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Biomedical subjects

A Yamaguchi

Publications and source records attributed to A Yamaguchi.

At least 541 records · Page 30Linked to original sources

Transport of divalent cations with tetracycline as mediated by the transposon Tn10-encoded tetracycline resistance protein.

Tetracycline uptake into inverted membrane vesicles from Tn10-bearing Escherichia coli cells required divalent cations. The degree of the stimulation of tetracycline uptake by various divalent cations showed the following decreasing order: Co2+ greater than Mn2+ greater than Mg2+ greater than Cd2+ greater than Ca2+. This order is consistent with the increasing order of the dissociation constants for metal chelate complexes of tetracycline. The Hill constants for the tetracycline uptake rate with various divalent cation concentrations were one. These observations strongly suggested that a 1:1 complex of tetracycline and a divalent cation was transported by a tetracycline resistance protein. This notion was confirmed by our observations that 60Co2+ was actively taken up with tetracycline by the membrane vesicles prepared from resistant cells. In the absence of tetracycline, no uptake of 60Co2+ was observed. It is clear that the 60Co2+ uptake was mediated by the tetracycline resistance protein, because the membrane vesicles from tetracycline-sensitive cells did not show the uptake of 60Co2+ and tetracycline. The 60Co2+ uptake was inhibited in the presence of other divalent cations, without any significant effect on tetracycline uptake, indicating that these cations are also transported with tetracycline by the tetracycline resistance protein.

Biological Transport↗

Growth fractions in gastric carcinomas determined with monoclonal antibody Ki-67.

The growth fractions of 101 gastric carcinomas were determined in situ by immunostaining with the monoclonal antibody Ki-67 and the results correlated with the histopathologic findings, bromodeoxyuridine (BrdU) labeling index, and DNA ploidy pattern. DNA ploidy patterns were determined by flow cytometric analysis. The Ki-67 labeling rates are rated from 4.6% to 82% (mean, 22%). A significant correlation was found between Ki-67 labeling rates and BrdU labeling indices. Sixty-seven percent of tumors with lymph node metastases showed Ki-67 labeling rates of less than 22%, whereas 33% of tumors without lymph node metastases showed Ki-67 labeling rates of less than 22%. There was a significant correlation between these two groups. Tumors with vessel invasion more often have higher Ki-67 labeling rates than those without vessel invasion. By the DNA ploidy classification, the mean Ki-67 labeling rates of aneuploid tumors was significantly higher than that of diploid tumors. This method yielded similar results to those obtained by BrdU labeling and flow cytometric study. The measurement of Ki-67 labeling rates may be useful to decide the therapeutic modalities.

Antibodies, Monoclonal↗

Retrospective analysis of the prognostic significance of DNA ploidy patterns and S-phase fraction in gastric carcinoma.

Paraffin-embedded tumor samples from 493 gastric carcinoma patients were analyzed by DNA flow cytometry. The results were correlated with clinicopathological findings and S-phase fractions measured by in vivo bromodeoxyuridine (BrdUrd) labeling. Of the 493 patients, 183 (37%), 225 (46%), and 85 (17%) showed diploidy, single DNA-aneuploidy, and DNA-multiploidy patterns, respectively. When the DNA histogram and all the clinicopathological parameters were entered simultaneously into the Cox regression model, DNA ploidy, liver metastasis, peritoneal dissemination, and nodal status emerged as independent prognostic parameters. The relative risk of death was twofold higher in single DNA-aneuploid and threefold higher in DNA-multiploid tumors than in DNA-diploid tumors. BrdUrd labeling indices (LIs) also proved to be an independent prognostic factor. Multiploid tumors showed the highest median BrdUrd LI associated with the most frequent peritoneal dissemination and liver metastasis. The simultaneous evaluation of DNA ploidy patterns and BrdUrd LIs gave more prognostic information than the determination of tumor DNA ploidy only. Namely, DNA diploid, together with low BrdUrd LIs, was associated with favorable prognosis, whereas DNA aneuploid with high BrdUrd LIs was related to the poorest prognosis. These results indicate that DNA ploidy and BrdUrd labeling indices may be possibly useful prognostic factors for gastric carcinoma.

