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Biomedical subjects

Y Koga

Publications and source records attributed to Y Koga.

At least 289 records · Page 16Linked to original sources

Increase of Thy-1 antigen on the thymocytes accompanied with their augmented adhesion capacity to thymic epithelial cells in the mice infected with Listeria monocytogenes.

It becomes increasingly clear that adhesion systems such as CD2/LFA-3 (lymphocyte function-associated antigen-3), LFA-1/ICAM-1 (intercellular adhesion molecule-1) and Thy-1/putative Thy-1 ligand participate in the association between murine thymocytes and thymic epithelial cells. In the present study, thymocytes showed an increase in surface Thy-1 levels in mice infected with Listeria monocytogenes, but no significant changes in the levels of CD2 or LFA-1. No alteration was found either in the ratio of CD3high/CD3low/CD3- or in that of CD4/CD8 subsets in these thymocytes compared with uninfected control thymocytes which excluded the possibility of enrichment of 'cortical thymocytes' with Thy-1high/CD3low/CD4+ CD8+ in the thymocyte population of infected mice. Moreover such Thy-1high thymocytes exhibited a highly augmented ability of adhesion to a thymic epithelial cell line due to the increase of surface Thy-1 antigens as an adhesion molecule. At such intervals after infection, the total number of thymocytes was found to be reduced. These results suggest that the expression level of surface Thy-1 on thymocytes is regulated in response to in vivo stimulation and may play a role in the intrathymic development of thymocytes by affecting the adhesion of thymocytes with thymic stromal cells. The implication of the enhanced ability of adhesion in the decrease in the number of thymocytes is discussed.

Animals↗

Optimal shape of prosthesis for tricuspid valve replacement.

To develop an optimal prosthesis for use in the tricuspid valve, we determined the change in cardiac performance associated with the change in shape of the anulus of the tricuspid valve using a metal ring of variable flat ratio (defined as the long/short axis). In experiment I in an isolated autoperfusion model with six dogs, the left ventricular stroke work under a constant left atrial pressure of 7 mm Hg were, in grams per beat per minute, 11.88 +/- 0.52 with a flat ratio of 1.0, 11.88 +/- 0.70 with a flat ratio of 1.3, 16.23 +/- 0.61 with a flat ratio of 1.6, and 11.22 +/- 0.38 with a flat ratio of 2.3 (mean +/- standard error of the mean). The volume was significantly higher with a flat ratio of 1.6 than with the other ratios (p < 0.05). In experiment II with six dogs in vivo, the blood flow of the pulmonary trunk artery was 0.57 +/- 0.03 L/min with a flat ratio of 1.0, 0.66 +/- 0.03 L/min with a flat ratio of 1.6, and 0.58 +/- 0.03 L/min with a flat ratio of 2.3; the flow was significantly larger with a ratio of 1.6 than with the other ratios (p < 0.05). Right ventriculography was performed in five dogs. The percentage of radial shortening of the apex close to the acute margin was 19.4% +/- 3.1% with a flat ratio of 1.0 and 49.2% +/- 5.1% with a flat ratio of 1.6 (p < 0.05). In conclusion, the best hemodynamic results were obtained with a flat ratio of 1.6, which showed more advantageous hemodynamics than do the ratios of conventional circular prostheses.

Animals↗

[Inducing ability of co-planar PCBs toward bilirubin UDP-glucuronyltransferase of liver microsomes: the remarkable difference between guinea pigs and rats].

The induction of liver microsomal UDP-glucuronyltransferase (UGT) activity toward bilirubin by pretreatment with 3, 4, 3', 4'-tetrachlorobiphenyl (TCB), 3, 4, 5, 3', 4'-pentachlorobiphenyl (PenCB) and 3-methylcholanthrene (MC) was studied in guinea pigs and rats. In addition, microsomal benzo(a)pyrene 3-hydroxylase and cytosolic DT-diaphorase activities were also measured for the comparison. All of the PenCB, TCB and MC significantly induced the bilirubin UGT activity of guinea pig liver microsomes. The highest induction (6-fold over the control) was seen in the PenCB-treated animal, and MC (3.2-fold) and TCB (2.4-fold) were less effective. On the other hand, the induction of benzo(a)pyrene 3-hydroxylase and DT-diaphorase activities of guinea pigs was not so remarkable as that of bilirubin UGT activity. In the guinea pig, the inducibility of bilirubin UGT activity seemed to be correlated with the toxicity induced with PenCB, TCB and MC. In contrast to the guinea pig, UGT activity toward bilirubin in the rat was significantly decreased by the treatment with the inducers described above. These results suggest that bilirubin UGT activity in the guinea pig can be an index for the toxicity of polychlorinated biphenyls as like as benzo(a)pyrene 3-hydroxylase and DT-diaphorase activities in the rat.

