SummaryThe enzyme arylsulfatase B (N-acetylgalactosamine-4-sulfatase; ARSB; ASB) removes 4-sulfate groups from the sulfated glycosaminoglycans (sGAG) chondroitin-4-sulfate (C4S) and dermatan sulfate (DS). Inborn deficiency of ARSB leads to the lysosomal storage disease mucopolysaccharidosis VI, characterized by accumulation of sGAG in vital organs, disruption of normal physiological processes, severe morbidity, and premature death. Recent published work demonstrated extra-lysosomal localization with nuclear and cell membrane ARSB observed in bronchial and colonic epithelial cells, cerebrovascular cells, and hepatic cells. In this report, the authors present ARSB immunostaining in a colonic microarray and show differences in distribution, intensity, and pattern of ARSB staining among normal colon, adenomas, and adenocarcinomas. Distinctive, intense luminal membrane staining was present in the normal epithelial cells but reduced in the malignancies and less in the grade 3 than in the grade 1 adenocarcinomas. In the normal cores, a distinctive pattern of intense cytoplasmic positivity at the luminal surface was followed by reduced staining deeper in the crypts. ARSB enzymatic activity was significantly greater in normal than in malignant tissue. These study findings affirm extra-lysosomal localization of ARSB and suggest that altered ARSB immunostaining and reduced activity may be useful indicators of malignant transformation in human colonic tissue. (J Histochem Cytochem 59:328-335, 2011)
Findings report that nectin-1 is widely expressed in murine ocular tissues. Only fibroblasts in the corneal stroma and sclera of uninfected tissues were devoid of nectin-1 expression. HSV-1-infected inflamed corneas contained some stromal fibroblasts with detectable nectin-1 expression, which potentially could be targeted by the virus. Widespread nectin-1 expression in the eye suggests that this receptor may play a role in the pathogenesis of ocular HSV infections.
Nectin-1 is an adherens junction protein that serves as an entry receptor for neurotropic herpes simplex virus (HSV). The expression of nectin-1 in the central nervous system (CNS) has not been well defined. Furthermore, it is not known whether HSV infection has an effect on nectin-1 expression in the brain. To better understand nectin-1 expression in normal and HSV-infected brain, the authors used immunohistochemistry to characterize the expression of nectin-1 in brain tissue of uninfected adult mice and mice infected with HSV-1. In the CNS of untreated and mock-infected mice, virtually all neurons, ependymal cells, choroid plexus epithelial cells, meningothelial cells, and vascular endothelial cells expressed nectin-1. Many oligodendrocytes, astrocytes, and vascular smooth muscle cells also demonstrated nectin-1 expression, but a minority of these cells did not stain for nectin-1. Brain tissue derived from mice euthanized 5 to 8 days after intracerebral inoculation of HSV-1 showed inflammation and widespread expression of HSV-1 proteins in neurons. In HSV-1-infected brains, many inflammatory cells showed nectin-1 expression and neuronal nectin-1 staining showed a wider variation in signal strength than that detected in uninfected tissues. Many neurons showing nuclear fragmentation consistent with the morphologic appearance of apoptosis showed little or no evidence of nectin-1 expression, whereas occasional neurons stained more intensely positive for nectin-1 than those in uninfected brain tissue. These findings confirm and extend previous observations of nectin-1 expression in the nervous system and suggest that HSV-1 infection leads to changes in nectin-1 expression in the CNS, which may contribute to HSV-induced pathology and dissemination.
The purpose of this article is to assess recent data supporting the safety and efficacy of black cohosh products for the mitigation of menopause-related symptoms. Searches of the published literature in Napralert, Cochrane Library and PubMed databases were performed from 2003 to 2006. Information from drug regulatory agencies from five different countries was obtained to evaluate safety. While there are a few contradictory studies, the majority of the clinical trials indicate that extracts of black cohosh (Actaea racemosa L.) improve menopause-related symptoms. However, to date, at least 50 cases of possible hepatotoxicity have been reported. Although previous safety reviews suggest that black cohosh is well tolerated, the increasing numbers of these case reports indicates that further preclinical toxicological evaluations of black cohosh are urgently needed. At this time, it appears prudent to advise menopausal women with underlying liver disease, autoimmune diseases or those taking medications that may impact liver function not to use products containing black cohosh.
The purpose of this article is to assess recent data supporting the safety and efficacy of black cohosh products for the mitigation of menopause-related symptoms. Searches of the published literature in Napralert, Cochrane Library and PubMed databases were performed from 2003 to 2006. Information from drug regulatory agencies from five different countries was obtained to evaluate safety. While there are a few contradictory studies, the majority of the clinical trials indicate that extracts of black cohosh (Actaea racemosa L.) improve menopause-related symptoms. However, to date, at least 50 cases of possible hepatotoxicity have been reported. Although previous safety reviews suggest that black cohosh is well tolerated, the increasing numbers of these case reports indicates that further preclinical toxicological evaluations of black cohosh are urgently needed. At this time, it appears prudent to advise menopausal women with underlying liver disease, autoimmune diseases or those taking medications that may impact liver function not to use products containing black cohosh.
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