PubMed HealthSearch

Biomedical subjects

T Matsubara

Publications and source records attributed to T Matsubara.

At least 19 recordsLinked to original sources

Role of liver-type glucose transporter (GLUT2) in transport across the basolateral membrane in rat jejunum.

To obtain information on the regulation of glucose transport across the basolateral membrane (BLM) of intestinal epithelial cells, we measured the number of [3H]cytochalasin B binding sites and the level of liver-type glucose transporter (GLUT2) protein in the BLM in the jejunum of rats (i) with diabetes (ii) given a high-carbohydrate diet or (iii) with experimental hyperglycemia (12 h infusion of a high-glucose solution). A glucose uptake and the number of D-glucose inhibitable [3H]cytochalasin B binding sites in BLM vesicles were significantly increased in all three conditions. Western blot analysis showed that the amount of GLUT2 protein in BLM vesicles was increased in rats with diabetes and those given a high-carbohydrate diet, but not in those with experimental hyperglycemia. These results suggest that there is a mechanism for rapid regulation of glucose transport in the BLM that does not depend on change in the amount of GLUT2.

Animals

UK-14,304, R(-)-alpha-methyl-histamine and SMS 201-995 block plasma protein leakage within dura mater by prejunctional mechanisms.

Intravenous administration of an alpha-adrenoceptor agonist, UK-14,304, a histamine H3 receptor agonist, R(-)-alpha-methyl-histamine (alpha-MeHA) or SMS 201-995 (a synthetic octapeptide analogue of somatostatin), blocked plasma protein (125I-albumin) extravasation within rat and/or guinea pig dura mater following unilateral electrical trigeminal ganglion stimulation or capsaicin administration. The extravasation caused by the administration of the neuropeptide mediator, substance P, was not inhibited by any of the three compounds. Blockade by UK-14,304 was completely antagonized by pretreatment with the highly selective alpha 2-antagonist, idazoxan, as was alpha-MeHA by pretreatment with the highly selective histamine H3 antagonist, thioperamide. Taken together, the results are consistent with blockade by prejunctional alpha 2, histamine H3 and probably somatostatin receptors which may be coupled to inhibition of neuropeptide release. Because 5-HT1-like agonists, which are useful for treating migraine and related headaches, share similar inhibitory properties in this in vivo model, the significance of prejunctional alpha 2, histamine H3 and somatostatin receptors to treatment of vascular headaches is suggested.

Adrenergic alpha-Agonists

Capillary gas chromatographic method for the determination of the thromboxane A2 receptor antagonist S-1452 and its metabolites in human plasma.

A capillary gas chromatographic method for the determination of a newly developed thromboxane A2 antagonist, S-1452, and its metabolites in human plasma has been developed. This nitrogenous compound was detected as the free acid (+)-S-145 using a nitrogen-phosphorus detector. The two metabolites bisnor-(+)-S-145 and tetranor-(+)-145 were also assayed. The three compounds, which all possess carboxylic acid group, were converted into their hexafluoro-2-propyl esters with hexafluoropropan-2-ol-pentafluoropropionic anhydride as reagent. The esterification resulted in a decreased background response from the detector, and hence higher sensitivity and better precision. The glucuronides of the three compounds were also assayed after alkaline hydrolysis. The plasma concentration of the glucuronide of I was more than twice that of the free acid. This method allows determination of the three compounds at more than 2 ng/ml with a precision of 2-6% and an accuracy variation of less than +/- 5%. The analysis was performed within 2 min after injection to assay the sample rapidly from the Phase I test. The method is suitable for pharmacokinetic studies.

Bridged Bicyclo Compounds

Capillary gas chromatographic method for the determination of the thromboxane A2 receptor antagonist S-1452 and its metabolites in human urine.

A capillary gas chromatographic method using a sulphur-specific detector (Hall's electrolytic conductivity detector) was established to determine the thromboxane A2 antagonist S-1452 and its metabolites in human urine. The target species were the free acid (+)-S-145 of the drug and its nine metabolites: the three hydroxyl forms of (+)-S-145 (I, II and III), bis-nor-(+)-S-145 (IV) the hydroxylated forms of IV (V and VI), tetranor-(+)-S-145 (VII) and the hydroxylated forms of VII (VIII and IX). These ten compounds, which have the same sulphur-containing functional group in common, were determined simultaneously. Their conjugated forms, which were assumed to be glucuronides, were also assayed after hydrolysis. The first derivatization was esterification with diazomethane. The second, for the hydroxylated compounds, was trimethylsilylation with bis(trimethylsilyl)trifluoroacetamide. The ten analytes appeared as separate peaks without mutual interference during 5 min. Hall's detector distinguished the ten analytes selectively from the other urinary components, which removed the need for complex clean-up procedures and led to higher sensitivity with a lower noise level. The method is sensitive enough for the assay of substances present at more than 0.1 micrograms/ml of urine. All the compounds could be determined with a high level of precision and accuracy, with 2-5% relative standard deviation and within +/- 5% deviation from the actual value. Day-to-day measurements verified the reproducibility of the method. Recovered substances were quantified by following the time course, and the analytical data together with previously obtained plasma data clarified the metabolism pharmacokinetically.