Aneuploidy↗

Relation of proliferative activity to survival in patients with gastric carcinoma.

The prognostic significance of proliferative activity in 167 gastric carcinomas was studied by means of an in vitro labeling method with bromodeoxyuridine (BrdU), using specimens obtained by endoscopic biopsy, and the results were correlated with conventional prognostic factors. The BrdU labeling indicates (BrdU LI) varied from 2.1 to 45%. When the in vitro BrdU LI were plotted against in vivo BrdU LI, a significant correlation was found between in vitro and in vivo BrdU LI (P less than .01). These results show that the in vitro BrdU LI of specimens obtained by endoscopic biopsy indicate accurate proliferative activities of gastric cancers. The BrdU LI were closely correlated with nodal status, vessel invasion, and tumor size. With regard to the correlation of BrdU LI and prognosis, patients whose tumors had a high BrdU LI (BrdU greater than LI less than 10%). When the BrdU LI and all the pathologic findings were entered simultaneously into the regression model, nodal status, tumor size, serosal involvement, and BrdU LI emerged as independent prognostic parameters. The present studies demonstrated the usefulness of the in vitro BrdU-labeling method to estimate the malignancy of gastric cancer preoperatively, and this method may be useful in designing the operative procedure and multimodal therapy for individual patients.

Antibodies, Monoclonal↗

Detection of the growth fraction in colorectal tumours by a monoclonal antibody against DNA polymerase alpha.

The cell kinetics of 54 colorectal tumours were examined by immunohistochemical methods, using the monoclonal antibody DNA polymerase alpha which reacts with an antigen found only in proliferating cells. The rate of DNA polymerase alpha positive cells in colorectal cancer was 44.8%, a figure that was significantly higher than the 21.9% found in colorectal adenomas. The rate of DNA polymerase alpha positive cells tended to rise as the degree of differentiation decreased according to the standard histological grading criteria for colorectal cancer. Positive cells were detected in much greater numbers in tumours with liver metastasis (55.4%) than in those without metastasis (41.7%). The rate of DNA polymerase alpha positive cells for aneuploid lesions was higher than that for lesions with a diploid pattern. The determination of growth fractions with a monoclonal antibody (DNA polymerase alpha) may be a biological marker of great prognostic significance.

Adenocarcinoma↗

Activation of PKC inhibits NaF-induced inositol phospholipid turnover in rat insulinoma cells.

An investigation was done to elucidate the regulatory role of protein kinase C (PKC) in insulin release and also the effects of PKC activation on NaF-induced inositol phospholipid (PI) turnover in and insulin release from rat insulinoma cells (RINr). NaF stimulated insulin secretion in association with an increase in [3H]inositol phosphate formation in RINr cells. Furthermore, NaF induced a rapid decrease in 32P-labeling of phosphatidylinositol-4,5-diphosphate (PIP2) with a concomitant increase of [32P]phosphatidic acid in prelabeled cells. In contrast, NaF had no effect on cyclic AMP production. Although phorbol 12,13-dibutyrate (PDBu) also stimulated insulin release, on concomitant administration of NaF and PDBu, insulin secretion was clearly less than that expected on the basis of an additive action. Moreover, PDBu significantly inhibited NaF-enhanced PI turnover. However, this inhibition was abolished after downregulating PKC by pretreating RINr cells with PDBu. Thus NaF-induced insulin release from RINr cells appears to involve enhancement of PI turnover. Moreover, because NaF is known to activate guanine nucleotide binding proteins (G proteins) directly, PKC activation appears to induce a mechanism that inhibits stimulus-secretion coupling at a level between G protein and phospholipase C-induced PIP2 hydrolysis.

