[Effect of recombinant human granulocyte-colony stimulating factor (rhG-CSF) on growth of stomach cancer cell lines: preliminary report].
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Cell Division↗
Biomedical subjects
K Miwa
Publications and source records attributed to K Miwa.
[Flow cytometric quantitation of the proliferation-associated nuclear antigen p105 and DNA content in gastric cancer: preliminary report].
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Cell Cycle↗
[Flow cytometric quantitation of the proliferation associated nuclear antigen p105 and DNA content of advanced gastric cancers as a prognostic factor: preliminary report].
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Antigens, Neoplasm↗
Development of collateral circulation after acute myocardial infarction: its role in preserving left ventricular function.
The present study evaluated the effects of coronary collateral circulation developing after acute myocardial infarction on global and regional left ventricular function during the chronic stage. The study group consisted of 16 patients with initial myocardial infarction having total occlusion of the proximal left anterior descending coronary artery. To eliminate the effects of collateral circulation existing at the onset of infarction, patients with pre-infarction angina were excluded from this study. The patients were categorized in two groups depending on the extent of their collateral circulation (collateral index: CI 0-3): group A--patients with significant collateral circulation (CI = 2 or 3) to the infarct-related coronary artery; group B--patients without significant collateral circulation (CI = 0 or 1). Their heart rate, left ventricular peak systolic and end-diastolic pressures and cardiac index were similar in the two groups. The left ventricular end-systolic volume index in the group B was significantly greater than that in the group A (60 +/- 21 ml/m2 vs 34 +/- 9 ml/m2, p less than 0.05). Left ventricular ejection fraction in the group A was significantly greater than that of the group B (55 +/- 9% vs 39 +/- 15%, p less than 0.05), and a significant difference was observed in the percentage of segment shortening in the infarct area between the groups A and B (10.8 +/- 9.2% vs -0.2 +/- 5.4%, p less than 0.01). It was concluded that coronary collateral circulation which develops after acute myocardial infarction exerts beneficial effects on global and regional left ventricular function during the chronic stage.
Adult↗
[Walk-through phenomenon by gradual recruitment of collateral circulation].
The present study was performed to investigate whether coronary collateral vessels open immediately after occurrence of myocardial ischemia. Multistage bicycle exercise was performed to determine the maximum tolerable workload until the onset of angina and significant ST segment depression in 10 patients with well-developed collateral circulation. On a different day, exercise using the maximum tolerable workload was repeated for comparable exercise durations. In two of the 10 patients, anginal pain was gradually alleviated despite the continuation of exercise using the fixed workloads. The extent of ST segment depression during three min exercise with the fixed workload was 0.20 +/- 0.10 (SD) mV, which was significantly (p less than 0.05) greater than 0.16 +/- 0.08 mV at the end of exercise with fixed workload. By contrast, the pressure-rate product was smaller at three min than at the end of exercise using the fixed workload (20,900 +/- 5,500 vs 22,700 +/- 5,700 mmHg-beats/min; p less than 0.05). It was concluded that delayed collateral openings play a critical role in the pathogenesis of the walk-through phenomenon.
Adult↗
[Neoadjuvant chemotherapy of far advanced gastric cancer--effect of preoperative chemotherapy by PMUE (CDDP, MMC, UFT, etoposide].
Preoperative chemotherapy with CDDP, MMC, UFT and etoposide (PMUE) was performed on cases of far advanced gastric cancer whose curative resection was impossible. The therapy comprised 1-5 courses of either intravenous or arterial infusion, or intraperitoneal administration of CDDP 75 mg/m2, MMC 10 mg/body and Etoposide 50 X 3 mg/body at 3-week intervals in combined use of UFT 400 mg/body. The effect of the preoperative PMUE therapy was CR, PR, NC and PD in 0, 7, 1 and 0 cases, respectively, the rate of effectiveness being 88% (7/8). 5 of 7 cases with PR were operated on, 2 cases succeeded in curative resection, but 3 cases did not. Histological judgment of effects confirmed Grade II-a, II-b and III in 2, 2 and 1 cases, respectively; these 5 cases further received 1-4 courses of PMUE therapy as postoperative adjuvant chemotherapy and are still alive at P.S. 0-2, suggesting the great efficacy of this PMUE therapy as a neoadjuvant chemotherapy for improvement in prognosis in far advanced gastric cancer. Abnormally high values of the tumor marker were noted in 5 of 8 cases, 4 of which had tumor marker values lowered in exponential function by the preoperative chemotherapy, which constituted an effective index in determining chemotherapeutic effects and the determination of the operative timing.
Adult↗
[Significance of collateral circulation in reversible asynergy].