Animals↗

[Combined spinal and epidural analgesia for caesarean section].

We compared the combined spinal and thoracic epidural analgesia with 2% lidocaine for caesarean section, with spinal analgesia using 2% lidocaine, tetracaine or dibucaine, and also with lumbar epidural analgesia. The analgesia at high thoracic level could be achieved with combined spinal and epidural analgesia more easily than with others. The frequency of side effects with the combined spinal and epidural analgesia, such as hypotension, decrease of fetal heart rate and so on, was less than that with others. In conclusion, the combined spinal and thoracic epidural analgesia with 2% lidocaine is more useful for caesarean section, than the spinal analgesia or the lumbar epidural analgesia alone.

Anesthesia, Epidural↗

[Peritoneal dialysis following open heart surgery in children].

From 1982 to 1991, 13 (3.9%) of 336 children who underwent open heart surgery required peritoneal dialysis postoperatively, including 5 with transposition of the great arteries, 4 with tetralogy of Fallot, 2 with ventricular septal defect, 1 each with atrioventricular canal defects and total anomalous pulmonary venous connection. Patients ages ranged from 12 days to 4 years (mean, 1 year and 4 months). The infusion catheter was directed toward diaphragm from the right lower quadrant, and the drainage catheter was placed in the pelvis from the left upper quadrant. Dialysis solution was instilled and drained simultaneously. Seven children (54%) recovered renal function, with six (46%) longterm survivors. Differences between patients who did and did not recovered renal function (Group A and Group B respectively) were examined. No significant intergroup difference existed in age or weight. PD was initiated significantly sooner in Group B (1.2 +/- 0.8 days) than in Group A (3.2 +/- 1.9 days) (p < 0.05). The negative fluid balance was 88.0 +/- 31 mL/kg/day in Group A and 78.4 +/- 25.0 mL/kd/day (NS). BUN and serum creatinine concentrations were slightly elevated in both group, but were not significant different. Patients in Group A were dialyzed from 3 days to 21 days (mean 9.9 +/- 6.4 days), and patients in Group B were dialyzed from 1 day to 14 days (mean 5.3 +/- 5.2 days) (NS). The central venous pressure (CVP) in Group A decreased while blood pressure (BP) and renal perfusion pressure (RPP) increased following initiation of PD. CVP increased in Group B, while BP and RPP decreased. All patients died of low cardiac output syndrome.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Kidney Injury↗

Cardioplegic effect of University of Wisconsin solution on hypothermic ischemia of rat myocardium assessed by mitochondrial oxidative phosphorylation.

The effectiveness of the University of Wisconsin solution and the Collins' M solution for preservation of rat hearts was compared by examining histologic appearance, tissue water content, and mitochondrial respiratory functions after prolonged hypothermic storage and subsequent heterotopic transplantation. Survival of transplanted hearts after 5 days of reperfusion was markedly lowered by storage in Collins' M solution for 15 hours. Hearts stored in University of Wisconsin solution for 10 hours showed no increase in myocardial necrosis after 5 days of reperfusion, whereas hearts stored in University of Wisconsin solution for 15 hours and Collins' M solution for 10 and 15 hours showed a significant increase in tissue necrosis. University of Wisconsin solution reduced tissue swelling during hypothermic storage, whereas Collins' M solution did not cause such reduction. The yield of mitochondrial protein after reperfusion was significantly decreased by storage in either solution, especially after 15 hours in Collins' M solution. Mitochondrial oxidative phosphorylation was significantly inhibited by storage, especially by storage in Collins' M solution and subsequent reperfusion. These results indicate that myocardial injury, after prolonged ischemia and reperfusion, results in a decrease in functionally and structurally intact mitochondria that is dependent on preservation conditions. University of Wisconsin solution protects isolated hearts against ischemia and reperfusion injury possibly by preventing cellular and mitochondrial deterioration.

