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Biomedical subjects

T Kagawa

Publications and source records attributed to T Kagawa.

At least 37 records · Page 2Linked to original sources
PubMed2000

The serum soluble HLA-DR antigens as a predictive marker of the response to interferon-alpha treatment in patients with chronic hepatitis C.

The serum concentrations of soluble HLA-DR antigens (sDR) were monitored in 40 patients with chronic hepatitis C (CHC) who received interferon treatment. The expression of HLA-class II antigens in liver tissues was also studied by immunohistochemistry. The sDR levels in patients with chronic hepatitis C were significantly higher than those in healthy subjects (416+/-236 [mean +/- S.D.] ng/ml vs. 286+/-163 ng/ml) (P<0.05). There was no correlation between the sDR levels and serum alanine aminotransferase levels, suggesting that sDR do not reflect the extent of liver necrosis. Although there was no difference in pretreatment sDR levels between interferon complete responders and non-responders, sDR significantly declined in complete responders, while they did not in non-responders. The hepatic expression of HLA-DR antigens was observed in dendritic cells, lymphocytes and Kupffer cells in portal area, while in Kupffer cells and endothelial cells in central acinus. These expression significantly decreased in complete responders. From these results, sDR, reflecting the hepatic expression of HLA-DR antigens, could be a predictive marker of response to inteferon treatment.

Biomarkers↗
PubMed1999

Effects of sevoflurane and enflurane on lower esophageal sphincter pressure and gastroesophageal pressure gradient in children.

PURPOSE: The effects of sevoflurane and enflurane on the intraluminal pressure of the lower esophagus (LE), lower esophageal sphincter (LES), and stomach were investigated in paralyzed and mechanically ventilated children under general anesthesia. METHODS: A total of 14 children, ASA physical status class I without risk factors for regurgitation, scheduled for orthopedic surgery were studied. After induction of anesthesia, we inserted a gastrointestinal pressure sensor nasally and monitored the intraluminal pressure of the LE, LES, and stomach under various concentrations of sevoflurane or enflurane with 66% nitrous oxide in oxygen prior to surgical incision. The barrier pressure (BrP), which is the difference between LES pressure and intragastric pressure, was calculated. RESULTS: Sevoflurane at 2.0 and 2.5 minimum alveolar concentration (MAC) decreased LES pressure, and enflurane at 2.0 and 2.5 MAC decreased both LES pressure and BrP in anesthetized children. The intraluminal pressure of the LE and stomach were not altered in either group. CONCLUSION: Sevoflurane and enflurane have an inhibitory effect on LES smooth muscle in anesthetized children. However, since the reduction was relatively low, even at high concentrations, these inhalation anesthetics are unlikely to influence gastroesophageal reflux during anesthesia.

Journal Article↗
PubMed1999

Absence of R1066X mutation in six Japanese patients with Dubin-Johnson syndrome.

The Dubin-Johnson syndrome (DJS) is a rare autosomal recessive liver disease characterized by chronic conjugated hyperbilirubinemia. The phenotype of this syndrome is thought to be caused by the impaired expression of the canalicular multispecific organic anion transporter (cMOAT), which transports non-bile salt organic anions into the bile. Recently, a mutation from arginine (Arg) to stop-codon at codon 1066 in the cMOAT gene has been reported in one Caucasian patient with DJS. In this study, we investigated whether this mutation is found in Japanese patients with DJS. Genomic DNAs were extracted from the leukocytes of six Japanese patients and the fragments spanning codon 1066 were amplified by polymerase-chain reaction. The digest of the amplified fragments with a restriction enzyme, Taql, demonstrated that all of six patients did not exhibit an R1066X mutation. No mutation at Arg1066 was also confirmed by direct sequencing of the amplified products. These findings suggested that this R1066X mutation was not a major mutation in Japanese patients with DJS. Further investigation will be required in an attempt to search other mutations in cMOAT gene in Japanese patients with DJS.

