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Biomedical subjects

T Yamauchi

Publications and source records attributed to T Yamauchi.

At least 181 records · Page 10Linked to original sources

[Detection rate of TTV-DNA in healthy medical workers].

We examined the positive rate in healthy medical workers about TT virus (TTV) which was a new hepatitis virus reported in 1997. The healthy medical workers showed a positive rate of 24%. Because there was no significant difference of the positive rate between the medical workers and general healthy persons we could not conclude that the positive rate was influenced by their profession. Generally it is known that a positive rate changes according to PCR primers used for the measurement. As for TTV as well, it is reported that a positive rate is greatly dependent on the selected region of primer. Therefore, we must pay attention to the evaluation of the positive rate for each assay system, especially using different primers.

Adult↗

Successful treatment of cytomegalovirus retinitis in a patient with malignant lymphoma: a case report and review of the literature.

A 52-year-old Japanese woman was diagnosed as having angioimmunoblastic T-cell lymphoma (stage IV-B). She received 6 courses of chemotherapy including cyclophosphamide, doxorubicin, vincristine, and prednisolone every two weeks (biweekly CHOP), and was considered to be in partial remission. She complained of loss of visual acuity in her right eye during her last cycle of chemotherapy. Cytomegalovirus (CMV) retinitis was suspected from the characteristic ophthalmoscopic appearance. This diagnosis was further supported by the detection of CMV DNA in blood and antigens in polymorphonuclear leukocytes, a sign of CMV reactivation. Although DNAemia and antigenemia became negative, retinitis remained slightly active despite a 4-week systemic treatment of ganciclovir. Intraocular injection of ganciclovir was started and continued until the retinitis became inactive ophthalmoscopically. The patient received high-dose chemotherapy with peripheral blood stem cell transplantation and achieved complete remission. During the after this therapy no recurrence of CMV infections was observed. This case shows that 1) a quick and accurate diagnosis of CMV retinitis was possible by applying DNAemia and antigenemia and 2) intensive treatment for the CMV infection enabled the accomplishment of cure-oriented chemotherapy of the lymphoma without the recurrence of CMV retinitis.

Cytomegalovirus Retinitis↗

[Early phase II study of quetiapine fumarate on schizophrenia].

The efficacy and safety of quetiapine fumurate in the treatment of patients with schizophrenia were evaluated in an 8-week, multicenter, open-label study. The results of this study which included a total of 54 patients showed good efficacy and safety profile for quetiapine fumarate as seen by the improvement rate (moderate or above in the final global improvement rating) of 49.1% and safety rate (no problem in overall safety rating) of 66.0%. The mean BPRS total score decreased significantly from 55.5 +/- 10.9 points at baseline to 45.4 +/- 13.0 points at the completion of administration. The PANSS scores also showed significant improvement on all scales; the mean scores decreased from 20.7 +/- 6.3 points at baseline to 17.7 +/- 6.9 points at withdrawal or completion of administration on the positive scale, from 27.8 +/- 5.8 points to 24.0 +/- 7.3 points on the negative scale, and from 51.4 +/- 10.1 points to 44.7 +/- 12.4 points on the general psychopathology scale. Although the most frequent adverse reactions were somnolence (18.9%), insomnia (17.0%), nervousness (13.2%), dizziness (13.2%), malaise (13.2%), postural hypotension (11.3%), tachycardia (9.4%), and constipation (9.4%), the incidence of extrapyramidal symptoms was low (11.3%). From these results, quetiapine fumarate was suggested to be highly effective and safe for the treatment of schizophrenia.

Adult↗

[Giant psoas abscess with aggressive extension: report of a case].

