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Biomedical subjects

R Abe

Publications and source records attributed to R Abe.

At least 163 records · Page 9Linked to original sources
PubMed1996

The role of pituitary-adrenal counterregulation of inflammation in cerulein-induced pancreatitis: a comparison between Fischer and Lewis rats.

The role of the hypothalamic-pituitary-adrenal axis (HPA axis) in acute pancreatitis has not yet been clarified. In the present study, the concentrations of serum corticosterone and amylase, the severity of pancreatic edema, and the histology of the pancreas during cerulein-induced pancreatitis were compared in two strains of rats whose HPA axes have been reported to be hyperresponsive (Fischer female) and hyporesponsive (Lewis female) to inflammatory mediators. First, we confirmed that the secretory response of corticosterone to lipopolysaccharide was remarkably blunted in Lewis rats compared with Fischer rats. With a single intraperitoneal injection of cerulein at a dose of 50 micrograms/kg, the serum corticosterone of Fischer rats increased promptly, and their serum levels were significantly higher than those of Lewis rats at all points after the induction of pancreatitis. The edema formation and infiltration of inflammatory cells into the pancreas were more severe in Lewis rats than in Fischer rats. The serum amylase concentration was not significantly different between the two strains, except at 2 h after the induction of pancreatitis. The in vitro study using dispersed pancreatic acini showed that there was no significant difference in cerulein-stimulated amylase secretion between the two strains. These findings suggest that the responsiveness of the HPA axis and the consequent secretion of glucocorticoids might modify the pathological features of acute pancreatitis.

Acute Disease↗
PubMed1996

Establishment and characterization of new human Burkitt's lymphoma cell lines (HBL-7 and HBL-8) that are highly metastatic in SCID mice: a metastatic SCID mouse model of human lymphoma lines.

Two newly established human Burkitt's lymphoma cell lines (HBL-7 and HBL-8) were characterized by immunophenotypic, cytogenetic and molecular studies. Both cell lines were negative for Epstein-Barr virus (EBV) genome and had chromosomal translocation: t(8;14) (q24;q32). Immunoglobulin (Ig) gene rearrangement analyses confirmed that both cell lines were derived from primary lymphoma cells. These cell lines were heterotransplanted subcutaneously into severe combined immunodeficiency (SCID) mice to investigate the metastatic capacity. The most striking feature of both cell lines was to show highly spontaneous metastasis to distant organs, particularly spleen, bone marrow and ovaries in SCID mice. To elucidate the metastatic factors involved in the process of spontaneous metastasis, cell surface adhesion molecules or extracellular matrix receptors were analyzed. However, the results did not allow a significant correlation between expression levels of those molecules or matrix receptors and spontaneous metastasis in the SCID mouse model. The HBL-7 and HBL-8 cell lines, however, may be a useful tool to elucidate the metastatic mechanisms of human lymphomas in an animal model.

Adolescent↗
PubMed1996

Immunohistochemical evaluation of lymph node micrometastases from breast cancer.

The lymph node micrometastasis was retrospectively immunohistochemically investigated in 185 patients with node-negative breast cancer and compared with the routine conventional findings. The monoclonal antibodies to epithelial membrane antigen (EMA) and mucinous-like carcinoma antigen (MCA) were used. Of 19 EMA-positive cases, 16 were false positive. Therefore only 3 cases were found to show staining with both EMA and MCA. The patients are all living and well and free of recurrence. No micrometastasis was immunhistochemically demonstrated in 11 node-negative breast cancer patients with subsequent metastases. The results of the present study indicate that the detection rate containing occult cells afforded by conventional routine evaluation is sufficient, at least in Japanese.

Adult↗
PubMed1996

[A randomized controlled study of maintenance therapy with (2"R)-4'-O-tetrahydropyranyladriamycin for advanced and recurrent breast cancer. Clinical Study Group of THP for Breast Cancer in Japan].

We conducted a randomized controlled study to evaluate the clinical usefulness of (2"R) -4'-O-Tetrahydropyranyladriamycin (THP)-based combination therapy subsequent to induction therapy which was consisted with THP, 5'-DFUR, and CPA in the treatment of advanced or recurrent breast cancer. In maintenance therapy, Arm C received CPA and TAM, and Arm T received these two drugs plus THP. Survival time of 50% for all cases in which maintenance therapy was conducted was 26.9 months in Arm T and 20.9 months in Arm C, showing no significant difference by the log-rank test (p = 0.64). Survival time in all cases in which therapy had been completed was 54.6 months in Arm T and 28.1 months in Arm C, showing a significant difference by the log-rank test (p = 0.03) although the number of cases was few. A few cases showed a decrease in total leukocyte count to below 2,000/mm3 at the time of induction therapy, but this was transient in all cases. No significant difference in count was noted between two arms at the time of maintenance therapy. However, many cases in Arm T showed decreased total leukocyte count and hemoglobin content, and thrombocytopenia. These results suggest that combination therapy including THP conducted as maintenance therapy after induction is useful in the prolongation of survival time in patients with advanced or recurrent breast cancer.

