Search PubMedSearch

Biomedical subjects

T Sugiura

Publications and source records attributed to T Sugiura.

At least 19 recordsLinked to original sources

Novel 5-HT3 antagonists. Isoquinolinones and 3-aryl-2-pyridones.

Synthesis and pharmacological evaluation of a series of 1,2-dihydro-1-[(5-methyl-1-imidazol-4-yl)methyl]-2-oxopyridine 5-HT3 antagonists are described. The key pharmacophoric elements were defined as a basic nitrogen, a linking group capable of hydrogen bonding interactions, and an aromatic moiety. 1,2-Dihydro-2-oxopyridine moiety could be a good linking group because of its nicely planar structure. The steric limitations of the aromatic moiety were investigated by X-ray analysis and computer analysis and shown to be optimal when the aromatic moiety was constrained within an arched planar system, which could be successfully replaced by 3-(2-thienyl)-2-oxopyridine function or 6-amino-7-chloro-1-isoquinolinone function without any loss of the activity. Among the synthesized compounds, 42 showed the most potent activity in the inhibition of Bezold-Jarisch reflex in rats. Compounds 44a and 64 were orally active in the protection against cisplatin-induced emesis in dogs or ferrets. Structure-activity relationships are discussed.

Animals

Distribution of alkyl and alkenyl ether-linked phospholipids and platelet-activating factor-like lipid in various species of invertebrates.

The levels of alkenylacyl, alkylacyl and diacyl subclasses of choline glycerophospholipid (CGP) and ethanolamine glycerophospholipid (EGP) fractions in 28 species of various invertebrates were studied. We found that only small amounts of either 1-alkyl-2-acyl-sn-glycero-3-phosphocholine (alkylacyl-GPC) or 1-alkenyl-2-acyl-sn-glycero-3-phosphoethanolamine (alkenylacyl-GPE) are present in most species of insects. On the other hand, almost all species examined in various phyla other than Arthropoda were shown to contain large amounts of both alkylacyl-GPC and alkenylacyl-GPE. The highest proportion of alkylacyl subclass in CGP was noted in sponge, Halichondria japonica (81.8% of CGP) and the highest proportion of alkenylacyl subclass in EGP was found in clam worm, Marphysa sanguinea (88.7% of EGP). We next surveyed the presence of platelet-activating factor (PAF)-like lipid in 45 species of invertebrates. PAF-like lipid was widely distributed among various lower animals. The highest value was obtained for sea cucumber, Stichopus japonicus, in which PAF-like lipid was present throughout the body. We also confirmed the presence of acetyltransferase activity in several lower animals. These results suggest that alkyl and alkenyl ether-linked phospholipids including PAF are physiologically important molecules particularly for invertebrates belonging to lower phyla.

Animals

Malignant lymphoma of mucosa-associated lymphoid tissue arising in the thymus of a patient with Sjögren's syndrome. A morphologic, phenotypic, and genotypic study.

A 59-year-old woman with Sjögren's syndrome had an anterior mediastinal tumor. The tumor had epithelium-lined thymic cysts. Histologically, centrocyte-like (CCL) cells were present as clusters intermingling with small lymphocytes and plasma cells, invaded the epithelium, and formed characteristic lymphoepithelial lesions; the tumor was identified as malignant lymphoma arising in mucosa-associated lymphoid tissue (MALT). Within the tumor, trapped Hassall's corpuscles were recognized. Immunohistochemical staining demonstrated monotypic cytoplasmic kappa light chains in a small portion of the CCL cells. Furthermore, Southern blot hybridization studies showed rearrangements of immunoglobulin heavy chain, immunoglobulin kappa light chain, and T-cell receptor beta genes. The findings are consistent with thymic low-grade B-cell MALT lymphoma.

Cytoplasm

Clinical significance of serum colloid osmotic pressure in relation to pulmonary edema and coronary instability in patients with unstable angina.

Several investigators demonstrated that severe reduction of colloid osmotic pressure (COP) predicts a fatal outcome in patients with cardiopulmonary failure. To evaluate the clinical significance of COP in relation to pulmonary edema, we studied 117 patients with unstable angina admitted in the hospital within 24 h after the chest pain. The mean COP of all 117 patients was 24.8 +/- 3.7 mmHg. COP was significantly lower in patients with pulmonary edema, according to the chest x-ray findings, compared with the patients without it. Among 26 patients with emergency coronary arteriography, a fairly good correlation was observed between coronary jeopardy score and COP (r = -0.57, p less than 0.005). Furthermore, COP in patients who survived 26 months after the hospital discharge was significantly higher than that of the nonsurvivors. Thus, measurement of COP is advised for monitoring patients with unstable angina.