Adult↗
PubMed1999

Chloroplast-avoidance response induced by high-fluence blue light in prothallial cells of the fern adiantum capillus-veneris as analyzed by microbeam irradiation

Chloroplast movement was induced by partial cell illumination using a high-fluence blue microbeam in light-grown and dark-adapted prothallial cells of the fern Adiantum capillus-veneris. Chloroplasts inside the illuminated area moved out (high-fluence response [HFR]), whereas those outside moved toward the irradiated area (low-fluence response [LFR]), although they stopped moving when they reached the border. These results indicate that both HFR and LFR signals are generated by high-fluence blue light of the same area, and that an LFR signal can be transferred long-distance from the beam spot, although an HFR signal cannot. The lifetime of the HFR signal was calculated from the traces of chloroplast movement induced by a brief pulse from a high-fluence blue microbeam to be about 6 min. This is very short compared with that of the LFR (30-40 min; T. Kagawa, M. Wada [1994] J Plant Res 107: 389-398). These data indicate that the signal transduction pathways of the HFR and the LFR must be distinct.

Journal Article↗
PubMed1999

Serum soluble HLA-DR antigens in autoimmune hepatitis.

To investigate the significance of HLA-class II, especially DR antigens, in autoimmune hepatitis (AIH), the serum concentrations of soluble HLA-DR antigen (sDR) were measured in 16 patients with AIH. The expression of HLA-DR antigens in the liver tissues of AIH patients was also studied by immunohistochemistry. AIH at diagnosis showed markedly higher serum sDR levels than controls, in which the liver tissues exhibited positive staining of HLA-DR antigens. Seven patients received corticosteroid therapy, in whom the serum sHLA-DR concentration was reduced dramatically from activated to remission stage. In sequentially follow-up cases, sDR correlated well with the disease activity, and also with the change of surface DR expression in the liver. A single major band with a molecular size of 60 kDa was detected, both in patient's sera and in normal control sera, by Western blotting. In conclusions, serum sHLA-DR level could be a marker reflecting immunological activity of the disease.

Alanine Transaminase↗
PubMed1998

Proximal promoter region is sufficient to regulate tissue-specific expression of UDP-galactose: ceramide galactosyltransferase gene.

UDP-galactose:ceramide galactosyltransferase (CGT) is the enzyme which catalyzes the final step of the biosynthesis of galactocerebroside (GalC), the most abundant glycolipid in myelin. We identified regulatory elements which are related to the tissue-specific expression of the mouse CGT gene by promoter assay using chimeric CGT-luciferase constructs. By comparing promoter activity in oligodendroglial CG4 cells and NIH3T3 fibroblasts, only a few hundred base pairs spanning from -309 to -98 were shown to be necessary for the tissue-specific activity of CGT promoter. A negative regulatory element was found in a more distal region, from -709 to -527, and it also worked in tissue-specific manner. Sequence analysis suggests that several known elements found commonly in myelin-related genes may explain these tissue-specific regulations of the transcriptional activity.

Animals↗
PubMed1998

Intravenous glucose tolerance test-derived glucose effectiveness in strength-trained humans.

The effect of long-term strenuous resistance training on glucose effectiveness (SG) was examined by comparing 11 strength-trained and 20 sedentary males by a minimal model approach. Lean body mass (LBM) was measured by hydrostatic weighing. The LBM in strength-trained subjects (65.7 +/- 3.1 kg) was significantly larger than in sedentary subjects (56.6 +/- 1.2 kg, P < .01). The glucose disappearance constant ([KG] 3.07% +/- 0.45% min(-1)) and insulin sensitivity ([SI] 17.5 +/- 2.0 x 10(-5) x min(-1) x pmol/L(-1)) in strength-trained subjects were significantly higher than in sedentary subjects (2.06% +/- 0.14% x min(-1) and 10.3 +/- 1.2 x 10(-5) x min(-1) x pmol/L(-1), P < .05). SG in strength-trained subjects (0.024 +/- 0.003 min(-1)) was significantly higher than in sedentary subjects (0.018 +/- 0.001 min(-1), P < .05). These results thus suggest that the improved glucose tolerance in strength-trained subjects was due to increased SG and SI.

Adult↗
PubMed1998

Differential expression of multidrug resistance (mdr) and canalicular multispecific organic anion transporter (cMOAT) genes following extrahepatic biliary obstruction in rats.

