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Biomedical subjects

K Miwa

Publications and source records attributed to K Miwa.

At least 217 records · Page 12Linked to original sources
PubMed1995

Concanamycin B inhibits the expression of newly-synthesized MHC class II molecules on the cell surface.

We screened natural chemical compounds which inhibit the expression of newly-synthesized MHC class II molecules on the cell surface. IFN-gamma stimulates Colo 205 adenocarcinoma cells to induce the expression of MHC class I, MHC class II, and ICAM-1 molecules on the cell surface. We show here that concanamycin B inhibits the expression of MHC class II molecules on Colo 205 cells, whereas it does not affect the expression of MHC class I and ICAM-1 molecules. Concanamycin B also abrogates the enhancement of the MHC class II expression by IL-4 on mouse lymphocytes. Furthermore, concanamycin B suppresses the antigen presentation by MHC class II molecules.

Animals↗
PubMed1995

[Correlation between the expression of urokinase-type plasminogen activator, E-cadherin and malignancy in gastric cancer].

We aim to elucidate the correlation between clinicopathological parameters and uPA and ECD expression in gastric cancer. Some 125 patients with primary gastric cancer, who were treated at the Second Department of Surgery, Kanazawa University, between 1988 and 1993, were enrolled in this study. The expression of uPA and ECD was evaluated by immunohistochemical staining using a anti-uPA and an anti-ECD monoclonal antibody. The nuclear DNA contents were measured by flow cytometry. Among 125 tumors, 42 (34%) were found to have preserved ECD expression (ECD (+)), and 83 (66%) reduced ECD expression (ECD (-)). uPA immunoreactivity was observed in 82 (65%) of 125 tumors. According to the expression of uPA and ECD status, groups of 22 uPA (-)/ECD (+), 21 uPA (+)/ECD (+), 17 uPA (-)/ECD (-) and 65 uPA (+)/ECD (-) were identified. There was a significant correlation between uPA (+)/ECD (-) status and depth of invasion, liver metastasis, peritoneal dissemination, lymph node metastasis, and venous invasion. Patients with uPA (+)/ECD (-) tumors showed the poorest prognosis and the highest rate of recurrence, as compared with the other groups of patients. No significant correlations were found between uPA (+)/ECD (-) status and DNA ploidy patterns, and histological type. Immunohistochemical analysis of the combination of uPA and ECD expression could be a useful method for the evaluation of metastasis and prognosis in gastric cancer patients. Our results indicate that uPA may have an important role in cancer infiltration and ECD in cancer infiltration and metastasis.

Cadherins↗
PubMed1995

[Correlation of DNA ploidy, c-erB-2 protein tissue status, level of PCNA expression and clinical outcome in gastric carcinomas].

One-hundred and sixty-four patients with gastric carcinomas, who underwent gastrectomy during 1979-1985, were studied. The nuclear DNA contents were measured by cytofluorometry, and immunohistochemical study on the expression of c-erbB-2 protein was performed using a monoclonal antibody against the c-erbB-2 oncogene product. Furthermore immunohistochemical detection of proliferating cell nuclear antigen (PCNA) was performed using a monoclonal antibody against the PCNA. The patients with aneuploid tumor had a significantly worse prognosis than those with diploid tumor. The group with positive staining for c-erbB-2 had a significantly worse prognosis than negative one. The higher group of PCNA indices had a worse prognosis. The patients with tumor showing both aneuploid and positive staining for c-erbB-2 tissue status and PCNA indices. But no correlation was formed between c-erbB-2 tissue status, PCNA indices and DNA contents. From these results, it can be concluded that DNA ploidy, c-erbB-2 protein, and PCNA may reflect the malignant potential of gastric carcinoma.

Aneuploidy↗
PubMed1995

Lymph node metastasis and surgical management of gastric cancer invading the esophagus.

In 88 resected patients with esophagus-invading gastric cancer, the factors determining the prognosis of this disease were investigated by multivariate analysis. Neither, age, sex, macroscopic type, thoracotomy, nor histological type proved to be independent prognostic factors. The presence or absence of lymph node metastasis, serosal invasion, tumor size, and the extent of esophageal invasion were found to be significant independent prognostic factors. Among lymph node metastases, involvement of para-aortic lymph nodes was especially important. The prognosis was significantly better in cases in which these nodes were carefully dissected (R4 gastrectomy), than in cases in which selected dissection was performed (R2). However, no patient with mediastinal lymph node metastasis survived for any lengthy period, and thus the mediastinal lymph nodes seemed to be nodes, the dissection of which brought little effect. Postoperative results were very poor in cases in which the extent of the esophageal invasion was 3 cm or more. These patients should be treated with multi-modal therapy such as neoadjuvant chemotherapy.

