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S Kato

Publications and source records attributed to S Kato.

At least 937 records · Page 52Linked to original sources

Steric and electronic requirements for chloroflavone congeners as hepatic microsomal monooxygenase inducers.

We previously classified chloroflavone congeners into 3-methylcholanthrene (MC)-type, phenobarbital (PB)-type and mixed (MC plus PB)-type inducers of hepatic microsomal monooxygenases in rats. In the present study, we examined the structure-activity relationship involved in the capability of congeners to induce the described regioselective O-demethylation activity of scoparone. The steric and electronic parameters of congeners were calculated by the MM2 molecular mechanics and Extended Hückel MO methods, respectively. The molecular rectangle-area/depth ratios related well to the ratios of scoparone 6-/7-O-demethylation activities induced by the congeners. The molecular dimensions characterized the MC-type congeners as nearly planar molecules and the PB-type congeners as bulky and nonplanar. Moreover, the ratio of scoparone 6-/7-O-demethylation activities had significant correlation with both the LUMO energy (ELUMO) and the difference (delta E) between ELUMO and HOMO energy for the congeners. The ELUMO and delta E were less in the MC-type congeners than in the PB-type. These correlations suggest that the steric and electronic features of chloroflavone congeners are responsible for the induction of cytochrome P450 isozymes and associated monooxygenase activities.

1-Octanol↗

Urinary levels of gamma-carboxyglutamic acid and its clinical significance.

Urinary gamma-carboxyglutamic acid (gamma-Gla) levels were determined in healthy subjects of all ages. The urinary gamma-Gla levels were highest in infants (0-1 years), then fell in an age-dependent manner, again in subjects reaching a minimum value in adults, then gradually increased over 60 years of age. Urinary gamma-Gla levels therefore change markedly with aging. The relationships between the urinary gamma-Gla excretion and plasma levels of prothrombin and protein C in patients with various hepatic diseases or diabetes mellitus were examined and compared with those in healthy adults. Both plasma prothrombin and protein C levels were decreased in all patients with liver disease compared with healthy adults. In patients with hepatitis and liver cirrhosis, the decrease did not, however, affect the gamma-Gla excretion. In addition, in patients with hepatoma or carcinoma with liver metastases, the urinary gamma-Gla levels were increased. In patients with diabetes mellitus, the urinary gamma-Gla levels and plasma levels of prothrombin and protein C tended to increase, but this was not significant. The present results indicate that simultaneous measurement of the levels of urinary gamma-Gla and plasma prothrombin and protein C is a useful tool for the diagnosis of liver diseases and diabetes mellitus.

1-Carboxyglutamic Acid↗

Synthesis and biological activities of the optical isomers of (+/-)-4-amino-5-chloro-2-ethoxy-N-[[4-(4-fluorobenzyl)-2- morpholinyl]methyl]benzamide (mosapride).

The enantiomers, (S)-(-)-1 and (R)-(+)-1, of (+/-)-4-amino-5-chloro-2-ethoxy- N-[[4-(4-fluorobenzyl)-2-morpholinyl]methyl]benzamide (mosapride) [(+/-)-1], a new and selective gastroprokinetic agent, were prepared from optically active [4-(4-fluorobenzyl)-2-morpholinyl]methylamines (S)-(-)-4 and (R)-(+)-4, respectively. The requisite (S)-(-)-4 and (R)-(+)-4 were prepared by optical resolution of [4-(4-fluorobenzyl)-2-morpholinyl]methyl p-toluenesulfonate [(+/-)-5] using (-)- and (+)-N-(p-toluenesulfonyl)glutamic acids, followed by amination of the tosyloxy groups of (R)-(-)-5 and (S)-(+)-5, respectively. The absolute configurations of (R)-(-)-5 and (S)-(+)-5 were determined on the basis of an asymmetric synthesis of (R)-(-)-5 from (S)-(+)-benzyl glycidyl ether [(S)-(+)-11]. Mosapride and its enantiomers, (S)-(-)-1 and (R)-(+)-1, were essentially equipotent in serotonin 5-HT4 receptor agonistic activity on the electrically evoked contractions in isolated guinea pig ileum.

