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Biomedical subjects

S Kato

Publications and source records attributed to S Kato.

At least 1,009 records · Page 56Linked to original sources

Changes in pulmonary hemodynamics during normoxia and hypoxia in awake rats treated with intratracheal bleomycin.

Pulmonary hemodynamics of bleomycin-induced interstitial fibrosis model (group-BLM, n = 10) and saline-treated control (group-C, n = 12) were studied in awake rats. Four weeks before hemodynamic study, bleomycin sulfate and normal saline was intratracheally instilled to the group-BLM and the group-C, respectively. Pulmonary artery and abdominal aortic catheters were indwelled two days before the hemodynamic study. In room air, mean pulmonary artery pressure (Ppa) was significantly higher and systemic artery pressure was significantly lower in group-BLM than in group-C; Ppa = 21 +/- 1 cmH2O (mean +/- S.E.) for group-C and 38 +/- 4 cmH2O for group-BLM. Cardiac output did not differ among the groups. Mean pulmonary vascular resistance (PVR) of group-BLM was double that of group-C. Right ventricle was hypertrophic in group-BLM. When exposed to 10% O2, PVR of group-C significantly rose, whereas PVR of group-BLM showed very little increase, showing attenuation of the hypoxic pulmonary vasoconstriction (HPV). Magnitude of the HPV was inversely related to Ppa during air breathing. We conclude that notable pulmonary hypertension and right ventricular hypertrophy occur, and HPV is blunted four weeks after bleomycin instillation, at the most severe period of this lung fibrosis model. We speculate that the high intravascular pressure partly contributed to the blunted HPV in bleomycin-treated group.

Animals↗

Structural organization of the initial lymphatics in the monkey mesentery and intestinal wall as revealed by an enzyme-histochemical method.

The structure and distribution of the initial lymphatics in whole mount preparations of the mesentery and intestinal walls of the Japanese monkey (Macaca fuscata) were studied using an enzyme-histochemical method (Kato et al., 1991, 1993). The lymphatic walls, colored dark brown by their positive 5'-nucleotidase (5'-Nase) activity, were clearly distinguished from the blood vessels (especially capillaries and arterioles) which were colored blue due to their positive alkaline phosphatase activity. The specificity and localization of both enzyme reactions were confirmed by comparative histochemical studies of the same specimen under a light microscope and scanning or transmission electron microscopes. Application of this staining method takes advantages of the overview preparation of flat membranous organs. The mesenterial area was generally lobulated in distribution with collecting lymphatics and blood vessels. At about the center of each lobule enclosed by the vessels, 5'-Nase-positive initial lymphatics assumed tubulo-saccular shapes, branching antler-like figure to form dense networks in the main lymph vascular pathway. Their apical parts revealed marked knob-like blind endings demarcated by a thin endothelial wall. No direct interconnection was recognizable between the lymphatic space and the tissue interstitium as a prelymphatic fluid pathway. In such preparations, 5'-Nase-positive lymphatic islands could be found isolated from the lymphatic network.

5'-Nucleotidase↗

Glucose sensitivity of ATP-sensitive K+ channels is impaired in beta-cells of the GK rat. A new genetic model of NIDDM.

In the Goto-Kakizaki rat, a new genetic model of NIDDM, insulin response to glucose is selectively impaired. To elucidate the mechanism of this abnormality, we studied the properties of ATP-sensitive K+ channels, the inhibition of which is a key step of insulin secretion induced by fuel substrates, using the patch-clamp technique. The glucose-sensitivity of KATP channels was considerably reduced in GK rats. However, the inhibitory effects of ATP on channel activity and unitary conductance were not significantly different between control and GK rats. Thus, it appears that the impaired insulinotropic action of glucose in beta-cells of GK rats is attributable to insufficient closure of the KATP channels, probably because of deficient ATP production by impaired glucose metabolism. KATP-channel activities in both control and diabetic beta-cells were found to be equally suppressed by glyceraldehyde and 2-ketoisocaproate. These results strongly suggest that the step responsible for the metabolic dysfunction of diabetic beta-cells is located within the glycolytic pathway before glyceraldehyde-3-phosphate or in the glycerol phosphate shuttle.

Adenosine Triphosphate↗

Gene expression of cellular retinol-binding protein I (CRBP I) is affected by dietary proteins in the rat liver.

The effect of dietary proteins and vitamin A status on the gene expression of cellular retinol-binding protein I (CRBP I) was studied in the rat liver. The gene expression was estimated as amounts of transcript (mRNA) by Northern blot analysis using rat CRBP I cDNA. Though vitamin A status is known to positively regulate the gene expression of CRBP I in the extrahepatic tissues, in the present study we observed that the amount of the CRBP I transcript in liver was neither reduced by vitamin A-deficiency, nor affected by replenishment with an excess dose of all-trans retinoic acid. These results indicate that in the liver, different from the extrahepatic tissues, the gene expression of CRBP I may not be controlled by vitamin A. However, when the rats were fed on the diets that differed in dietary proteins, the gene expression of CRBP I in liver was enhanced by higher quality and quantity of dietary proteins, though no effect of dietary proteins was observed upon the hepatic contents of retinol. The concentrations of serum retinol were almost proportional to the mRNA levels of CRBP I. In contrast, the hepatic gene expression of another retinol-binding protein, RBP, and one subtype of retinoic acid receptor, RAR alpha was not influenced in the nutritional condition tested here. Our findings suggest that the gene expression of CRBP I in liver may be under control of the intake of dietary proteins. Thus, it is likely that in the light of the function of CRBP I on cellular transport and metabolism of retinol, dietary proteins may affect the actions of vitamin A in the extrahepatic tissues through changing the amounts of CRBP I in liver.