Adenocarcinoma↗
PubMed1995

[Effect of chemotherapy using irinotecan (CPT-11) against recurrent colorectal cancer].

Irinotecan (CPT-11) is a camptothecine derivative with antitumor activity and inhibitor of DNA topoisomerase I. CPT-11 showed a excellent and broad anticancer activity against several malignant tumors. In this study, as in the Japanese phase II study, CPT-11 was administered at 100 mg/m2 weekly by intravenous infusion against 10 patients with recurrent colorectal cancer. Median total dose was 513 mg. Partial responses were obtained in 4/10 patient (40%). Lung metastases showed a 33.3% response and lymphnode metastases showed a 60% response. However, liver metastases showed no response. The median duration to the onset of partial response was 20 days and the median overall response duration was 89 days. Adverse effects were leukopenia (40%), nausea, vomiting and diarrhea (80%), fever (20%), and general malaise (30%). These were generally well tolerated and reversible. From these results, CPT-11 seemed to become an effective drug for recurrent colorectal cancer. Further trials of combination chemotherapy utilizing CPT-11 seem to be warranted.

Adult↗
PubMed1994

Prostaglandin F2 alpha receptor is coupled to Gq in cDNA-transfected Chinese hamster ovary cells.

We examined intracellular signal transduction of prostaglandin F2 alpha (PGF2 alpha) receptors by transfection and stable expression of the receptor cDNA in Chinese hamster ovary (CHO-PGF2 alpha) cells. The binding to the membrane was specific for PGF2 alpha, and the Scatchard plot analysis showed a single high-affinity binding site (Kd = 25.2 nM). PGF2 alpha gradually elevated intracellular Ca2+ and stimulated phosphoinositide metabolism in CHO-PGF2 alpha cells. In whole-cell clamp recordings, PGF2 alpha induced an outward current in the presence of external Ca2+, but it induced a long-lasting inward Ca2+ current in a Na(+)-free solution containing K+ channel blockers. Gq alpha antibody applied intracellularly blocked both outward and inward currents induced by 1 microM PGF2 alpha. These results demonstrate that the PGF2 alpha receptor is coupled to phosphoinositide metabolism in CHO-PGF2 alpha cells via Gq.

Animals↗
PubMed1994

Molecular cloning and expression of a cDNA of the bovine prostaglandin F2 alpha receptor.

Capitalizing on the significant sequence homology comprising the transmembrane motif regions of known prostanoid receptor family, we targeted the cloning of a cDNA clone for prostaglandin (PG) F2 alpha receptor from a bovine corpus luteum cDNA library. By using several pairs of degenerated primers created from a common motif of transmembrane domains, polymerase chain reaction gave a clone SN463 carrying the homologous sequence, which covered transmembrane motif IV-VI of the thromboxane (TX) A2 receptor. This polymerase chain reaction product was used as a DNA probe for the following cross-hybridization, and a clone BC2211 carrying a 2.2-kilobase pair DNA insert was isolated. This clone encodes a protein of 362 amino acid residues (M(r) = 40,983) with seven potential transmembrane domains and represented significant overall sequence homology to human TXA2 receptor protein (34% in amino acid). Injection of the mRNA synthesized in vitro from the cloned cDNA into a Xenopus oocyte elicited electrophysiological response to PGF2 alpha. Ligand binding displacement in membranes of mammalian COS-7 cells transfected with the cDNA indicated the rank order of affinity of the receptor to PGs: PGF2 alpha > PGD2 > PGE2 > STA2, a TXA2 agonist. PGF2 alpha activated inositol phosphate formation in COS-7 cells transfected with receptor cDNA. Northern blot analysis and in situ hybridization indicated that the PGF2 alpha receptor mRNA is highly expressed and accumulated in corpus luteum. This is the first report on a successful cloning of functional receptor cDNA for PGF2 alpha.

Amino Acid Sequence↗
PubMed1994

Increased actin cable organization after single chromosome introduction: association with suppression of in vitro cell growth rather than tumorigenic suppression.

We previously showed that introduction of a single human chromosome 1, 6, or 9 derived from normal fibroblasts into HHUA endometrial carcinoma cells resulted in suppression of tumorigenicity. The tumorigenic suppression was accompanied by remarkable morphological changes in the microcell hybrids containing an extra copy of chromosome 1. The study presented here was undertaken to search for target cytoskeletal components affected by chromosome 1 transfer into endometrial carcinoma cells. We found that the microcell hybrids containing an extra copy of chromosome 1 were characterized by intracellular actin bundle formation and an excessive accumulation of actin and vinculin. The latter was a result of increased stabilization of the proteins. Additionally, chromosome 3 introduction into RCC23 human renal carcinoma cells resulted in prolongation of cell division and in senescence of a significant proportion of the microcell hybrids. In these microcell hybrids, the intracellular actin network was also reorganized, but the amounts of actin and vinculin protein were not increased. These findings suggest that the increased actin organization, which appeared not to cause tumorigenic suppression in the microcell hybrids, is associated with complementation of tumor suppressor genes and senescence by multiple mechanisms.

