Pigmented epithelioid melanocytoma: report of first Japanese cases previously diagnosed as cellular blue nevus

Background:  The term 'pigmented epithelioid melanocytoma (PEM)' was recently used for borderline melanocytic tumor/low-grade melanoma including cases previously diagnosed as human animal-type melanoma and epithelioid blue nevus. No Japanese cases have been reported.
Methods:  We reviewed 219 cases previously diagnosed as blue nevus in Japan. Common blue nevus was identified in 154 cases and cellular blue nevus in 65 cases.
Results:  We have found two Japanese cases of PEM previously diagnosed as cellular blue nevus. Two patients were female. The age at presentation was 32 and 28 years. Two lesions were on the buttock. Two cases fulfilled histological criteria proposed for PEM. There is no evidence of recurrence or metastases.
Conclusions:  PEM is a distinct melanocytic tumor and the unifying diagnostic term. PEM is present in Japanese, but these cases may be previously diagnosed as cellular blue nevus. Japanese pathologists should recognize a new concept of PEM, and when they make a diagnosis of PEM, they should be recommended sentinel lymph node sampling.     

Neurological disorders and violence: a systematic review and meta-analysis with a focus on epilepsy and traumatic brain injury

The objectives of this study were to systematically review and meta-analyze the research literature on the association of common neurological disorders and violence. Keywords relating to neurological disorders and violence were searched between 1966 and August 2008. Case–control and cohort studies were selected. Odds ratios of violence risk in particular disorders compared with controls were combined using fixed-effects meta-analysis with the data presented in forest plots. Sensitivity analyses were conducted to identify possible differences in risk estimates across surveys. Information on risk factors for violence was extracted if replicated in more than one study. Nine studies were identified that compared the risk of violence in epilepsy or traumatic brain injury compared with unaffected controls. For the epilepsy studies, the overall pooled odds ratio for violent outcomes was 0.67 [95% confidence interval (CI) 0.46–0.96]. For traumatic brain injury, the odds ratio was 1.66 (95% CI 1.12–2.31). An additional 11 case–control studies investigated factors associated with violence in epilepsy and traumatic brain injury. It was not possible to meta-analyze these data. Comorbid psychopathology was associated with violence. Data on other neurological conditions was limited and unreplicated. In conclusion, although the evidence was limited and methodological quality varied, epilepsy and traumatic brain injury appeared to differ in their risk of violence compared with control populations. Longitudinal studies are required to replicate this review’s provisional findings that epilepsy is inversely associated with violence and that brain injury modestly increases the risk, and further research is needed to provide information on a broader range of risk factors.     

Involvement of ADAM10 in axonal outgrowth and myelination of the peripheral nerve

The disintegrin and metalloproteinase 10 (ADAM10) is a membrane‐anchored metalloproteinase with both proteolytic and disintegrin characteristics. Here, we investigate the expression, regulation, and functional role of ADAM10 in axonal outgrowth and myelination of the peripheral nerve. Expression pattern analysis of 11 ADAM family members in co‐cultures of rat dorsal root ganglia (DRG) neurons and Schwann cells (SCs) demonstrated the most pronounced mRNA expression for ADAM10. In further studies, ADAM10 was found to be consistently upregulated in DRG‐SC co‐cultures before the induction of myelination. Neurons as well as SCs widely expressed ADAM10 at the protein level. In neurons, the expression of ADAM10 was exclusively limited to the axons before the induction of myelination. Inhibition of ADAM10 activity by the hydroxamate‐based inhibitors GI254023X and GW280264X resulted in a significant decrease in the mean axonal length. These data suggest that ADAM10 represents a prerequisite for myelination, although its activity is not required during the process of myelination itself as demonstrated by expression analysis of myelin protein zero (P0) and Sudan black staining. Hence, during the process of myelin formation, ADAM10 is highly upregulated and appears to be critically involved in axonal outgrowth that is a requirement for myelination in the peripheral nerve. © 2009 Wiley‐Liss, Inc.     

