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Biomedical subjects

G Ueda

Publications and source records attributed to G Ueda.

At least 73 records · Page 4Linked to original sources

[Expression of blood group antigens A, B, H, Lewis a, Lewis b, in malignant lesions of the uterine cervix].

The fetal, normal adult, and malignant squamous epitheliums of the cervix were immunohistochemically examined by the avidin-biotin-peroxidase complex method with monoclonal antibodies for blood group antigens (BGAs) A, B, H, Lewis a, and Lewis b. The results were as follows. 1) ABH antigen compatible with ABO status was found in most normal squamous epithelium of fetal and adult cervix. 2) Compatible ABH and A antigen were abolished in small cell nonkeratinizing squamous cell carcinomas (SNKCs) and large cell nonkeratinizing squamous cell carcinomas (LNKCs), respectively. But no remarkable change in ABH antigen expression was observed in other types of cervical lesions. 3) Precursor H antigen was accumulated in all types of malignant lesions. 4) Incompatible expression of A or B antigen was observed in some cases of LNKCs and keratinizing squamous cell carcinomas. 5) Lewis antigens were abolished to various degrees in malignant lesions of the cervix. The present study showed the change in BGAs expression during carcinogenesis of the cervix, but further investigation is needed to elucidate the interaction between these changes in BGAs and the biological behavior of cancer cells.

ABO Blood-Group System↗

[Altered expression of Lewis antigens associated with malignant transformation in endometrial tissues].

Fetal, normal adult, and malignant tissues of the uterine endometrium were examined by immunoperoxidase staining for Lewis antigens. Pronounced expression of Lewis-a, Lewis-b, and Lewis-Y antigens in malignant tissues was observed, compared with that in normal adult tissues. Moreover, the amplified expression of Lewis-b antigen was considerably higher than that of Lewis-a and Lewis-Y antigens. On the other hand, Lewis-X antigen was less expressed in malignant tissues than in normal adult tissues. These results suggest that fucose-transferase activity might be increased in malignant tissues and that the type I carbohydrate chain may play a role in the malignant transformation. In addition, Lewis-b and Lewis-Y antigens can be considered to be oncofetal antigens since they were frequently expressed in fetal and malignant tissues, but not in normal adult tissues. However, the functional significance of these changes in the expression of Lewis antigens remains to be investigated.

Cell Transformation, Neoplastic↗

[Phase II study of carboplatin in cervical carcinoma].

A phase II multi-center study of carboplatin for cervical carcinoma was carried out in 22 institutes throughout Japan. The patients registered consisted of 40 women with 39 cervical carcinomas and an endometrial carcinoma, of whom 31 were evaluable. Carboplatin was administered intravenously every 4 weeks at a dose of 400 mg/m2, in cases with no prior therapies and/or P.S. 0-1, and 300 mg/m2 in cases with prior therapies and/or P.S. 2-3. The overall response rate of 31 evaluable cases was 19.4% with 2 cases of CR and 4 cases of PR. The response rates by histological classification were 18.5% (5/27) for squamous cell carcinoma and 25.0% (1/4) for adenocarcinoma. Response rates analysed by lesion sites were 12.5% for primary tumors, 30.0% for local lesions and 20.0% for metastases. The response rate among patients without prior therapies was 14.3%, while those for patients with prior radiotherapy and for prior radiotherapy and chemotherapy were 33.3% and 13.3%, respectively. Major adverse effects observed were nausea and/or vomiting (52.9%), anorexia (44.1%) and malaise (35.3%). Hematologically, thrombocytopenia, leukopenia and anemia were frequently observed (52.9%, 35.3% and 32.4%, respectively). As for renal toxicity, elevation of BUN (2.9%) or serum creatinine (2.9%) and the decrease of creatinine clearance (14.3%) were observed, but they were mild, and tolerable. These results suggest that carboplatin is one of the most useful drugs against cervical carcinoma.

Adenocarcinoma↗

Expression of blood group antigens A, B, H, Lewis-a, and Lewis-b in fetal, normal, and malignant tissues of the uterine endometrium.

Fetal, normal adult, and malignant tissues of the uterine endometrium were examined by immunoperoxidase staining for the blood group antigens (BGA) A, B, H, Lewis-a, and Lewis-b. Antigens A, B, and H compatible with the ABO status of fetuses were detected in 20 of the 22 fetal tissues that were examined. Lewis-b immunoreactivity was also found in 21 fetuses, and Lewis-a was present in a third of the cases. In adult endometrium the expression of BGA H and Lewis-b was considerably lower than in fetal tissues. Malignant endometrial glands extensively reexpressed H and Lewis-b regardless of ABO status. BGA A and B were neither absent nor accumulated in cancer tissues. Thus, H and Lewis-b can be considered as oncofetal antigens since they were frequently expressed in fetal and cancer tissues, but not in normal adult tissues. The increased expression of Lewis-a antigen might be associated with malignant transformation as it was observed only in malignant tissues. However, the functional significance of alterations in BGA expression that may be associated with oncogenesis remains to be investigated.

