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Biomedical subjects

K Miwa

Publications and source records attributed to K Miwa.

At least 361 records · Page 20Linked to original sources

Coronary collateral development after acute myocardial infarction.

In 31 patients without a history of preinfarction angina, coronary collateral circulation to the completely obstructed coronary artery was evaluated by coronary angiography during a convalescent period of their first myocardial infarction. Collateral visualization (collateral index) was found to be significantly greater in patients with involvement of the right coronary artery (2.1 +/- 1.1, SD) than in those with obstruction of the left anterior descending coronary artery (1.2 +/- 1.0, p less than 0.05). The time interval from the onset of symptoms of acute myocardial infarction to angiographic evaluation did not affect the extent of collateral visualization or the degree of coronary artery disease. These findings indicate that the collateral vessels develop after acute myocardial infarction regardless of the extent of coronary artery disease and accomplish the proliferative process within one month. It is also suggested that the collateral visualization is dependent on the size of perfusion territory of the infarct-related coronary artery.

Angiography↗

Covalent binding of 4-nitrobenzyl mercaptan S-sulfate to the sulfhydryl groups of hepatic cytosolic proteins and bovine serum albumin with mixed disulfide bond formation.

4-Nitrobenzyl [35S]mercaptan S-sulfonic acid ([35S]NBM S-sulfate), a new type of reactive metabolite of the thiol [35S]NBM in rat liver cytosol fortified with 3'-phosphoadenosine 5'-phosphosulfate, bound rapidly and covalently at pH 7.4 and 37 degrees C to the sulfhydryl groups of rat liver cytosolic proteins with formation of disulfide bonds. From the radioactive proteins was isolated and identified the sole amino acid adduct, S-([35S]NBM)cysteine, after their acid hydrolysis under the anaerobic conditions. Bovine serum albumin (BSA), a model protein with a single SH group, also reacted readily with radioactive NBM S-sulfate to form a disulfide bond in stoichiometric manner. S-([35S]NBM)-cysteine was also isolated and identified as the sole amino acid adduct from the well-washed, radioactive BSA after the same anaerobic acid hydrolysis. A normal hepatic level of GSH not only retarded the BSA-NBM adduct formation completely, but also detached the radioactivity from BSA by the reduction of the disulfide bond with formation of [35S]NBM and its disulfide. Of twenty-one amino acids examined at pH 7.4 and 37 degrees C, only cysteine reacted with NBM S-sulfate and afforded S-(NBM)cysteine with concomitant formations of S-sulfocysteine, cystine, NBM, and its disulfide.

Animals↗

DNA ploidy in early gastric cancer and its relationship to prognosis.

The relationship between DNA ploidy and clinical prognosis was determined in 65 patients who underwent gastroectomy for early gastric cancer. Of the 65 patients, 16 had intramucosal and 49 submucosal tumours. Five-year survival rates were 100 and 79.6% for patients with intramucosal and submucosal tumours respectively. Diploid tumours were observed more frequently among the patients with intramucosal neoplasms. Among the patients with submucosal invasion, the presence of polyploid cells (greater than or equal to 6c) in less than 10% of the malignant population was associated with a superior survival at 5 years, than those with greater than or equal to 10% of polyploid cells (92.1% vs. 36.3%). When the macroscopic type and the ploidy status were evaluated together, patients who had greater than or equal to 10% of cells with DNA greater than or equal to 6 c and a protruding type of tumour, had a 5 year survival rate of only 12.5%. Finally when factors such as the level of wall invasion, percentage of polyploid cells, type of histogram, and macroscopic type were evaluated by multiple regression analysis, macroscopic type and percentage of polyploid cells were the only significant prognostic factors. On the basis of these findings, the DNA ploidy pattern and the macroscopic type may be useful markers of patients who will develop recurrence.

Biomarkers, Tumor↗

[Correlation of epidermal growth factor receptor status and clinical outcome in gastric carcinoma].

Analysis of epidermal growth factor receptor (EGFR) was performed on 242 primary gastric carcinomas and the results correlated with histologic findings and S-phase fractions measured by bromodeoxyuridine (BrdU) labeling. They were stained for EGFR by means of an indirect immunoperoxidase technique using a monoclonal antibody against the receptor. Seventy-six of these cancer tissues exhibited EGFR reactivities. All the cancer cell membranes were stained and sometimes the stroma were stained. These EGFR status were then compared on the basis of pathologic findings including macroscopic type, depth of invasion, differentiation type, vascular invasion and lymph node metastasis. Staining for EGFR in Borrmann's 3 or 4 type was significantly stronger than those in other macroscopic types. The staining for EGFR was closely related to the poorly differentiated type and frequent serosal involvement. BrdU labeling index was studied in 25 cases. These values were from 2.3% to 18.6%, with a mean of 10.4%. The mean BrdU labeling index of EGFR positive cases was 12.2%, of negative cases 7.6%, respectively. There was a good correlation between BrdU labeling index and EGFR status. In addition, There was a signifiCANT 8P less than 0.05) correlation between the presence of the EGFR and poor prognosis. However, EGFR status was not significantly correlated with the lymph node metastasis, vessel invasion and size of the tumors. These results indicate that demonstration of EGFR status may be useful in prognosis and this receptor may be a suitable target for therapy.