Animals↗

Effects of perfusion rate and glucose concentration on glucose absorption in intestinal thiry-vella loop in sheep.

The effects of the perfusion rate and glucose concentration in perfusate on glucose absorption in the intestinal Thiry-Vella loop of conscious sheep were studied. When 10 mM glucose was perfused at the rates of 0.5, 1, 2 and 4 ml/min, the absorption rates were 77.1 +/- 2.2, 54.9 +/- 2.3, 31.6 +/- 2.1 and 12.9 +/- 0.3%, respectively. When 5, 10, 20 and 40 mM glucose solutions were perfused at 1 ml/min, the absorption rates were 75.5 +/- 1.7, 52.2 +/- 2.2, 29.4 +/- 1.9 and 19.5 +/- 0.1%, respectively. We conclude that the perfusion of 10 mM glucose solution at 1 ml/min, in which about a 50% absorption rate was obtained, are the optimal conditions for the study of glucose absorption in the intestinal loop of sheep.

Animals↗

In vitro growth and maturation of pig oocytes.

Preantral follicles containing oocytes of 70-89.5 microns in diameter were isolated from pig ovaries and cultured in collagen gel for up to 16 days, in the presence of serum, FSH and oestradiol. Formation of follicular antra occurred as the culture proceeded. The oocytes had been enclosed by granulosa cells and contacts between the oocytes and processes of the enclosing cumulus cells were maintained over the culture period. After 16 days of culture, 30-40% of the oocytes were of normal appearance, and the diameters of about half of these oocytes were larger than 100 microns. When the oocytes grown in vitro were liberated from the follicles and cultured for a further 48 h in modified Krebs-Ringer bicarbonate solution, 6, 30 and 60% of the oocytes larger than 90, 100 and 110 microns underwent germinal vesicle breakdown, respectively. Progression to metaphase II was observed in 40% of oocytes that were over 110 microns in diameter, whereas no oocyte less than 90 microns in diameter resumed meiosis. The relationship between the size and meiotic competence of oocytes was similar for oocytes grown in vitro or in vivo. Oocytes grown and matured in vitro were penetrated by spermatozoa and formed a female pronucleus, but decondensation of the sperm head was incomplete. The results demonstrate for the first time that pig oocytes from preantral follicles can grow up to their final size, acquire meiotic competence, and be penetrated by spermatozoa in vitro.

Animals↗

Establishment of new inbred strains derived from Japanese wild rats (Rattus norvegicus).

Inbreeding of Japanese wild rats (Rattus norvegicus) resulted in five new strains. The conception rates of wild rat strains were lower than those of inbred laboratory strains, and maternal aggressiveness was observed in some wild strains. The body size of domesticated animals was larger than that of captured ancestors. Two strains have been established as inbred strains; the MITA strain has been tamed to the level of laboratory rats, while the nature of the MITD strain is wild. The MITB strain was derived from the MITA strain as a coat color variant. The MITC and MITE strains have been bred to the F15 and F11 generations, respectively. The new strains can provide new genetic variations against a wild type background and might be useful for physiological and psychological experiments.

Animals↗

Orally administered beraprost sodium inhibits pulmonary hypertension induced by monocrotaline in rats.