We report a case of giant psoas abscess with aggressive extension outside the muscles of the iliopsoas component. A 57-year-old man was admitted to our hospital, presenting with right flank pain and severe general malaise. He had been diabetic, but no treatment had been performed for diabetes. Leukocytosis, positive CRP and hyperglycemia were noted, but he was nearly afebrile on admission. Computerized tomography revealed a large multilocular mass in the right retroperitoneal space involving the ipsilateral psoas muscle. The diagnosis was not apparent until the 12th hospital day, when moderate grade fever was noted and brownish purulent fluid was obtained by percutaneous puncture of the mass. Staphylococcus aureus was isolated on culture. Antibiotic chemotherapy was started, and ultrasound-guided percutaneous drainage was then performed under the diagnosis of psoas abscess. At that time, the abscess was aggressively extending from the iliopsoas component into the pelvic floor, involving the rectus muscle, the gluteal muscles and formation of subucutaneous lesions. At 46 days after drainage, surgical resection of the abscess with removal of the adjucent tissue was performed because of persistent discharge of pus and multiple residual lesions. The postoperative course was uneventful, and there has been no recurrence. Many cases of psoas abscess have been reported in the Japanese literature. Prompt drainage, either percutaneously or surgically are required. Surgical resection of the abscess, with not only opening the cavity but also removal of the adjacent tissue, may be recommended in some cases, especially those diffuse or multilocular lesions.

Anti-Bacterial Agents↗

[A case of multiple early gastric cancer showing complete response to UFT-E after endoscopic mucosal resection].

A 78-year-old male underwent endoscopic mucosal resection for early gastric cancer (type II a) in the anterior wall of antrum. Follow-up endoscopy showed another early gastric cancer (type II c) in the posterior wall of cardia. He refused an operation. UFT-E 300 mg/day has been administered daily since then. After 6 months, a complete tumor response was observed. The patient has been in good health without any sign of relapse for 14 months after achievement of the complete response.

Adenocarcinoma↗

Cerebrosides A and C, sphingolipid elicitors of hypersensitive cell death and phytoalexin accumulation in rice plants.

When plants interact with certain pathogens, they protect themselves by generating various chemical and physical barriers called the hypersensitive response. These barriers are induced by molecules called elicitors that are produced by pathogens. In the present study, the most active elicitors of the hypersensitive response in rice were isolated from the rice pathogenic fungus Magnaporthe grisea, and their structures were identified as cerebrosides A and C, sphingolipids that were previously isolated as inducers of cell differentiation in the fungus Schizophyllum commune. Treatment of rice leaves with cerebroside A induced the accumulation of antimicrobial compounds (phytoalexins), cell death, and increased resistance to subsequent infection by compatible pathogens. The degradation products of cerebroside A (fatty acid methyl ester, sphingoid base, and glucosyl sphingoid base) showed no elicitor activity. Hydrogenation of the 8E-double bond in the sphingoid base moiety or the 3E-double bond in the fatty acid moiety of cerebroside A did not alter the elicitor activity, whereas hydrogenation of the 4E-double bond in the sphingoid base moiety led to a 12-fold decrease in elicitor activity. Furthermore, glucocerebrosides from Gaucher's spleen consisting of (E)-4-sphingenine and cerebrosides from rice bran mainly consisting of (4E,8E)-4,8-sphingadienine and (4E,8Z)-4,8-sphingadienine showed no elicitor activity. These results indicate that the methyl group at C-9 and the 4E-double bond in the sphingoid base moiety of cerebrosides A and C are the key elements determining the elicitor activity of these compounds. This study is the first to show that sphingolipids have elicitor activity in plants.

Anti-Infective Agents↗

Growth hormone and prolactin stimulate tyrosine phosphorylation of insulin receptor substrate-1, -2, and -3, their association with p85 phosphatidylinositol 3-kinase (PI3-kinase), and concomitantly PI3-kinase activation via JAK2 kinase.