Adenocarcinoma, Scirrhous↗

[Malignancy in gastric carcinoma, with special reference to the DNA ploidy and proliferative activity].

Analysis of DNA ploidy patterns was performed on 129 primary gastric cancers and the results correlated with histologic findings and in vivo bromodeoxyuridine (BrdU) labeling. Forty-nine cases were diploid (38%) and 80 cases were aneuploid. There was no correlation between DNA ploidy and histologic type. In aneuploid cancers, incidence of lymphatic invasion, lymph node metastasis and rate of advanced cases were significantly higher than those in diploid tumors. During the follow-up period of 5-10 years, 23 of the 40 patients (55%) with aneuploid tumors died of disease within 3-120 months. Only 13 of the 36 patients (36%) with diploid tumors died of disease. The BrdU labeling indices (BrdU LI) were from 2.8% to 26.7%, with a mean of 10.4%. There was no correlation between BrdU LI and histologic type or stage. The mean BrdU LI of early cancers was 8.1%, of advanced cancers, 11.9%. BrdU LI of cancers with lymphatic invasion or lymph node metastasis was higher than those without them. The mean BrdU LI of diploid cancer was 6.0%, of aneuploid cancers, 11.9%. There was a good correlation between BrdU labeling indices and DNA ploidy patterns. These results indicate that determination of DNA ploidy patterns and growth fractions by BrdU labeling may be useful in the conjecture of prognosis of the patient and in the selection of patients from various modalities.

Aneuploidy↗

The occurrence of acute lymphoblastic leukemia shortly after the cessation of human growth hormone therapy.

We encountered a case of a 21-year-old man who had developed acute lymphoblastic leukemia (ALL) shortly after the cessation of approximately six years' human growth hormone treatment for pituitary dwarfism. The patient had also been treated with thyroid preparations and methylandrostanolone, a kind of anabolic steroid. Factors relating to the onset of ALL in this case are discussed.

Child↗

[Human epidermal growth factor (h-EGF) in gastric carcinomas].

Two hundred and twenty one gastric carcinomas were immunohistochemically stained for h-EGF and we examined the correlation between h-EGF immunoreactivities and histologic findings. Regarding macroscopic and histologic types, incidence of h-EGF immunoreactivities in infiltrating type and in poorly differentiated type was significantly higher than those in localized type and in differentiated type, respectively. In addition, h-EGF producing carcinomas showed high positive rate in prognostic serosal involvement and scirrhous type in stroma. Prognosis in patients with h-EGF producing tumors was poorer than that in those with h-EGF non-producing tumors, especially in stages II and III. These results suggest that h-EGF immunoreactivities serves as a biological marker of high malignancy.

Adenocarcinoma↗

Identification of a novel 1,4-dihydropyridine- and phenylalkylamine-binding polypeptide in calcium channel preparations.

A 1,4-dihydropyridine- and phenylalkylamine-binding polypeptide has been identified by photoaffinity labeling of purified rabbit and guinea pig skeletal muscle calcium channel preparations. The arylazide ligands (-)-[3H]azidopine and (-)-5-[(3-azidophenethyl)[N-methyl-3H]methylamino]-2-(3,4,5- trimethoxyphenyl)-2-isopropylvaleronitrile [( N-methyl-3H]LU 49888) were used to label 1,4-dihydropyridine- and phenylalkylamine-binding sites, respectively. A single, 155 to 170-kDa polypeptide was specifically labeled by both ligands in rabbit and guinea pig preparations provided that the skeletal muscle membranes used for purification were derived from fresh and not previously frozen and thawed tissue. The photoaffinity labeled polypeptide (termed here alpha 1) is different from the previously described alpha subunit in that it has the identical electrophoretic mobility in sodium dodecyl sulfate-polyacrylamide gels irrespective of pretreatment either with N-ethylmaleimide or with dithiothreitol. The use of transverse tubular membranes isolated from previously frozen and thawed skeletal muscle results in a purified calcium channel preparation devoid of the alpha 1 subunit. In these preparations proteolytic degradation products of alpha 1 are labeled with both (-)-[3H]azidopine and [N-methyl-3H]LU 49888. Another large molecular weight polypeptide (termed here alpha 2) was also present in every purified calcium channel preparation studied. alpha 2 is distinct from alpha 1 in that reduction with dithiothreitol changes its apparent mass from 160-190 to 130-150 kDa. The alpha 2 subunit is not photoaffinity labeled either with (-)-[3H]azidopine or [N-methyl-3H]LU 49888. These data suggest that two distinct high molecular weight polypeptides (termed alpha 1 and alpha 2) are putative subunits of skeletal muscle calcium channels. Only the alpha 1 subunit contains both 1,4-dihydropyridine and phenylalkylamine receptors. alpha 2 is the same as the previously described alpha subunit (Curtis, B. M., and Catterall, W. A. (1984) Biochemistry 23, 2113-2118), but is neither a 1,4-dihydropyridine- nor a phenylalkylamine-binding protein.

