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Biomedical subjects

T Shimada

Publications and source records attributed to T Shimada.

At least 847 records · Page 47Linked to original sources
PubMed1987

Vibrio fluvialis: a new serogroup (19) possessing the Inaba factor antigen of Vibrio cholerae O1.

A serogroup of Vibrio fluvialis possessing the C (Inaba) antigen but not the B (Ogawa) nor A antigen of V. cholerae O1 is described. The O-antigen of this serogroup was identical with that of bioserogroup 1875-variant of a marine Vibrio species. As the O-antigen of this serogroup was not agglutinated by any of O-antisera for the 18 serogroups of V. fluvialis already recognized, it was designated O-serogroup 19 of this species.

Antigens, Bacterial↗
PubMed1987

[Right ventricular function in patients with chronic obstructive pulmonary disease measured by krypton-81m].

Right ventricular function was assessed at rest and during exercise in patients with chronic obstructive pulmonary disease (COPD). Right ventricular ejection fraction (RVEF) was measured by first-pass radionuclide angiography using ultrashort-lived radionuclide krypton-81m. The half-life of this nuclide is only 13 sec, and it is completely expired from the lungs. These properties allow measurement of RVEF without correcting for background activity. In 30 patients with cardiac or pulmonary disease, RVEF was first measured by krypton-81 m scintigraphy (Kr-RVEF), then by technetium-99m (Tc-RVEF), without changing the patients' positions. In eight of the 30 cases, right ventricular cineangiography (RVG) was performed within 72 hrs after the radionuclide study, and RVEF was measured according to the Chapman's rule (RVG-RVEF). Kr-RVEF correlated significantly with Tc-RVEF (r = 0.87), and also with RVG-RVEF (r = 0.80). In 10 patients with stable COPD, who had severe hypoxemia (PaO2 less than or equal to 60 mmHg) and pulmonary hypertension [mean pulmonary arterial pressure (mean PAP) greater than or equal to 20 mmHg], and in seven normal control subjects, radionuclide angiographic and hemodynamic monitoring were performed at rest and during supine ergometer exercise. Kr-RVEF at rest was 47.6 +/- 5.4% (mean +/- SD) in patients with COPD and was 54.1 +/- 4.8% in normal subjects. Kr-RVEF during exercise was 51.8 +/- 7.3% in the patients, and 62.3 +/- 3.2% in the normal subjects. Hemodynamically, mean PAP and pulmonary vascular resistance (PVR) increased significantly during exercise, but the RV end-diastolic volume index (RVEDVI) did not change. There was inverse correlation between Kr-RVEF and mean PAP (r = -0.51) or PVR (r = -0.47) as an index of RV afterload. However, there was no correlation between Kr-RVEF and RVEDVI as an expression of RV preload. These findings suggest that a poor response by RVEF during exercise in patients with COPD is associated with elevation of afterload. Thus, right ventricular imaging techniques using the ultrashort-lived nuclide krypton-81 m allow noninvasive, serial and accurate assessments of right ventricular function in patients with COPD.

Aged↗
PubMed1986

Chromatin structure of the human dihydrofolate reductase gene promoter. Multiple protein-binding sites.

The chromatin structure of the promoter region of the human dihydrofolate reductase gene was determined using a variety of nucleases including DNase I, micrococcal nuclease, several restriction endonucleases, exonuclease III, and Bal31. Two separate regions from -670 to -340 (the distal hypersensitive region) and from -170 to +150 (the proximal hypersensitive region) were shown to be essentially free of proteins as indicated by their accessibility to both endo- and exonucleases. Within the proximal hypersensitive region, one protein appears to be bound at the start site for transcription. A 170-base pair fragment between the two hypersensitive regions was highly resistant to all nucleases tested. Multiple barriers against exonuclease digestion and resistance to dissociation by high salt concentrations suggest that more than one protein is tightly bound to this region. The upstream sequence from -670 and the downstream sequence from +150 were shown to be packaged into nucleosomes. The selective accessibility of certain sites to micrococcal nuclease cutting indicates that the initial nucleosomes are phased upstream from the distal hypersensitive region. There appears to be a protein bound between the phased nucleosomes and the upstream boundary of the distal hypersensitive region. These results suggest that the normal nucleosome array is interrupted by about 900 base pairs of nucleosome-free DNA to which several nuclear proteins bind in a DNA sequence-specific manner.

Chromatin↗
PubMed1986

Human liver microsomal cytochrome P-450 mephenytoin 4-hydroxylase, a prototype of genetic polymorphism in oxidative drug metabolism. Purification and characterization of two similar forms involved in the reaction.