Rats were fed on distilled water (DW) or DW containing beraprost sodium (BPS). BPS concentration was 1.5 or 3.0 mu/ml in DW for the low BPS groups and 6.0 or 10.0 mu/ml in DW for the high BPS group. Monocrotaline (MCT) was subcutaneously given (60 mg/kg), and saline was injected as control. Data were analyzed among the following groups; Groups (Saline + DW), (Saline + Low BPS), (MCT + DW), (MCT + Low BPS) and (MCT + High BPS). Three weeks later, pulmonary (Ppa) and systemic (Psa) arterial pressure were measured under anesthesia. MCT caused significant elevation of Ppa [18.3 +/- 0.6 cmH2O for Group (Saline + DW) vs. 27.2 +/- 1.2 cmH2O for Group (MCT + DW), p < 0.001, mean +/- S.E.] and Ppa was significantly and dose-dependently suppressed by BPS; Group (MCT + DW) vs. Groups (MCT + Low BPS), 23.4 +/- 0.7 cmH2O and (MCT + High BPS), 22.5 +/- 0.5 cmH2O, p < 0.05, mean +/- S.E.). Psa was not lowered dose-dependently by BPS. We conclude that oral beraprost sodium suppresses pulmonary hypertension produced by monocrotaline in rat.

Administration, Oral↗

Acute cervical spinal epidural hematoma with spontaneous resolution--case report.

A 54-year-old male presented with spontaneous acute epidural hematoma in the ventral cervical spine. The neurological deficits gradually improved spontaneously before surgery commenced. Serial magnetic resonance imaging demonstrated disappearance of the hematoma. He was managed conservatively and was discharged without deficits about 1 month after onset. Immediate surgical decompression may not be necessary if neuroimaging and clinical examinations suggest that spinal epidural hematoma will resolve spontaneously.

Acute Disease↗

The true nature of the adductor brevis dually innervated by the anterior and posterior branches of the obturator nerve in humans.

To clarify the true nature and the mechanism of the human adductor brevis (specific adductor brevis, SAB) innervated dually by the anterior and posterior branches of the obturator nerve, we have carried out gross anatomical examination of 100 body halves of 50 adult Japanese cadavers. The SAB was found in 23 of the 100 thighs (23.0%), and its anterior and posterior surfaces received respectively the twigs from the anterior branch of the obturator nerve and the filament(s) from the posterior branch. The filament(s) was either indirectly derived from the medial stratum of the posterior branch through the formation of a common trunk with the twigs distributed in the obturator externus (14/23 thighs, 60.9%) or directly originating in the medial stratum of the posterior branch of the obturator nerve (9/23 thighs, 39.1%). In the close examination of the intramuscular distribution of the nerve to the SAB, the region innervated by the anterior branch of the obturator nerve could clearly be distinguished from that innervated by the posterior branch. The obturator nerve received fibers from L1234 (2/23 thighs) or from L234 (21/23 thighs), and the posterior branch of the obturator nerve ran through the obturator externus (18/23 thighs, 78.3%) or ran over the obturator externus (5/23 thighs, 21.7%), and finally emerged into the thigh. In view of the mode of origin of the filament(s), the structural element of the filament(s), and the pattern of entry of the filament(s) into the SAB, the fasciculus of the SAB, which is innervated by the posterior branch of the obturator nerve, was considered to originate in the obturator externus. Thus, the true nature of the SAB was concluded to be a complex product which was formed by a mechanism in which the fasciculus, which had separated from the obturator externus during the process of ontogeny, fused secondarily to the posterior surface of the regular adductor brevis. From findings in our series of studies, it was estimated that the maximum frequency of occurrence of the SAB could be 56%. Furthermore, from a statistical point of view, the segmental composition or course of the obturator nerve is not considered to be related to either the formation or the incidence of this muscle.

Humans↗

Surfactant-producing epithelium in the dorsal part of the cartilaginous eustachian tube of mice. Light, transmission, and scanning electron microscopic observations.

The nonciliated area in cartilaginous roof tubothelium of 14 conventional mice was examined histologically and classified as a modified transitional respiratory epithelium. On the free cell surface numerous short microvilli were found. On the lower roof surface in the midcartilaginous portion and especially near the pharyngeal orifice, a convoluted pattern of ridges and pits was observed. These structural peculiarities are interpreted as adaptive features, ensuring survival of the cells in a dynamic tubal environment. On the basis of systematic observations of the multilamellar bodies in the cytoplasm resembling the phospholipid lamellar bodies of pulmonary surfactant, which are discharged in the tubal lumen and to be found in the pits, it is suggested that the nonciliated cells are "specialized" surfactant-producing tubocytes. The synthesis of surfactant-precursors starts in the basal layer. Different phases of the secretory process were observed in the neighboring cells. This finding is related to the cell-cooperation constantly releasing the secretory product, and natural cell-turnover. Unlike the previously reported surfactant-producing cells in the lower tubothelium of other species, roof tubothelial cells of mice are morphologically similar to type II pneumocytes.