1-Methyl-3-isobutylxanthine↗

Assessment of tumor cell kinetics by monoclonal antibody Ki-67.

The expression of Ki-67 antigen in 71 patients with advanced gastric cancer was studied by immunohistochemical technique. Immunohistochemical staining with Ki-67 produced clear labeling of a portion of tumor cell nuclei, and the nucleoli stained intensely. The Ki-67 labeling rates of the 71 specimens ranged from 7.7 to 70.5% (mean: 29.2%; standard deviation: 12.9%). There was no significant association between Ki-67 labeling rates and macroscopic type, peritoneal metastasis, or serosal invasion. The tumors showing high Ki-67 labeling rates (greater than 25%) are more likely to have liver metastasis and lymph node involvement. Larger tumors, with a diameter greater than 6 cm, more frequently showed high Ki-67 labelling rate than those with a diameter less than 6 cm. When the Ki-67 labeling rate and 9 clinicopathologic parameters, as conventional prognostic factors, were entered simultaneously into the regression model, nodal status and Ki-67 labeling rate emerged as independent prognostic factors. These results indicate that the in situ determination of the growth fraction by Ki-67 antibody may be a reliable prognostic marker of advanced gastric cancer.

Antibodies, Monoclonal↗

Correlation of DNA ploidy and clinical outcome in early gastric carcinomas.

The nuclear DNA content was measured in 120 early gastric carcinomas and the results correlated with histologic findings and S-phase fractions measured by in vivo bromodeoxyuridine (BrdU) labeling. Forty-six cases (38%) were diploid and 74 cases were aneuploid. In aneuploid tumors, incidence of submucosal invasion, vascular invasion, and lymph node involvement were significantly higher than that in diploid tumors. In addition, the S-phase fractions in aneuploid tumors were significantly higher than those in diploid tumors. There was no recurrence in diploid tumors; whereas 21% of cases with aneuploid tumors recurred. These results indicate that DNA content may be a prognostic factor in early gastric carcinoma.

Adult↗

Flow-cytometric analysis of colorectal cancer with hepatic metastases and its relationship to metastatic characteristics and prognosis.

Studying the DNA ploidy patterns of 52 primary tumors, diploid tumors accounted for 48.1% and aneuploid tumors for 51.9%. Out of 31 patients with liver metastases, 35.5% had diploid tumors and 64.5%, aneuploid tumors. Heterogeneity (difference in DNA ploidy pattern between the primary lesion and liver metastases) was found in 20% of the patients examined. In 28 of the patients, the liver metastases were unresectable, and their prognoses were such that the 1- and 2-year survival rates from the diploid tumors were 42.9 and 14.3%, respectively, while 1-year survivors from aneuploid tumors died within 2 years. In resected cases of hepatic metastases, the DNA ploidy pattern of the metastatic lesions did not correlate with the metastasis period, extent of spread or number of lesions. The recurrence rate of aneuploid tumors in the residual livers was 50%, which was slightly higher than the rate of 36.4% for diploid tumors. The prognoses in patients with diploid tumors were significantly better than those in patients with aneuploid tumors: 5-year survival was 71.1% in diploid tumor patients, compared with 21% in aneuploid tumor patients.

Colorectal Neoplasms↗

[Interaction between polyethylene films and brombexine HCl in solid dosage form. II. Effects of moisture property on the sorption of the drug].

The interaction between bromhexine HCl and polyethylene containers was studied in solutions and in tablet packaging systems. Various bromhexine HCl aqueous solutions of different pHs were stored in polyethylene containers at 25 degrees C. The remaining amount of bromhexine HCl was determined by high performance liquid chromatography. It was observed that the transition of bromhexine HCl to polyethylene was inhibited by the addition of some surfactants into the solution, and by lowering the solution pH. In the solid dosage forms, influences of the additives were also studied. It was observed that the decrease of the content of bromhexine HCl in the solid dosage form was inhibited by the addition of acids (citric acid, tartaric acid) and surfactant (sodium dodecyl sulfate) and accelerated by the addition of sodium bicarbonate, similarly to those in solutions. The results indicated that the transition to polyethylene films was influenced by the molecular state of bromhexine HCl.