Adult↗
PubMed1996

[Flow cytometric DNA analysis of malignant potential in colorectal cancer].

Significance of flow cytometric DNA analysis for assessing malignant potential and survival of colorectal cancer was investigated using paraffin-embedded materials from 163 patients who underwent resection of curability A from 1971 to 1985, excluding intramucosal carcinoma. DNA diploid was confirmed in 46% (75 cases) of the patients and DNA aneuploid in 54% (88 cases). No significant correlation was seen between DNA ploidy and clinicopathological factors, such as tumor location, macroscopic type, histological type, depth of invasion, lymph node metastasis and stage. Cumulative survival rates after curable resection of colorectal cancer were significantly lower in patients with DNA aneuploid tumor than those with DNA diploid tumor. Furthermore, in patients in stage of II and III, survival rates were lower in DNA aneuploid patients than DNA diploid patients, respectively. A multivariate analysis of survival data using Cox's proportional hazard model showed that DNA ploidy was the significant discriminating factor on survival in stage II and III cancer. In conclusion, nuclear DNA ploidy in patients with stage II and III colorectal cancer undergoing curable resection may represent malignant potential and may be an independent prognostic factor.

Colorectal Neoplasms↗
PubMed1996

[K-ras gene mutations in adenomas from familial adenomatous polyposis].

A 18-year-old woman underwent total colectomy for familial adenomatous polyposis. In order to clarify the significance of K-ras mutations in early colorectal carcinogenesis, K-ras mutations were analyzed in multiple adenomas by PCR-SSCP method. A total of 256 adenomas were found throughout the entire colon and rectum, and the distribution was a sparse type. The correlation between K-ras gene and clinicopathological factors was examined in 90 adenomas. There was no correlation among K-ras mutations and anatomical distribution, or morphological classification, but K-ras mutation was more frequent in severe compared with slight atypia. We investigated the correlation between the size of adenoma in the horizontal and vertical directions and K-ras mutation. K-ras mutation was more frequent in the horizontal size greater than 6 mm in diameter, and also more frequent in vertical size greater than 20 mm in height. It was concluded that the adenomas detecting K-ras mutations might have proliferating potential, and would be applied to determine polypectomy.

Adenoma↗
PubMed1996

Flow cytometric DNA analysis of gastric cancer that is invading the muscularis propria.

OBJECTIVE: To find out if there is any correlation between the DNA aneuploidy in gastric cancer that is invading the muscularis propria and survival. DESIGN: Retrospective study. SETTING: Teaching hospital, Japan. SUBJECTS: 52 patients who underwent gastric resection for gastric cancer that was invading the muscularis propria, and for whom clinical follow-up data were available. INTERVENTIONS: Flow cytometric measurement of DNA in paraffin-embedded tissue. MAIN OUTCOME MEASURES: Correlation between survival and clinicopathological variables including ploidy. RESULTS: 22 (42%) of the cases were aneuploid and 30 (58%) were diploid. The lymph node status and DNA ploidy were the significant prognostic variables, but a multivariate analysis showed that only DNA ploidy was significant. CONCLUSIONS: Nuclear DNA ploidy is an independent prognostic factor in gastric cancer that is invading the muscularis propria.

Aneuploidy↗
PubMed1996

Lack of the relationship between menstrual status and timing of surgery in survival of premenopausal patients with breast cancer.

To clarify the relation between menstrual cycle at surgery for breast cancer and prognosis, we have retrospectively investigated 159 women with premenopausal breast cancer. The end of follicular phase was determined putatively as 15 days before the coming menstrual period, and the luteal phase was assumed to commence with the fourteenth day. The mean observation period was 49.7 months. At surgery, 86 patients were in the follicular phase and 73 in the luteal. There was no difference in distribution of age, family history, parity, tumor size or nodal status between the two groups. There were no differences in disease-free or overall survival rate. The follow-up period was not sufficient, but the current result found no relation between the timing of surgery and prognosis.

Adult↗
PubMed1996

The evaluation of mammographic microcalcification as biological malignancy in breast cancer.

The biological significance of mammographic microcalcification (MM) was investigated in breast cancer. 119 (39.8%) had evidence of microcalcification, while 170 were negative. Fifty-three (44.5%) of those with MM had nodal metastases. There is no significant correlation between MM and nodal metastases. Five-year survival of patients with MM was significantly shorter than that without. This suggests that MM may be of biological significance in breast cancer, and thereby attention should to be paid to assessing breast cancer patients with mammographic microcalcification.