Animals↗

Analysis of mdr-1 gene expression in human leukemic cells by quantitative competitive PCR.

The ability to recognize the acquisition of multidrug resistance (MDR) in leukemia patients would improve our ability to predict the responsiveness of patients to chemotherapy. To quantitate the degree of MDR acquisition, we determined the amount of mdr-1 mRNA in leukemic cells from patients by competitive polymerase chain reaction (PCR) analysis. Twenty-one patients including 12 patients prior to treatment and nine relapsed patients with acute myelogenous or lymphoblastic leukemia were examined. The amount of mdr-1 gene expression in K562, K562/ADR500 cells and their mixtures showed a proportional correlation between the ratio of resistant to non-resistant cells and the amount of the mdr-1 gene. Mean mdr-1 gene expression in relapsed patients was greater than that in pretreatment patients. Patients refractory to chemotherapy (NR) showed higher levels of mdr-1 gene expression than the patients who achieved complete remission (CR). Because of the wide variations in values, no statistical differences were observed between pretreatment and relapsed patients, or CR and NR patients. These results suggest that the competitive PCR technique is a reliable method to quantitatively determine mdr-1 gene expression, but it may be difficult to predict responsiveness to chemotherapy by using this technique alone.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Evidence for other binding component(s) than retinoid receptors specifically interacting with a retinoic acid response element in the rat liver.

A nuclear component interacting with a retinoic acid response element (RARE-beta) derived from the all-trans-retinoic acid receptor beta (RAR beta) gene promoter was detected in the rat liver by gel-shift assay. Competition experiments using the competitors of the other retinoid response elements and non-specific sequences upon the binding of this hepatic component (HBC) to the RARE-beta revealed that the binding of the HBC to the RARE-beta was competed only by the self competitor, but not the other elements, suggesting that the HBC is specific for the RARE-beta. Moreover, although the specific monoclonal antibodies for RAR alpha, RAR beta, and RAR gamma reacted and shifted up the DNA complexes of endogenous as well as recombinant RARs, the DNA complex with HBC was not subjected to the immunoreaction with the antibodies. Thus, newly identified HBC, which is distinct from the characterized retinoid receptors, may modulate retinoid signaling through its direct binding upon the RARE-beta.

Animals↗

Isolation of human CD34+ peripheral blood stem cells using an immunomagnetic positive selection system: prior monocyte depletion using a nylon-wool column.

An immunomagnetic separation system has been used to collect CD34+ cells in mobilized blood after treatment with a nylon-wool column. Cell purities were increased from 2.6% preseparation to 94.6% postseparation, with a mean yield 45.2% (n = 4). Forty percent of CD34+ cells separated by the immunomagnetic procedure formed colonies in the presence of hematopoietic growth factors in a limiting dilution assay. Eleven percent of these clones proliferated to over 10(5) cells and contained megakaryocytes.

Antigens, CD↗

Hepatic mitochondrial changes in experimental obstructive jaundice complicated by biliary infection.

The effects of biliary infection on the structural and functional changes in the liver in obstructive jaundice was studied using rats as experimental animals. Biliary infection with obstructive jaundice was induced in the animals by injecting Escherichia coli into the common bile duct through a nylon tube cannulated into the duct. This was followed by the clamping of the tube. For the controls, the tube was clamped in the absence of Escherichia coli. After 3, 7, 14 and 21 days, the animals were sacrificed, and some serum enzyme activities, histological changes in the liver, and the coupling efficiency of mitochondria isolated from the liver were investigated. The phosphorylating ability of hepatic mitochondria was more seriously affected when the obstruction was complicated by cholangitis. We suggest that, when associated with obstructive jaundice, biliary infection should be carefully treated prior to hepatectomy.