Growth hormone (GH) and prolactin (PRL) binding to their receptors, which belong to the cytokine receptor superfamily, activate Janus kinase (JAK) 2 tyrosine kinase, thereby leading to their biological actions. We recently showed that GH mainly stimulated tyrosine phosphorylation of epidermal growth factor receptor and its association with Grb2, and concomitantly stimulated mitogen-activated protein kinase activity in liver, a major target tissue. Using specific antibodies, we now show that GH was also able to induce tyrosine phosphorylation of insulin receptor substrate (IRS)-1/IRS-2 in liver. In addition, the major tyrosine-phosphorylated protein in anti-p85 phosphatidylinositol 3-kinase (PI3-kinase) immunoprecipitate from liver of wild-type mice was IRS-1, and IRS-2 in IRS-1 deficient mice, but not epidermal growth factor receptor. These data suggest that tyrosine phosphorylation of IRS-1 may be a major mechanism for GH-induced PI3-kinase activation in physiological target organ of GH, liver. We also show that PRL was able to induce tyrosine phosphorylation of both IRS-1 and IRS-2 in COS cells transiently transfected with PRLR and in CHO-PRLR cells. Moreover, we show that tyrosine phosphorylation of IRS-3 was induced by both GH and PRL in COS cells transiently transfected with IRS-3 and their cognate receptors. By using the JAK2-deficient cell lines or by expressing a dominant negative JAK2 mutant, we show that JAK2 is required for the GH- and PRL-dependent tyrosine phosphorylation of IRS-1, -2, and -3. Finally, a specific PI3-kinase inhibitor, wortmannin, completely blocked the anti-lipolytic effect of GH in 3T3 L1 adipocytes. Taken together, the role of IRS-1, -2, and -3 in GH and PRL signalings appears to be phosphorylated by JAK2, thereby providing docking sites for p85 PI3-kinase and activating PI3-kinase and its downstream biological effects.

Androstadienes↗

Effect of continuous infusion of vasopressin on glomerular growth response in spontaneously hypertensive rats.

Vasopressin (VP) is thought to play an important role in the pressor and proliferative responses of renal glomeruli. We have utilized the spontaneously hypertensive rat (SHR) model to determine if glomerular proliferation is induced by chronic infusion of exogenous VP. SHR were continuously infused with 0.1 ng/kg/min VP (H-VP group), 1.0 ng/kg/min (H-VP group), or vehicle alone (control group) for fifteen days using osmotic minipumps, and the histological alterations and level of expression of platelet-derived growth factor B-chain (PDGF-B) and transforming growth factor (TGF)-beta1 mRNA were determined. We observed no significant differences in systolic blood pressure, heart rate, serum electrolytes, protein and creatinine among the three groups of rats, but urine volume was found to be significantly decreased, and urine osmolality significantly increased, in the H-VP group. Kidney weight was significantly higher in the H-VP and L-VP groups than in the control group, and glomerular diameter was higher in the H-VP group. When we measured mesangial injury score and cellularity in the glomeruli of these animals, we observed VP dose-dependent proliferative changes. In the immunofluorescence study, although we did not find an obvious difference in depositions of collagen types III, IV and VI, alpha-smooth muscle actin and PDGF-B among the groups, the collagen type I and TGF-beta1 increased in several glomeruli in the H-VP group. Reverse transcription polymerase chain reaction (RT-PCR) revealed no significant differences in the glomerular levels of PDGF-B mRNA among the three groups of rats, but the level of expression of TGF-beta1 mRNA was significantly higher in the L-VP and H-VP groups than in the control group. These findings suggest that VP may contribute to glomerular proliferation, and that VP may exert its effects in part through the induction of TGF-beta1 expression. These results also raise the possibility that blockade of VP receptors may be useful in the treatment of some forms of glomerular disease.

Animals↗

Regional differences between the immunohistochemical distribution of Ca2+/calmodulin-dependent protein kinase II alpha and beta isoforms in the brainstem of the rat.