Angina, Unstable

Effects of endurance training on myosin heavy-chain isoforms and enzyme activity in the rat diaphragm.

We investigated the effects of endurance training (20 m/min, 60 min/day, 5 days/week) on myosin heavy-chain (MHC) isoforms and succinic dehydrogenase (SDH) activity in rat crural and costal diaphragms, and plantaris muscles. Although the 4-week endurance training produced significant (P less than 0.05) increases, both in SDH activity and the percentage of isoform HCIIa in the plantaris of the trained rat compared with the sedentary control rat, these alterations did not occur in either the crural or costal diaphragms. After 10 weeks of endurance training, trained animals had significantly (P less than 0.05) higher SDH activity in the costal diaphragm and the plantaris. Moreover, a significant (P less than 0.05) decrease occurred in the percentage of HCIIb in the costal diaphragm, and a significant (P less than 0.01) decrease in the percentage of HCIIb concomitant with a significant (P less than 0.05) increase of HCIIa resulted in the plantaris. However, the crural diaphragm did not show any significant changes after 10 weeks of endurance training. These results indicate that endurance training induces an alteration in the expression of an MHC phenotype, in addition to causing an increase in oxidative enzyme activity. However, the alterations in response to endurance training are apparently not uniform, varying between regions and/or kinds of muscles.

Animals

Heart rate and body temperature sensitive diaphragm pacing.

Two ways of rate control for diaphragm pacing are proposed. One is rate control using only the patients' body temperature (method I). The other is rate control by both the patients' heart rate and body temperature (method II). To test the effectiveness of these methods, a diaphragm pacemaker which can be controlled by both heart rate and body temperature has been developed. It was applied to nine mongrel dogs. The pacing rate is controlled by atrial blood temperature (method I) or by both heart rate and temperature (method II). The animal's metabolism was elevated by the administration of a pyrogenic drug. It was found that method I is not suited to rapid changes in metabolism; however, it is useful in extreme metabolic elevation. An animal's metabolism was supported by using method II in all ranges of metabolism. This method proved more effective than method I for rate-responsive diaphragm pacing.

Animals

Hypoglycemic activities of MTP-3631, a novel thiopyranopyrimidine derivative.

MTP-3631 is a novel thiopyranopyrimidine derivative structurally different from any existent hypoglycemic agents. MTP-3631 markedly decreased basal blood glucose and improved glucose intolerance in genetically diabetic C57BL/6J ob/ob mice, which was not affected by tolbutamide. MTP-3631 also caused hypoglycemic effects in normal rats, but no change was observed in plasma insulin level. Unlike buformin, MTP-3631 did not change plasma lactate level in ob/ob mice. These results suggest that the hypoglycemic mechanism of MTP-3631 may be essentially different from those of sulfonylureas and biguanides.

Animals

Effects of running training on the blood glucose and lactate in rats during rest and swimming.

The purpose of this study was to examine the effect of physical training on the concentrations of glucose and lactate in the blood of rats during rest and after an acute bout of exercise. We used the following types and periods of training; (i) swimming for 4 weeks, (ii) running for 4 weeks, and (iii) running for 10 weeks. The results clearly show that the resting levels of blood glucose was significantly lower in groups trained by either swimming or running than untrained groups. In addition, after the acute exercise of swimming, animals trained by either running or swimming showed a lower increase in the blood lactate than untrained animals. Furthermore, the increases in the blood glucose after swimming were significantly lower in the group trained by swimming for 4 weeks and by running for 10 weeks than in untrained groups. These results suggest that after physical training by running, animals show an adaptation in the changes in the blood glucose and the blood lactate that are induced by a different type of physical stress, swimming.

Adaptation, Physiological

Factors influencing expression and post-translational modification of recombinant protein C.

Factors affecting the production of recombinant human protein C were investigated. When recombinant cells producing human protein C were cultured with microcarrier in two different scales, we found that (1) as cells grew to confluence, specific productivity of the protein was decreased and that (2) the efficiency of gamma-carboxylation of the generated protein C was lower in a larger culture than in a smaller culture. Higher cell density was shown to influence the specific productivity unfavorably. On the other hand, the amount of oxygen supply as demonstrated by oxygen consumption rate in the Opticell culture system correlated well with the efficiency of gamma-carboxylation, suggesting that oxygen metabolism is somehow implicated in the post-translational modification of recombinant protein C.

Animals

Myosin light chain patterns in histochemically typed single fibers of the rat skeletal muscle.

1. This study was conducted to investigate the relationship between histochemical fiber types and myosin light chain patterns in rat single muscle fibers. 2. The hybrid of fast and slow light chains was observed in type I and II fibers of the soleus and type II fibers of the red portion of lateral head of the gastrocnemius muscles. 3. We also observed 7 types of light chain composition. Of the 7 types, 5 types were explainable by assuming the coexistence of isomyosins with either fast or slow light chains. However, the other 2 types could not be accounted for without hypothesizing the presence of isomyosins with promiscuous light chain distribution.