Bridged Bicyclo Compounds

Immediate effects of percutaneous transvenous mitral commissurotomy on pulmonary hemodynamics at rest and during exercise in mitral stenosis.

Hemodynamics were evaluated during exercise in 33 patients with mitral stenosis who underwent percutaneous transvenous mitral commissurotomy (PTMC). PTMC was performed using an Inoue balloon. Each patient underwent a supine ergometer exercise test before and on the day after PTMC. Ergometer work load was started at 20 W and increased in increments of 20 W at 3-minute intervals until terminated by the patient's fatigue or shortness of breath. Mitral valve area increased by 0.8 +/- 0.4 cm2 (1.1 +/- 0.3 to 1.9 +/- 0.4 cm2, p less than 0.001). Mean mitral pressure gradient decreased (12 +/- 5 to 6 +/- 2 mm Hg, p less than 0.001). Pulmonary arterial pressure significantly decreased and the cardiac index significantly increased both at rest and during exercise after PTMC. Before PTMC, the increases in pulmonary arterial pressure, total pulmonary resistance and pulmonary arteriolar resistance during exercise were greater in patients with a mitral valve area less than 1.0 cm2 than in patients with an area greater than or equal to 1.0 cm2. After PTMC, total pulmonary resistance still increased during exercise. However, pulmonary arteriolar resistance did not change during exercise in patients with a mitral valve area greater than or equal to 1.5 cm2, whereas it increased in patients with an area less than 1.5 cm2. An enlarged mitral valve area greater than or equal to 1.5 cm2, which may prevent pulmonary vasoconstriction and permits a greater increase in pulmonary blood flow during exercise, is considered a good result immediately after PTMC.

Cardiac Catheterization

Differential mechanisms of induction of ornithine decarboxylase in rat intestine by L- and D-amino acids.

A single intragastric administration of glycine, L- and D-alanine, and L-and D-serine into rats resulted in a more than 20-fold stimulation of intestinal mucosal ornithine decarboxylase (ODC) within 4 h. The stimulation of ODC activity was accompanied by an increase in the amount of immunoreactive ODC protein. The induction of ODC by D-amino acids was in all likelihood attributable to an enhanced accumulation of ODC-specific mRNA species as revealed by Northern blot and dot-blot hybridization analyses. However, the induction by glycine and L-amino acids was not explainable by changes of mRNA since the changes in mRNA contents were only marginal. Since the turnover rates of L-serine-induced and D-serine-induced intestinal ODC protein were the same as the non-induced control, we concluded that the induction by glycine and L-amino acids was brought about by an increased efficiency of translation of the ODC message.

Amino Acids

Increased levels of circulating intercellular adhesion molecule 1 in Kawasaki disease.

OBJECTIVE: We investigated whether levels of intercellular adhesion molecule 1 (ICAM-1) antigen shed into the circulation increase during acute Kawasaki disease (KD). We also compared ICAM-1 levels in acute KD with those in anaphylactoid purpura (AP) and in measles. METHODS: Serum ICAM-1 levels were measured by a double-determinant immunoassay using 2 monoclonal antibodies in the FAST (Falcon assay screening test) system. Serum levels of tumor necrosis factor alpha (TNF alpha) were measured by a specific and sensitive sandwich enzyme immunoassay. RESULTS: Patients with KD, but not those with AP or measles, had increased levels of shed ICAM-1 antigen in serum samples obtained during acute stages. Moreover, during the acute stage, KD patients with coronary artery lesions (CAL) had still higher levels of shed ICAM-1 than did those without CAL. We found a positive correlation between serum levels of shed ICAM-1 and levels of TNF alpha during acute KD. CONCLUSION: Our findings suggest that the serum ICAM-1 level is an important immunologic parameter for determining the severity of vascular damage during acute KD.

Cell Adhesion Molecules

Coronary angioplasty using an over-the-wire balloon catheter through a new 6 French guiding catheter.