The functional role of collateral circulation in reversible asynergy of the left ventricle was evaluated. Cineventriculograms were obtained before and after the administration of sublingual nitroglycerin (0.3 mg) in 19 patients with complete occlusion of the proximal portion of the left anterior descending coronary artery. In nine patients with well-developed collateral circulation, both left ventricular ejection fraction and regional wall motion were significantly improved by nitroglycerin. By contrast, in 10 patients without significant collateral circulation, there were no detectable changes in both global and regional wall motions before and after nitroglycerin. The left ventricular hemodynamic changes caused by nitroglycerin were comparable in both groups. These findings support the view that the improvement in asynergy caused by nitroglycerin appears to depend mainly on the extent of collateral circulation, rather than on decreases in both preload and afterload.
Aged↗
[Malignancy in gastric cancer, with special reference to the distribution of BrdU-labelled cells].
Analysis of the distribution of BrdU-labelled cells was performed on 50 gastric cancers and the results correlated with histologic findings and DNA ploidy patterns. Patients were administered a intravenous infusion of 1g BrdU 1 hour before laparotomy. The resected specimen was fixed in 70% ethanol, embedded in paraffin, and cut into thin sections. The sections were stained by ABC method. The BrdU labelling index (LI) was calculated by counting 1000 tumor cells in superficial, internal and deep layers, respectively. DNA ploidy was analyzed using flow cytometry. The mean of BrdU LI of superficial layer was 19.6%, which was significantly higher than that of internal layer and deep layer. The distribution patterns were classified into three types (labelling types) as follows: Superficial type, BrdU LI of superficial or internal layer was higher than that of deep layer; deep type, BrdU LI of deep layer was higher than that of superficial or internal layer; diffuse type, BrdU LI of each layer was equal. Thirty of 50 cases were superficial type. But in diffuse type (13 cases), incidence of lymph node metastasis, vessel invasion, larger than 4 cm in tumor size, differentiated type and aneuploid were significantly higher than those in superficial type.
Bromodeoxyuridine↗
[A study on 29 patients with cancers of the gastric remnant--a speculation on a remnant cancer-promoting factor from the aspect of tumor location].
We reviewed 29 patients who developed carcinomas of the gastric remnant more than 10 years after the initial gastrectomy. The median age was 59 years (29-75), with a male-to-female ratio of 3.8:1. The reason for previous operation was stomach ulcer in 16 patients, chronic gastritis in 2, stomach polyp in 2, duodenal ulcer in 5 and stomach cancer in 4 patients. Regarding the type of the original operations, Billroth's operation I (B-I) was performed for 10 patients, Billroth's II (B-II) for 18 and Roux-en Y operation for one. The site of tumor was classified into three groups, stoma (gastroenterostomy), stump (gastric cut-end except stoma) and others (the site except stoma and stump). The patients reconstructed with B-II developed significantly more carcinomas in the stoma than those reconstructed with B-I, with the incidence of 10/18 and 0/10, respectively (p less than 0.05). The interval between the initial operation and the second one was significantly longer in patients with stomal cancer than in those with stump cancer (p less than 0.05). There were no significant difference in the frequency and degree of histologic change, such as intestinal metaplasia or glandular cystification in noncancerous areas, between the B-I and B-II patients. This study suggested that cancers of the gastric remnant, especially those developed in the stoma after B-II were different from the other remnant cancers in terms of carcinogenesis or cancer promotion, and that they were probably induced by duodenogastric reflux to the gastrojejunostomized area.
Adult↗
[Metastasis and its relation to cell kinetics in human colorectal cancers].
The difference of the cell kinetics between primary tumor and its metastasis was studied on six cases of human colorectal cancers (four cases at synchronous liver metastases and two metachronous) with migration chase method using flow cytometry in vivo. The bromodeoxyuridine labeling indices (LI), DNA synthesis time (Ts), and generation time (Tg) were measured in normal colonic mucosae, primary tumors, lymph node metastases, and liver metastases. The LI, Ts, and Tg were 4.9 +/- 2.2%, 11.6 +/- 1.4 hours, and 11.3 +/- 3.7 days, respectively, in normal mucosa. In cancer, they were 13.9 +/- 7.1%, 16.9 +/- 4.8 hours, and 6.0 +/- 2.5 days, respectively. LI was higher and Ts was longer in cancer than in normal mucosa. Tg was shorter in cancer than in normal mucosa. In lymph node metastases, LI, Ts, and Tg were 12.0 +/- 4.5%, 14.4 +/- 6.0 hours and 5.0 +/- 0.5 days, respectively. Ts was faster in lymph node metastases than in primary tumors. In liver metastases, they were 30.1 +/- 18.1%, 28.0 +/- 10.2 hours, and 4.8 +/- 2.1 days, respectively. LI was higher and Ts was longer in liver metastases than in primary tumors. In both metastatic lesions, Tg was shorter than in primary tumors. The proliferation rate correlated with LI/DNA index significantly (r = 0.7868, p less than 0.00001). From the results, it was revealed that the proliferation rate was higher in metastatic lesions than primary tumors in vivo. The application of this method for clinical and experimental use would be expected.
