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Biomedical subjects

K Miwa

Publications and source records attributed to K Miwa.

At least 289 records · Page 16Linked to original sources
PubMed1992

[Proliferative activity in gastric cancer with Ki-67 and propidium iodide: analysis by flow cytometry].

Growth fractions in the cell cycle were demonstrated by flow cytometry with monoclonal antibody Ki-67 for gastric cancer. By setting the cut off line at the lowest channel number of S-phase, the Ki-67 labeling rate was calculated by Ki-DNA dual fluorescence analysis. In addition to 32 gastric cancers, we examined three cell lines (Colo 320, NUGC4 and MKN28) and compared the result with the BrdUrd labeling rate. The G0G1 ratio obtained with BrdUrd was generally correlated with the G0 + G1 ratio obtained with Ki-67. The S-phase fractions obtained with Ki-67, however were a little different from those obtained with BrdUrd because of the existence of S0. The mean Ki-67 labeling rate of gastric cancer was 45.1% (16.2-66.3%). Fifteen cases received Ki-67 immunohistochemical study in the same samples. The results of flow cytometric analysis were parallel to those of microscopic study, and a correlation line: y = 0.626x + 15.9145, r = 0.8031, (p less than 0.001) was obtained. Ki-67 antibodies may provide useful information on cell kinetics.

Antibodies, Monoclonal↗
PubMed1991

Expression of c-erbB-2 oncoprotein in gastric carcinoma. Immunoreactivity for c-erbB-2 protein is an independent indicator of poor short-term prognosis in patients with gastric carcinoma.

Correlations of c-erbB-2 protein expression with clinical outcomes of gastric carcinomas were studied in 189 gastric carcinomas. There were 23 (12.2%) carcinomas with evidence of c-erbB-2 protein in which the reaction was localized to the cell membrane. There was no significant association between c-erbB-2 staining and the macroscopic or histologic type of the carcinomas. c-erbB-2-stained tumors were more likely to be associated with serosal invasion, nodal involvement, and peritoneal metastasis, than c-erbB-2-unstained ones. In addition, c-erbB-2 was stained in none of early gastric carcinomas. The 5-year survival rates of the c-erbB-2 protein-positive and the protein-negative group were 11% and 50%, respectively. When the c-erbB-2 tissue status and seven clinicopathologic variables as conventional prognostic factors were entered simultaneously into the Cox regression model, serosal invasion, hepatic metastasis, peritoneal metastasis, nodal status, and c-erbB-2 tissue status emerged as independent prognostic variables. The results suggested that c-erbB-2 protein expression might be enhanced in advanced stages during the progression of gastric carcinoma. In this particular group of patients, immunoreactivity for c-erbB-2 protein is an indicator of poor short-term prognosis.

Adult↗
PubMed1991

An assay system for the modulators of plasminogen activation on the cell surface.

Plasminogen activation on the cell surface is regulated by a variety of modulators which balance surface-bound plasminogen activators (PAs) and plasminogen activator inhibitors (PAIs). In this study, we developed as assay system to assess modulation of cell-associated plasminogen activation. Plasmin generation by endogenous plasminogen activators was measured with a combination of exogenously added plasminogen and a chromogenic substrate, S-2251, in the presence of living cells. A cell surface PA activity was quantitated by adopting a rate of plasmin generation. We used HT-1080, a human fibrosarcoma cell line, as representative of cells which have both PAs and PAIs on their cell surface. A basal level of cell surface PA activity was specifically reduced by anti-urokinase-type PA IgG and enhanced by anti-PAI-1 IgG, suggesting that the basal level is determined by a balance between uPA and PAI-1 on the cell surface. We examined effects of dexamethasone and thrombin on cell surface PA activity in the assay system. Dexamethasone appeared to suppress the cell surface PA activity by enhancing de novo synthesis of PAI-1, whereas thrombin suppressed it by inactivating single-chain urokinase-type plasminogen activators. These results indicate that our assay system can be adapted for the screening of various types of PA modulators.

Cell Membrane↗
PubMed1991

The expression of proliferative-associated nuclear antigen p105 in gastric carcinoma.