ABO Blood-Group System↗

Class-specific regulation of anti-DNA antibody synthesis and the age-associated changes in (NZB x NZW)F1 hybrid mice.

Investigations of regulatory helper and suppressor T cells in the in vitro anti-DNA antibody synthesis in NZB x NZW (B/W) F1 hybrid mice were initiated by the development of an in vitro system in which G10-passed B cells from B/W F1 mice were cocultured with mitomycin C-treated T cells in the presence of Con A and either in the presence or in the absence of LPS. It was revealed that each IgG and IgM anti-DNA antibody synthesis was under the regulation of separate L3T4+ helper and Ly-2+ suppressor T cells. The function of these class-specific regulatory T cells was age-dependent. Although the helper effect of L3T4+ T cells on IgG antibody synthesis increased, the effect of L3T4+ T cells on IgM antibody production decreased in B/W F1 mice with aging. The IgG anti-DNA antibody production in the cocultures of L3T4+ T cells and B cells was suppressed by addition of Ly-2+ T cells from young but not aged B/W F1 mice, whereas the production of IgM anti-DNA antibodies was suppressed by Ly-2+ T cells from aged but not young B/W F1 mice. We also found that although IgM anti-DNA antibody-producing B cells were already present in 2-mo-old mice, B cells producing IgG antibodies under the influence of L3T4+ T cells appeared in mice at 7 mo of age. These data clearly indicate that separate class-specific regulatory T cells are involved in the production of IgM and IgG anti-DNA antibodies and that the total serum level of the antibodies is reflected by both their age-associated changes and the generation of antibody-forming B cells in B/W F1 mice.

Aging↗

Unique cell surface phenotypes of proliferating lymphocytes in mice homozygous for lpr and gld mutations, defined by monoclonal antibodies to MRL/Mp-lpr/lpr T cells.

In mice bearing the autosomal recessive gene of either lpr or gld, generalized T-cell proliferation and autoimmunity occurs. The surface antigen profiles of these proliferating cells were analyzed using two-color flow cytometry analysis with two newly established rat monoclonal antibodies (ALP-1, ALP-2) directed to lpr cells. The Lp-1 antigen, defined by ALP-1, is expressed exclusively on approximately one-half of proliferating lpr and gld lymph node cells. The Lp-2 antigen, like B 220, is expressed on 80-90% of lpr and gld lymph node cells, the cells in B-cell lineage and a small population of Ly-2+ T cells from normal mice. Thus, the lpr and gld lymph node cells were classified into three subsets, Lp-1+/Lp-2+, Lp-1-/Lp-2+ and Lp-1-/Lp-2-. After stimulation with Con A or a combination of IL-2 and phorbol ester, a small population of T cells from normal mice became Lp-1+. The same treatment increased Lp-2+/Ly-2+ and induced Lp-2+/L3T4+ T-cell populations. Therefore, it seems likely that these phenotypically unique T cells are generated at some stage during the proliferation and differentiation of certain normal T-cell subpopulations. The aberrant T cells in mice with lpr and gld mutations may even be normal regulatory T cells, if they are not proliferating abnormally.

Animals↗

Detection of chromogranin in argyrophil cells of endometrial carcinoma.

Normal and neoplastic endometrial tissues were examined immunohistochemically for chromogranin which was shown to be a specific marker for neuroendocrine cells. All 20 normal endometriums and 20 endometrial carcinomas without argyrophilia were chromogranin negative. Endometrial carcinomas with argyrophilia tested were composed of three groups; 10 with type I argyrophil cells, 20 with type II argyrophil cells, and 10 with both type I and II argyrophil cells. Type I argyrophil cells of 20 endometrial carcinomas were all chromogranin positive. Chromogranin immunoreactivity was also intimately correlated with the Grimelius reactivity in type II argyrophil cells of 19 endometrial carcinomas, 13 with only type II argyrophil cells and 6 with mixed type of argyrophil cells. Chromogranin was absent in type II argyrophil cells of 11 endometrial carcinomas, 7 with type II argyrophil cells and 4 with mixed type of argyrophil cells. Chromogranin negativity was related to the disappearance of argyrophilia after diastase digestion in 5 of these 11 tumors, and also partly to mucinous substances in the remaining 6 tumors. In conclusion, the results obtained suggest that some of type II argyrophil cells are neuroendocrine in nature as well as type I argyrophil cells.

Carcinoma↗

Effects of angiotensin converting enzyme inhibitor and calcium channel blocker on normoxic and hypoxic pulmonary vascular tone in unanesthetized sheep.

