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Biomedical subjects

T Yamauchi

Publications and source records attributed to T Yamauchi.

At least 163 records · Page 9Linked to original sources
PubMed1999

Treatment with a Ca(2+) channel blocker, barnidipine, reduces platelet-derived growth factor B-chain mRNA in glomeruli of spontaneously hypertensive rats.

We investigated the effect of barnidipine hydrochloride, a Ca(2+) channel blocker, on the glomerular level of mRNA expression of platelet-derived growth factor (PDGF) B-chain and transforming growth factor (TGF)-beta(1) in spontaneously hypertensive rats (SHR) with reverse transcription and polymerase chain reaction. Thirteen-week-old SHR were provided with food containing barnidipine (0.6 mg/g of food, average dose during treatment: 53 mg/kg of body mass/day) for 3 weeks. A stable reduction in systolic blood pressure relative to that of age-matched control SHR was recorded after week 1 of therapy. Although no renal histological changes were observed after 3 weeks of treatment with barnidipine, the level of expression of PDGF B-chain mRNA in glomeruli was significantly reduced relative to that in control SHR. The glomerular level of TGF-beta(1) mRNA expression was not affected by the treatment. Treatment with barnidipine significantly reduced the excretion of urinary protein. Thus, the stable reduction in systemic blood pressure by barnidipine is associated with a reduction in PDGF B-chain mRNA expression in the glomerulus and reduction in urinary protein excretion in SHR.

Animals↗
PubMed1999

Glucose or diabetes activates p38 mitogen-activated protein kinase via different pathways.

Hyperglycemia can cause vascular dysfunctions by multiple factors including hyperosmolarity, oxidant formation, and protein kinase C (PKC) activation. We have characterized the effect of hyperglycemia on p38 mitogen-activated protein (p38) kinase activation, which can be induced by oxidants, hyperosmolarity, and proinflammatory cytokines, leading to apoptosis, cell growth, and gene regulation. Glucose at 16.5 mM increased p38 kinase activity in a time-dependent manner compared with 5.5 mM in rat aortic smooth muscle cells (SMC). Mannitol activated p38 kinase only at or greater than 22 mM. High glucose levels and a PKC agonist activated p38 kinase, and a PKC inhibitor, GF109203X, prevented its activation. However, p38 kinase activation by mannitol or tumor necrosis factor-alpha was not inhibited by GF109203X. Changes in PKC isoform distribution after exposure to 16.5 mM glucose in SMC suggested that both PKC-beta2 and PKC-delta isoforms were increased. Activities of p38 kinase in PKC-delta- but not PKC-beta1-overexpressed SMC were increased compared with control cells. Activation of p38 kinase was also observed and characterized in various vascular cells in culture and aorta from diabetic rats. Thus, moderate hyperglycemia can activate p38 kinase by a PKC-delta isoform-dependent pathway, but glucose at extremely elevated levels can also activate p38 kinase by hyperosmolarity via a PKC-independent pathway.

Adenoviridae↗
PubMed1999

Characterization of selective resistance to insulin signaling in the vasculature of obese Zucker (fa/fa) rats.

Both insulin resistance and hyperinsulinemia have been reported to be independent risk factors for cardiovascular diseases. However, little is known regarding insulin signaling in the vascular tissues in insulin-resistant states. In this report, insulin signaling on the phosphatidylinositol 3-kinase (PI 3-kinase) and mitogen-activated protein (MAP) kinase pathways were compared in vascular tissues of lean and obese Zucker (fa/fa) rats in both ex vivo and in vivo studies. Ex vivo, insulin-stimulated tyrosine phosphorylation of insulin receptor beta subunits (IRbeta) in the aorta and microvessels of obese rats was significantly decreased compared with lean rats, although the protein levels of IRbeta in the 2 groups were not different. Insulin-induced tyrosine phosphorylation of insulin receptor substrates 1 and 2 (IRS-1 and IRS-2) and their protein levels were decreased in the aorta of obese rats compared with lean rats. The association of p85 subunit to the IRS proteins and the IRS-associated PI 3-kinase activities stimulated by insulin in the aorta of obese rats were significantly decreased compared with the lean rats. In addition, insulin-stimulated serine phosphorylation of Akt, a downstream kinase of PI 3-kinase pathway, was also reduced significantly in isolated microvessels from obese rats compared with the lean rats. In euglycemic clamp studies, insulin infusion greatly increased tyrosine phosphorylation of IRbeta- and IRS-2-associated PI 3-kinase activity in the aorta of lean rats, but only slight increases were observed in obese rats. In contrast, insulin stimulated tyrosine phosphorylation of MAP kinase (ERK-1/2) equally in isolated microvessels of lean and obese rats, although basal tyrosine phosphorylation of ERK-1/2 was higher in the obese rats. To our knowledge, these data provided the first direct measurements of insulin signaling in the vascular tissues, and documented a selective resistance to PI 3-kinase (but not to MAP kinase pathway) in the vascular tissues of obese Zucker rats.

Animals↗
PubMed1999

Smoothness of human jaw movement during chewing.