Alanine Transaminase↗

Pituitary adenylate cyclase-activating polypeptide (PACAP) stimulates exocrine pancreas in conscious preruminating calves.

The effects of new hypothalamic peptides, PACAP-27 and PACAP-38, and secretin and VIP on the interdigestive pancreatic secretion and duodenal myoelectric activity during the asecretory phase of the pancreatic interdigestive cycle, compared with the milk ingestion phase, were examined in five calves. Peptides were infused for 5 min into the external jugular vein (0, 3, 10, 30 and 100 pmol/kg body wt during the asecretory phase of the pancreatic interdigestive cycle, and the pancreatic secretory response was compared with that obtained during milk ingestion. Intravenous infusion of PACAP-27 caused dose-related stimulation of pancreatic juice flow and bicarbonate and protein output; this effect was identical to infusion of secretin. The effect of PACAP-38 was less pronounced, and that of VIP was the weakest. Pancreatic juice volume and bicarbonate responses during milk ingestion were similar to responses obtained with the highest doses of hypothalamic peptides and secretin, whereas postprandial protein secretion was much greater than the secretion stimulated with peptides. It was concluded that PACAP from the VIP/secretin family may stimulate pancreatic exocrine secretion in conscious calves and a part of the pancreatic response to food intake can be mediated by PACAP.

Animals↗

Transition of T cell receptor gamma/delta expressing double negative (CD4-/CD8-) lymphocytes after allogeneic bone marrow transplantation.

We studied peripheral blood CD4-CD8- gamma/delta T cells in recipients of allogeneic marrow grafts, using three-color immunofluorescence and flow cytometry, and investigated changes in their numbers in relation to the administration of hematopoietic growth factors or chronic graft-versus-host disease (GVHD). In the early post-bone marrow transplantation (BMT) period, the relative and absolute numbers of peripheral CD4-CD8- gamma/delta T cells in 22 allogeneic marrow graft recipients in relation to the use of hematopoietic growth factors were studied. During the first 4 weeks, increased numbers of CD4-CD8- gamma/delta T cells were observed in recipients of either recombinant human granulocyte colony-stimulating factor (rhG-CSF) or granulocyte macrophage colony-stimulating factor (GM-CSF). However, 4-8 weeks after BMT, the number of these cells was similar in both groups whether or not growth factors had been administered. At a later stage after BMT (3-12 months), peripheral CD4-CD8- gamma/delta T cells from 43 allogeneic BMT recipients were studied. These cells were markedly decreased in patients with chronic GVHD, and this decrease correlated closely with the clinical signs of chronic GVHD. These results suggest that CD4-CD8- gamma/delta T cells may play an important role in the recovery of neutrophils associated with growth factors during the very early post-BMT period, and in the immunodeficient state of chronic GVHD at a later stage after BMT.

Adolescent↗

Biochemical improvement of chronic hepatitis C after gastrointestinal bleeding.

Although chronic hepatitis C is frequently complicated by iron overload, it remains unclear whether iron cytotoxicity is involved in the disease process. Five patients with chronic hepatitis C showed rapid reduction of serum aminotransferase activity after gastrointestinal bleeding. Posthemorrhagic reduction of liver enzyme levels lasted for more than one week. Anemia was associated with a reduction of serum ferritin concentration. Considering the short half-lives of circulating liver enzymes, reduced release of enzymes, that is inactivation of cell lysis, is the likely cause of the improved biochemical indices. Reactive iron, which is cytotoxic for patients infected by HCV, may be rapidly incorporated into hemoglobin when erythropoiesis is stimulated. Our observation also suggests that intensive iron removal by phlebotomy is a safe, economic treatment for patients with chronic hepatitis C.

Aged↗