We evaluated the effects of captopril and nifedipine on normoxic and hypoxic pulmonary vascular tone in unanesthetized sheep. Infusion of captopril (10 micrograms/kg/min) in normoxia revealed a tendency to increase the mean pulmonary arterial pressure (Ppa) and the pulmonary vascular resistance (PVR) following the systemic vasodilation. A statistically significant increase was reached by 20 minutes. Hypoxia of 10% oxygen in nitrogen produced a prominent pulmonary hypertensive response. Captopril significantly decreased the hypoxic values of Ppa and PVR from 20.3 +/- 1.3 to 17.1 +/- 1.1 mmHg (p less than 0.01) and from 4.31 +/- 0.45 to 3.49 +/- 0.45 mmHg/L/min (p less than 0.01), respectively. Infusion of nifedipine (10 micrograms/kg/min) in normoxia caused an increase in Ppa from 15.5 +/- 0.9 to 18.9 +/- 1.0 mmHg (p less than 0.01), but not in PVR. This elevation in Ppa was considered to be derived from the significant increase in the cardiac output. Nifedipine significantly decreased the hypoxic values of Ppa and PVR from 21.3 +/- 1.5 to 19.3 +/- 1.5 mmHg (p less than 0.05) and from 3.88 +/- 0.30 to 27.3 +/- 0.13 mmHg/L/min (p less than 0.01), respectively. Captopril and nifedipine produced systemic hypotensive responses during both normoxic and hypoxic ventilation. It is concluded that both captopril and nifedipine are potent pulmonary vasodilating drugs in animal subjects with a hypoxic condition and that they might be useful in the clinical vasodilator therapy of hypoxic pulmonary hypertension in man.

Angiotensin-Converting Enzyme Inhibitors↗

New human papillomavirus sequences in female genital tumors from Japanese patients.

Tissues from 52 cervical carcinomas, 15 cervical intraepithelial neoplasias III (CINs III), and 3 vulvar carcinomas were examined for the presence of human papillomavirus (HPV) sequences by Southern blot hybridization with HPV 16 or 18 DNA as the probe. HPV 16 or 18 DNA was detected in only 17 cervical carcinomas (33%), 5 CINs III (33%), and 1 vulvar carcinoma (33%). These frequencies are lower than those reported by others. However, new, as yet unidentified, HPVs were also detected at rather high frequency under less stringent conditions of hybridization using HPV 16 and 18 DNAs as probes. These HPVs did not hybridize with HPV 6, 11, 16, or 18 under stringent conditions, and were different from two other known types of genital tumor-associated HPVs, HPV 31 and HPV 33, judging from the patterns of their restriction enzyme digests. The total frequencies of HPV sequences were 48% (25/52) for cervical carcinomas, 53% (8/15) for CINs III, and 67% (2/3) for vulvar carcinomas.

Carcinoma↗

[The clinical value of sialyl SSEA-1 antigen in patients with gynecologic tumors].

In order to estimate the clinical significance of sialyl SSEA-1 antigen, the antigen was measured with an "FH-6" Otsuka Kit in sera from patients with various gynecologic tumors. Among the patients with uterine malignancies and benign ovarian tumors, the incidence of elevated sialyl SSEA-1 antigen levels was very low. However, among the patients with ovarian malignancies, serum sialyl SSEA-1 antigen was significantly increased in the following order: clinical stage I (40%), stage II (67%) and stage III (75%). The serum antigen values were also correlated with the effect of treatment. In addition, high antigen values were also observed in all 14 malignant ovarian cyst fluids tested. The immunohistochemical localization of sialyl SSEA-1 antigen was determined by an immunoperoxidase method using FH-6 monoclonal antibody. A weak positive reaction was observed in normal glands of female genital tracts. However, the intense staining was shown on the mocus materials or on the luminal surface of some malignant glands as well as in the cytoplasm of some adenocarcinoma cells of gynecologic malignancies, although there were few positive cases or positive cells. Thus, sialyl SSEA-1 antigen appears to be a useful marker in the diagnosis of ovarian malignancies.

Adenocarcinoma↗

Requirement of H-2 heterozygosity for autoimmunity in (NZB X NZW)F1 hybrid mice.

In the F1 hybrid of autoimmune New Zealand Black (NZB) and phenotypically normal New Zealand White (NZW) mice, there occurs a severe systemic lupus erythematosus (SLE)-like autoimmune disease more fulminant than that found in the parental NZB mice. To determine the role of the H-2 complex in the pathogenesis of autoimmune disease of the (NZB X NZW)F1 hybrid, we developed H-2-congenic NZB (NZB.H-2z) and NZW (NZW.H-2d) strains, and compared the degree of autoimmune features between congenic H-2d/H-2d and H-2z/H-2z homozygous F1 hybrids and the original H-2d/H-2z heterozygous (NZB X NZW)F1 hybrid. We found that autoimmune features such as productions of IgG class anti-DNA antibodies and retroviral gp70 immune complexes and the development of renal disease were to a great extent reduced in both H-2 homozygous F1 hybrids, as compared with the H-2 heterozygous (NZB X NZW)F1 hybrid. It would thus appear that the heterozygosity of H-2d haplotype derived from NZB and H-2z from NZW is essential for the autoimmune disease characteristic of the (NZB X NZW)F1 hybrid.

Animals↗