Animals↗

Paradoxical augmentation of (-)Bay K 8644-induced calcium influx by nitrendipine.

(-)Bay K 8644 produced a concentration-dependent contraction of porcine coronary artery rings with the maximal contraction at 10(-6) M. Pretreatment of the rings with 10(-6) M nitrendipine inhibited (-)Bay K 8644-induced contraction, while pretreatment with 10(-8) M nitrendipine potentiated the contraction elicited by (-)Bay K 8644. (-)Bay K 8644 (10(-6) M) significantly stimulated Ca2+ influx. Although 10(-8) M nitrendipine never stimulated Ca2+ influx, Ca2+ influx induced by (-)Bay K 8644 was significantly potentiated by pretreatment with 10(-8) M nitrendipine. Pretreatment with 10(-6) M nitrendipine significantly decreased Ca2+ influx in tissues treated with (-)Bay K 8644. Our results suggest that the increased Ca2+ influx might be involved in the mechanisms by which (-)Bay K 8644-induced contraction was potentiated by pretreatment with nitrendipine.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗

The HLA-DQ beta gene upstream region contains an immunoglobulin-like octamer motif that binds cell-type specific nuclear factors.

A method is described for scanning relatively large fragments of DNA for sequences which bind nuclear factors. This method was used to identify an octamer (ATTTGTAT) in the DQ beta gene upstream region which differs from the immunoglobulin gene octamer (ATTTGCAT) by only 1 bp. The DQ beta gene octamer binds two proteins, one (B2) appears to be B cell specific while the other (B1) is not. These factors are either similar or identical to factors which bind to the octamer motif in immunoglobulin genes. All other class II MHC genes for which sequence information is available contain an octamer motif in their upstream region. Thus, the possibility that these sequences regulate B cell specific expression of class II MHC genes requires careful evaluation.

Base Sequence↗

Long-chained 1-mercapto-n-alkanes as potent inhibitors toward liver alcohol dehydrogenase.

Long-chained 1-mercapto-n-alkanes showed potent inhibitory effects on horse liver alcohol dehydrogenase (HLADH). The inhibitory effect of the thiols was enhanced by increasing the number of the alkyl carbon atoms up to 10-12 and steeply lowered by further increase in the carbon number. The HLADH activity was almost completely inhibited in competitive manner by an equivalent concentration of 1-mercapto-n-decane or -n-dodecane to that of the subunit of the dimeric zinc enzyme; inhibition constant Ki was 0.55 nM for the former. The present study strongly suggests that the thiols interact simultaneously with at least two sites of HLADH; the primary one could be the zinc atom in the active site of the enzyme, interacting with the sulfhydryl groups, and the other a hydrophobic binding site for the their alkyl carbons.

Alcohol Dehydrogenase↗

Node dissection in gastric cancer.

Three hundred patients who underwent absolute and relative curative gastrectomy and lymph node dissection for gastric cancer were reviewed with respect to postoperative mortality; proportion of patients with node involvement according to the extent of dissection; number of metastatic nodes dissected according to the extent of dissection; accuracy of macroscopic evaluation of node involvement and microscopic node involvement according to tumour location. If more nodes were dissected the proportion of patients with node involvement and the total number of metastatic nodes increased; conversely within R0 and R3 the extent of dissection did not affect postoperative survival. Finally when the presence and extent of node involvement was only macroscopically evaluated, the patients were classified incorrectly in 9.5 per cent of the N0 group and 20.2 per cent of the N1 group. The data suggest that lymph node dissection may be useful in the treatment of gastric cancer, and within the extent studied the employment of this procedure does not affect the postoperative mortality.

Evaluation Studies as Topic↗