Adenosine↗

[A case of a traumatic diaphragmatic true hernia manifesting itself 12 years after the accident].

A case of surgical treatment of a traumatic diaphragmatic true hernia was presented, which manifested itself as symptoms of left chest oppression 12 years after the accident. The patient was a 66-year-old woman, who met traffic accident in 1976. She was first pointed out abnormal shadow on the chest X-ray in 1981 and began to feel chest oppression in 1988. Barium examination of the upper gastrointestinal tract and chest CT scan revealed a part of corpus ventriculi and colon herniated into the left hemithorax. Diaphragmatic hernia was diagnosed and the operation was performed through the thoracic approach in June 1991. The diaphragm was found to have a hernia sac and a defect at the central tendon. The hernia sac containing the stomach and colon was opened to reduce it's contents into the abdominal cavity. The defect was closed by mattress suture with pledgets and continuous over and over suture. The patient ran a favorable post operative course. A true type among traumatic diaphragmatic hernia is a very rare case in the literature.

Aged↗

[Effect of Na-L-glutamate on mitochondrial function of ATP synthesis after prolonged preservation in rat heart].

We studied the effect of Na-L-glutamate (Glu) on mitochondrial functions of ATP synthesis after prolonged hypothermic preservation of rat hearts. We divided isolated rat hearts into the following three groups: group A, hearts without immersion as control; group B, hearts immersed in Euro-Collins solution (E-C) without Glu for 24 h at 4 degrees C; group C, hearts immersed in E-C with 10mM Glu for 24 h at 4 degrees C. Number of each group used was 6. Mitochondrial functions of ATP production were determined by measuring respiratory control index (RCI). P/O ratio and state III respiration rate. The ability of ATP production (oxidative phosphorylation rate, OPR) was calculated. RCI and P/O ratio of groups B and C were significantly lower than those of group A. RCI and P/O ratio of group C were significantly higher than that of group B. S3 rates of groups B and C were significantly lower than those of group A. S4 rate of group B was significantly higher than those of groups A and C. OPRs of groups B and C were significantly lower than that of group A. OPR of group C was significantly higher than that of group B. We concluded that Na-L-glutamate effectively protected mitochondrial functions to synthesize ATP during prolonged hypothermic preservation.

Adenosine Triphosphate↗

Prognostic significance of electrocardiographic findings in patients with dilated cardiomyopathy.

The prognostic significance of electrocardiographic variables was retrospectively investigated in 88 patients with dilated cardiomyopathy and with normal coronary arteriograms. During an average follow-up of 3.7 +/- 2.9 years, 43 patients died, 26 of progressive heart failure, 15 patients with sudden death, and one due to cerebral embolism. Excluding one patient, who died of esophageal cancer, the cumulative survival rate was 73% at 2 years and 60% at 5 years. By univariate life table analysis, abnormal Q-waves, a QRS duration > or = 0.12s, a cardiothoracic ratio > or = 60%, systolic blood pressure < 110mmHg, and left ventricular end-diastolic pressure > or = 15mmHg were significantly associated with increased mortality within 5 years. Multivariate analysis using Cox's proportional hazards model determined the major independent risk factors in the following order: (1) for all patients; the presence of abnormal Q-waves, left bundle branch block or intraventricular conduction disturbances, left ventricular end-diastolic pressure, systolic blood pressure and the cardiothoracic ratio; (2) for patients without left bundle branch block or intraventricular conduction disturbances; abnormal Q-waves, left ventricular end-diastolic pressure and systolic blood pressure. The present study thus demonstrated that the electrocardiogram could provide independent prognostic predictors in patients with dilated cardiomyopathy, possibly reflecting the severity of myocardial damage.

