Expression of human lymphocyte antigen (HLA)-DR on tumor cells in basal cell carcinoma

Immunohistologic studies of eight patients with basal cell carcinoma were undertaken using a series of monoclonal antibodies. In all of the patients, the majority of dermal infiltrates reacted with OKT3 and OKIa1 (HLA-DR), with a slight predominance of OKT4+ helper/inducer T cells (the mean OKT4/OKT8 ratio was 1.8). Both OKT4+ and OKT8+ cells were seen infiltrating the tumor masses. In addition, in five cases, human lymphocyte antigen (HLA)-DR was demonstrated on some tumor cells close to a vast number of HLA-DR+ infiltrates surrounding the carcinoma, but not on epidermal keratinocytes and tumor cells devoid of the HLA-DR+ infiltrates. A considerable number of OKT6+ dendritic cells were also observed surrounding the carcinoma. Staining with OKB7 and OKM1 revealed negligible reactive cells, and virtually none of the dermal infiltrates reacted with Leu-7 (HNK-1). These findings suggest that in addition to varied immunologically competent cells, expression of HLA-DR antigen on tumor cells may participate in a cellular immune reaction, a defense mechanism against tumor cell proliferation in basal cell carcinoma.     

TECHNIQUES AND PITFALLS OF ENDOSCOPIC SUBMUCOSAL DISSECTION FOR COLORECTAL TUMORS

Endoscopic submucosal dissection (ESD) for colorectal tumors is steadily being developed. Safety and standardization of ESD for colorectal tumors have not been yet established because of the technical difficulties and the unsuitable anatomical characteristics of the colon and rectum. The authors mainly use a Flex knife for mucosal incision and a Hook knife for submucosal dissection to perform ESD safely. Skillful colonoscopic control, selection of scope, distal attachment tip hood, adequate high‐frequency generator and correct approach strategy should all be considered for safe performance of ESD. However, the incidence of indicative lesions is rare because the majority of colorectal tumors are adenomatous large laterally spreading tumors, which can be cured by intentional endoscopic piecemeal resection. At present, ESD for colorectal tumors should be performed only at central facilities that have expert colonoscopists. With the development of new devices and associated techniques, technical standardization of ESD for colorectal tumors is expected in the near future.     

Analysis of DNA copy number aberrations in hepatitis C virus-associated hepatocellular carcinomas by conventional CGH and array CGH.

To clarify the genetic aberrations involved in the development and progression of hepatitis C virus-associated hepatocellular carcinoma (HCV-HCC), we investigated DNA copy number aberrations (DCNAs) in 19 surgically resected HCCs by conventional CGH and array CGH. Conventional CGH revealed that increases of DNA copy number were frequent at 1q (79% of the cases), 8q (37%), 6p (32%), and 10p (32%) and that decreases were frequent at 17p (79%), 16q (58%), 4q (53%), 13q (42%), 10q (37%), 1p (32%), and 8p (32%). In general, genes that showed DCNAs by array CGH were usually located in chromosomal regions with DCNAs detected by conventional CGH analysis. Increases in copy numbers of the LAMC2, TGFB2, and AKT3 genes (located on 1q) and decreases in copy numbers of FGR/SRC2 and CYLD (located on 1p and 16q, respectively) were observed in more than 30% of tumors, including small, well-differentiated carcinomas. These findings suggest that these genes are associated with the development of HCV-HCC. Increases of MOS, MYC, EXT1, and PTK2 (located on 8q) were detected exclusively in moderately and poorly differentiated tumors, suggesting that these alterations contribute to tumor progression. In conclusion, chromosomal and array CGH technologies allow identification of genes involved in the development and progression of HCV-HCC.     

Hypoxia‐inducible factor 1α may be a marker for vasculitic neuropathy

Neuromuscular biopsy is still an essential method for diagnosing vasculitic neuropathy, although its diagnostic sensitivity is at most 60%. Our objective was to examine the expression of hypoxia‐inducible factor 1α (HIF‐1α) in peripheral nerves and to evaluate its usefulness in diagnosing vasculitic neuropathy, especially for discrimination from other axonal neuropathies. Forty‐one patients with vasculitic neuropathy consisting of 20 definite, 14 probable and seven possible diagnoses, 15 patients with metabolic neuropathy, five with motor neuron disease and six with chronic inflammatory demyelinating polyneuropathy were included. Nerve biopsy specimens were immunohistochemically examined for HIF‐1α and various cell markers. Distinct immunoreactivity (IR) was observed in nuclei of endoneurial cells in 54% (22/41) of vasculitic patients, while specimens from metabolic neuropathies showed less nuclear IR and the difference of mean density of HIF‐1α‐positive nuclei was significant. Two patients with possible vasculitis who showed HIF‐1α‐positive nuclei in endoneurium, were later confirmed to have vasculitis by skin biopsies. Most of the cells expressing HIF were demonstrated to be Schwann cells. There was a trend in the vasculitic patients with early phase nerve damage to display higher endoneurial HIF‐1α‐IR. HIF‐1α may be an immunohistochemical marker for vasculitic neuropathy, especially when the observed section contains no vasculitic lesions.     

Ethanol Feeding Causes Inactivation of Both State 1 and State 2 Rat Hepatic Asialoglycoprotein Receptors

Previous studies have shown that ethanol feeding in rats causes inactivation and redistribution of ˜50% of the total asialoglycoprotein receptors (ASGPRs) in hepatocytes (Tworek et al., J. Biol. Chem. 271:2531, 1996), and that two equal populations of hepatic ASGPRs mediate ligand uptake and processing via two functionally different pathways (Weigel in Glycoconjugates: Composition, Structure and Function , Marcel Dekker, 1992, p. 421). The purpose of this study was to determine if ethanol feeding causes preferential inactivation of only one of these two ASGPR populations, which have been designated state 1 and state 2 ASGPRs. The state 2, but not state 1, ASGPRs are inactivated in isolated hepatocytes by a variety of drugs and inhibitors. State 2 ASGPRs can also be inactivated in permeable cells by ATP treatment and then reactivated by treatment with fatty acyl coenzyme As. In the present study, permeable cell assays for state 2 ASGPR inactivation and reactivation were used to assess whether hepatocytes from ethanol-fed rats contain inactive state 2 ASGPRs. The results show that preferential inactivation of one ASGPR population does not occur after ethanol feeding. That inactive ASGPRs could not be reactivated by treatment with palmitoyl-coenzyme A to a greater extent in ethanol-fed versus control cells indicates there is not a larger pool of inactivated state 2 ASGPRs in treated cells. We conclude that ethanol feeding causes equal inactivation of both state 1 and state 2 ASGPRs. Ethanol feeding may represent the first treatment found to inactivate state 1 ASGPRs.