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Biomedical subjects

A Takada

Publications and source records attributed to A Takada.

At least 271 records · Page 15Linked to original sources

Clinical backgrounds of the patients having different types of hepatitis C virus genomes.

Hepatitis C virus (HCV) genomes were recently detected in biological materials, and variations of nucleotide sequences were reported. In the present study, typing of the HCV genomes was performed in 91 HCV-RNA-positive patients and the clinical features of patients with different types of HCV were compared. From the nucleotide sequences of the cDNA fragments, HCV can be divided into at least two types: HCV-K1-PT and HCV-K2. All cDNAs amplified from 91 patients were hybridized with cDNA probes of either HCV-K1-PT or HCV-K2. HCV-K1-PT was found in about 80% of the patients, and HCV-K2 was found in about 20% of the patients. These results indicate that types of HCV are limited to two types, i.e., K1-PT and K2, and the major type is HCV-K1-PT, at least in Japan. Detection rate of antibodies to C-100-3 protein were not different between the patients having HCV-K1-PT and HCV-K2, indicating that the antibodies may develop in HCV-related patients without relation to the types of the HCV genomes. Prevalence of the two types of HCV were nearly the same in various forms of NANB-related liver disease. However, the prevalence was somewhat different in alcoholic liver disease. HCV-K2 was found in patients younger than the patients with HCV-K1-PT. Frequency of a history of blood transfusion tended to be lower and the initial response to interferon treatment was clearly better in patients having HCV-K2 versus patients having HCV-K1-PT. These results suggest the possibility that clinical features due to HCV-K1 may be somewhat different from those due to HCV-K1-PT. However, the number of patients examined was too small to allow a definite conclusion, indicating a necessity for further study with a larger number of patients.

DNA, Viral↗

Influence of the tumor mass on the valine rate constants and on valine incorporation into proteins in an experimental brain tumor model.

Quantitative autoradiography was used to estimate regional transfer coefficients for valine incorporation and the rate of valine (exogenous and total) incorporation into proteins in an implanted brain-tumor model (AA ascites tumor). Special attention was paid to the evaluation of the tumor mass influence on the transfer coefficients and the rate of incorporation. The size of the tumors used in this study ranged from 2 to 5 mm in diameter. Nine groups of two to three animals each were used to determine the transfer coefficient. The transfer coefficients for movement of the label between different compartments were significantly greater in the tumor than in the normal brain. There is no tumor mass effect on the transfer coefficients or the rate of valine incorporation into proteins in surrounding or remote brain structures. The ratio between specific radioactivities of the free value in tissue and plasma was also measured. Results indicate that approximately the same fraction of the total valine is recycled in cortex as in the tumor tissue. The mean rates of exogenous valine incorporation into proteins (nmol g-1 min-1) is about one order of magnitude greater in the tumor than in the contralateral parietal cortex.

Animals↗

Blood-brain barrier transfer of L-Trp and alpha-MTrp in Li-treated rats.

Blood-brain barrier (BBB) transport for L-Trp and alpha-methyl-L-tryptophan was evaluated in Li-treated rats. Five different brain areas as well as left to right differences were examined. No left to right difference in the PS product was observed. Lithium treatment had a significant effect on the plasma concentration of Val, Leu and Ile but no effect on plasma total or free Trp. The ratio of plasma Trp to the sum of Leu, Val, Ile, Phe, Met and Tyr is increased in the Li-treated rats but not significantly. However, the ratio of Trp/(Val+Leu+Ile) is significantly increased in the Li-treated rats. The Km apparent (Kmapp) for the BBB Trp transport is significantly decreased (affinity of the carrier for Trp is increased) in the Li-treated rats. A decrease in the Kmapp is one of the possible factors responsible for an increase in the brain Trp concentration and subsequent increase in the brain serotonin synthesis in Li-treated rats.

Animals↗

Purification and characterization of formaldehyde dehydrogenase from rat liver cytosol.

