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Biomedical subjects

H Ota

Publications and source records attributed to H Ota.

At least 19 recordsLinked to original sources

BCL-6 gene product, a 92- to 98-kD nuclear phosphoprotein, is highly expressed in germinal center B cells and their neoplastic counterparts.

The BCL-6 gene is known to be located on chromosome 3q27, at the breakpoint of the 3q27-associated translocations that occur frequently in human non-Hodgkin's lymphomas (NHLs). To identify the BCL-6 protein, two antibodies that recognized distinct domains of this protein were raised in rabbits. Immunoprecipitation and immunoblotting of lysates of BCL-6-expressing cells using both antibodies showed a broad 92- to 98-kD band. Dephosphorylation of BCL-6 protein reduced the size of this band to 87 kD, suggesting that BCL-6 may be expressed in a phosphorylated form. Immunostaining with both antibodies showed that BCL-6 protein was localized in the nuclei of most of the germinal center B cells and a small number of marginal zone B cells. Furthermore, BCL-6 protein was expressed in follicular, Burkitt's, and diffuse large B-cell lymphomas. These results suggest that the BCL-6 protein, expressed in B cells of the germinal centers which are important in the maturation of immune responses, may play some physiological role(s) in the germinal center B cells.

Animals

Proliferative markers in gastric carcinoma and organoid differentiation.

The present study was undertaken to elucidate the relationship between the distribution of potentially proliferative tumor cells and the organoid differentiation of tumor cells in gastric carcinomas. One hundred four specimens of surgically removed human gastric carcinomas, including 68 and 36 specimens of early and advanced carcinomas, respectively, were studied by using a battery of histochemical techniques. Serial 3-microns thick paraffin sections were stained by galactose oxidase-cold thionine Schiff-paradoxical concanavalin A staining (GOCTS-PCS), or were immunostained for pepsinogen types I and II, lysozyme, and proliferating cell nuclear antigen (PCNA). In addition, to identify proliferative tumor cells parts of fresh carcinoma tissues were incubated in a solution containing bromodeoxyuridine (BrdU), embedded in paraffin, and immunostained for BrdU. The results indicated that in intramucosal carcinoma tissues showing organoid differentiation the proliferative tumor cells were located predominantly between the covering epithelial cell type tumor cells and the glandular mucous cell type tumor cells, and the disturbance in the distribution of proliferative cells coincided with the submucosal invasion.

Biomarkers, Tumor

Role of micro-chimerism in inducing immunological tolerance by intraportal injection of donor spleen cells in rats.

Recently, we reported that intraportal (IP) injection of donor spleen cells (SPCs) prevented liver allograft rejection. Moreover, we developed a new method using polymerase chain reaction (PCR)-mediated restriction fragment length polymorphism (RFLP) analysis, and demonstrated micro-chimerism (MC) at the DNA level in the spleen 14 days after IP injection. In the present study, the long-term presence of injected allogeneic SPCs was investigated at the cellular level by immunofluorescence staining as well as the DNA level using RFLP analysis. Male ACI (RT1a) rats were used as the donors and Lewis (RT1(1)) rats as the recipients. After DNA preparation from the lymphoid organs, RT1B beta domain 1 region was amplified by PCR, and RFLP analysis was performed with PvuII restriction enzyme. In the immunofluorescence staining, the monoclonal antibody, MN4-91-6, was used to detect the injected donor ACI SPCs in a frozen specimen. We did not detect MC in Lewis rats intravenously injected with 5 x 10(7) ACI SPCs on day 14. On the other hand, stable chimerism in the spleen was observed in intraportally injected rats up to 28 days after injection at not only the DNA level but also the cellular level. No chimerism was detected in other organs (including the thymus, lymph nodes, and liver). In conclusion, the long-term presence of injected allogeneic SPCs in the spleen was demonstrated after IP injection but not after IV injection, and this phenomenon may be one of the mechanisms involved in portal venous immunosuppression.

Animals

Enhanced production of transforming growth factor-beta (TGF-beta) during autologous mixed lymphocyte reaction of systemic sclerosis patients.

Systemic sclerosis (SSc) is characterized by systemic fibrosis and microvascular lesions. As TGF-beta is suggested to be related to skin fibrosis, we examined the production of TGF-beta from peripheral mononuclear cells (MNC) of SSc patients. Since anti-TGF-beta neutralizing antibody improved the defective proliferative response in autologous mixed lymphocyte reaction (AMLR) of SSc patients, TGF-beta was thought to participate in the decreased AMLR of SSc patients. Greater amounts of TGF-beta in the active as well as in the latent forms were produced during AMLR of SSc patients than that of normal subjects. It was suggested that TGF-beta excessively produced from the MNC of SSc patients might play a major role in the fibrosis of the patients during AMLR-like in vivo responses.