The distribution of Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) alpha and beta isoforms in the brainstem of adult rats was investigated using an immunohistochemical method with two monoclonal antibodies which specifically recognize the alpha and beta isoform, respectively. We found that these isoforms were differentially expressed by neurons in the substantia nigra, red nucleus, dorsal cochlear nucleus, pontine nuclei and inferior olivary nucleus. Neurons in the inferior olivary nucleus express the alpha isoform, but not the beta isoform. In contrast, neurons in the substantia nigra, red nucleus and pontine nuclei were immunostained with the beta antibody, but not with the alpha antibody. In the dorsal cochlear nucleus, neurons in layers I and II were alpha-immunopositive, whereas neurons in layers III and IV were beta-immunopositive. Therefore, the distribution of the CaM kinase II alpha-immunopositive neurons is completely different from that of CaM kinase II beta-immunopositive neurons. Next we examined the possible coexistence of CaM kinase II alpha isoform and glutamate or that of CaM kinase II beta isoform and glutamic acid decarboxylase (GAD) in the single neuron by double immunofluorescence labelling using a pair of anti-alpha and anti-glutamate antibodies, or a pair of anti-beta and anti-GAD antibodies. The results indicated that neurons expressing anti-alpha immunoreactivity were also immunopositive against anti-glutamate antibody, and neurons expressing beta isoform were also immunopositive against anti-GAD antibody, suggesting that alpha-immunopositive neurons are classified as excitatory-type neurons, and on the contrary, beta-immunopositive neurons are classified as inhibitory-type neurons. In conclusion, the present study confirmed that alpha- and beta-isoforms of CaM kinase II are differentially expressed in the nuclei of the brainstem and have different roles.

Animals↗

Potential role of protein kinase B in insulin-induced glucose transport, glycogen synthesis, and protein synthesis.

Various biological responses stimulated by insulin have been thought to be regulated by phosphatidylinositol 3-kinase, including glucose transport, glycogen synthesis, and protein synthesis. However, the molecular link between phosphatidylinositol 3-kinase and these biological responses has been poorly understood. Recently, it has been shown that protein kinase B (PKB/c-Akt/Rac) lies immediately downstream from phosphatidylinositol 3-kinase. Here, we show that expression of a constitutively active form of PKB induced glucose uptake, glycogen synthesis, and protein synthesis in L6 myotubes downstream of phosphatidylinositol 3-kinase and independent of Ras and mitogen-activated protein kinase activation. Introduction of constitutively active PKB induced glucose uptake and protein synthesis but not glycogen synthesis in 3T3L-1 adipocytes, which lack expression of glycogen synthase kinase 3 different from L6 myotubes. Furthermore, we show that deactivation of glycogen synthase kinase 3 and activation of rapamycin-sensitive serine/threonine kinase by PKB in L6 myotubes might be involved in the enhancement of glycogen synthesis and protein synthesis, respectively. These results suggest that PKB acts as a key enzyme linking phosphatidylinositol 3-kinase activation to multiple biological functions of insulin through regulation of downstream kinases in skeletal muscle, a major target tissue of insulin.

3T3 Cells↗

Endothelin 1 aggravates acute liver injury in perfused livers of rats after treatment with D-galactosamine.

The effects of endothelin 1 (ET-1) on hemodynamics and acute liver damage were studied using perfused livers of rats treated with D-galactosamine. In control liver perfused in situ with constant pressure, infusion of ET-1 into the portal vein at a concentration of 0.1 nmol/L decreased the flow rate without a significant leakage of lactate dehydrogenase (LDH) or aspartate transaminase (AST) into the effluent. In contrast, in similarly perfused liver 24 hours after treatment with D-galactosamine (800 mg/kg intraperitoneally), ET-1 caused rapid and remarkable increases in the leakage of LDH and AST from the liver accompanied by the reduction of perfusion flow to the extent similar to that observed in control livers. In addition, ET-1 decreased oxygen uptake and bile secretion in galactosamine-treated livers. The potentiating effects of ET-1 on enzyme leakage were also observed under constant flow conditions. Moreover, infusion of the thromboxane A2 analogue at a concentration of 10 nmol/L decreased the flow rate markedly, yet the rapid increases in enzyme leakage were not observed. Infusion of ET-3 induced the responses of flow reduction and the potentiation of rapid enzyme leakage similar to those obtained with ET-1. Neither the endothelin A-receptor antagonist BQ485 nor the endothelin B-receptor antagonist BQ788 could inhibit the acute liver damage caused by ET-1; instead they exaggerated its effects. The combination of both antagonists together, however, almost completely suppressed the flow reduction and the potentiation of enzyme leakage caused by ET-1. These results indicate that ET-1 is capable of aggravating acute liver damage not merely through reduction of the flow rate but through direct action on liver cells. They also suggest that both the endothelin A and endothelin B receptors are involved in this action of ET-1.

