Particle-associated retroviral RNA and tandem RGH/HERV-W copies on human chromosome 7q: possible components of a 'chain-reaction' triggered by infectious agents in multiple sclerosis?

Different groups have observed retrovirus particle (RVP) production in cell cultures from patients with multiple sclerosis (MS). This in vitro production appeared relatively specific for MS versus healthy controls, but was likely to be enhanced or activated by infectious triggers such as Herpesviruses (e.g. HSV, EBV). Independent molecular analysis of retroviral RNA associated with RVP revealed two different genetic families of endogenous retroviral elements (HERV): MSRV/HERV-W and RGH/HERV-H. Interestingly, these sequences were detected by mutually exclusive primers in RT - PCR amplifications. Surprisingly, these two HERV families both contain an ancestral proviral copy inserted in chromosome 7q21-22 region at about 1 kb of distance of each other. Another HERV-W proviral sequence is located within a T-cell alpha-delta receptor (TCR) gene in chromosome 14q11.2 region. Interestingly, these two regions correspond to genetic loci previously identified as potentially associated with 'multigenic' susceptibility to MS and TCR alpha chain genetic determinants have been reported to be statistically associated with MS. A plausible role for infectious agents triggering a co-activation of the chromosome 7q HERV tandem (replicative retrovirus and/or other virus and/or intracellular bacteria) and, eventually, other HERV copies, is discussed. The role of particular HERV polymorphism and the production of pathogenic molecules (gliotoxin and superantigen) possibly associated with retroviral expression are also evoked. An integrative concept of pathogenic 'chain-reaction' in MS involving several step-specific pathogenic 'agents' and 'products' somewhat interacting with particular genetic elements would federate most partial data obtained on MS, including retroviral expression.     

Weight cycling did not increase tumor incidence in high fat–fed rats treated with a low-dose 7,12-dimethylbenzyl(1)anthracene

The present study tested the hypothesis that weight cycling (WC, repeated weight gain and loss) increases the tumorigenesis in rats exposed to carcinogen. Female Wistar rats consumed a high-fat diet (35% weight per weight) and were divided: (1) ad lib–fed rats that were treated with 7,12-dimethylbenzyl(1)anthracene (DMBA, 2 mg) at 55 days of age (AL-DMBA); (2) WC rats that were treated with DMBA (WC-DMBA); and (3) vehicle-treated WC rats (WC-VEH). In this study, WC did not alter blood parameter concentrations and did not influence insulin sensitivity. Mammary tissue F₂-isoprostane concentrations were lowest in WC-VEH and highest in AL-DMBA groups. Tumor incidence and burden were similar among all groups. The data obtained from this study do not support our hypothesis. This may be due to low dose of DMBA used, strain and age of the rats, number of WC cycles, and the amount of trans–fatty acids in the diets.     

Mutations in the tyrosine kinase domain of the epidermal growth factor receptor in non-small cell lung cancer.

We evaluated somatic genetic alterations in the kinase domain of the EGFR gene in the tumors of 219 non-small cell lung cancer patients of primarily Caucasian and African American origins. We identified 26 patients (12%) whose tumors had a mutation in the EGFR gene, and 11 (5%) patients carried novel genomic variations consistent with germ-line polymorphisms. All but one mutation were identified in Caucasian patients affected with adenocarcinoma. EGFR mutations were more frequent in women and in nonsmokers, but a significant portion of the affected patients were men (12 of 26) and current or past smokers accounted for half of the patients affected (13 of 26). Screening subjects with EGFR mutations may identify patients whose tumors could respond to targeted therapy using tyrosine kinase inhibitors.     

Automated Computational Detection of Interstitial Fibrosis,Tubular Atrophy,and Glomerulosclerosis

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CIP2A is a poor prognostic factor and can be a diagnostic marker in papillary thyroid carcinoma

Papillary thyroid carcinoma (PTC) is the most common type of thyroid carcinoma. CIP2A has recently been described as a prognostic marker in many cancers. In this study, we assessed the value of this novel prognostic marker in PTC. A total of 178 surgical specimens of both benign and malignant thyroid tumors were collected. Immunohistochemical staining for CIP2A, HBME‐1, galectin‐3, and CK19 was performed. Western blotting for CIP2A was also performed. CIP2A was expressed in 85.3% of malignant tumors and 12.1% of benign tumors. ROC analysis showed that the AUC for CIP2A was higher than those for other tumor markers. Western blotting showed that CIP2A expression was higher in PTC than in other tumors. Poor progression‐free survival was observed in the high‐CIP2A expression group. High CIP2A expression is a poor prognostic factor and can be a diagnostic marker in PTC. The presence of any two of the three indicated makers (CIP2A, galectin‐3, and HBME‐1) is strongly correlated with the diagnosis of PTC.     

Effects of Supraphysiological Testosterone Treatment and Orchiectomy on Ischemia/Reperfusion‐Induced Bladder Dysfunction in Male Rabbits

IntroductionThe roles of testosterone and orchiectomy on male bladder subjected to ischemic/reperfusion (I/R) injuries received little attention. To fill this gap, the present study intended to examine testosterone and orchiectomy effects on male rabbits subjected to I/R damages.AimTo elucidate the effects of testosterone and orchiectomy on contractile response, bladder morphology, interstitial fibrosis, and oxidative stress in male rabbit bladder subjected to I/R surgery.MethodsMale New Zealand rabbits were distributed into five groups as follows: Group 1 received sham surgical procedure. In group 2, I/R surgery was performed. In group 3, testosterone (100 μg/kg/day) was intramuscularly injected prior to I/R surgery. In group 4, orchiectomy was performed prior to I/R surgery. In group 5, orchiectomy was performed with subsequent testosterone administration, followed by I/R surgery. All the rabbits were euthanized 7 days after I/R. Comparative studies were analyzed to elucidate the effects of testosterone and orchiectomy on bladder dysfunction subjected to I/R injuries.Main Outcome MeasuresBladder contractile function was evaluated. Masson's trichrome staining and immunohistochemical studies were performed to evaluate bladder morphology and intramural nerve terminals. Western blotting was examined to investigate the expressions of fibrosis and oxidative stress markers.ResultsI/R surgery significantly decreased bladder contractility in response to various stimulations with and without testosterone treatment. I/R damages decreased bladder nerve density with and without testosterone. The expressions of fibrosis and oxidative stress‐related proteins were increased by I/R injuries with or without testosterone treatment. Testosterone depletion significantly decreased the expressions of transforming growth factor‐β and fibronectin expressions after I/R injury. Supraphysiological testosterone treatment after orchiectomy greatly increased the expressions of these fibrosis proteins; however, orchiectomy alone ameliorated I/R injuries.ConclusionsTestosterone treatment or orchiectomy affected I/R‐induced bladder damages in male rabbits. Orchiectomy decreased the level of fibrosis and oxidative stress markers and increased neurofilament densities. Supraphysiological exogenous testosterone administration after orchiectomy further exacerbated such detrimental effects of I/R.