provided parametric images of mid-band-fit (MBF), spectral-slope (SS), spectral-intercept (SI), average-scatterer-diameter (ASD), and average-acoustic-concentration (AAC) in 78 patients with locally advanced breast cancer (LABC) undergoing NAC. Ultrasound radiofrequency data were collected from Sunnybrook Health Sciences Center (SHSC), University of Texas MD Anderson Cancer Center (MD-ACC), and St. Michaels Hospital (SMH) using two different systems. Texture analysis was used to quantify heterogeneities of QUS parametric images. Further, a second-pass texture analysis was applied to obtain texture-derivate features. QUS, texture- and texture-derivate parameters were determined from both tumour core and a 5-mm tumour margin and were used in comparison to histopathological analysis for developing a response predictive model to classify responders versus non-responders. Model performance was assessed using leave-one-out cross-validation. Three standard classification algorithms including a linear discriminant analysis (LDA), k-nearest-neighbors (KNN), and support vector machines-radial basis function (SVM-RBF) were evaluated.Results: A combination of tumour core and margin classification resulted in a peak response prediction performance of 88% sensitivity, 78% specificity, 84% accuracy, 0.86 AUC, 84% PPV, and 83% NPV, achieved using the SVM-RBF classification algorithm. Other parameters and classifiers performed less well running from 66% to 80% accuracy.Conclusions: A QUS-based framework and novel texture-derivative method enabled accurate prediction of responses to NAC. Multi-centric response predictive model provides indications of the robustness of the approach to variations due to different ultrasound systems and acquisition parameters.     

Association of the PTPN22 R620W polymorphism with anti-topoisomerase I- and anticentromere antibody-positive systemic sclerosis

OBJECTIVE: To determine any associations of the PTPN22 R620W single-nucleotide polymorphism (SNP) with systemic sclerosis (SSc) or with anticentromere antibody (ACA)-positive or anti-topoisomerase I (anti-topo I) antibody-positive SSc, in a case-control study of US white, black, Hispanic, and Choctaw Indian individuals. METHODS: A total of 850 white, 130 black, 120 Hispanic, and 20 Choctaw Indian patients with SSc were compared with 430 white, 164 black, 146 Hispanic, and 76 Choctaw Indian control subjects, respectively. All subjects were living in the US. PTPN22 SNP (rs2476601) genotyping was performed by TaqMan 5' allelic discrimination assay and pyrosequencing. RESULTS: The PTPN22 CT/TT genotype showed significant association with anti-topo I antibody-positive SSc in white patients (odds ratio [OR] 2.21, 95% confidence interval [95% CI] 1.3-3.7) and with ACA-positive white patients with SSc (OR 1.70, 95% CI 1.1-2.7). Frequency of the PTPN22*T allele also showed significant association with anti-topo I antibody-positive SSc in white patients (OR 2.03, 95% CI 1.3-3.2). When data for patients in the 3 ethnic groups (black, white, and Hispanic) were combined, a significant association with both genotype and allele frequencies was observed, suggesting a trend toward association in ACA-positive and anti-topo I antibody-positive SSc. Stepwise logistic regression analysis (controlled for the confounding effects of sex and race) showed that the PTPN22 CT/TT genotype was associated with a significantly higher risk of SSc compared with the CC genotype (for patients with SSc, OR 1.64, 95% CI 1.2-2.2; for ACA-positive patients with SSc, OR 1.63, 95% CI 1.0-2.6; for anti-topo I antibody-positive SSc, OR 2.33, 95% CI 1.5-3.7). CONCLUSION: Our results indicate that the PTPN22 R620W polymorphism is associated with ACA-positive and anti-topo I antibody-positive subsets of SSc and represents a risk factor in both white patients and black patients. The association of subsets of SSc with the PTPN22 R620W polymorphism further strengthens the classification of SSc within the spectrum of autoimmune diseases and strongly suggests the involvement of common susceptibility genes and similarly disordered immunoregulatory pathways.     

Identification of novel targets in scleroderma: update on population studies, cDNA arrays, SNP analysis, and mutations

PURPOSE OF REVIEW: Systemic sclerosis, or scleroderma, is an uncommon autoimmune connective tissue disease that results in systemic fibrosis. Its etiologic basis remains unclear. The pathogenesis of systemic sclerosis involves a proliferative and obliterative vasculopathy resulting from endothelial cell dysfunction, extensive fibrosis secondary to fibroblast activation, and autoimmunity as demonstrated by the presence of disease-specific autoantibodies. Although there is no clear and convincing evidence for an environmental trigger in most cases, accumulating data emphasize the role of genetic factors in systemic sclerosis. As in other complex human diseases, multiple genes likely contribute to disease susceptibility and the clinical manifestations of systemic sclerosis. This review will cover the application of genomics to the complex genetics of systemic sclerosis. RECENT FINDINGS: The following review is an update on novel targets identified in scleroderma based on published reports (May 2000-May 2003) of mutation/polymorphism analysis (using SNP and haplotyping), the results from a recent genome-wide scan on a Native American population with systemic sclerosis, and gene expression studies (microarrays). SUMMARY: The use of genomics has revealed novel targets and genetic associations that may contribute to the cause, the onset, and the subsequent pathologic changes that constitute systemic sclerosis. The identification of potential candidates for gene therapy or disease-specific targets amenable to pharmacologic intervention will benefit patients with systemic sclerosis who are currently being treated for their symptoms and not the disease process itself.     

Separate influences of birth order and gravidity/parity on the development of systemic sclerosis

Objective

Birth order has been valuable in revealing the role of environmental influences on the risk of developing certain diseases such as allergy and atopy. In addition, pregnancy has profound effects on the immune system such as short‐term effects that permit fetal survival as well as longer‐term effects that could influence late‐onset diseases. In order to better evaluate these influences, we studied the association of birth order and gravidity/parity as risk factors for systemic sclerosis (SSc; scleroderma).

Methods

Data regarding SSc cases and their unaffected sibling controls were obtained from the Scleroderma Family Registry and DNA Repository. The case‐sibling design was used to minimize confounding due to differences in age, race, ethnicity, or calendar time. The gravidity/parity analysis was based on sibships with at least one SSc‐affected and one unaffected sister.

Results

Birth order was examined in 974 sibships, comparing SSc cases (n = 987) with their unaffected siblings (n = 3,088). The risk of scleroderma increased with increasing birth order (odds ratio [OR] 1.25, 95% confidence interval [95% CI] 1.06–1.50 for birth order 2–5; OR 2.22, 95% CI 1.57–3.15 for birth order 6–9; and OR 3.53, 95% CI 1.68–7.45 for birth order 10–15). Gravidity/parity was analyzed in 168 sibships (256 unaffected sisters, 172 SSc cases). We found an association between a history of one or more pregnancies and SSc (OR 2.8).

Conclusion

Birth order and pregnancy were independently associated with a higher risk of developing SSc. These findings suggest that immune development in early childhood and/or pregnancy‐associated events, including but not limited to microchimerism, plays a role in SSc susceptibility.