Acute Disease↗

Effect of exercise-induced acidosis on aldosterone secretion in men.

The present study was carried out to elucidate whether an exercise-induced increase in plasma hydrogen ion concentration influences aldosterone secretion. Six healthy men (aged 22-25 years) performed two intermittent exercise tests with and without drug administration. The intensities of these exercise tests were 40% maximal oxygen uptake (VO2max) and 90% VO2max, respectively. Administration of 2-mg Dexamethasone and 50-mg Captopril caused an almost complete suppression of adrenocorticotropic hormone (ACTH) and an enhancement of the elevation in renin concentration during exercise, indicating successful inhibition of ACTH release and angiotensin II production during exercise. While the magnitude of the increase in aldosterone in the drug experiment was depressed compared with the control experiment, a significant increase in aldosterone concentration was observed at the end of the 90% VO2max exercise. Whilst the change in aldosterone concentration did not correlate with the change in plasma potassium concentration, there was a significant correlation between aldosterone and plasma hydrogen ion concentrations in the drug experiment. Since the correlation coefficient was low (r = 0.455), the biological meaning of this correlation should be further investigated. These results would suggest that an elevation of plasma hydrogen ion concentration induced by exercise per se appears to be related, at least in part, with increased aldosterone secretion, independent of the pituitary-adrenal axis, and the renin-angiotensin system.

Acidosis↗

Noradrenaline and ATP decrease the secretion of triglyceride and apoprotein B from perfused rat liver.

To explore the role of hepatic sympathetic nerves on the secretion of very low density lipoprotein (VLDL), the effects of sympathetic neurotransmitters, noradrenaline and ATP, on the secretion of triglyceride and apoprotein B (ApoB) from the liver were studied using rat liver perfused in situ with recirculation. During liver perfusion with physiological medium, the amount of triglyceride in the perfusate was increased linearly for up to 120 min. The addition of noradrenaline to the perfusion medium at a final concentration of 1 muM increased the portal pressure and suppressed the secretion of triglyceride to about 60% of control without an increase in free fatty acid production. The administration of ATP increased the portal pressure with kinetics different from those induced by noradrenaline, but suppressed the triglyceride secretion to an extent similar to that induced by noradrenaline. The suppressive effect of noradrenaline on triglyceride secretion was mimicked by an alpha-adrenoceptor agonist, phenylephrine, and was retained after the haemodynamic changes were prevented by sodium nitroprusside. The secretion of ApoB from the perfused liver was also inhibited by noradrenaline or ATP to about 70% of control. However, hepatic levels of mRNA for ApoB were not significantly altered by noradrenaline and ATP. Since ApoB is the major apoprotein in VLDL, these results suggest that the sympathetic neurotransmitters noradrenaline and ATP suppress the secretion of ApoB-containing lipoprotein including VLDL from the liver, probably acting on post-transcriptional processes.

Adenosine Triphosphate↗

Phosphorylation-dependent reversible translocation of Ca2+/calmodulin-dependent protein kinase II to the postsynaptic densities.

The translocation of soluble Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) to postsynaptic densities (PSDs) was investigated. When soluble CaM kinase II previously autophosphorylated was incubated with PSDs, the kinase was precipitated by centrifugation, indicating that the soluble kinase associated with PSDs and formed a PSD-CaM kinase II complex. Ca2+-independent activity generated by autophosphorylation of the kinase was retained in the complex. A number of PSD proteins were phosphorylated by the kinase associated with PSDs in both the absence and presence of Ca2+. When PSD-CaM kinase II complex was incubated at 30 degrees C, the enzyme was dephosphorylated and released from the complex. These results indicate that CaM kinase II reversibly translocates to PSDs in a phosphorylation-dependent manner.

Animals↗