Formaldehyde dehydrogenase was purified to electrophoretic and column chromatographic homogeneity from rat liver cytosolic fraction by a procedure which includes ammonium sulfate precipitation, DEAE-cellulose-, hydroxyapatite-, Mono Q-chromatography, and gel filtration. Its molecular mass was estimated to be 41 kDa by gel filtration and SDS-PAGE, suggesting that it is a monomer. It utilized neither methylglyoxal nor aldehydes except formaldehyde as a substrate. It has been reported that liver class III alcohol dehydrogenase and formaldehyde dehydrogenase are the same enzyme and oxidize formaldehyde and long chain primary alcohols. However, the enzyme examined here did not use n-octanoi as a substrate. The Km values for formaldehyde and NAD+ were 5.09 and 2.34 microM at 25 degrees C, respectively. The amino acid sequences of 10 peptides obtained from the purified enzyme after digestion with either V8 protease or lysyl endopeptidase were determined. From these results, the enzyme was proved to be different from the previously described mammalian formaldehyde dehydrogenase and is the first true formaldehyde dehydrogenase to be isolated from a mammalian source.

Aldehyde Oxidoreductases↗

The role of growth factor in wound healing.

A pig wound healing model was developed to study the morphological processes involved in incisional and excisional wound healing, the immunohistochemical localization of TGF-alpha in wound healing, and the latter's relevance. In incisional wounds, a few layers of epidermis were regenerated after only 32 hours. In contrast, several layers of epidermis were regenerated on day 7 in excisional wounds. In general, the incisional wound model is useful for evaluating tensile strength, while the excisional wound model is suitable for evaluating epidermal regeneration. Immunohistochemical study showed that keratinocytes migrating from wound edges expressed TGF-alpha very faintly, while TGF-alpha was present prominently in the upper several layers of the epidermis adjacent to the wound, which resembled normal epidermis and showed no changes during the wound healing process.

Animals↗

The 55-kilodalton protein in an oriC complex fraction is glycogen synthase.

Three proteins with molecular masses of 35, 55, and 75 kDa were found in an oriC complex fraction after purification through CsCl density gradient centrifugation (W. G. Hendrickson, T. Kusano, H. Yamaki, R. Balakrishnan, M. King, J. Murchie, and M. Schaechter, Cell 30:915-923, 1982). Of these three proteins, the 55-kDa protein was determined to be glycogen synthase on the basis of the N-terminal amino acid sequence and the molecular weight. The oriC complex was formed in glgA mutant cells, which produce no detectable glycogen, as well as in wild-type cells. None of the 35-, 55-, and 75-kDa proteins were detected in the fraction from this mutant. The results indicate that these proteins were not constituents of the oriC complex.

Bacterial Proteins↗

Expression of the angiotensinogen gene and localization of its protein in the human heart.

BACKGROUND: There have been no reports on the presence of the tissue renin-angiotensin system in the human heart, although the presence of angiotensinogen has been described in the animal heart. METHODS AND RESULTS: To determine whether angiotensinogen is synthesized in the human heart, we examined angiotensinogen messenger RNA (mRNA) synthesis in autopsy hearts by using ribonuclease protection assay. As a result, angiotensinogen mRNA was detected in the atrial muscle, muscles of the conduction system, and the left ventricular wall. In the left ventricular wall, mRNA expression was more prominent in the subendocardial muscles than in the midcardial or epicardial muscles. Using a monoclonal antibody to human angiotensinogen in immunoblotting experiments, we detected two closely spaced bands at approximately 70 kd in the heart, which was quite consistent with the human angiotensinogen molecule. Immunohistochemical studies with this monoclonal antibody demonstrated intense immunoreactivity in the atrial muscles, the muscles of the conduction system, and those of the subendocardial layers. CONCLUSIONS: We conclude that angiotensinogen was synthesized in the human heart. It was evident that the localization of angiotensinogen was not ubiquitous in the cardiac muscles, showing its predilection for the atrial muscles, muscles of the conduction system, and subendocardial layer of the left ventricle.

Angiotensin II↗

[Endoscopic studies on refractory gastric ulcers, especially, linear ulcers, treated with proton pump inhibitor].