Human limb movements are successfully modeled based on the assumption that the central nervous system controls the movements by maximizing movement smoothness. Movement smoothness is quantified by means of a time integral of squared jerk (jerk-cost), where jerk is defined as the rate of change in acceleration. This study was performed to investigate whether the control of human masticatory vertical jaw movements can also be explained by a minimum-jerk (maximum-smoothness) model. Based on the assumption that minimum-jerk models account for vertical jaw-opening and -closing movements during chewing, the actual time profile of the movement trajectory was simulated by the model. The simulated jerk-costs and peak velocities were compared with those obtained by actual measurements of jaw movements during chewing. Jerk-costs and peak velocities of the jaw movements during chewing were significantly correlated with those predicted by minimum-jerk models (P < 0.0001, r between 0.596 and 0.799). The minimum-jerk models predicted closing movement trajectories more accurately than opening movement trajectories (jaw opening, root-mean-square error = 1.19 mm; jaw closing, 0.52 mm, t = 4.375, P < 0.0001). The results indicated that the vertical jaw movement control during chewing was represented by the minimum-jerk control model and that the vertical jaw-closing movement is smoother than the opening movement during gum-chewing.

Adult↗
PubMed1999

Electron microscopic in situ DNA nick end-labeling in combination with immunoelectron microscopy.

We describe an in situ DNA nick end-labeling method that can be performed at the electron microscopic level and can also be combined with immunoelectron microscopy. As the materials, we used skin tissues from normal skin and from Bowen's disease that had been cryofixed, freeze-substituted, and embedded in Lowicryl K11M resin. Ultrathin sections were cut and incubated with a reaction buffer containing digoxigenin-dUTP and terminal deoxynucleotidyl transferase. Digoxigenin nucleotides were labeled with anti-digoxigenin antibodies conjugated with colloidal gold. Specific signals were detected in the condensed chromatin of differentiated epidermal cells and hair follicles in normal skin and of dyskeratotic cells in Bowen's disease. The labeling density over chromosomal areas of apoptotic cells was significantly higher than that over chromosomal areas of mitotic cells or cytoplasmic areas. Ultrastructure was well preserved and double staining with an anti-keratin antibody was also successfully performed. This simple method has a wide range of applications to identify the nature of apoptotic cells and explore the mechanisms of apoptosis.

Adult↗
PubMed1999

Pregnanes and pregnane glycosides from Hoya carnosa.

Eleven pregnanes were isolated from the hydrolysate of the CHCl3 extract fractionated from the caules of Hoya carnosa. Among these, six pregnanes, including 19-acetoxydigipurpurogenin II, were new, and their structures were elucidated. The structures of twenty new pregnane tetraosides and pentaosides, named hoyacarnosides A-T, besides three known ones from the CHCl3 extract, were determined.

Carbohydrate Sequence↗
PubMed1999

Giant insulinoma in a patient with multiple endocrine neoplasia-type I: a case report.

We report a case of giant cystic insulinoma constituting part of multiple endocrine neoplasia (MEN) type I. A 29-year-old Japanese man presented with a history of recurrent hypoglycemic attacks. Endocrine examination showed hyperinsulinemia discordant with hypoglycemia, and a giant cystic insulinoma (11 x 10 cm) located in the pancreatic tail was detected radiologically. Hyperprolactinemia due to pituitary adenoma and hyperparathyroidism due to parathyroid hyperplasia were also present. The insulinoma, prolactinoma and hyperplastic parathyroid gland were surgically removed. Fluorescent microsatellite analysis detected loss of heterozygosity (LOH) in chromosome 11q13 in DNA samples from all resected tissues but not from white blood cells. This is a rare case of MEN type I because of the giant cystic insulinoma and the evidence of common LOH detected in all MEN type I tissues.

Adult↗
PubMed1999

The mechanism of insulin-induced signal transduction mediated by the insulin receptor substrate family.

Distinct from other growth factor receptors, insulin and insulin-like growth factor-I (IGF-I) receptors phosphorylate endogenous substrates on tyrosine residues which in turn associate with the SH2 domain-containing proteins transducing signals to downstream pathways. Among the cellular substrates of insulin and IGF-I receptors, insulin receptor substrate (IRS)-1 has been shown to play an important role in mediating the actions of these hormones. Recently, several proteins with similar structures and different tissue distributions were cloned as IRS-2, -3 and -4. To study the roles of these IRSs in mediating insulin actions, we analyzed liver, muscle and adipocytes, the major targets of insulin actions, from IRS-1 null mice which we previously generated, and showed that: 1) insulin-stimulated activation of PI 3-kinase, mitogen-activated protein kinase and glucose transport were impaired in muscles from IRS-1 null mice which was in contrast to the grossly normal signaling and actions in livers from these mice; 2) the difference in the degree of insulin resistance in these two major insulin targets appeared to depend on the amount of tyrosine phosphorylation of IRS-2 compensating for IRS-1 deficiency; 3) insulin-induced activation of PI 3-kinase, glucose transport and GLUT4 translocation were impaired but not abolished in adipocytes from these mice in which IRS-3 was the major tyrosine-phosphorylated protein activating PI 3-kinase and at least partially mediating some residual insulin actions in the absence of IRS-1. These data suggest that the members of the IRS family redundantly regulate insulin actions in each target organ in a distinct fashion.