Adult↗
PubMed1995

Lipopolysaccharide induces manganese superoxide dismutase in the rat pancreas: its role in caerulein pancreatitis.

Intraperitoneal injection of lipopolysaccharide (LPS) at a dose of 50 micrograms/kg increased the activity and the mRNA level of manganese superoxide dismutase (Mn-SOD) but did not change those of copper/zinc-SOD (Cu/Zn-SOD) in the rat pancreas. Both the formation of pancreatic edema and the elevation of serum amylase during caerulein pancreatitis were significantly relieved in the rats pretreated with LPS (50 micrograms/kg) compared with the rats without the pretreatment. These results support the view that superoxides play a key role in the pathogenesis of caerulein pancreatitis, and that Mn-SOD in the pancreas may work as a defense against the development of this disease.

Animals↗
PubMed1995

Acute graft-versus-host reaction can be aborted by blockade of costimulatory molecules.

Injection of parental lymphocytes into an unirradiated adult F1 host results in an acute GVH reaction characterized by immune deficiency, attack on host lymphohematopoietic tissues, and repopulation with donor-derived cells. All of these events result from the initial activation of donor lymphocytes by host alloantigens. Interaction of pairs of host and donor costimulatory molecules, in particular CD28/CTLA4 and B7-1/B7-2, play a crucial role in this initial activation of donor T cells. We demonstrate here that in vivo treatment of the host with high doses of CTLA4-Ig solely during the initial period of donor alloactivation can completely abort the subsequent development of GVH reaction. Although donor T cells are retained, CTLA4-Ig treatment reduces the initial endogenous cytokine production and arrests the subsequent expansion of donor T cells, the differentiation of anti-host effectors, and the development of severe immune deficiency. This result is consistent with the establishment of host-specific tolerance in the donor population, while maintaining host immune competence.

Abatacept↗
PubMed1995

Intraductal extension of primary invasive breast carcinoma treated by breast-conservative surgery. Computer graphic three-dimensional reconstruction of the mammary duct-lobular systems.

BACKGROUND: Intraductal tumor extension is a characteristic feature of primary breast carcinoma, and is an important consideration in patients undergoing breast conservative surgery. However, there have been no reports of studies of intraductal extension within the mammary ductal tree. METHODS: Quadrantectomy specimens from 20 patients with primary invasive breast carcinoma were examined by subgross and stereomicroscopic technique to visualize intraductal tumor extension. Serial 2 mm-thick sections were subjected to two-dimensional (2-D) tumor mapping, measuring the distances and angles of extension, and to three-dimensional (3-D) reconstruction of the mammary duct-lobular systems by means of computer graphics. RESULTS: Intraductal tumor extension was found in 16 of 20 specimens (80.0%), extending continuously from the primary invasive carcinoma through the mammary ductal tree. The distances and angles of extension were larger in tumors with microcalcifications, papillotubular invasive ductal carcinoma, 30% or more of intraductal component, and comedo-type intraductal tumor extension. The 3-D reconstructions demonstrated three types of extension; central (11 cases), peripheral (3 cases), and mixed (2 cases). Further, there were some ductal branches anastomosing with different mammary duct-lobular systems at various sites. In one specimen, intraductal tumor extended widely from the primary invasive carcinoma through a branch connecting adjacent mammary duct-lobular systems. CONCLUSIONS: Three-dimensional reconstruction images of intraductal extension of invasive breast carcinomas are presented for the first time to the authors' knowledge. Examples of ductal anastomoses were observed, and should be considered as a risk factor for possible widespread intraductal extension through multiple mammary duct-lobular systems.

Adult↗
PubMed1995

Role of B7:CD28/CTLA-4 in the induction of chronic relapsing experimental allergic encephalomyelitis.

T cell activation requires both Ag/MHC recognition and costimulatory signals. The present studies were designed to test whether the loss of tolerance to myelin basic protein (MBP) requires costimulation by members of the B7 receptor family. CTLA-4Ig, a fusion protein ligand for B7-1 and B7-2, was used to assess the role of B7-mediated costimulation in chronic relapsing experimental allergic encephalomyelitis (EAE) induced by the transfer of MBP specific T cell lines. In adoptively transferred EAE, administering CTLA-4Ig to donor mice or during in vitro activation of MBP specific-T cells resulted in diminution of clinical disease. The presence of CTLA-4Ig during both the immunization and in vitro activation stages was most effective in preventing clinical signs of disease. This diminution in clinical disease was paralleled by a decreased proliferative response and reduced production of IL-2 and IL-4, but not IFN-gamma, after antigenic stimulation of encephalitogenic T cells in vitro. In contrast, CTLA-4Ig treatment of recipient animals after the transfer of MBP-activated T cells affected neither disease course nor severity. These results indicate that additional costimulatory pathways may be involved in established EAE, or that some cells are independent of costimulation or, alternatively, that CTLA-4Ig does not enter brain parenchyma in therapeutic concentrations. Thus, we conclude that costimulation provided by B7 molecules plays a major role in the development of encephalitogenic T cells and in the establishment of chronic relapsing EAE, a prototypic CD4+ T cell-mediated autoimmune disease.