The expression of proliferation-associated nuclear antigen p105 of gastric carcinomas was studied by multiparameter flow cytometric and immunohistochemical technique. Multiparameter flow cytometric analysis revealed that p105 expression was rarely observed in the resting cells of normal gastric epithelium. On the contrary, the immunofluorescence (IF) intensity of cancer cells in G1 phase was approximately two-fold to three-fold greater than that of G0 phase of cancer cells or normal gastric epithelium. The p105 antigen content of cancer cells increased with cell cycle progression, and increased more rapidly in cells in late S-phase than in cells in G0 and early S-phase. Microphotometric study demonstrated that cells in M-phase exhibited a dramatic increase in the amount of the antigen, and the IF intensity of the mitotic cells were approximately five-fold to ten-fold greater than that of cells in G1 and S-phase. These results indicate that the antigen demonstrated by the p105 monoclonal antibody is present in the G1, S, G2, M-phases, but not in the G0 phase. Immunohistochemical technique demonstrated that patients with lymph node metastases are more likely to have high p105-positive rates than did node-negative patients. The mean p105-positive rates of aneuploid tumors was significantly higher than those of diploid tumors. From these results the authors speculate that the measurement of p105-positive rates may be a powerful prognostic indicator of gastric carcinoma.

Antigens, Neoplasm↗
PubMed1991

Heparin exercise treatment following percutaneous transluminal coronary angioplasty in a patient with effort angina.

A 63-year-old female with chronic stable effort angina underwent percutaneous transluminal coronary angioplasty (PTCA) for a donating coronary artery of the collateral circulation to the jeopardized region. Because of the inefficacy of the procedure in increasing the collateral flow reserve, the patient was then put on an exercise regimen and also received heparin pretreatment. Her exercise tolerance improved remarkably with the development of improved collateral circulation.

Angina Pectoris↗
PubMed1991

Usefulness of intracoronary injection of acetylcholine as a provocative test for coronary artery spasm in patients with vasospastic angina.

In order to examine both the sensitivity and specificity of coronary artery spasm induced by intracoronary injection of acetylcholine in patients with vasospastic angina, incremental doses of acetylcholine (20, 30, and 50 micrograms) were injected directly into each coronary artery in 21 patients with variant angina (group A), in 28 patients with other types of vasospastic angina (group B), and in 20 patients without any significant coronary artery disease (group C). Coronary artery spasm was defined as severe vasoconstriction (greater than or equal to 90% of reduction in luminal diameter) with chest pain and/or ischemic changes in the electrocardiogram. Intracoronary injection of acetylcholine induced spasm of at least one coronary artery in 20 patients (95%) of group A, in 27 patients (96%) of group B, and in only 2 patients (10%) of group C. The low dose of acetylcholine (20 micrograms) induced coronary spasm more frequently in group A patients (81%) than in group B patients (43%) (P less than 0.05). ST-segment elevation associated with anginal attacks was significantly (P less than 0.05) more frequent in group A (71%) than in group B (39%). When acetylcholine was injected separately into the left and right coronary arteries, spasm of both coronary arteries was observed in 7 out of 14 of group A (50%), in 8 out of 22 of group B (36%), and in none of the 20 of group C. We concluded that intracoronary injection of acetylcholine is a sensitive and reliable method for the induction of coronary spasm in patients with vasospastic angina as well as in those with variant angina.

Acetylcholine↗
PubMed1991

Collateral circulation as a marker of the presence of viable myocardium in patients with recent myocardial infarction.

The relationship between the presence of viable myocardium and the extent of coronary collateral circulation to the infarct area was evaluated in 20 patients with a recent anterior myocardial infarction who had complete obstruction of the left anterior descending coronary artery. The viability of myocardial tissue was assessed by exercise thallium-201 myocardial scintigraphy, and the collateral circulation was angiographically evaluated by means of a collateral index ranging from 0 to 3. Patients were divided into two groups according to the presence (group 1, n = 10) or absence (group 2, n = 10) of viable myocardium in the perfusion territory of the infarct-related artery. The collateral index in group 1 was 2.5 +/- 0.5 (SD), which was significantly higher than the 0.7 +/- 0.8 in group 2. These findings indicate that the presence of ischemic but viable myocardium is intimately related to the development of collateral circulation in patients with myocardial infarction, and the existence of well-developed collateral channels predicts the presence of viable myocardium in the infarct area.

Collateral Circulation↗
PubMed1991

Comparative effect of heparin treatment with and without strenuous exercise on treadmill capacity in patients with stable effort angina.