Adult

Expression of the thrombospondin receptor (CD36) on the cell surface in megakaryoblastic and promegakaryocytic leukemias: increment of the receptor by megakaryocyte differentiation in vitro.

In this report we describe four cases of acute megakaryocytic leukemia demonstrated by the presence of megakaryocyte-platelet-related cell-surface antigens. These were detected utilizing flow cytometry and monoclonal antibodies in addition to both platelet peroxidase activity, which was shown by ultrastractural cytochemistry, and emergence of differentiation antigens, while culturing these leukemic cells. The blasts of one patient possessed both platelet GpIb and GpIIb/IIIa cell-surface antigens detected by AN51(CD42b), J15, P2, and HPL2(CD41), respectively, whereas the remaining three patients almost completely lacked GpIb cell-surface antigen. Hence the former were diagnosed as immature(pro)megakaryocytic leukemia and the latter as acute megakaryoblastic leukemia from the viewpoint of immunophenotypic analysis. While we cultured these leukemic cells in conditioned medium prepared from phytohemagglutinin-stimulated leukocytes and interleukin 3, expression of CD36(OKM5) antigen (thrombospondin receptor) increased gradually according to the differentiation and maturation of these cells. Finally, all leukemic cells differentiated to mature megakaryocytes. The function of CD36 on these cells remains to be elucidated.

Antigens, CD

Endoscopic resection of early gastric carcinoma: results of a retrospective analysis of 308 cases.

The purpose of this study was to define the indications and limitations of endoscopic resection (ER) of early gastric carcinoma (EGC). Over the 15 year period from 1978 to 1992, 308 early cancers were resected endoscopically either through a single operative intervention or in stages. Of 266 lesions resected in a single step, 222 (85%) entered remission. Forty-four cases had either residual or recurrent lesions. The size, histology and location affected the curability; 89% of Type IIa lesions less than 2 cm were resected curatively, while only 50% of those larger than 2 cm were resected completely. In Type IIc, 83% of lesions less than 1 cm and 57% of those greater than 1 cm were excised completely by ER. In Type IIc, curative ER was possible in 85% of differentiated carcinomas and 43% of undifferentiated carcinomas. The rate of incomplete resection was higher for lesions of the anterior or posterior wall, than for those of the lesser curvature. Semiserial sections of the resected specimens made at 2 mm intervals, indicated that, if the positive margin was confined to one section, cure may be possible by the burning effect. Follow-up showed that there was no single case undergoing endoscopic resection which subsequently died of gastric carcinoma. The lesions that are suitable for ER comprise Type IIa EGC of less than 2 cm in diameter, and Type IIc differentiated adenocarcinoma of less than 1 cm. Lesions in which the entire margin is difficult to observe by front-view endoscopy should be smaller than defined by the above criteria.

Adenocarcinoma

Nucleolar organizer regions and PCNA expression in prostatic cancers.

Argyrophilic nucleolar organizer regions (AgNOR) of 79 prostatic adenocarcinomas, and an immunohistochemical stain using a monoclonal antibody against proliferating cell nuclear antigen (PCNA) of 54 prostatic adenocarcinomas, obtained by needle biopsy and transurethral resection of the prostate between 1986 and 1989, were investigated. A morphological classification was devised to count silver dots based on the relations between intra- and extra-nucleolar AgNOR (type A, B, C and D). Total AgNOR counts were significantly higher in carcinoma (4.2 +/- 1.57) than in the benign prostatic lesions (1.90 +/- 0.24). Count differences of AgNOR were evident in histological differentiation, nuclear anaplasia, and presence of nucleoli, mitosis, lymphatic invasion and vascular invasion. Higher total AgNOR counts were almost always associated with type B and C AgNOR (intranucleolar AgNOR), but were not associated with type A (nucleolus without small dot) nor type D (extra-nucleolar AgNOR). This study shows the diagnostic value of AgNOR in prostatic cancer, and the importance of morphological classification of AgNOR. The survival of patients with higher AgNOR counts (> or = 4.3) was significantly poorer than survival of those with lower AgNOR counts (< 4.3). Significantly more PCNA positive cells were identified in cancer by immunohistochemical stain and correlated with the presence of mitosis, but there was no significant difference in survival rate groups classified by PCNA positivity. It is also suggested that PCNA can be a useful marker of cell proliferation in prostatic lesions, but the AgNOR counts were diagnostically and prognostically more valuable than immunohistochemical PCNA in prostatic lesions. The correlation between AgNOR and PCNA immunoreactivity was not significant.