Actin Cytoskeleton↗
PubMed1994

Surgical results of performing R4 gastrectomy for gastric cancer located in the upper third of the stomach.

Because gastric cancers located in the upper third of the stomach are difficult to detect at an early stage, the surgical results remain poor. We performed R4 gastrectomy as a radical procedure for 25 patients, involving complete resection of the latero-aortic and interaorticovenous lymph modes above and below the left renal vein, in combination with the ordinary R2 or R3 gastrectomy (the R4 group). These patients were compared with 156 others who underwent R2 gastrectomy alone (the R2 group). There were no significant differences in operation time, blood loss, or the incidence of complications between the two groups; however, when the survival rates of the patients with tumors invading beyond the subserosa were compared, the 5-year survival rate was found to be significantly higher in the R4 group than in the R2 group. Furthermore, in patients with para-aortic nodal involvement, a significant survival advantage was observed in the R4 group, as compared with the R2 group. These results suggest that the R4 gastrectomy is a rational approach for patients with advanced gastric cancer located in the upper third of the stomach.

Female↗
PubMed1994

Central squamous cell carcinoma of the mandible. Computed tomographic findings.

Five cases of central squamous cell carcinoma of the mandible were investigated with the use of computed tomography. Bucco-lingual extent and spread along the mandibular division of the trigeminal nerve were evaluated. Three patients with trismus showed involvement of the masseter or medial pterygoid muscle on computed tomography. Involvement of more than two landmarks along the trigeminal nerve were observed in cases with both paresthesia of the lower lip and severe pain that resembled neuralgia. Perineural invasion was confirmed histologically in four cases, and all of these patients had both severe pain and mandibular canal involvement that could be demonstrated with computed tomography. When localized soft tissue changes are evident along the course of the trigeminal nerve in the region between the mandibular foramen and foramen ovale, ascending perineural spread should be suspected. Computed tomography findings correlated well with clinical symptoms but added information about the spread of the lesion within the surrounding soft tissue.

Carcinoma, Squamous Cell↗
PubMed1994

Beneficial effects of smoking cessation on the short-term prognosis for variant angina--validation of the smoking status by urinary cotinine measurements.

To examine whether smoking cessation would improve the short-term prognosis for patients with variant angina, 37 smokers with variant angina who were discharged after the complete disappearance of angina by medical treatment with calcium blockers were advised to stop smoking and were followed-up for 1 year. Urinary cotinine radioimmunoassay was used to evaluate their current smoking status. Patients with a urinary cotinine concentration above 50 ng/ml were classified as current smokers. The prevalence of smokers was underestimated by self-reports (11% by self-reports vs. 35% by urinary cotinine measurements after 3 months; 17% by self-reports vs. 36% by urinary cotinine measurements after 1 year). The presence of angina during the first 3 months was significantly (P < 0.05) more prevalent in those who continued to smoke (8/13, 62%) than in those who succeeded in smoking cessation (5/24, 21%) when the current smoking status was determined by urinary cotinine measurements. Smoking cessation definitely improved the prognosis for variant angina even during a relatively short follow-up period.

Angina Pectoris, Variant↗
PubMed1994

Preferential dilation of recipient coronary arteries of the collateral circulation by intracoronary administration of nitroglycerin.

OBJECTIVES: The purpose of this study was to test the hypothesis that the sensitivity to nitroglycerin of collateral vessels and recipient arteries is greater than that of donor arteries of the collateral circulation. BACKGROUND: The collateral circulation responds vigorously to nitroglycerin. However, the mechanisms of the efficacy of nitroglycerin for improving collateral circulation are not fully elucidated. METHODS: The diameter of donor and recipient arteries of the collateral circulation was measured with a computer-assisted analysis system in eight patients with well developed collateral vessels. Coronary angiography was repeated before and after the intracoronary injection of 50 micrograms of nitroglycerin. RESULTS: After nitroglycerin, the mean diameter +/- SD of donor arteries increased to 1.61 +/- 0.53 from 1.29 +/- 0.39 mm (p < 0.01), whereas the diameter of recipient arteries increased to 1.59 +/- 0.50 from 1.10 +/- 0.49 mm (p < 0.01). The change in the diameter of recipient arteries was significantly greater than that of donor arteries (52.3 +/- 24.6% vs. 24.7 +/- 11.5%, p < 0.05). These changes induced by the intracoronary injection of nitroglycerin were accompanied by a decrease in pacing-induced ST segment depression (0.16 +/- 0.06 to 0.06 +/- 0.04 mV, p < 0.01), suggesting increased flow reserve through collateral channels. CONCLUSIONS: These findings indicate that the sensitivity to nitroglycerin of recipient arteries of the collateral circulation is significantly greater than that of donor arteries. This observation may explain the strong response of the collateral circulation to nitroglycerin in patients with functionally significant collateral channels.