The hepatic canalicular membrane has transporters that play an important role as efflux pumps in the excretion of endogenous bile constituents or xenobiotics into bile canaliculi. To elucidate functional significance of canalicular transporters in the mechanism of cholestasis, mRNA expression levels of multidrug resistance (mdr) 1b, mdr2 and canalicular multispecific organic anion transporter (cMOAT) genes were analyzed by Southern blotting of reverse-transcribed PCR products of liver mRNA obtained from cholestatic rats that had been subjected to bile duct ligation. Both mdr1b and mdr2 mRNA expression increased after ligation. Immunohistochemical study revealed that the products of both mdr1b and mdr2 were present on the canaliculi, and that their levels increased after ligation. In contrast, cMOAT mRNA expression was not increased, but rather attenuated by ligation. The expression of canalicular transporters was differentially regulated in extrahepatic biliary obstruction, indicating the different roles are played by mdr and cMOAT in the pathogenesis of cholestasis.

ATP Binding Cassette Transporter, Subfamily B↗
PubMed1998

The effect of halothane and sevoflurane on fatigue-induced changes in hamster diaphragmatic contractility.

UNLABELLED: The purpose of this study was to examine the effect of halothane and sevoflurane on fatigue-induced changes in diaphragmatic contractility. Forty-two hamster diaphragm strips were randomly allocated according to anesthetics (no anesthesia control, 1%-3% halothane, 2%-6% sevoflurane) and stimulated directly in an organ bath. Under the influence of the anesthetics, muscle fatigue was induced by repetitive tetanic contraction, and diaphragmatic contractilities (i.e., peak twitch and tetanic tension, twitch contraction time, and half-relaxation time) were measured before and after fatigue. Neither halothane nor sevoflurane changed tension generation before or after fatigue, but each anesthetic significantly enhanced fatigue-induced prolongations of the contraction time and half-relaxation time after fatigue. Specifically, the half-relaxation times after fatigue in the 3% halothane, 4% sevoflurane, and 6% sevoflurane groups (225.6 +/- 37.6, 236.0 +/- 76.5, and 287.3 +/- 55.5 ms, respectively) were more than twice as long as those of the control group (104.7 +/- 19.7 ms, P < 0.05). We conclude that halothane and sevoflurane augment fatigue-induced prolongations of the contraction and relaxation times. Diaphragmatic function may deteriorate when there is a fatiguing task during the clinical administration of halothane or sevoflurane anesthesia. IMPLICATIONS: This study implicates diaphragmatic fatigue during anesthesia. An in vitro hamster diaphragm muscle preparation was used to study the effect of halothane and sevoflurane on fatigue-induced change in contractility. Our findings suggest that increased load on the diaphragm during volatile anesthesia may lead to impaired diaphragmatic contractility.

Anesthetics, Inhalation↗
PubMed1998

Comparison of two interferon alfa treatment regimens characterized by an early virological response in patients with chronic hepatitis C.

OBJECTIVE: We investigated the efficacy of an interferon regimen characterized by an early virological response in patients with chronic hepatitis C and evaluated whether the patient's virological status during therapy would be useful for predicting a complete response. METHODS: We treated 62 patients with chronic hepatitis C with 6 million units (MU) of human lymphoblastoid interferon daily for 4 wk. The serum HCV RNA was assayed at week 2 by the reverse transcription-polymerase chain reaction. HCV RNA-negative patients (group A) received 6 MU of interferon three times weekly for an additional 22 wk (total dose, 564 MU). HCV RNA-positive patients were randomly assigned to group B-1, which received the same regimen as group A, or to group B-2, which received 6 MU of interferon daily for 4 wk followed by 6 MU three times weekly for 18 wk (total dose, 660 MU). RESULTS: Complete responses were achieved by 19 (63.3%) of 30 group A patients, compared with one (6.3%) of 16 group B-1 patients and none of 16 group B-2 patients. The virological response at week 2 and the pretreatment serum HCV RNA level were independent significant predictors of a complete response. CONCLUSION: Patients who were still HCV RNA-positive at week 2 were unlikely to achieve a complete response after interferon therapy. An increase in the total dose of interferon failed to yield further benefit in these patients.