Workplace status and risk of hypertension among hourly and salaried aluminum manufacturing employees

An inverse relationship between workplace status and morbidity is well established; higher job status has been associated with reduced risks of heart disease, hypertension, and injury. Most research on job status, however, has focused on salaried populations, and it remains unclear whether job status operates similarly among hourly workers. Our objectives were to examine whether hourly status itself influences risk of hypertension after adjustment for socioeconomic confounders, and to explore the role of fine-scale job grade on hypertension incidence within hourly and salaried groups. We examined data for 14,999 aluminum manufacturing employees in 11 plants across the U.S., using logistic regression with adjustment for age, sex, race/ethnicity and other individual characteristics. Propensity score restriction was used to identify comparable groups of hourly and salaried employees, reducing confounding by sociodemographic characteristics. Job grade (coded 1 through 30, within hourly and salaried groups) was examined as a more refined measure of job status. Hourly status was associated with an increased risk of hypertension, after propensity restriction and adjustment for confounders. The observed effect of hourly status was stronger among women, although the propensity-restricted cohort was disproportionately male (96%). Among salaried workers, higher job grade was not consistently associated with decreased risk; among hourly employees, however, there was a significant trend, with higher job grades more protective against hypertension. Increasing the stringency of hypertension case criteria also increased the risk of severe or persistent hypertension for hourly employees.     

Angiostatin overexpression in Morris hepatoma results in decreased tumor growth but increased perfusion and vascularization.

Growth of malignant tumors is dependent on sufficient blood supply. Thus, inhibition of tumor angiogenesis is emerging as a promising target in the treatment of malignancies. Human angiostatin (hANG) is one of the most potent inhibitors of endothelial cell proliferation, angiogenesis, and tumor growth in vivo. However, its mechanisms operating in vivo are not well understood. METHODS: To obtain more information about functional changes in the angiogenic process, we established Morris hepatoma (MH3924A) cell lines expressing hANG (hANG-MH3924A). The effects of hANG expression on proliferation and apoptosis of human umbilical vein endothelial cells (HUVECs) were measured in coculture experiments in vitro. To evaluate changes in tumor perfusion and blood volume, H2 15O and 68Ga-DOTA-albumin (DOTA is 1,4,7,10-tetraazacyclododecane-N,N',N',N'-tetraacetic acid) were used for PET studies in vivo. Additionally, immunohistologic quantification of vascularization, apoptosis, and proliferation as well as gene array analyses were performed. RESULTS: Our in vitro experiments demonstrate reduced proliferation and increased apoptosis in HUVECs when being cocultured with hANG-MH3924A. In support, tumor growth of hANG-MH3924A is diminished by 95% in vivo. However, tumor perfusion and blood volume are increased in hANG-MH3924A corresponding to an increased microvessel density. Furthermore, hANG-transfected tumors show changes in expression of genes related to apoptosis, stress, signal transduction, and metabolism. CONCLUSION: hANG expression leads to inhibition of tumor growth, increased apoptosis, and changes in the expression of multiple genes involved in stress reactions, signal transduction, and apoptosis, which indicates a multifactorial reaction of tumors. An enhanced microvessel density is seen as part of these reactions and is associated with increased perfusion as measured by PET.     

Immunohistological identification of cell subsets in human gingival after local treatment for gingivitis or periodontitis

The cellular infiltrate present in human diseased gingiva was analyzed in biopsies from 12 patients with gingivitis or periodontitis. The samples studied had been obtained in the course of surgery at inflammatory sites remaining after institution of periodontal treatment. Histological and immunological techniques were used to identify macrophages, B-cells, plasma-cells, T-cells and T cell subsets, as well as cells expressing class II HLA membrane antigens. T-cells appeared as the predominant population, but plasma-cells were also visualized in nearly all samples. Both OKT4+ and OKT8+ cells were seen in all cases, the latter being more numerous in periodontitis patients. Interdigitating-like cells were observed, positively labelled for class II antigens, as well as macrophages which were more numerous in periodontitis patients. These results suggest the participation of all components of the immune response in gingival disease, in a way resembling chronic recurrent inflammatory diseases.     

Perfusion imaging

The term perfusion has varied connotations in different situations. The word perfusion comes from the Latin to pour or diffuse through or over. Myocardial perfusion depends on (a) coronary artery or vessel flow, and (b) myocardial or muscle flow. The factors which determine perfusion at rest and during stress in coronary vessels and within the myocardium are clearly related but not with a predictable linear relationship. In animals there is extensive literature concerning the regulation of coronary flow and perfusion obtained by many sophisticated methods. In contrast, the techniques that are applicable to humans are relatively crude. To date, the clinical data available suggests that the normal control of coronary flow in man and in dogs is fairly similar but that models of pathology in animals bear little relation to the compensatory changes found in the coronary circulation in man. Although the data available is limited and subject to many technical inaccuracies, this article is confined to the assessment of myocardial perfusion in clinical practice.