Aged↗
PubMed1994

Induction of oesophageal and forestomach carcinomas in rats by reflux of duodenal contents.

A study was designed to determine whether oesophageal carcinomas can be induced through reflux of duodenal contents. Male Wistar rats weighing 230-250 g were divided into three groups according to the surgical procedure performed: (1) the duodenal contents were directed into the forestomach through a stoma (duodeno-forestomach reflux); (2) the duodenal contents were regurgitated into the forestomach through the glandular stomach (duodeno-glandular-forestomach reflux); and (3) a sham operation was performed as a control. Animals were fed standard CRF-1 solid food and tap water that was not exposed to carcinogens and were sacrificed 50 weeks post-operatively. While no neoplasia was observed in any of the 32 control rats, 4/11 (36%) with duodeno-forestomach reflux and 3/18 (17%) animals with duodeno-glandular-forestomach reflux developed carcinomas in the lower oesophagus and forestomach. The incidence in each group was significantly higher than in the controls (P < 0.01 and P < 0.05 respectively). Six of the seven lesions consisted of squamous cell carcinomas, and one was a mucinous adenocarcinoma. Oesophageal columnar epithelial metaplasia was observed in two (18%) of the animals with duodeno-forestomach reflux. Carcinomas were always surrounded by chronic inflammatory changes, including regenerative thickening, basal cell hyperplasia and dysplasia. Additional well-differentiated adenocarcinomas were observed in the prepyloric antrum of 6/18 (33%) animals with duodeno-glandular-forestomach reflux. These findings indicate that chronic reflux of duodenal contents may cause oesophageal carcinoma.

Adenocarcinoma, Mucinous↗
PubMed1994

Rapid assay for detection of toxic shock syndrome toxin 1 from human sera.

A noncompetitive enzyme-linked immunosorbent assay that enables the quantitation of toxic shock syndrome toxin 1 (TSST-1) to as little as 30 pg/ml and the detection of TSST-1 to 10 pg/ml in phosphate-buffered saline including 33% human serum or plasma was developed. It takes only 3 h to complete this assay after plate preparation. In this study, 64 human serum samples obtained from 30 patients with toxic shock syndrome or toxic shock syndrome-like symptoms were subjected to testing for the detection of TSST-1. With a cutoff level for TSST-1 of less than 100 pg/ml, 28 samples obtained from 12 patients were positive for TSST-1. The mean and maximum concentrations for these TSST-1-positive samples were 440 and 5,450 pg/ml, respectively. Of these 12 patients, 8 were Staphylococcus aureus culture positive, 3 were negative upon bacterial culturing, and 1 had no cultures done.

Adolescent↗
PubMed1994

Vasodilation induced by substance P in guinea pig carotid arteries.

In the guinea pig carotid artery with an intact endothelium, substance P (SP, 10(-10)-10(-7) M) relaxed the norepinephrine- (NE) contracted smooth muscles transiently, in a concentration-dependent manner. Acetylcholine (ACh, 10(-6) M) produced a sustained relaxation. SP and ACh also relaxed muscles contracted with high-K (29.6 mM) solution, with a similar form but with a reduced amplitude compared with findings in NE-contracted muscles. In the presence of nitroarginine (10(-5) M) and NE, the ACh-induced relaxation was transient, with a reduced amplitude, whereas the SP-induced relaxation was not significantly changed. In muscles contracted with high-K solution containing nitroarginine, neither SP nor ACh produced relaxation. SP (> 10(-11) M) transiently hyperpolarized the membrane, but only when this peptide was applied from the intimal side of the intact vessel, and the peak amplitude reached approximately 20 mV from the resting potential at 10(-8) M. ACh transiently hyperpolarized the membrane (the peak amplitude being approximately 10 mV), in both the adventitial and intimal applications. In high-K solution, neither SP nor ACh produced hyperpolarization. The amplitude of hyperpolarizations produced by SP did not significantly change in the presence of nitroarginine, oxyhemoglobin, or indomethacin. Thus, SP-induced relaxation seems to be produced mainly by endothelium-derived hyperpolarizing factor-induced hyperpolarization.

Animals↗