Bromodeoxyuridine↗
Proliferative activity of early gastric cancer measured by in vitro and in vivo bromodeoxyuridine labeling.
Forty seven patients with early gastric cancer received a 30-minute intravenous injection of bromodeoxyuridine (BrdU), 1000 mg each 1 hour before laparotomy, to label tumor cells in the S phase. In 13 of 47 patients, specimens obtained by endoscopic biopsy were cultured in vitro at 37 degrees C for 1 hour under three times the atmospheric pressure in a vial with 400 microM BrdU. Labeled cells were detected in the resected specimen and the cultured specimen by immunohistochemical staining procedure. The BrdU labeling index (LI, defined as the percentage of labeled cells in relation to the 1000 tumor cells) was calculated for each specimen. All patients without lymph node metastasis had an in vivo BrdU LI of less than 12%. In contrast, 31% of patients with early gastric cancer with an in vivo BrdU LI greater than 12% had lymph node metastasis. There was a correlation between the in vivo and the in vitro LI. Therefore, the in vitro BrdU LI of specimens obtained by endoscopic biopsy may be a useful indicator of lymph node status in patients with individual early gastric cancers before operations. If the in vitro BrdU LI is less than 12% lymph node dissection may not be necessary.
Bromodeoxyuridine↗
Deletion of 3' untranslated region of human BSF-2 mRNA causes stabilization of the mRNA and high-level expression in mouse NIH3T3 cells.
Most lymphokine genes have an mRNA-destabilizing signal in their 3' untranslated sequences. In this study we demonstrated the usefulness of deletion of this sequence for lymphokine production. By expression of B cell stimulatory factor 2 (BSF-2) cDNAs with and without this region in mouse NIH3T3 cells, it was shown that mRNA of BSF-2 with the 3' destabilizing sequence was very unstable, and that by deletion of this region, the mRNA was stabilized. More than 10-fold BSF-2 productivity was observed in cells harboring the plasmid without the 3' region than in those with it.
Amino Acid Sequence↗
Gastric cancer heterogeneity.
This study was carried out on 222 samples from 37 gastric carcinomas to assess the incidence of multiple stem lines in primary tumors and metastasis as reflected by multiple DNA stem lines and their relationship to epidermal growth factor (EGF) receptor expression, histologic grade, tumor size, and degree of wall infiltration. Fifteen primary tumors (40.5%) were homogeneously diploid/peridiploid whereas 22 (59.5%) were aneuploid. In the lymph node metastasis, seven patients (29.2%) had an homogeneous diploid/peridiploid pattern in all metastatic lymph nodes. On the other hand, 17 (70.8%) had at least one aneuploid peak in the lymph node metastasis. DNA content heterogeneity was seen in 12 (33%) of primary tumors whereas 14 (66.6%) of 21 patients had multiple cell clones in the metastasis. Therefore, 12 patients had a metastatic clone which was not observed in the primary tumor. DNA content heterogeneity was seen even in tumors with submucosal invasion suggesting that this phenomenon is also present at earlier stages. No correlation between the histologic grade and the DNA distribution was observed. Furthermore, histologic heterogeneity was independent of DNA content heterogeneity. The EGF receptor expression was observed in six of the 23 patients in whom this analysis was done. The EGF receptor expression was constant in all samples which were studied and even samples with a different DNA content and histologic grade were stables for the EGF receptor expression.
Carcinoma↗
Correlation of DNA ploidy and clinical outcome in Borrmann type 4 gastric carcinoma.
The correlation between DNA ploidy pattern and clinical outcome was studied in 76 patients with Borrmann type 4 gastric carcinomas. Twenty-six tumors were diploid, and 50 tumors were aneuploid. There was no correlation among DNA ploidy and histologic type, lymph-node status, wall invasion, or clinical stage. The incidence of vascular invasion in the aneuploid tumors was significantly higher than that in the diploid tumors. Five year survival was achieved in 28% of the patients with diploid tumors and 8% of those with aneuploid tumors, respectively. Among the patients undergoing curative resection, 5 year survival rate was 54% in the patients with diploid tumors compared to 28% with aneuploid tumors. There was a significant survival advantage in patients with diploid tumors. These results indicate that DNA ploidy might be an important prognostic factor in Borrmann type 4 gastric carcinomas.
Adult↗
The alpha 3 beta 3 complex, the catalytic core of F1-ATPase.