Cardiomyopathy, Dilated↗

A lymphocyte-specific protein tyrosine kinase, p56lck, regulates the PMA-induced internalization of CD4.

p56lck, a member of the src family of non-receptor protein tyrosine kinases (PTKs), is expressed predominantly in T-lymphocytes. Association of p56lck with CD4 and CD8 T-cell receptor (TcR) accessory molecules suggests that p56lck may play a specialized role in antigen-induced T-cell activation. CD4 and CD8 molecules are known to stabilize the interaction between TcR and the major histocompatibility complex during T-cell activation. To examine the role of p56lck in the dynamics of the CD4 molecule, p56lck-expressing transfectant cell clones were prepared by the transfection of an lck-gene plasmid containing an inducible promoter into a CD4+lck- human monocytoid cell line. When these transfectant cells were stimulated with phorbol ester, CD4 internalization on these p56lck-expressing cell lines was selectively and markedly retarded, as compared to p56lck-negative control cell lines. When cell-surface CD4 and intracellular CD4 were selectively precipitated after stimulation, the intracellular CD4 molecules were dissociated from p56lck whereas the surface-retained CD4 molecules were still associated with p56lck. Moreover, the dissociation of p56lck from CD4 appeared to occur prior to the PMA-induced internalization of CD4. These data indicate that p56lck regulates the PMA-induced internalization of CD4 possibly via its association with CD4. Treatment with genistein, a PTK inhibitor, revealed that the PTK activity of p56lck might not be involved in this regulatory effect of p56lck on CD4 internalization.

Blotting, Western↗

Differential expression of genes specifying two isoforms of subunit VIa of human cytochrome c oxidase.

Subunit VIa of mammalian cytochrome c oxidase (COX; EC 1.9.3.1) exists in two isoforms, one present ubiquitously ('liver' isoform; COX VIa-L) and the other present only in cardiac and skeletal muscle (COX VIa-M). We have now isolated a full-length cDNA specifying human COX VIa-M. The deduced mature COX VIa-M polypeptide is 62% identical to the human COX VIa-L isoform, but is approximately 80% identical to the bovine and rat COX VIa-M isoforms, suggesting that the two COX VIa isoform-encoding genes arose prior to the mammalian radiation. Transcriptional analysis showed a tissue-specific pattern: whereas COXVIa-L is transcribed ubiquitously, COXVIa-M is transcribed only in heart and skeletal muscle. The cDNA specifying COX VIa-M is a prime candidate for use in investigations of Mendelian-inherited COX deficiencies with primary involvement of muscle.

Amino Acid Sequence↗

Role of acetylcholinesterase in airway epithelium-mediated inhibition of acetylcholine-induced contraction of guinea-pig isolated trachea.

To seek evidence for the involvement of acetylcholinesterase activity in the modulatory influence of the airway epithelium, we examined responses to acetylcholine (ACh), bethanechol, histamine or KCl in isolated epithelium-intact and epithelium-denuded guinea-pig trachealis preparations. The concentration-response curves to ACh were shifted 26-fold to the left by epithelial denudation but the contractile response to KCl was not altered. The response to histamine in epithelium-denuded preparations increased 4-fold with no attenuation in the presence of physostigmine (30 nM). Physostigmine (30 nM) potentiated the response to ACh in epithelium-intact tissues more (about 26-fold) than in epithelium-denuded tissues (about 3.5-fold). Thus, in the presence of physostigmine removing the epithelium had only a slight effect (not statistically significant) on the potency of ACh to contract the trachea. Removing the epithelium had no effect on the potency of bethanechol, a muscarinic receptor agonist that is not a substrate for cholinesterases. Physostigmine itself contracted the trachealis muscle but the pD2 values and maximum responses in epithelium-intact and denuded preparations were not significantly different. The frequency-response curves to electrical field-stimulated cholinergic contractions were unaffected by removing the epithelium. In conclusion, the principal mechanism by which the epithelium inhibits contraction of guinea-pig trachea to exogenously applied ACh is via epithelium-derived acetylcholinesterase activity.

Acetylcholine↗

The mitochondrial tRNA(Leu)(UUR)) mutation in MELAS: a model for pathogenesis.

The A----G transition at nucleotide 3243 of the mitochondrial tRNA(Leu)(UUR)) gene has been associated with MELAS, a maternally-inherited mitochondrial disorder. We recently transferred mitochondria harboring this mtDNA mutation into a human cell line devoid of endogenous mtDNA (rho degrees cells), and showed: (1) decreased rate of synthesis and of steady-state levels of mitochondrial translational products, (2) reduced respiratory chain function and (3) increased amounts of a novel unprocessed RNA species (termed by us RNA 19) derived from transcription of the 16S rRNA + tRNA(Leu)(UUR) + ND 1 genes. Because RNA 19 contains rRNA sequences, we propose that this molecule is incorporated into mitochondrial ribosomes, and interferes disproportionately with mitochondrial translation, thereby causing the phenotypic changes associated with MELAS.