Two forms of cytochrome P-450 (P-450), designated P-450MP-1 and P-450MP-2, were purified to electrophoretic homogeneity from human liver microsomes on the basis of mephenytoin 4-hydroxylase activity. Purified P-450MP-1 and P-450MP-2 contained 12-17 nmol of P-450/mg of protein and had apparent monomeric molecular weights of 48,000 and 50,000, respectively. P-450MP-1 and P-450MP-2 were found to be very similar proteins as judged by chromatographic behavior on n-octylamino-Sepharose 4B, hydroxylapatite, and DEAE- and CM-cellulose columns, spectral properties, amino acid composition, peptide mapping, double immunodiffusion analysis, immunoinhibition, and N-terminal amino acid sequences. In vitro translation of liver RNA yielded polypeptides migrating with P-450MP-1 or P-450MP-2, depending upon which form was in each sample, indicating that the two P-450s are translated from different mRNAs. When reconsituted with NADPH-cytochrome-P-450 reductase and L-alpha-dilauroyl-sn-glyceryo-3-phosphocholine, P-450MP-1 and P-450MP-2 gave apparently higher turnover numbers for mephenytoin 4-hydroxylation than did the P-450 in the microsomes. The addition of purified rat or human cytochrome b5 to the reconstituted system caused a significant increase in the hydroxylation activity; the maximum stimulation was obtained when the molar ratio of cytochrome b5 to P-450 was 3-fold. Rabbit anti-human cytochrome b5 inhibited NADH-cytochrome-c reductase and S-mephenytoin 4-hydroxylase activities in human liver microsomes. In the presence of cytochrome b5, the Km value for S-mephenytoin was 1.25 mM with all five purified cytochrome P-450s preparations, and Vmax values were 0.8-1.25 nmol of 4-hydroxy product formed per min/nmol of P-450. P-450MP is a relatively selective P-450 form that metabolizes substituted hydantoins well. Reactions catalyzed by purified P-450MP-1 and P-450MP-2 preparations and inhibited by anti-P-450MP in human liver microsomes include S-mephenytoin 4-hydroxylation, S-nirvanol 4-hydroxylation, S-mephenytoin N-demethylation, and diphenylhydantoin 4-hydroxylation. Thus, at least two very similar forms of human P-450 are involved in S-mephenytoin 4-hydroxylation, an activity which shows genetic polymorphism.

Amino Acid Sequence↗
PubMed1986

Thioridazine enhances lysosomal accumulation of epidermal growth factor and toxicity of conjugates of epidermal growth factor with Pseudomonas exotoxin.

Thioridazine, a phenothiazine calmodulin inhibitor, aggravated the cytotoxic effect of a conjugate (EGF-PE) of epidermal growth factor (EGF) coupled with Pseudomonas exotoxin against cultured HeLa cells. Other phenothiazine calmodulin inhibitors, trifluoperazine and chlorpromazine, also intensified the cytotoxic effect of EGF-PE, whereas N-(6-aminohexyl)-5-chloro-1-naphthalene sulfonamide (W7) had no such effect. By using iodinated epidermal growth factor ( [125I]EGF), the effect of thioridazine on intracellular transport of EGF was examined. The release of radioactivity associated with [125I]EGF into medium was slow in the presence of thioridazine. The Percoll gradient centrifugation pattern showed that thioridazine delayed both the appearance of [125I]EGF in lysosomes and the disappearance of [125I]EGF from the lysosomes. The pH value in lysosomes was 5.28 in thioridazine-treated HeLa cells, while that in untreated cells was 5.15. Thioridazine was found to inhibit lysosomal enzyme activities of cathepsin B and acid phosphatase, but not beta-hexosaminidase when cell extracts were treated with the drug. Electron microscopy showed an increased number of electron-dense bodies, possibly autophagosomes/lysosomes in HeLa cells grown for 48 h with 3 micrograms/ml thioridazine. The potentiating action of EGF-PE by thioridazine is discussed in relation to the altered lysosomal function in treated cells.

ADP Ribose Transferases↗
PubMed1986

A comparative study of specificity of the intestinal Na+/sugar cotransport among vertebrates.

Kt values for various monosaccharides were determined from sugar-induced increments of the transmural potentials in isolated small intestines of the goldfish, bullfrog, turtle, quail, guinea pig, rat and rabbit, and specificity patterns of the Na+/sugar cotransporters were compared among these animal species. Absolute requirement of the D-pyranose ring structure was seen in all animals. Requirements of C2-OH and C6 were strong, but not absolute, and OH groups on C3, C4, C6 and the O-atom of the pyranose ring were also suggested to participate, in some degree, in the interaction with the carrier. Comparison of the disaccharide-evoked potentials revealed that there were considerable species differences in activities of trehalase, sucrase and lactase among animals examined, but the differences were relatively small for maltase activity.

Animals↗
PubMed1986

Effects of sodium vanadate on various types of vascular smooth muscles.