A new 6 French (F) guiding catheter with a large, teflon-coated internal lumen (4.2F) was developed, permitting use of the standard ultralow profile (less than 3F) over-the-wire system. This small coronary angioplasty system (6F-PTCA) was evaluated in 48 lesions in 45 of 137 patients (33%) who underwent coronary angioplasty between September 1990 and January 1991. The mean age was 64 years (range 49 to 82); 37 (82%) were male. The procedure was via the brachial artery in 28 patients (62%). The overall primary success rate was 96%. It was 100% via the brachial artery and 90% via the femoral artery. There were no major complications. The puncture compression time with the 6F-PTCA via the brachial artery and via the femoral and with 8F-PTCA via the femoral was 3.8, 9.6, and 16.9 hr, respectively (P less than 0.001), although the procedure time of the 6F-PTCA via brachial and via femoral and of the 8F-PTCA was not significantly different. The mean hospital stay was 3.1, 4.5, and 5.5 days, respectively (P less than 0.01). A small hematoma occurred in 2 patients (4.4%) after the 6F-PTCA and in 3 (3.3%) after 8F-PTCA, and a large hematoma (greater than 5 cm) was noted in 7 patients (7.6%) after 8F-PTCA. These results indicate that coronary angioplasty using the over-the-wire system through the new 6F guiding catheter is technically feasible. Moreover, this approach, especially when advanced via the brachial artery, could shorten the hemostasis time and facilitate early ambulation.

Aged

Hypophyseal metastatic hypernephroma mimicking a pituitary adenoma. Case report.

A patient with a remote history of nephrectomy for hypernephroma presented a visual field defect with hypopituitarism. Neuro-imaging studies showed a highly vascularized sellar mass with suprasellar extension. Surgery, which was performed via the subfrontal approach, disclosed the pituitary tumor to be a hypernephroma. Although anterior pituitary involvement is rare, chiasmal compression is much rarer in metastatic pituitary carcinomas, a review of previously reported cases of metastatic pituitary hypernephroma and our own case indicated that pituitary metastasis from this carcinoma, in contrast to other metastatic pituitary tumors, often mimics pituitary adenoma.

Adenoma

Damage of cultured chondrocytes by hydrogen peroxide derived from polymorphonuclear leukocytes: a possible mechanism of cartilage degradation.

To study the mechanisms of chondrocyte damage, chondrocyte cytotoxicity as shown by chromium-51 release induced by polymorphonuclear leukocytes (PMNLs) was examined. PMNLs significantly enhanced chondrocyte cytotoxicity in the presence of phorbol dibutyrate. This chondrocyte damage was abolished by the addition of catalase, whereas superoxide dismutase and scavengers of hydroxyl radicals and protease inhibitors failed to reverse it. When cartilage matrix components such as hyaluronic acid and various proteoglycans were added to the PMNL-chondrocyte cultures, these components failed to affect the chromium-51 release. These results suggest that the increase in chondrocyte cytotoxicity is due to hydrogen peroxide generated by the PMNLs, and that cartilage matrix components do not prevent it. Hydrogen peroxide from PMNLs may therefore play an important role in cartilage degradation through direct damage of chondrocytes during inflammatory process.

Animals

Recombinant human glucagon: large-scale purification and biochemical characterization.

Recombinant glucagon was expressed in Escherichia coli as a fusion protein including the glucagon sequence therein as previously reported [Ishizaki et al. (1992). Appl. Microbiol. Biotechnol. 36, 483-486]. We developed a large-scale method for the isolation and purification of recombinant glucagon. After cell disruption, the resultant pellets were solubilized with 2 M guanidine-HCl, to which Staphylococcus aureus V8 protease had been added, and were digested into intermediates composed of 53- and 60-residue peptides containing the glucagon moiety. After the digestion came to an end, the solution was desalted, and the remaining V8 protease was allowed to resume digestion of the intermediates into glucagon, followed by partial purification by S-Sepharose and Sephacryl S-100 chromatographies. The glucagon obtained was found to be not less than 99.5% pure by analytical HPLC. One liter of culture produced about 180 mg of pure glucagon. The amino acid composition and the sequence agreed well with the theoretical values. Radioreceptor assay gave an affinity constant similar to that of pancreatic glucagon, and similar activities in cAMP production and glycogenolysis were also observed. Thus, the recombinant glucagon was confirmed to be biochemically identical with pancreatic glucagon.

Amino Acid Sequence

Kawasaki disease differs from anaphylactoid purpura and measles with regard to tumour necrosis factor-alpha and interleukin 6 in serum.

It has been reported that tumour necrosis factor-alpha (TNF-alpha) is capable of inducing vascular injury, and interleukin 6 (IL-6) of inducing production of acute phase proteins and the maturation of megakaryocytes. Kawasaki disease (KD) is a systemic vasculitis with severe inflammation. We investigated whether TNF-alpha and IL-6 activities in serum from patients with KD differs from those in anaphylactoid purpura (AP) and measles. Serum TNF-alpha levels were measured by a sandwich enzyme immunoassay and IL-6 activities in serum were assessed by a colorimetric assay. Both KD and AP patients but not patients with measles had increased serum TNF-alpha levels during the acute stage. With respect to IL-6, patients with KD and measles, but not AP, had increased IL-6 activities in serum during the acute stage. IL-6 activities in serum of KD patients correlated with serum C-reactive protein levels and correlated to some extent with maximum platelet counts during the course of illness. These results suggest that KD differs from AP and measles regarding both cytokines. The combination of TNF-alpha, which may be responsible for severe vascular injury, and IL-6, which may be responsible for severe inflammation, may play an important role in acute KD.