Adenocarcinoma

Expression of Forssman antigen in human large intestine.

Forssman antigen is a commonly occurring heterophile antigen but is thought not to be present in most humans. Recent biochemical studies, however, have shown the presence of Forssman antigen in several forms of human cancer, including gastric, colon, and lung cancers. Immunohistochemical staining with both monoclonal and polyclonal antibodies has failed to demonstrate this antigen in human tissues. In this study we conclusively demonstrated the presence of Forssman antigen in cytoplasm of colon goblet cells, especially those in the so-called transitional mucosa adjacent to carcinoma. Specimens from 69 of 70 patients with colon cancer contained the antigen in goblet cells in transitional mucosae. The antigen was successfully demonstrated only after removal of sialic acid by alkaline hydrolysis-neuraminidase digestion. Localization of the antigen was quite different from that of Tn and human blood group A, B, and H antigens. This antigen was thought to be associated exclusively with globo-series glycolipids, and its existence in glycoproteins has not been conclusively demonstrated. However, the results presented here, based on proteolytic digestion and lipid extraction studies, strongly suggest that the antigen is also contained in glycoproteins.

Adult

OK-432 chemical pleurodesis for the treatment of persistent chylothorax.

A 52-year-old woman with thoracic esophageal carcinoma was admitted to our hospital. Standard radical esophagectomy was carried out via a right posterolateral thoracotomy and laparotomy. A drainage tube was removed from the right side of the chest on the 9th postoperative day. Three days later a chest roentgenogram showed massive left pleural effusion, and a tube was inserted into the left pleural cavity. The volume of the effusion was 900 ml/day and chylothorax was diagnosed. Conservative therapy was applied for 30 days, but chyle leakage persisted. Intra-pleural infusion of OK-432, a Su-strain of Streptococcus pyogenes, and doxycycline hydrochloride was carried out to seal the leakage point. The effusion stopped immediately after the procedure. There were no major side effects. This procedure should be considered the treatment of choice for patients with persistent chylothorax not responding to initial conservative management.

Chronic Disease

[Autoimmune hemolytic anemia associated with multicentric Castleman's disease with a 28-year history].

A 49-year-old female admitted because of anemia. had skin rashes since age 20. Generalized lymphadenopathy and fever appeared and the patient was diagnosed as multicentric Castleman's disease (MCD) at 40 years of age. Lymphadenopathy and fever improved with combined chemotherapy. In November, 1992, anemia increased with reticulocytosis (11.8%) and laboratory examination revealed a positive result for Coombs test and increased indirect bilirubin. A diagnosis of autoimmune hemolytic anemia (AIHA) was made. Steroid and plasmapheresis showed temporary effects, but anemia relapsed when steroids were decreased. Immunosuppressive drugs, vincristine and danazole were ineffective. Anemia improved on the second attempt at steroid therapy. The level of Hb rose to 11.2 g/dl after 3 months. The relationship between MCD and AIHA was discussed.

Anemia, Hemolytic, Autoimmune

Benign stricture of the intrahepatic bile duct with arterial involvement.

The absence of arterial change is one of the definitive findings of benign bile duct stricture. Here we report on a patient with a stricture of the intrahepatic bile duct with arterial involvement. Histological examination of the resected specimen revealed fibrous replacement of arterial media, with no evidence of malignancy.

Bile Duct Diseases

Circulating abnormal cells detected in a patient with immunoblastic lymphadenopathy.

An unusual case of immunoblastic lymphadenopathy (IBL) with circulating CD3-CD4+ cells is reported. A lymph node biopsy specimen showed the characteristic features of IBL. Two-color analyses demonstrated that the circulating abnormal cells were CD3-, CD4+, HLA-DR+, and CD25-. Chromosomal analysis revealed unrelated clones in the lymph node. Though 48% of the peripheral blood lymphocytes were abnormal, no clonal rearrangement of the TcR beta chain gene was detected in the peripheral blood. This case might point out the possibility that some cases of IBL truly had no TcR gene rearrangement and were dysplasias.

CD3 Complex