Animals↗

Phenazoviridin, a novel free radical scavenger from Streptomyces sp. Taxonomy, fermentation, isolation, structure elucidation and biological properties.

Phenazoviridin is a newly discovered free radical scavenger from microorganisms. It was isolated from the culture of Streptomyces sp. HR04. The structure of phenazoviridin was determined as 6-(3-methyl-2-butenyl)phenazine-1-carboxylic acid 6-deoxy-alpha-L-talopyranose ester on the basis of its spectroscopic and physico-chemical properties. The novel substance showed strong inhibitory activity against lipid peroxidation in rat brain homogenate and exhibited antihypoxic activity in mice.

Animals↗

Thiazohalostatin, a new cytoprotective substance produced by Actinomadura. I. Taxonomy, production, isolation and biological activities.

Thiazohalostatin has been isolated from the culture broth of Actinomadura sp. by a screening program designed to find novel cytoprotective substances. It was purified by use of column chromatography on silica gel, reversed phase HPLC and then isolated as colorless powder. Thiazohalostatin prevented cell death caused by calcium overload and exhibited an inhibitory activity against lipid peroxidation.

Actinomycetaceae↗

In vitro and ex vivo free radical scavenging activities of carazostatin, carbazomycin B and their derivatives.

Free radical scavenging activities of various carbazole compounds, carazostatin, carbazomycin B and their chemically modified derivatives were studied in vitro and ex vivo. Among these compounds, carazostatin, which was isolated as a free radical scavenger from the culture of Streptomyces chromofuscus, showed the most potent inhibitory activity against lipid peroxidation of rat brain homogenate in vitro. Carbazomycin B, a known antimicrobial antibiotic, also exhibited strong activity in this system. Although O-modified derivatives of carazostatin and carbazomycin B retained considerable activity, N,O-dimethyl derivatives did not suppress the peroxidation. On the other hand, the results from the ex vivo evaluation of these carbazoles in the lipid peroxidation system of mouse blood plasma showed that the original compounds as well as their O-modified derivatives had a strong inhibitory activity upon oral administration to mice. These findings suggest that these natural carbazoles and their effective derivatives can protect tissues from the peroxidative damage due to generation of free radicals.

Administration, Oral↗

Rumbrin, a new cytoprotective substance produced by Auxarthron umbrinum. I. Taxonomy, production, isolation and biological activities.

Rumbrin has been isolated from a fungus, Auxarthron umbrinum, by a screening program designed to find microorganism-produced cytoprotective substances. It was purified by use of column chromatography on silica gel, reversed phase HPLC and then isolated as fine red needles. Rumbrin prevented cell death caused by calcium overload and exhibited a potent inhibitory activity against lipid peroxidation.

Animals↗

Pyrrolostatin, a novel lipid peroxidation inhibitor from Streptomyces chrestomyceticus. Taxonomy, fermentation, isolation, structure elucidation and biological properties.

Pyrrolostatin, a new lipid peroxidation inhibitor, was isolated from the culture of Streptomyces chrestomyceticus EC40. The structure was determined to be 4-geranylpyrrole-2-carboxylic acid on the basis of its spectroscopic and physico-chemical properties. Pyrrolostatin inhibited lipid peroxidation in rat brain homogenate.

Animals↗

Down-regulation in the production of matrix metalloproteinase 1 by human aortic intimal smooth muscle cells.

Effects of dexamethasone, retinoic acid, prostaglandin E2 (PGE2), and Iloprost as a agonist of prostacyclin (A-PGI2) on DNA synthesis and production of a precursor of matrix metalloproteinase 1 (tissue procollagenase/proMMP-1) by human aortic smooth muscle cells were investigated. When after treatment with platelet-derived growth factor (PDGF), these agents were added to the cultures, DNA synthesis and production of proMMP-1 were inhibited in a dose-dependent manner. These results suggest that these agents are negative regulators of PDGF. Since these agents are present in the blood or produced in the blood wall, in addition, since PDGF plays the most important role in the process of atherosclerosis, we propose that these agents function in vivo as a systems of protection against atherosclerosis.

Aorta↗

Bone marrow transplantation for Fanconi anemia. Adjustment of the dose of cyclophosphamide for preconditioning.