Adult↗
PubMed1997

In situ expression of PLP/DM-20, MBP, and CNP during embryonic and postnatal development of the jimpy mutant and of transgenic mice overexpressing PLP.

We analyzed by in situ hybridization the spatiotemporal expression of dm-20, myelin basic protein (MBP) and 2'-3' cyclic nucleotide phosphodiesterase (CNP) during embryonic and postnatal development of the normal mouse and two plp/dm-20 mutants: the jimpy mouse and a transgenic mouse overexpressing the plp gene. In the central nervous system (CNS) of the normal mouse, dm-20 mRNA was detected at embryonic day (E)9.5 in the laterobasal plate of the diencephalon. The pattern of expression of CNP transcript was superimposable on that of dm-20, but appeared slightly later, at E12.5. MBP mRNA was detected even later (E14.5), and, in addition, only in the caudal (rhombencephalon and spinal cord) territories of expression of dm-20 and CNP. These observations support our previous proposals: (1) dm-20-expressing cells in the germinative neuroepithelium are precursors of oligodendrocytes, and (2) oligodendrocytes emerge from distinct pools of precursors along the neural tube (Timsit et al., 1995). In the jimpy mutant, despite the mutation in the plp gene, cells of the oligodendrocyte lineage developed normally. It is only at the time of myelin deposition that oligodendrocytes die. During embryonic development of the transgenic mutant overexpressing plp, there were no alterations in the spatiotemporal pattern or the level of expression of dm-20 in the CNS, in contrast to the higher levels of dm-20 observed in the peripheral nervous system (PNS).

2',3'-Cyclic-Nucleotide Phosphodiesterases↗
PubMed1997

Immune system-related CD9 is expressed in mouse central nervous system myelin at a very late stage of myelination.

CD9 is a tetra-membrane-spanning glycoprotein involved in cell adhesion, migration, and proliferation in both the immune and the immature nervous system. In this study, CD9 expression was detected in myelin of mouse brain, starting at postnatal day 16. The amount of CD9 protein continuously increased with age and persisted in the adult brain. It appeared later than myelin proteolipid protein (PLP), a typical late myelin marker. Mature oligodendrocytes were abundant in CD9, although it was also detected in astrocytes and microglial cells in vitro. CD9 appeared at the end of the myelination process and was localized along the outermost membrane of compact myelin. CD9 is known to associate with integrins, which are candidate receptors for extracellular matrix and transmit extracellular signals into the cells. Taken together, CD9 at the surface of central nervous system (CNS) mature myelin may have a unique function to facilitate signal transduction and enhance myelin membrane adhesion to extracellular matrices at very late stages of development.

Animals↗
PubMed1997

Serum concentrations of soluble HLA-class I and CD8 forms in patients with viral hepatic disorders.

Soluble HLA-class I and CD8 molecules were determined by sandwich ELISA in patients with viral-induced hepatic disorders. As a whole, the patients with hepatic disorders (acute hepatitis: AH; chronic hepatitis: CH; liver cirrhosis: LC; hepatocellular carcinoma: HCC) showed higher sHLA-class I and sCD8 levels than normal controls (P < 0.001). AH patients had the highest sHLA-class I levels (mean, 3513 +/- 2112 ng/ml), followed by CH (2896 +/- 1290 ng/ml), LC (2293 +/- 1266 ng/ml), and HCC (2221 +/- 1212 ng/ml) sCD8 levels wer highest in AH, followed by HCC, LC, and CH, in that order. Among histologically defined C virus-positive patients, sHLA-I levels were higher in those with chronic active hepatitis (CAH) 2A (3802 +/- 1124 ng/ml) than in those with chronic persistent hepatitis (CPH; 2200 +/- 711 ng/ml; P < 0.01), the levels then decreased as the disease progressed (CAH2B, 3564 +/- 1783 ng/ml, LC, 2376 +/- 1265 ng/ml). In contrast, sCD8 values showed little difference among the disorders. sHLA-class I levels showed a positive correlation with sCD8 values both in whole patients and in patients with AH (P < 0.01), but no correlation was shown, in any patients, with biochemical parameters such as GPT and GOT. These findings, taken together, suggest that hepatic destruction is not the only cause of sHLA-class I production, but that sHLA-class I levels, together with sCD8 levels, may reflect immunological activity in hepatic disorders.