Animals

Myosin heavy chain isoform transition in ageing fast and slow muscles of the rat.

Using gradient sodium dodecyl sulphate-polyacrylamide gel electrophoresis, myosin heavy chain (MHC) isoforms were studied in the extensor digitorum longus (EDL) and the soleus muscles of male Wistar rats at different ages (5, 10, 20 weeks, 1 and 2 years). In the EDL muscle, four types of MHC isoforms were observed in all age groups. There was an increase in the percentage of HCIId and a concomitant decrease in the percentage of HCIIb with increasing age. No significant difference was observed in the percentages of HCI and HCIIa isoforms in all the age groups. In contrast, the soleus muscle contained two MHC isoforms, HCI and HCIIa. There was an increase in the percentage of HCI and a concomitant decrease in the percentage of HCIIa with increasing age. These results suggest that age-related changes in the MHC isoforms in both the fast-twitch EDL and the slow-twitch soleus muscles are one factor underlying the age-related decrease in the speed of muscle contraction.

Aging

Regional differences in myosin heavy chain isoforms and enzyme activities of the rat diaphragm.

Myosin heavy chain isoforms and enzyme activities were compared between the costal and crural regions of the rat diaphragm. The percentage of heavy chain (HC) IIb in the crural region of the diaphragm was significantly (P less than 0.05) higher than that in the costal region (mean 7.3 vs. 3.0%), and the percentage of HCI was significantly lower in the crural than in the costal diaphragm (22.7 vs. 27.9%). The distributions of HCIIa and HCIId were relatively homogeneous in both regions. Succinate dehydrogenase activity in the costal diaphragm was 21% greater (P less than 0.01) than in the crural diaphragm. In contrast, there was no significant difference in the activity of phosphofructokinase in the crural and costal diaphragms. These results demonstrate that a difference in myosin heavy chain isoforms and oxidative capacity exists between the costal and crural regions of the rat diaphragm.

Animals

Difference in the residual left ventricular pump function between anterior and inferior myocardial infarctions.

To evaluate the left ventricular regional ejection fraction (EF) of noninfarcted area in relation to the left ventricular end-diastolic volume (EDV) in patients with recent myocardial infarction (MI), 75 patients with Q-wave MI (anterior: 51 patients; inferior; 24 patients) were studied. The regional EF of noninfarcted area was obtained by radionuclide angiocardiography 4 weeks after the onset of MI and was used to estimate the left ventricular regional function of the noninfarcted area. Peak creatine kinase and QRS scores were not significantly different between anterior and inferior MI in each left ventricular EDV (EDV < or = 100, 101-139 and > or = 140 ml). Global EF and regional EF of noninfarcted area in anterior MI with left ventricular EDV > or = 140 ml was significantly lower than in those with EDV < or = 139 ml (p < 0.01), whereas there were no significant differences in global EF and regional EF of noninfarcted area in the three groups of left ventricular EDV in inferior MI. Thus, the effect of left ventricular EDV on regional EF of noninfarcted area and on the total cardiac performance was more important in anterior than in inferior MI, because a similar degree of left ventricular dilatation resulted in more severe derangements after anterior MI.

Adult

Epizootiological aspects of type 1 and type 4 equine herpesvirus infections among horse populations.

The dissemination of equine herpesvirus types 1 (EHV-1) and 4 (EHV-4) among various horse populations in Japan was investigated through the isolation and typing of virus strains from horses with respiratory diseases. Type specific monoclonal antibody pools were used for the typing of isolates. The 42 strains of EHV-1 and 64 strains of EHV-4 were isolated from 4593 nasal swabs and/or blood plasma samples collected from 3326 horses during a period from 1979 to 1990. All the strains of EHV-1 were isolated from racehorses only and during the winter season exclusively, when the epizootic of respiratory diseases occurred among racehorse populations at two Training Centers of the Japan Racing Association. In contrast, the strains of EHV-4 were isolated from horses irrespective of the season, facility, or horse population; foals and yearlings in breeding farms and our institute, rearing horses in rearing farms, and racehorses. Especially, 4 strains of EHV-4 were isolated from plasma samples containing buffy coat cells. We believe this is the first reported case of EHV-4 cell-associated viremia in the world. All 87 strains isolated from aborted fetuses were identified as EHV-1. The results suggest that EHV-1 is responsible for epizootic respiratory diseases in racehorses in the winter and abortion among mares at the late stage of gestation, and that EHV-4 causes respiratory diseases throughout the year among all horse populations.

Abortion, Veterinary