Akihiko Kurata

Cytokine regulation of HLA on thyroid epithelial cells

The regulation of class I and class II HLA expression in human thyroid follicular cells was studied in vitro. Tumour necrosis factor‐alpha (TNF‐α) enhanced the expression of class I antigen on thyrocytes, but these cytokines had little effect on the expression of class II antigen. Interleukin‐lβ (IL‐ lβ) and interleukin‐6(IL‐6) did not affect class I and class II antigen expression. The combination of interferon‐gamma (IFN‐γ) with TNF‐α or IL‐1β enhanced the induction of class I and class II antigens, compared with the effect of IFN‐β alone. Neither class I nor class II expression was induced by lL‐6 alone or in combination with IFN‐γ. These findings suggest that TNF‐α and IL‐1β may have an important role in inappropriate expression of HLA antigens on thyrocytes in thyroid gland.

Mechanism of inhibitory effect of dextran sulfate and heparin on human T-cell lymphotropic virus type I (HTLV-I)-induced syncytium formation in vitro: role of cell-to-cell contact.

Cell-to-cell contact is usually essential for syncytium formation by HTLV-I-infected cell lines. The present study was undertaken to determine the inhibitory effect of polyanionic compounds, dextran sulfate and heparin, on HTLV-I-induced syncytium formation, as demonstrated by the fusion of HTLV-I-infected cells with target cells. These two compounds almost completely blocked syncytium formation in the early phase of the reaction at a concentration of 125 micrograms/ml, but dextran, as a control, did not inhibit it at concentrations up to 625 micrograms/ml. 50% inhibition of syncytium formation was detected at a concentration of 2 micrograms/ml of dextran sulfate 5000, 3 micrograms/ml of dextran sulfate 8000 and 8 micrograms/ml of heparin. The binding of radiolabeled HTLV-I-infected cells (HCT-1) to the target cells was inhibited by addition of dextran sulfate and heparin, and the inhibitory effects were concentration-dependent. No marked changes were detected in the expression of adhesion molecules on the virus-infected cells and target cells, and in the expression of envelope proteins on the virus-infected cells after exposing them to the polyanionic compounds. These results suggest that the blocking of cell-to-cell contact by polyanionic compounds, probably independent of surface adhesion molecules, is important for their inhibitory effect on HTLV-I-induced syncytium formation.

Different B-cell responses to human T-cell lymphotropic virus type I (HTLV-I) envelope synthetic peptides in HTLV-I-infected individuals.

HTLV-I (human T-cell lymphotropic virus type I) is the retrovirus related to two distinct diseases, adult T-cell leukemia/lymphoma (ATLL) and HTLV-I-associated myelopathy (HAM). We analyzed the difference in antibody activities against the viral protein and the difference in specificities of anti-HTLV-I envelope antibodies among HTLV-I-infected individuals from the same HTLV-I-endemic area using a HTLV-I-gag-env hybrid protein and HTLV-I-env-encoded synthetic peptides as antigens, respectively. The difference in the responses of IgG anti-HTLV-I envelope antibody production among HTLV-I-infected individuals was qualitative as well as quantitative. Sera from patients with HAM showed significantly higher activities of antibodies against HTLV-I-gag-env hybrid protein than sera from other HTLV-I-infected individuals including ATLL patients. The specificities of IgG anti-HTLV-I-envelope antibodies, tested on seven synthetic envelope peptides, were directed mainly against four sites, V1E7 (residues 97–111), V1E8 (191–209), and V1E9 (268–286) on gp46 and V1E1 (342–363) on gp21. Three of these sites were shown to be immunodominant T-cell sites in mice in our previous study. Whereas patients in all categories made antibodies specific for V1E1 and V1E8, only HAM patients made antibodies to the V1E7 and V1E9 epitopes, suggesting a qualitative difference in response. Whether this difference is of pathogenetic significance is not clear. The antibody activities and the specificities against the envelope protein were also analyzed in nine HTLV-I-infected polyarthritis patients because a clinical entity of specific arthritis related to HTLV-I infection has been suggested; the activities of anti-HTLV-I antibodies in sera from HTLV-I-infected polyarthritis patients were not different from the activities of the antibodies from normal HTLV-I-carriers, and no envelope peptide-specificity unique for the arthritis patients was detected.

Endoscopic Resection of Gastric Plasmacytoma

Gastric plasmacytoma is a rare form of extramedullary plasmacytoma. It is usually diagnosed with a barium meal or endoscopy for various gastrointestinal symptoms. Most gastric plasmacytomas are treated by surgical resection, even when they are confined to gastric mucosal lamina propria or submucosa, that is, in the early stages. We present here a case of gastric plasmacytoma showing an endoscopic feature of submucosal tumor approximately 2.5 cm in diameter, found through an X‐ray study in a mass screening. Endoscopic ultrasonography revealed a hypoechoic tumor located in the submucosal layer, and the tumor appeared to be safely excised by routineendoscopic resection. In order to obtain histlogical diagnosis, we resected the tumor, which was diagnosed as a plasmacytoma. The patient did not shown any sign of local and/or generalized recurrence during follow up for 2.5 years. We have not found a successful case of endoscopic resection of gastric plasmacytoma reported previously.

Synergistic effects of phorbol ester and interferon-α: Target cell class I HLA antigen expression and resistance to natural killer and lymphokine-activated killer cell-mediated cytolysis

This study was undertaken to investigate whether target cell class I HLA antigen expression induced by phorbol ester and interferon-alpha (IFN-alpha) was associated with resistance to natural killer (NK) cells and lymphokine-activated killer (LAK) cell-mediated cytotoxicity. Class I antigen expression on the surface of the K562 erythroleukemia cell line was enhanced by either IFN-alpha or phorbol ester (PDBu). Addition of PDBu together with IFN-alpha had a synergistic effect on class I antigen expression on the cells. Furthermore, synergism between IFN-alpha and PDBu was also found in class I antigen expression by MOLT-3 cells. This synergistic effect on class I antigen expression was blocked by the protein synthesis inhibitor (cycloheximide). Pretreatment of K562 cells with PDBu and IFN-alpha made them more resistant to lysis by NK and LAK cells than did either PDBu or IFN-alpha. In contrast to PDBu, 4 alpha PDD, a biologically inactive phorbol analogue, alone or combination with IFN-alpha, had no effect on class I antigen expression and susceptibility to lysis by NK and LAK cells. Kinetic experiments showed an inverse relationship between the expression of class I antigens and susceptibility to NK cell-mediated cytolysis. Using cold target competition analysis, target cells pretreated with PDBu and IFN-alpha clearly competed less effectively than did untreated cells for lysis of untreated target cells. These results demonstrate that target cells pretreated with PDBu and IFN-alpha decrease their sensitivity to natural killer and lymphokine-activated killer cells inversely with target cell class I HLA antigen expression.

Primary Gastric Carcinoma with the Bull's eye Sign in a Case of Breast Cancer — Immunohistochemical Differentiation from Metastatic Cancer—

Abstract: A 53‐year‐old female, who had undergone a mastectomy for breast cancer 4 years previously, was found to have gastric cancer. Judging from the Bulls eye sign of the upper GI series and endoscopy, it appeared to be a metastatic gastric cancer. Histopathological findings of biopsy specimens revealed adenocarcinoma and metastases from the breast cancer were not negligible. However, the surgically resected specimen had different immunohistochemical staining for CEA, Alcian blue, 115D8, and C‐erb B2 from the breast cancer. The tumor was finally diagnosed as a primary gastric carcinoma. This case shows that immunohistochemical studies are useful for differentiation between metastatic and primary gastric cancer