Brain Diseases, Metabolic↗

Archaea contain a novel diether phosphoglycolipid with a polar head group identical to the conserved core of eucaryal glycosyl phosphatidylinositol.

The structure of a major ether polar lipid of the methanogenic archaeon Methanosarcina barkeri was identified as glucosaminyl archaetidylinositol. This lipid had archaeol (2,3-di-O-phytanyl-sn-glycerol) as a core lipid portion, and the polar head group consisted of 1 mol each of phosphate, myo-inositol and D-GlcN. The polar head group was identified by means of chemical degradations, phosphatidylinositol-specific phospholipase C treatment, permethylation analysis, and fast atom bombardment-mass spectrometry as glucosaminylinositol phosphate, which was linked to the glycerol backbone via a phosphodiester bond. The stereochemical configuration of the phospho-myo-inositol residue of glucosaminyl archaetidylinositol was determined to be 1-D-myo-inositol 1-phosphate by measuring optical rotation of phospho-myo-inositol prepared by nitrous acid deamination and alkaline hydrolysis from the lipid. 1H NMR of the intact lipid showed that GlcN was linked to C-6 position of myo-inositol as an alpha-anomer. It is, finally, concluded that the complete structure of this lipid is 2,3-di-O-phytanyl-sn-glycero-1-phospho- 1'[6'-O-(2"-amino-2"-deoxy-alpha-D-glucopyranosyl)]-1'-D-myo-inositol. This lipid has a hybrid nature of an archaeal feature in alkyl glycerol diether core portion and an eucaryal feature in the polar head group identical to the conserved core structure (GlcNp(alpha 1-6)-myo-inositol 1-phosphate) of glycosylated phosphatidylinositol which serves as a membrane protein anchor in eucaryal cells.

Carbohydrate Sequence↗

Preventative effect of PGE1 for postoperative liver damage.

The efficacy of a low dose of PGE(1)-use on the postoperative liver damage was evaluated. PGE(1) was infused in with the mean rate of 0.026 microg.kg(-1).min(-1) during surgical procedure to 93 patients under GO-enflurane anesthesia (the PG). Serum GOT, GPT and total bilirubin (TBIL) values measured before, at the end of (End) and 3 days (3d) after the operation were compared to those obtained from 43 patients without PGE(1) administration (the control). This dose of PGE(1) did not change blood pressure and heart rate, but slightly decreased Pa(O)(2). In patients with preoperative normal values of GOT, GPT and TBIL, increases in GOT, GPT and TBIL observed at End in the PG were significantly lower than those in the control (31.9 vs 72.2 IU, 25.9 vs 61.9 IU, 0.68 vs 0.83 mg.dl(-1), respectively). GOT, GPT and TBIL at 3d significantly increased in both groups, and these levels were identical between the two groups. In patients with preoperative abnormal values, only GOT at End increased in both groups, while no significant difference between the PG and the control group was noted. GOT at 3d and GPT at End and 3d did not significantly changed in either group. These results suggest that the low dose of PGE(1) administered during an operation prevents the development of postoperative liver damage, but does not treat the damaged hepatic cells.

Journal Article↗

Point mutations in mitochondrial DNA in patients with hypertrophic cardiomyopathy.

Recent advances suggest that mutations in nuclear DNA are involved in the etiology of autosomal dominant hypertrophic cardiomyopathy. Mitochondria have their own DNA, and mutations in mitochondrial DNA have been shown to contribute to the genesis of various diseases. In this study, we developed rapid sequencing methods with the use of a fluorescence-based sequencing system and analyzed total mitochondrial DNA of seven patients with nonautosomal dominant hypertrophic cardiomyopathy. Multiple point mutations were observed in all patients with hypertrophic cardiomyopathy, although some of them were common among the subjects examined and the others are unique to each subject. Point mutations in transfer RNA genes were observed in five of the seven patients, and point mutations that replaced conserved amino acids were also observed. These mutations may result in the impairment of mitochondrial function. According to these results, mutations in mitochondrial DNA may contribute to the genesis of some cases of nonautosomal dominant hypertrophic cardiomyopathy, and our methods may be useful for the detection of point mutations in mitochondrial DNA.

Adult↗