It has recently been demonstrated that treadmill capacity and collateral circulation improve as a result of exercise with heparin pretreatment in patients with effort angina. In the present study, we assessed whether heparin alone is effective in increasing treadmill capacity in 14 patients with effort angina. Patients were randomly assigned to one of two treatment arms: (1) group A--20 treadmill exercise periods with standard Bruce protocol twice a day for 10 days with heparin (5000 IU intravenously) pretreatment (seven patients) or (2) group B--10 injections of heparin calcium (10,000 IU subcutaneously) once a day for 10 days (seven patients). In group A, total exercise time was increased from 6.9 +/- 1.2 (SD) to 9.9 +/- 1.9 minutes (p less than 0.0005), as was the maximal double product, from 21,700 +/- 3,500 to 27,000 +/- 4,800 mm Hg/min (p less than 0.05). The double product at the onset of angina was also increased by 34% (p less than 0.05), and the double product at which ST depression (0.1 mV) first appeared was 22% (p less than 0.05) greater after treatment. In contrast, in group B, all of the above-mentioned parameters of treadmill capacity remained unchanged. These data indicate that heparin does not serve as an angiogenic factor by itself, but that it potentiates the ischemia-derived angiogenic factor.

Angina Pectoris↗
PubMed1991

Hyperpolarization of arterial smooth muscle induced by endothelial humoral substances.

A sandwich preparation was obtained by placing a segment of the endothelium-free guinea pig coronary artery over the intact carotid artery with the objective being to determine whether the endothelium-dependent hyperpolarization by acetylcholine chloride (ACh) is mediated by a humoral factor. ACh hyperpolarized the sandwiched coronary smooth muscle membrane, the amplitude being larger than that of the carotid artery and smaller than that of the intact coronary artery. When spontaneously active smooth muscles (stomach antrum or portal vein) were used as the donor tissue, no electrical signal was transducted to the overlying coronary smooth muscles. In the sandwiched coronary artery, the ACh-induced hyperpolarization was not inhibited by ouabain, indomethacin, or nitroarginine. Pinacidil hyperpolarized the coronary smooth muscle membrane; the responses were inhibited by glybenclamide but not by tetraethylammonium chloride (TEA). The ACh-induced hyperpolarization was inhibited by TEA but not by glybenclamide. These results suggest that the ACh-induced hyperpolarization is mediated by an endothelium-derived humoral substance (endothelium-derived hyperpolarizing factor). Possible contribution of Ca-dependent K channels, but not ATP-sensitive K channels, to the endothelium-derived hyperpolarizing factor-induced hyperpolarization was considered.

Acetylcholine↗
PubMed1991

Importance of coronary collateral circulation for increased treadmill exercise capacity by nitrates in patients with stable effort angina pectoris.

The purpose of this study was to elucidate the mechanism that induces an improvement in exercise capacity by nitrates in patients with stable effort angina pectoris. The study population was composed of 19 patients: group A, 10 patients with chronic stable effort angina who had a well-developed coronary collateral circulation to the potentially ischemic region; group B, 9 patients with chronic stable effort angina who had no collateral circulation to the jeopardized myocardium. Treadmill exercise was performed according to the standard Bruce protocol with and without pretreatment with orally administered 10 mg isosorbide dinitrate. Percent increases (mean +/- SE) in exercise duration were not significantly different between groups A and B (25 +/- 6 vs. 14 +/- 6%). Percent increases in the maximal rate-pressure product tended to be greater in group A than in group B (27 +/- 6 vs. 10 +/- 6%). Percent increases in the rate-pressure product at the onset of angina pectoris were significantly greater in group A than in group B (37 +/- 7 vs. 7 +/- 6%; p less than 0.01). Percent increases in the rate-pressure product at 0.1 mV S-T segment depression were also significantly greater in group A than in group B (26 +/- 6 vs. 1 +/- 5%; p less than 0.01). These results suggest that isosorbide dinitrate dilates epicardial collateral vessels with smooth muscle layers, but fails to dilate the coronary arteries with significant organic stenoses.

Angina Pectoris↗
PubMed1991

Expression of c-myc gene product in gastric carcinoma.

The expression of c-myc oncogene product was studied in 213 cases with gastric carcinoma by an immunoperoxidase method using a monoclonal antibody (MYC-1). Fifty (23.5%) of 213 tumors showed immunoreactivity to MYC-1. The distribution of c-myc-product-positive cells was observed mainly at the marginal area of the tumor. Excess reactivity to c-myc product occurred more frequently in invasive cancers than in localized cancers, and c-myc production expression in cancer tissue correlated well with peritoneal dissemination. Patients with c-myc-protein-positive tumor had significantly poorer prognosis than those with c-myc-protein-negative tumor in invasive gastric carcinomas, and the c-myc product status correlated well with the recurrence of cancer by peritoneal dissemination. These results suggest that the expression of c-myc gene product might be related to the proliferative activity of gastric carcinoma and serve as a new biologically relevant tumor marker for determining the prognosis.

Animals↗
PubMed1991

[Correlation of p105 expression and malignancy in gastric cancers].