Effects of sodium vanadate on various vascular smooth muscles of guinea pigs, rabbits, and Wistar Kyoto rats (WKY) were studied. Sodium vanadate of concentrations higher than 10(-5) M induced contractions in the aortae of all animals. The contractile effects varied among vascular smooth muscles, and mesenteric arteries showed no or only weak contractile response to the drug, while aortae showed higher contractile responses. In the portal veins, potentiation of spontaneous contractions was observed by the application of sodium vanadate. These responses were not blocked by treatments with adrenergic blocking agents or indomethacin, indicating the direct action of the drug on vascular smooth muscles. Treatment with 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid (DIDS) blocked completely the contractile effects of sodium vanadate, whereas it showed no effect on K-contractures. Partial depolarization of the membrane by elevations of K concentration potentiated sodium vanadate-induced contractions and minimized the variations of responses among preparations. In K-depolarized preparations, sodium vanadate often induced relaxation of preparations. The contractile effects of sodium vanadate were not blocked by treatment with ouabain, though ouabain also showed contractile actions in a number of preparations. It was suggested that vanadate acts directly on vascular smooth muscles and causes contractions without relation to the inhibition of Na,K-ATPase. It may cause contractions inhibiting Ca-ATPase of sarcoplasmic reticulum and/or of cell membrane, and cause relaxation by inhibiting ATPase of contractile proteins. The variations of the responses may be explained by differences of membrane permeability to vanadate.

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid↗
PubMed1986

Masked thyroid dysfunction among elderly patients with atrial fibrillation.

Seventy-five elderly patients with atrial fibrillation (41 males and 34 females with a mean age of 75.6 years) were studied to evaluate the incidence of masked thyroid dysfunction. A thyrotropin (TSH)-releasing-hormone (TRH) test (intravenous injection of 250 micrograms of synthetic TRH) was performed in the patients and 30 age matched controls without atrial fibrillation. In the controls, no abnormal TRH stimulated TSH response was observed. In the patients with atrial fibrillation, no response of TSH to TRH (hyperthyroidism) was found in 5 cases (6.6%), while hyperresponse of TSH to TRH (hypothyroidism) was found in 6 cases (8.0%). Thyroid dysfunction (hyper or hypothyroidism) was more frequently observed in the patients than in the controls (p less than 0.05). Two of 5 hyperthyroid patients had normal thyroid hormone levels. All patients with hyperthyroidism were treated with antithyroid drugs or 131I. Unfortunately, atrial fibrillation persisted in all but 1 case. It is concluded that the TRH test is a useful screening test for detecting those patients with abnormal thyroid function among elderly patients with atrial fibrillation, and that hypothyroidism should be considered as a cause of atrial fibrillation in the elderly.

Aged↗
PubMed1986

Comparison of contractile effects of sodium vanadate and ouabain in vascular smooth muscles of guinea-pigs and rats.

Ouabain and vanadate are known as potent inhibitors of Na, K-ATPase in various tissues including smooth muscles. Both agents showed contractile action on various smooth muscles in a similar fashion: stronger contractile action on the aortae of rats (WKY and stroke prone spontaneously hypertensive rats, SHRSP) and guinea-pigs, and weaker contractile actions on basilar and mesenteric arteries of the same animals. Time to peak tension, however, was far longer in ouabain-induced contraction. Phentolamine depressed ouabain-induced contractions, while vanadate-induced contractions were not affected. Elevation of K+ concentration to 20 or 30 mM potentiated vanadate-induced contraction markely, while it potentiated ouabain-induced contraction only slightly. DIDS blocked vanadate-induced contraction but showed no effect on ouabain-induced contraction. Removal of Ca abolished ouabain-induced contractions, while vanadate-induced contractions of reduced height could be observed in the absence of Ca. Verapamil depressed both ouabain- and vanadate-induced contractions of WKY and SHRSP aorte aut exhibited no effect on the guinea-pig aorta. Thus, although similarities of the action of ouabain and sodium vanadate were observed, the modes of the actions were revealed to be different in the two agents. Inhibition of Na, K-ATPase might be involved in the case of ouabain-induced contractions, and inhibition of Ca-ATPase of membranous systems might be involved in vanadate-induced contraction.

Animals↗
PubMed1986

Functional morphology of the conduction system and the myocardium in the sheep heart as revealed by scanning and transmission electron microscopic analyses.

The pacemaker, Purkinje system and myocardium of the sheep heart were investigated by scanning electron microscopy (SEM) and transmission electron microscopy (TEM). In the case of SEM, the heart tissues were subjected to chemical digestion procedures. The nodal cells in both the sinoatrial (SA) node and atrioventricular (AV) node were small in size and contained few nexuses with poor sarcoplasmic reticulum and myofibrillar development. These nodal cells were spindle-shaped and their ends often showed ramifications. In addition, the strands of nodal cells in the central part of the AV node were considerably compact and connected with neighboring strands to form a complicated three dimensional architecture. The muscle cells in the common bundle and Purkinje system were cuboidal or oval in shape and were broader and shorter than the working cardiac muscle cells. They had abundant nexuses, but exhibited poor sarcoplasmic reticulum and myofibrillar development. Three-dimensionally, the Purkinje strands formed a delicate network resembling a fishing-net. The atrial and ventricular myocardium consisted of long cylindrical muscle cells which often bifurcated and connected with neighboring cells. These cells had abundant nexuses, rich sarcoplasmic reticulum and well-developed myofibrils. This report discusses such morphological findings in correlation with their physiological properties.

Animals↗