Seven patients with refractory gastric ulcers against H2-blocker therapy, were treated with omeprazole, and the endoscopic findings serially followed. Round ulcers improved steadily with treatment in two cases. However, healing of the ulcers was not complete and very small pin-point ulcers remained. Therefore, a prostaglandin E1 analogue was added at the 14 and 16th week of omeprazole therapy. The ulcers healed completely, two weeks later. In five cases with linear ulcers, one case discontinued the taking of omeprazole. The linear ulcers in the other four cases healed completely within 4 to 11 weeks. Endoscopically, some parts of the linear ulcers were initially scarred and the ulcers were divided into several short ulcers. The ulcers separated there after and healed respectively. These findings suggest that the healing process of linear ulcers may represent the reversed course of the developing process of linear ulcers. The results indicate that omeprazole is highly effective for the treatment of refractory gastric ulcers.

Adenosine Triphosphatases↗

[Microheterogeneity of serum glycoproteins in alcoholic liver disease].

It has been reported that microheterogeneity (M-HT) of serum glycoproteins including transferrin is found in alcoholic liver disease (ALD). In the present study, M-HT of serum glycoproteins in ALD patients was analyzed using the Western blotting technique after isoelectric focusing. M-HT was found in serum alpha 1-antitrypsin, alpha 2-macroglobulin, ceruloplasmin, alpha 1-acid glycoprotein and hemopexin as well as transferrin, but not in serum prealbumin. M-HT disappeared following treatment with sialidase in one group of glycoproteins, but not in another group of glycoproteins. In hemopexin, M-HT was recognized only after treatment with sialidase. These results suggest that mechanisms of the appearance of M-HT of serum glycoproteins in ALD may differ. One mechanism is the interference of glycosylation of glycoproteins in the Golgi apparatus, and another is the decrease of asialo-protein receptors in hepatocytes.

Blotting, Western↗

[Inhibition of serotonin-induced platelet aggregation by endothelins].

Endothelins are a family of three peptides that act as local hormones in all mammalian species. They were found to inhibit rabbit and dog platelet aggregation in vivo, whereas no effect was observed in vitro. In order to investigate the possible interaction between endothelins and human platelet serotonergic receptors, their effect on the platelet aggregation, induced by serotonin, was studied. Endothelin-1, -2 and -3 had a dual action for platelet aggregation induced by serotonin. When added simultaneously to serotonin endothelins aggregatory response to this amine was potentiated. On the contrary, preincubation of platelet suspension with endothelins resulted in a concentration-dependent inhibition of serotonin-promoted platelet response. Moreover, endothelin-1 inhibited serotonergic amplification of epinephrine-induced aggregation of platelets. It is proposed that endothelins bind to the platelet membrane and interact with serotonergic receptors and/or G proteins. The diverse effect of eodothelins on serotonin-induced aggregation of platelets may be due to stimulation of protein kinase C.

Blood Platelets↗

[Neo-adjuvant chemotherapy with cisplatin, 5-fluorouracil, vindesine in head and neck cancer].

Neo-adjuvant chemotherapy with CDDP combination was introduced into the treatment of advanced head and neck cancer. Twenty-three patients with s.c.c of head and neck were given combination chemotherapy consisting of CDDP, VDS and 5-FU before surgical treatment in our department. CR and PR of this trial in all patients were 4 and 35%, respectively. The WBC nadir occurred around 2 weeks later, but all the patients recovered prior to the next cycle or surgical treatment. Renal dysfunction, nausea, vomiting and depilation were generally mild. VDS is useful as one of the neo-adjuvant drugs for the treatment of head and neck cancer. Long-term observation in connection with this treatment is required.

Antineoplastic Combined Chemotherapy Protocols↗

Diurnal patterns of serotonin, 5-hydroxyindoleacetic acid, tryptophan and fibrinolytic activity in blood of depressive patients and healthy volunteers.