The alpha 3 beta 3 complex was reconstituted from alpha and beta subunits of the thermophilic bacterium PS3 F1-ATPase (TF1) and then isolated. It is less stable at high and low temperatures than TF1, and the complex dissociates into subunits during native polyacrylamide gel electrophoresis. The alpha 3 beta 3 complex has about 20% of the ATPase activity of TF1. Its enzymic properties are similar to those of the native TF1, exhibiting similar cooperative kinetics as a function of ATP concentration, similar substrate specificity for nucleotide triphosphates, and the presence of two peaks in its temperature-activity profile. Differing from TF1, the ATPase activity of the alpha 3 beta 3 complex is insensitive to N3- inhibition, its divalent cation specificity is less stringent, and its optimum pH shifts to the alkaline side. The addition of the gamma subunit to the alpha 3 beta 3 complex leads to the formation of the alpha 3 beta 3 gamma complex, indicating that the alpha 3 beta 3 complex is an intermediate in the process of assembly of the holoenzyme from each subunit. These results definitely show that the essential structure for eliciting the ATPase activity of F1-ATPase is trimeric alpha beta pairs and that the kinetic cooperativity of the F1-ATPase is an inherent property of this trimeric structure but is not due to the presence of single-copy subunits. In this sense, the alpha 3 beta 3 complex is the catalytic core of F1-ATPase.
Bacteria↗
Reconstituted F1-ATPase complexes containing one impaired beta subunit are ATPase-active.
Homogeneous populations of hybrid alpha 3 beta 3 gamma complexes of the thermostable F1-ATPase containing one, two, or three copies of the mutationally impaired beta subunits were produced using the solid phase reconstitution method. Two kinds of mutated beta subunits were used for the reconstitution, one of which lacked the ability to bind any adenine nucleotides. The complexes containing one impaired beta and two wild-type beta subunits retained a significant amount of ATPase activity with cooperative kinetics, whereas those containing two or three impaired beta subunits showed very little ATPase activity. These results imply that the catalysis of steady-state ATP hydrolysis can proceed even if one of the three beta subunits in F1-ATPase is not functional.
Adenosine Diphosphate↗
Cloning, nucleotide sequence, and expression in Escherichia coli of the gene for poly(3-hydroxybutyrate) depolymerase from Alcaligenes faecalis.
The extracellular poly(3-hydroxybutyrate) depolymerase gene from Alcaligenes faecalis T1 was cloned into Escherichia coli DH1 by using the plasmid pUC8. An A. faecalis T1 genomic library was prepared in E. coli from a partial Sau3AI digest and screened with antibody against the depolymerase. Of the 29 antibody-positive clones, 1 (pDP14), containing about 4 kilobase pairs of A. faecalis T1 DNA, caused expression of a high level of depolymerase activity in E. coli. The enzyme purified from E. coli was not significantly different from the depolymerase of A. faecalis in molecular weight, immunological properties, peptide map, specific activity, or substrate specificity. Most of the expressed enzyme was found to be localized in the periplasmic space of E. coli, although about 10% of the total activity was found in the culture medium. Results of a deletion experiment with pDP14 showed that a large SalI fragment of about 2 kilobase pairs was responsible for expression of the enzyme in E. coli. The nucleotide sequence of the large SalI fragment has been determined. Comparison of the deduced amino terminus with that obtained from sequence analysis of the purified protein indicated that poly(3-hydroxybutyrate) depolymerase exists as a 488-amino-acid precursor with a signal peptide of 27 amino acids.
Alcaligenes↗
Epidermal growth factor receptor status and S-phase fractions in gastric carcinoma.
The correlation with epidermal growth factor (EGF) receptor expression and clinicopathologic findings were studied in 242 gastric carcinomas. They were stained for EGF receptor by means of an immunohistochemical technique using a monoclonal antibody against the receptor. S-Phase fractions were measured by in vivo bromodeoxyuridine (BrdU) labeling and indirect immunohistochemical staining using anti-BrdU monoclonal antibody. In normal gastric epithelium, EGF receptor immunoreactivity could not be found. EGF receptor was found in 76 (31.4%) of 242 gastric carcinomas. Diffusely infiltrating types of carcinomas were more likely than localized tumors to be EGF receptor-positive. In addition, EGF receptor-positive tumors had significantly higher values of BrdU labeling indices than EGF receptor-negative tumors. The patients with EGF receptor-positive carcinomas also had a poorer prognosis than did negative cases. These results suggested that EGF receptor-positive tumors may have higher proliferative activity and local extension may progress more rapidly, and also seem to show that EGF receptor status may possibly be a useful prognostic marker for gastric carcinomas.
Bromodeoxyuridine↗