Adsorption↗

Calcitonin gene-related peptide and induction of hyperglycemia in conscious rats in vivo.

The effect of calcitonin gene-related peptide (CGRP) on glucose metabolism was investigated in conscious and unrestrained rats in vivo. Intravenous injection of rat CGRP (5.67 and 0.567 nmol/kg) caused a significant, dose-dependent increase in plasma glucose concentration and a simultaneous dose-dependent increase in plasma insulin level. In contrast, plasma glucagon level was not changed. On the other hand, intravenous infusion of CGRP (46.6 pmol.kg-1.min-1) decreased tolerance to intragastric administration of glucose (IGGTT). Plasma insulin response to IGGTT, however, was not affected by CGRP infusion. Moreover, although intravenous injection of CGRP (5.67 nmol/kg) elicited a significant increase in plasma epinephrine and norepinephrine concentrations, concomitant administration of epinephrine and norepinephrine, inducing a more prominent rise in plasma catecholamines than those induced by CGRP, affected neither plasma glucose nor insulin levels. Finally, plasma insulin levels obtained by simulating CGRP-induced changes in plasma glucose or glucose plus catecholamine levels by infusion of glucose or glucose plus catecholamines were not different from those induced by CGRP injection. These results suggest that CGRP has a hyperglycemic action that is not mediated by sympathetic outflow in conscious rats, and inhibition of insulin secretion, if any, does not play a major role in this hyperglycemic action of CGRP. We have demonstrated specific CGRP receptors linked to adenylate cyclase activation in rat liver plasma membranes; this hyperglycemic effect of CGRP in vivo may be partly due to its direct action on the liver.

Animals↗

Activation of adenylate cyclase by islet amyloid polypeptide with COOH-terminal amide via calcitonin gene-related peptide receptors on rat liver plasma membranes.

Both human and rat islet amyloid polypeptide with COOH-terminal amide (IAPP-NH2) dose-dependently displaced the specific binding of 125I-labeled [Tyr0] rat alpha-calcitonin gene-related peptide (CGRP) to rat liver plasma membranes, whereas human IAPP (IAPP-COOH) had no effect. Conversely, human or rat IAPP-NH2 but not human IAPP-COOH evoked dose-dependent activation of adenylate cyclase in the membranes, and these effects were significantly inhibited by the CGRP-receptor antagonist human CGRP-1(8-37). Moreover, the dose of human or rat IAPP-NH2 necessary for producing half-maximal activation of adenylate cyclase was comparable with that for producing a half-maximal inhibition of the label binding. Thus, IAPP-NH2 but not IAPP-COOH appears to induce adenylate cyclase activation via CGRP receptors on rat liver plasma membranes.

Adenylyl Cyclases↗

[A 17-year experience with ileal conduit urinary diversion--early and late complications].

A series of 185 patients, 133 males and 52 females, were treated by ileal conduit urinary diversion in the past 17 years. The patients ranged in age from 7 months to 81 years with an average of 59 years. Diversions were performed for malignant diseases in 174 patients, 85% of whom underwent a simultaneous radical surgery. The follow-up covered the postoperative period from 4 months to 16 years 8 months with an average of 4 years 8 months. Six patients (3%) died within 1 month of operation, and 43 of a total of 58 mortal cases died of cancer thereafter. The survival rates of 143 patients with bladder cancer were 84% for 1 year, 72% for 3 years, 67% for 5 years, 62% for 10 years and 54% for 15 years. Early complications were noticed in 38% of the patients. Delayed wound healing due to local infection (20%) and intestinal obstruction (10%) were the two major complications in this period. Late complications were encountered in 51% of the patients. Mild peristomal dermatitis (22%) and gradually developing renal complications (22%) are two major problems in the standard ileal conduit urinary diversion. The latter was significantly more frequent in patients who underwent the operation between 1973 and 1981 than in those who had the surgery between 1982 and 1989. Postoperative hydronephrosis was observed in 15 (13%) of 117 patients who showed normal urograms preoperatively. Ileoureteral reflux was observed in 50% of the cases with nonobstructing conduits, while it increased up to 70% along with obstruction of the conduit.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Characteristics of aztreonam as a substrate, inhibitor and inducer for beta-lactamases.