Diurnal changes of serotonin-related factors in whole blood and fibrinolytic activity were determined in depressed patients and healthy controls. Whole blood serotonin concentration of depressed patients showed marked changes throughout daytime, with maximum values in the evening and lowest values in the morning, whereas its metabolite 5-HIAA followed a contrary pattern. The circadian rhythm of 5-HT and 5-HIAA in the control group was quite different from depressed patients. Plasma levels of tPA decreased from 12:30 to 16:30. Concentrations of free plasminogen activator inhibitor (PAI-1) and complex of tPA-PAI-1 decreased from 8:30 to 16:30. Plasma levels of total PAI-1 decreased from 8:30 to 16:30. Plasma levels of the fibrinolytic parameters may be lower in depressive patients than in normal controls. These results support the changes in the circadian rhythm of serotonin and its related substances in the blood of depressive patients.

Adult↗

PAI-1 plays an important role in the expression of t-PA activity in the euglobulin clot lysis by controlling the concentration of free t-PA.

The antigen levels of tissue plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) were assayed in the plasma and in the euglobulin fraction, and their contributions to the euglobulin clot lysis time (ECLT) and t-PA activity were analyzed. Total and free PAI-1 levels in both fractions showed significant positive correlation with ECLT (p less than 0.001), whereas t-PA antigen level did not have a high correlation coefficient with ECLT. t-PA activity showed significant negative correlation with ECLT (p less than 0.001) and positive correlation with free t-PA level (p less than 0.001), which was calculated by the ratio of the concentrations of t-PA-PAI-1 complex and the free PAI-1. Thus free t-PA seems to dissolve the euglobulin clot and its concentration seems to be controlled by the concentration of free PAI-1. These findings were confirmed by the analyses of the effects of C1-inactivator and antibody against t-PA to regular ECLT and kaolin activated ECLT, the latter of which was only inhibited by the addition of C1-inactivator whereas the former was inhibited by anti-t-PA antibody.

Adolescent↗

Adhesion of human cancer cells to vascular endothelium mediated by a carbohydrate antigen, sialyl Lewis A.

Recently the lectin-like domain on ELAM-1 (endothelial leukocyte adhesion molecule-1) was shown to recognize a carbohydrate antigen, sialyl Lewis x. In this paper we demonstrate, by a series of inhibition experiments utilizing specific monoclonal antibodies and pure glycolipid preparations, that the sialyl Lewis a antigen serves as a specific ligand for ELAM-1 as well as sialyl Lewis x and plays a significant role in the ELAM-1-mediated binding of human cancer cells to activated endothelial cells.

Antibodies, Monoclonal↗

Increase in levels of plasminogen activator and type-1 plasminogen activator inhibitor in human breast cancer: possible roles in tumor progression and metastasis.

We measured antigen levels of two kinds of plasminogen activators, tissue type plasminogen activator (t-PA) and urokinase type plasminogen activator (UK), as well as their primary inhibitor, type-1 plasminogen activator inhibitor (PAI-1) in the tissue extracts of benign and malignant breast tumors. Tumor tissues of 36 fibroadenomas and 39 breast cancers were examined. t-PA levels were not different in both groups. Malignant tumors contained the significantly higher levels of UK than benign tumors (p less than 0.001). Furthermore in breast cancer tissues, UK antigen levels of tumors with axillary lymph node involvements were significantly higher than those of tumors without lymph node involvements (p less than 0.05). PAI-1 antigen levels of breast cancer tissues were dramatically higher than those of fibroadenoma (p less than 0.001). PAI-1 levels of node positive carcinomas showed also values significantly higher than node negative ones (p less than 0.01). When we divided cancer tissues into three groups as node negative tumors, tumors with positive axillary nodes fewer than four and tumors with four or more positive nodes, PAI-1 levels increased corresponding to the progression of lymph node involvements (p less than 0.05). Immunohistochemical studies, using mouse monoclonal antibodies to human UK and PAI-1, showed that those immunoreactivities were diffusely distributed in the cytoplasm of human breast cancer cells. Their staining patterns were very similar to each other.

Adenofibroma↗