CD8 Antigens↗
PubMed1997

[Influence of preanesthetic medication on the effect of a local anesthetic tape].

We investigated the influence of preanesthetic medication on the pain relieving effect of the lidocaine tape during needle insertion for venous cannulation. Ninety patients scheduled for elective surgery were randomly divided into three groups of 30 each; patients without preanesthetic medication (group N), patients who received 0.1 mg.kg-1 of diazepam (group D) and 5 micrograms.kg-1 of clonidine (group C) as a preanesthetic medication. Ninety minutes before the induction of anesthesia, we applied a lidocaine tape to each patient. The grade of pain at the pinprick test and at the venous puncture was evaluated in the operating room. No significant difference of the pain score was seen between the groups. We concluded that the effect of lidocaine tape was not influenced by the preanesthetic medication.

Adjuvants, Anesthesia↗
PubMed1996

Cell death of oligodendrocytes or demyelination induced by overexpression of proteolipid protein depending on expressed gene dosage.

The transgenic mice, which were produced by introducing the wild type proteolipid protein (PLP) gene, revealed different neurological symptoms depending on expressed gene dosage. Homozygotes, which bore four more copies of the extra PLP gene, died before 4 weeks old with severe tremors and convulsions, while histologically hypomyelination and death of the oligodendrocytes were particularly noticeable. Heterozygotes, which bore two more copies and survived nearly 1 year, suffered from severe hindlimb palsy and bladder-rectal disturbances before death. These symptoms probably resulted from striking demyelination which occurred abruptly at a later stage of life. The heterozygous PLP-transgenic mice are thus available for a model of demyelination diseases.

Animals↗
PubMed1996

Effects of a single bout of exercise on glucose effectiveness.

The effects of a single bout of exercise on glucose effectiveness (SG) and insulin sensitivity (SI) in 22 sedentary subjects were estimated with a minimal model approach. The intravenous glucose tolerance test (IVGTT) was performed 1) 11 h after an exercise bout on a cycle ergometer at the lactate threshold level (mild exercise) for 60 min, 2) 11 h after an exercise bout at the 4 mM lactate level (hard exercise) for 36 +/- 1 min, 3) 11 h after an exhaustive-exercise bout (exhaustive exercise) for 96 +/- 7 min, or 4) without any prior exercise (control). Only the exhaustive exercise increased the glucose disappearance constant (2.69 +/- 0.28 vs. 2.05 +/- 0.13%/min; P < 0.05) and SI (15.0 +/- 2.0 vs. 10.3 +/- 0.9 x 10(-5) min/pM: P < 0.05) in comparison with the control condition. The SG and SG at zero insulin (GEZI) were not affected by any exercise condition. However, a marked individual difference in GEZI emerged after the exhaustive exercise and could be divided into two subgroups: one decreased in GEZI (0.014 +/- 0.001 vs. 0.007 +/- 0.001 min-1) and the other increased in GEZI (0.014 +/- 0.001 vs. 0.021 +/- 0.003 min-1). The former subgroup was accompanied by elevated levels of plasma creatine kinase (100 +/- 16 vs. 598 +/- 315 IU/l; P < 0.05) and myoglobin (Mb; 46 +/- 4 vs. 126 +/- 47 ng/ml; P < 0.05), whereas the latter subgroup showed no significant change in creatinine kinase (99 +/- 10 vs. 128 +/- 9 IU/l; P > 0.05) and Mb (50 +/- 7 vs. 51 +/- 4 ng/ml; P > 0.05). In both subgroups, SI was similarly increased after the exhaustive exercise. These results thus suggest that a single bout of exercise that results in muscle damage or changes in muscle permeability, as reflected in the increased creatine kinase and Mb levels, decreases GEZI, whereas exhaustive exercise without such alterations increases GEZI.

Adult↗