Aztreonam was investigated as to its characteristics as a substrate, inhibitor and inducer for the well-defined beta-lactamases of Gram-negative bacteria, and its antibacterial efficacy as to bacterial cells producing eight types of beta-lactamases was also evaluated. Aztreonam was hydrolyzed at measurable rates by class A beta-lactamases, a TEM-2 type penicillinase and the Proteus vulgaris cephalosporinase with a broad substrate range. However, the affinity of aztreonam for the class A enzymes was low, this property being well reflected by its high antibacterial activity toward producers of class A beta-lactamases. Aztreonam was extremely stable as to the typical class C cephalosporinase of Citrobacter freundii, and acted as a competitive and progressive inhibitor for the beta-lactamase. While the MICs of aztreonam in the cases of the constitutive producers of class C beta-lactamases were evidently affected by enzyme production. An experiment involving aztreonam as a inhibitor in combination with a hydrolyzable beta-lactam gave ambiguous results, however, a strong synergistic effect was found in combination with mecillinam. Using Pseudomonas aeruginosa, aztreonam was confirmed to be a poor inducer of beta-lactamases.

Amdinocillin↗

[A flow cytometric cell cycle analysis of familial polyposis coli].

The cell cycle of Familial Polyposis Coli (FPC) has been determined by a flow cytometric (FCM) DNA/bromodeoxyuridine (BrdUrd) bivariate analysis. Specimens were obtained from one FPC cancer patient and, for our controls, from 8 single colon cancer patients and from 8 gastric cancer patients who underwent a colectomy. Procedurally, 1 g i.v. injection of BrdUrd was administered 5 to 7 hours before the resection. Later, the BrdUrd-labeling index (BULI) and the potential doubling time (Tpot) were measured by FCM. No significant differences were uncovered between the BULI of the cancer in the FPC patient and that of our controls, or between the BULI of the unaffected mucosa of the FPC patient and that of the controls. Further, with regard to the FPC patient, the mean BULI of the cancer was significantly higher than that of the adenoma and than that of the unaffected mucosa. Also, the mean Tpot of the cancer was significantly shorter than that of the unaffected mucosa. These results suggest that the BULI and the Tpot may change when an adenoma is generated from the unaffected mucosa in FPC patients.

Adenoma↗

[A case report of pleural involvement in primary macroglobulinemia].

A case of primary macroglobulinemia with pleural and gastric involvement was presented. A 48-year-old female was admitted with productive cough. On physical examination neither lymphoadenopathy nor hepatosplenomegaly were found. In addition, no bleeding tendency nor disturbance of the visual acuity were detected. Her chest roentgenogram showed a moderate amount of pleural effusion in the left pleural cavity without infiltration in the lung fields and no evidence of swollen hilar or mediastinal lymphnodes. A monoclonal M-band of to IgM-kappa type was observed in her serum and the pleural effusion. The diffuse ulcerative lesion in the gastric mucosa was detected by gastrofiberscopy. The lymphoid cells taken from the pleural effusion and the gastric mucosa stained positively with fluorescein-conjugated antiserum to u or the kappa chain. Pleural effusion and gastric infiltration of lymphoid cells improved remarkably following ACOP therapy.

Female↗