Abatacept↗
PubMed1995

Distinct signal transduction in mouse CD4+ and CD8+ splenic T cells after CD28 receptor ligation.

Current evidence suggests that recognition of Ag/MHC by the TCR alone is insufficient to lead to T cell proliferation or effector function. For a Th cell to produce sufficient IL-2 to allow autocrine-driven clonal expansion, there is a requirement for so-called "costimulatory" or "accessory" signals in addition to TCR ligation by Ag/MHC. Although the first signal delivered by TCR ligation has been well characterized, information regarding the biochemical nature of second signals is limited. In the present report, using a newly generated mAb specific for CD28, signal transduction by the CD28 receptor has been studied in mouse splenic T cells. When freshly isolated splenic T cells were assessed, cross-linking of CD28 by mAb did not induce increases in intracellular calcium concentration were assessed, cross-linking of CD28 by mAb did not induce increases in intracellular calcium concentration whereas TCR cross-linking was able to induce calcium mobilization. In contrast, when T cells were activated by phorbol ester treatment or by in vitro culture, CD28 ligation was able to induce calcium mobilization in 60 to 70% of splenic T cells. Unexpectedly, the CD28-induced calcium response was mainly limited to T cells of the CD4+ subset, whereas both CD4+ and CD8+ T cell subsets showed increases in [Ca2+]i of similar magnitude after CD3 epsilon ligation. The temporal nature of the CD28-induced signal was also different from TCR-induced calcium mobilization. CD28-induced signals were delayed in onset and sustained in duration in contrast to TCR signals that had short latency and brief duration. Differential expression of CD28 on the surface of activated CD4+ or CD8+ T cells did not appear to account for the differences in signal transduction between the two T cell subsets. The preferential responsiveness of the CD4+ T cell population to CD28-induced signaling was also observed in downstream events such as the induction of IL-2R, CD69 expression, and in cellular proliferation. These results indicate that the costimulatory signal delivered by CD28 may have fundamentally different biochemical properties in CD4 and CD8 T cell subsets, and therefore the functional role of CD28 may differ in these T cell subsets.

Animals↗
PubMed1995

Correlation between expression of sialosyl-T antigen and survival in patients with gastric cancer.

Intestinal metaplasia of the gastric mucosa is an important lesion in the pathogenesis of gastric cancer. The expression of a mucin-associated antigen, sialosyl-T antigen, in the tissue of gastric cancer was investigated immunohistochemically to assess its biological role. Sialosyl-T antigen, detected by the monoclonal antibody TKH2, was present in 30 (23.6 per cent) of 127 lesions, and expressed sporadically in intestinal metaplasia. Patients negative for sialosyl-T had a significantly better 5-year survival than those who were positive (70.4 per cent versus 47.2 per cent). Grading by sialosyl-T antigen expression and the DNA ploidy pattern had a predictive value for prognosis in patients with gastric cancer. The biological role of sialosyl-T antigen is not clear but the mucin alteration reflects upon the biological behaviour of gastric cancer.

Follow-Up Studies↗
PubMed1995

Argyrophilic nucleolar organizer region (AgNOR) area per nucleus as a prognostic factor in breast cancer.

Whether argyrophilic nucleolar organizer region (AgNOR) is a predictor of prognosis in breast cancer is controversial. The semiquantitative procedure used to calculate interphasic argyrophilic dots optically is neither reliable nor reproducible. We measured the mean area of AgNOR dots, the mean AgNOR area per nucleus (MA), and the mean AgNOR number per nucleus (MN) by automated image analysis in specimens from 131 patients with breast cancer. Higher MA (> 7.41 microns2), detected in 22 (16.8%) of 131 patients, did not correlate with clinicobiologic variables, except for DNA ploidy status. Overall survival was significantly better in patients with lower MA than in those with higher MA. On multivariate analysis, MA was a significant independent factor, followed by nodal status. These findings indicate that expression of AgNOR should be evaluated in terms of area occupied and that the mean area of AgNOR per nucleus (MA) is an important prognostic factor in the overall survival of breast cancer patients.

Adenocarcinoma, Scirrhous↗