The expression of proliferation-associated nuclear antigen p105 of gastric carcinomas was studied by multiparameter flow cytometry and immunohistochemical technique. Content of p105-antigen in cancer cells increased with cell cycle progression, and increased more rapidly in cells in late-S phase than in cells in G0 and early S-phases. Cells in M-phase exhibited a dramatic increase in the amount of the antigen, and the amount of IF intensity of mitotic cells were approximately 5-10-fold greater than that of cells in G1- and S-phases. Immunohistochemical technique demonstrated that patients with lymph node metastasis are more likely to have high p105 positive rates than node-negative patients. The mean p105 positive rates of aneuploid tumors were significantly higher than those of diploid tumors. These results indicate that the measurement of p105 positive rates may be a powerful prognostic indicator of gastric carcinoma.

Aneuploidy↗
PubMed1991

[Expression of proliferation associated nuclear antigen P-105 in human gastric cancers: as a new marker for metastasis].

Expression of proliferation associated nuclear antigen P-105 was examined with flow cytometry in forty-three patients with advanced gastric cancer. Expression of P-105 was observed abundantly in cancer, about four times than normal mucosa, but little in normal gastric mucosa. We evaluated the expression of P-105 in cancer as P-105 intensity: mean FITC levels of G0G1 of the cancer cells/those of normal cells. The P-105 intensity did not correlate with DNA index or S-phase fraction. Furthermore, it did not correlate with histologic type, stromal type, infiltrating type, and gross appearance. However, P-105 intensity was significantly higher in the patients with hepatic metastasis, and lower in those with peritoneal dissemination than those without metastasis, respectively. From the results, it was supposed that P-105 intensity might be a useful indicator for metastatic type different from those previously reported in human gastric cancers.

Antigens, Neoplasm↗
PubMed1991

L-cell growth stimulation by a beta-casein peptide: the importance of its phosphorylation site for activity.

L-cell proliferation was markedly enhanced by addition to the medium of a synthetic peptide corresponding to residues 1-18 of human beta-casein. Experiments using several synthetic peptides of decreasing length demonstrated that L-S-S-S-E-E (residues 7-12), a major phosphorylation site in beta-casein, appeared to be important for the activity. The phosphorylated beta-casein peptide showed no activity. Recent findings have demonstrated that a similar sequence, S-E-E-E or S-D-D-E, is commonly present in many oncoproteins derived from nuclear oncogenes such as myc, myb and E1A, and plays an important role in transformation functions. The beta-casein peptide may affect mammalian cell proliferation through a modification of of the oncoprotein functions.

Amino Acid Sequence↗
PubMed1991

[Study of para-aortic lymph node metastasis for advanced gastric cancer on consecutive lymph node slices].

Para-aortic lymph nodes (No. 16) from 21 patients with advanced gastric cancer who underwent extensive lymph node dissection, were sliced consecutively at intervals of 50 mu to study minute metastasis of No. 16 lymph nodes. Twenty-six of 30 metastatic lymph nodes had minute involvement, in which carcinoma cells were detected in marginal sinus of lymph node, microscopically. The rate of the metastases to No. 16 lymph nodes was 19% among N0-3 cases by conventional method (not consecutive slices). On the contrary, the percentage of metastasis to No. 16 lymph nodes by consecutive slices was 33% among N0-3 cases. Therefore, No. 16 nodes are involved in metastasis at high rate at operation and the extensive lymph node dissection including No. 16 nodes (R4) will be recommended to prevent lymph node recurrence caused by such a minute metastasis.

Aorta↗
PubMed1991

Relation of proliferative activity to survival in patients with advanced gastric cancer.

The proliferative activities of 98 biopsied specimens of advanced gastric cancers were measured by the in vitro bromodeoxyuridine (BrdU) labelling method. BrdU labelling indices (LIs) varied from 4.8 to 45.1%. There was no correlation of BrdU LIs and histological type, distant metastasis, serosal invasion, macroscopic type or tumor size. However, BrdU LIs of tumors with lymph node metastases were significantly higher than those without them. Patients with tumors showing high BrdU LIs had a three-fold relative risk of death, as compared with those showing low BrdU LIs. When the BRdU LIs and all the clinicopathological parameters were entered simultaneously into the Cox model, BrdU LIs, peritoneal dissemination and serosal invasion emerged as independent prognostic parameters. These results indicate that the in vitro BrdU labelling method using biopsied materials may be useful in predicting lymph node metastasis preoperatively and designing operative procedures for individual patients.

Bromodeoxyuridine↗