Extranodal rosai-dorfman disease presenting as incidental bone tumor: a case report

We report a case of primary extranodal Rosai-Dorfman disease presenting as a painless lesion in the left ilium of a 71-year-old African-American man.     

Cancer specific promoter CpG Islands hypermethylation of homeodomain only protein X gene and its potential tumor suppressive role in pancreatic carcinogenesis

ABSTRACT: BACKGROUND: We have recently identified homeodomain only protein X (HOPX) as a tumor suppressor gene candidate, characterized by tumor-specific promoter DNA hypermethylation in human cancers, and it can remarkably inhibit tumors' aggressive phenotypes. In this current study, we for the first time examined methylation level of HOPX and tested the functional relevance in pancreatic cancer (PC). METHODS: Clinical features of HOPX promoter hypermethylation was investigated in 89 PC tissues, and immunohistochemistry was added. We also examined its functional relevance in phenotype assays such as soft agar, proliferation, invasion, and cell cycle analysis. RESULTS: PC tissues had HOPX gene hypermethylation as compared to the corresponding normal pancreas tissues, and its uniqueness was robust to discriminate tumor from normal tissues (AUC = 0.85, P < 0.0001). Unexpectedly, HOPX was increased in expression in tumor tissues, and immunohistochemistry revealed its predominant expression in the Langerhans islet cells, where HOPX is reduced in expression for PC cells with promoter hypermethylation. HOPX transfectants exhibited G1 arrest with subG1 accumulation, and inhibit tumor forming and invasive ability. CONCLUSION: Defective expression of HOPX which is consistent with promoter DNA hypermethylation may explain aggressive phenotype of pancreatic cancer, and intense expression of HOPX in the Langerhans cells may in turn uniquely contribute to pancreatic carcinogenesis.     

Thalamic paramagnetic iron by T2* relaxometry correlates with severity of multiple sclerosis

Iron can contribute to the pathogenesis and progression of multiple sclerosis (MS) due to its accumulation in the human brain. We focus on the thalamus as an information transmitter between various subcortical and cortical areas. Thalamic iron seems to follow different rules than iron in other deep gray matter structures and its relation to the clinical outcomes of MS is still indistinct. In our study, we investigated a connection between thalamic iron and patients' disability and course of the disease. The presence of paramagnetic substances in the tissues was tracked by T2* quantification. Twenty-eight subjects with definite MS and 15 age-matched healthy controls underwent MRI examination with a focus on gradient echo sequence. We observed a non-monotonous course of T2* values with age in healthy controls. Furthermore, T2* distribution in MS patients was significantly wider than that of age matched healthy volunteers (P < 0.001). A strong significant correlation was demonstrated between T2* distribution spread and the expanded disability status scale (EDSS) (left thalamus: P<0.00005; right thalamus: P<0.005), and multiple sclerosis severity scale (MSSS) (left thalamus: P <0.05; right thalamus: P <0.005). The paramagnetic iron distribution in the thalamus in MS was not uniform and this inhomogeneity may be considered as an indicator of thalamic neurodegeneration in MS.     

Positive and negative regulatory roles of the WW-like domain in TEL-PDGFbetaR transformation

TEL-platelet-derived growth factor-beta receptor (TEL-PDGFbetaR) is expressed in chronic myelomonocytic leukemias associated with t(5;12)(q33;p13), and the fusion tyrosine kinase retains a conserved WW-like domain in the PDGFbetaR autoinhibitory juxtamembrane region. Here we report that mutation of the 2 conserved tryptophan residues of the WW-like domain has opposing effects on TELPDGFbetaR kinase activation. Alanine substitution of W593, essential for protein-protein interaction in the context of other WW domains, impaired TEL-PDGFbetaR-mediated transformation of hematopoietic cells due to inhibition of TEL-PDGFbetaR kinase activity. In contrast, alanine substitution of W566, essential for structural integrity of WW domain in other contexts, had no effect on TEL-PDGFbetaR activation and oncogenic activity. Surprisingly, however, the W566A mutation suppressed the W593A phenotype. Double mutant W566A/W593A was indistinguishable from the wild-type fusion protein with regard to kinase activity, ability to confer factor-independent growth to Ba/F3 cells, or ability to induce a myeloproliferative disease in mice. Additional mutational analysis identified other substitutions within the WW-like domain in addition to W566A that could also suppress the W593A phenotype, including mutations predicted to diminish the autoinhibitory function of the juxtamembrane region. Therefore, the WW-like domain in the context of TELPDGFbetaR may have both positive and negative regulatory roles in kinase activation.     

Reaching Latinas with Our Bodies,Ourselves and the Guía de Capacitación para Promotoras de Salud: Health Education for Social Change

As the cultural and linguistic diversity of the United States continues to grow and population shifts transform the communities where we live and work, health care providers continue to face challenges to deliver health services in demographically redefined terrains. This report describes the development of a Spanish‐language training guide for community health workers (Guía de Capacitación para Promotoras de Salud) based on the book Nuestros Cuerpos, Nuestras Vidas (NCNV), the Spanish‐language translation and cultural adaptation of the classic women's health book Our Bodies, Ourselves. The guide aims to 1) provide a tool for addressing the health education needs of immigrant Latinas and 2) facilitate the use of the book NCNV as a health education tool in Latino communities. Thirty telephone interviews with individuals working in agencies and organizations serving Latinos and 2 focus groups with Latinas were conducted to select the topics included in the training guide, all of which were drawn directly from NCNV. The guide contains 11 modules organized into 6 workshops. The modules address 11 topics related to women's health, ranging from sexuality and pregnancy to domestic violence and mental health. An ecological framework is used to deliver the health information. The materials acknowledge the roles of history, environment, culture, economic conditions, migration history, and politics as key determinants of health and illness. The workshops are designed to train community health workers on the women's health topics contained in the guide and to equip them for the delivery of health education among immigrant Latinas.     

Susceptible period for the teratogenicity of di-n-butyltin dichloride in rats.

Pregnant rats were given di-n-butyltin dichloride (DBT) by gastric intubation at a dose of 20 mg/kg on days 7-9, 10-12 or 13-15 of pregnancy or at a dose of 20 or 40 mg/kg on day 6, 7, 8 or 9 of pregnancy. While treatment with DBT on days 7-9 was significantly and highly teratogenic, no evidence of teratogenicity was detected when DBT was given on days 10-12 or 13-15. Treatment on day 7 or 8 with both doses of DBT, but neither on day 6 or 9, resulted in an increased incidence of fetuses with malformations. The highest incidence of malformed fetuses occurred after treatment on day 8. The incidence of malformed fetuses was proportional to the dose of DBT. Anomaly of tail, anal atresia, club foot, omphalocele, deformity of the vertebral column, defect of the ribs and anophthalmia or microphthalmia were predominantly observed. It could be concluded that, following maternal exposure to DBT in rats, developing offspring are not susceptible to teratogenic effects of DBT on day 6 and that day 7 is the earliest susceptible period, day 8 is the highest susceptible period and day 9 is no longer a susceptible period for teratogenesis of DBT.