PURPOSE: Five patients with Fanconi anemia have been treated by bone marrow transplantation. PATIENTS AND METHODS: They were conditioned with cyclophosphamide (CY) (20-150 mg/kg), antilymphocyte globulin, and thoracoabdominal irradiation (4-6 Gy). The dose of CY for preconditioning was adjusted individually, based on the in vitro effect of CY metabolites on the chromosomes of patients with Fanconi anemia. Four patients received marrow from human leukocyte antigen (HLA)-identical siblings, and one received marrow from his HLA phenotypically identical father. RESULTS: All patients achieved engraftment, and acute graft-versus-host disease (GVHD) grade II or more was not observed. Three developed chronic GVHD. All patients are surviving 2-5 years after grafting, with hematological improvement. CONCLUSIONS: These results indicate that the individual dose adjustment of CY used for preconditioning may prevent graft failure and severe acute GVHD.

Anemia, Aplastic↗

Combined micropreparative techniques with synchronous fluorescence spectroscopy or 32P-postlabelling assay for carcinogen-DNA adduct determination.

Methods for the detection of carcinogen-DNA adducts require both sensitivity and specificity. The 32P-postlabelling assay is highly sensitive but lacks adduct specificity. The strategy reported herein combines micropreparative techniques including HPLC and immunoaffinity chromatography (IAC) to enhance chemical specificity. The resultant assays have retained sensitivity for human DNA analysis. Combined HPLC and 32P-postlabelling has detected 7-methyldeoxyguanosine in human lung samples, while combined IAC and 32P-postlabelling has detected O6-methyldeoxyguanosine adducts in stomach tissue. The limits of detection are one adduct in 10(7) and 10(8) unmodified deoxyguanosine (dG), respectively. IAC was combined with 32P-postlabelling to detect polycyclic aromatic hydrocarbon (PAH)-DNA adducts in human lung. The detection limit was one adduct in 10(7) dG. Our laboratory has also employed synchronous fluorescence spectroscopy (SFS) for the detection of adducts formed from benzo[a]pyrene in human lung. Complex fluorescence matrices suggest the presence of other PAH-DNA adducts. Both the SFS assay and the 32P-postlabelling assay were applied to a series of human samples and a high correlation was found for adduct levels. The development of such assays using synthetic standards, internal standards, determination of calibration curves and validation with corroborating methods is required for chemically specific and sensitive adduct detection.

Benzo(a)pyrene↗

[Effects of epidural analgesia combined with general anesthesia on hemodynamics during neck surgery].

The aim of the present study was to investigate the effect of epidural analgesia combined with general anesthesia on hemodynamics. Thirty patients undergoing surgery for the treatment of cancer of the neck were studied. The patients were divided into two groups of those who received epidural analgesia combined with general anesthesia group (Group 1) and those with general anesthesia alone (Group 2). Blood pressure was not different between the groups. But heart rate and rate pressure products in Group 1 were significantly lower than those of Group 2. CVP in Group 1 increased significantly to 10.1 +/- 2.9 mmHg during surgery from 6.8 +/- 1.8 mmHg at the beginning of the surgery. There was no difference in intraoperative blood loss and the amount of fluid infused between the two groups. These results suggest that epidural anesthesia combined with general anesthesia is effective to stabilize hemodynamics during cervical surgery, but we have to be careful about using local anesthetics during long cervical procedures, because it increases CVP which might result from the depression of cardiac function.

Aged↗

[A case of icteric type hepatoma responding to MMC infusion therapy via cannulation into the hepatic artery].

Hepatoma rarely presents with obstructive jaundice. We describe a case of hepatoma, a 66-year-old woman, presenting with obstructive jaundice, whom we treated with intra-arterial infusion of the anticancer drug, MMC. The hepatic main tumor was situated in the border between the medial and lateral lobe, which caused an obstruction of the common hepatic duct, accompanied with multiple intrahepatic liver metastases. MMC was injected weekly into the reservoir of the Infuse-A-Port, which was located subcutaneously. Intra-arterial infusion therapy reduced the tumor size and tumor markers.

Aged↗

Hepatic copper accumulation in patients with primary biliary cirrhosis.

Liver biopsy specimens from 18 patients with primary biliary cirrhosis were examined histochemically and by energy-dispersive x-ray microanalysis. Using two indices, we classified hepatic copper accumulation into three stages based on the Cu x-ray intensity of cuproproteins that had accumulated in hepatocyte lysosomes and on the binding ratio of postulated copper transfer proteins between the cytosol and lysosomes. Eight patients were in stage 1 with an initial accumulation of lysosomal cuproproteins, mediated by transfer proteins not saturated with copper. Two patients were in stage 2, in which transfer proteins were saturated with copper. The first two stages gave negative results for histochemical copper. The remaining eight patients were in stage 3, in which copper accumulation detected by histochemical included transfer proteins saturated with copper and large amounts of lysosomal cuproproteins. Five patients (one each in stages 1 and 2, and three in stage 3) underwent a second liver biopsy after treatment with 600 mg of ursodeoxycholic acid daily for 14 to 39 months. Results of blood chemistry tests improved, but liver histologic findings and copper accumulation were unchanged in all five patients. It seems likely that ursodeoxycholic acid does not affect the copper accumulation in hepatocyte lysosomes that reflects the state of cholestasis in patients with primary biliary cirrhosis.

Adult↗