C-Reactive Protein

Balloon catheter with check valves for experimental relief of acute aortic regurgitation.

To evaluate the ability of a newly designed balloon catheter with check valves to temporarily relieve hemodynamic deterioration in acute aortic regurgitation, we produced an experimental model of acute aortic regurgitation in closed-chest dogs using endomyocardial biopsy forceps. Aortic regurgitation was produced until an increase in aortic pulse pressure of over 50% was achieved. Left ventricular end-diastolic pressure rapidly increased after the production of aortic regurgitation. Immediately after the catheter began functioning, pulse pressure decreased from 133 +/- 1 to 78 +/- 5 mm Hg (mean +/- SEM) and left ventricular end-diastolic pressure also decreased from 26 +/- 1 to 13 +/- 1 mm Hg. These effects lasted as long as the catheter functioned. Although a mild (21 +/- 8 mm Hg) pressure gradient between the left ventricular peak systolic pressure and the aortic peak systolic pressure was observed when this catheter was used, forward stroke volume was no less than in the group in which the catheter had not been used. These findings suggest that the balloon catheter with check valves may effectively reduce aortic regurgitation.

Animals

Stimulation of muscarinic cholinoceptive neurons in the hippocampus evokes a pressor response with bradycardia.

The injection of neostigmine into the hippocampus of anesthetized rats increased the mean arterial blood pressure (17% of baseline after 60 min injection) and decreased the heart rate (24% of baseline after 60 min injection). These changes were blocked by the co-administration of methylatropine into the hippocampus. Intrahippocampal injection of neostigmine stimulated the secretion of epinephrine and norepinephrine. Adrenodemedullation did not suppress the increase in blood pressure and the decrease in heart rate. It is concluded that the stimulation of muscarinic cholinoceptive neurons in the hippocampus evokes a hypertensive response via an increase in sympathetic drive to the heart and peripheral vasculature, with bradycardia possibly mediated via the parasympathetic system.

Animals

Tumor necrosis factor-alpha inhibitory activity in urine of Kawasaki disease.

Recently it has been reported that naturally occurring inhibitors of tumor necrosis factor alpha (TNF-alpha) were demonstrated in urine of some acute febrile patients. We investigated whether TNF-alpha inhibitory activity in urine increases during acute Kawasaki disease (KD). TNF-alpha inhibitory activities in urine were measured by a cytotoxicity assay on the TNF-susceptible cell line L929. KD patients had increased TNF-alpha inhibitory activities in urine during the acute stage and returned to a normal range during the convalescent stage. Our results suggest that the TNF-alpha inhibitor in urine is part of the regulatory system of TNF-alpha, which might be responsible for vascular injury during acute KD.

Child, Preschool

A novel ceramide trihexoside from the eggs of the sea urchin, Hemicentrotus pulcherrimus.

Glucosylceramide (Glc beta 1-1Cer) and a novel ceramide trihexoside (Gal beta 1-6Gal beta 1-6Glc beta 1-1Cer) were purified from the eggs of the sea urchin, Hemicentrotus pulcherrimus. Their chemical structures were determined by gas-liquid chromatography, methylation analysis, chromic acid oxidation, enzymatic hydrolysis, enzyme-linked immunosorbent assay, fast atom bombardment mass spectrometry, and proton nuclear magnetic resonance spectroscopy. The ceramide trihexoside has a novel carbohydrate structure, and its core structure, Gal beta 1-6Glc, is also novel. The ceramide moieties of these glycolipids are almost identical. Two fatty acids, 22:1 and 22h:1, constitute more than 80% of the total acids. Long-chain bases are all phytosphingosine, approximately 90% of which is n-t18:0. The finding of melibiosylceramide (Gal alpha 1-6Glc beta 1-1Cer) from the eggs of another sea urchin species [Kubo, H. et al. (1988) J. Biochem. 104, 755-760] and the present finding of the novel ceramide trihexoside suggest that there are a variety of unique sugar structures in sea urchin glycosphingolipids.

Animals

Mononuclear cell subsets and coronary artery lesions in Kawasaki disease.

The peripheral blood mononuclear cell subsets in patients with Kawasaki disease and coronary artery lesions were investigated. Of the 106 patients 14 had lesions. Patients with Kawasaki disease and coronary artery lesions were found to have increased counts of CD14+ macrophages/monocytes compared with those of patients with Kawasaki disease without lesions. The absolute counts of CD14+ macrophages/monocytes form an important parameter to determine the severity of vascular damage during acute Kawasaki disease.

Antigens, CD