Adipocytes↗
PubMed1999

Developmental retardation of XO mouse embryos at mid-gestation.

It is not known why XO mouse embryos, which develop more slowly than XX embryos until early mid-gestation, reach the same stage in their growth and development as their XX littermates at the mid-gestation stage. It is hypothesized that there is an effect of 'litter size' that causes an acceleration of the development of XO embryos at mid-gestation. The present study was performed to determine whether the development of XO embryos is retarded compared with that of their XX litermates at early mid-gestation (day 8 of gestation), before reduction of litter size. The percentage of pre-somite stage XO embryos was greater than the percentage of pre-somite stage XX embryos, and the mean number of somites was greater in XX embryos than it was in XO embryos. These findings indicate that the development of XO embryos was retarded when compared with that of their XX litermates at early mid-gestation. This result is discussed with respect to the compensatory development of XO embryos at mid-gestation and the reduction of litter size shortly after early mid-gestation.

Animals↗
PubMed1999

Paraganglioma in the frontal skull base--case report.

A 56-year-old female presented with a paraganglioma in the left anterior cranial fossa who manifesting as persistent headache. Computed tomography and magnetic resonance imaging showed a solid, enhanced tumor with a cystic component located medially. The tumor was attached to the left frontal base and the sphenoid ridge. Angiography demonstrated a hypervascular tumor fed mainly by the left middle meningeal artery at the left sphenoid ridge. The preoperative diagnosis was meningioma of the left frontal base. The tumor was totally resected via a left frontotemporal craniotomy. Histological examination revealed the characteristic cellular arrangement of paraganglioma generally designated as the "Zellbaren pattern" on light microscopy. Only 10 patients with supratentorial paraganglioma have been reported, seven located in the parasellar area. The origin of the present tumor may have been the paraganglionic cells which strayed along the middle meningeal artery at differentiation.

Cerebral Angiography↗
PubMed1999

Saline-jet aspiration thrombectomy catheter. Clinical results in patients with venous thrombosis.

PURPOSE: To evaluate hydraulic thrombectomy using a saline-jet aspiration thrombectomy catheter in the treatment of venous thrombosis. MATERIAL AND METHODS: Ten patients underwent 12 hydraulic thrombectomy procedures using 2.7 or 4.0 mm catheters. The site of the thrombus was either central, peripheral or in portal veins. The age of the thrombi was between 2 and 60 days (mean 19.7 days). The efficacy of hydraulic thrombectomy was evaluated based on the aspirated thrombus ratio (ATR), i.e. the volume of the thrombus aspirated divided by the volume of the thrombus before thrombectomy. ATR was estimated by comparing the angiograms of the lesion before and after thrombectomy. RESULTS: Soft thrombi were usually rapidly removed. ATR was >2/3 in 3, 2/3-1/3 in 2, 1/3-0 in 4, and 0 in 1 patient. The activation time of the injector was 23-224 s (mean 102 s) and the volume of aspirated blood was 30-680 ml (mean 250 ml). Compensatory infusion of saline was performed for blood loss, and 400 ml of packed red blood cells was transfused in 1 patient. No complications of the hydraulic thrombectomy were observed. Thrombolysis or additional treatment were performed in 9 patients. CONCLUSION: Hydraulic thrombectomy using this catheter can contribute to the treatment of venous thrombosis.

Equipment Design↗
PubMed1999

Stereoisomers of glutathione: preparation and enzymatic reactivities.

We synthesized a series of stereoisomers of glutathione (GSH) and glutathione disulfide (GSSG) by the solid-phase method. These peptides were used to examine their reactivities with enzymes acting on glutathione. The glutathione reductase of yeast acted only on LL-GSSG. Glutathione S-transferase catalyzed the conjugation of 1-chloro-2,4-dinitrobenzene with LL-GSH and DL-GSH (Km (mM): for LL-GSH, 0.035; and for DL-GSH, 0.62), but the DD- and LD-diastereomers were inert. gamma-Glutamyl transpeptidase catalyzed the transfer of gamma-glutamyl moiety of LL-GSH and DL-GSH to taurine forming gamma-glutamyl taurine and cysteinyl taurine (Km (mM): for LL-GSH, 0.336; and for DL-GSH, 0.628), but the other diastereomers were not the substrates. The occurrence of L-cysteinyl residue in the tripeptides is required for the glutathione analogue to be a substrate of the enzymes.

Chromatography, High Pressure Liquid↗
PubMed1999

Successful salvage treatment with irinotecan (CPT-11) of recurrent malignant lymphoma in an aged patient; and CPT-11 pharmacokinetics.

A 72-year-old patient with relapsed non-Hodgkin's lymphoma (diffuse large B-cell type) in the tongue was treated with irinotecan (CPT-11) as the 4th salvage therapy. A two-thirds reduced dose of 40 mg/m2 of CPT-11 was administered, as were granulocyte-colony stimulating factor and antidiarrheal agents. Complete remission was achieved. Although grade 3 leukopenia and grade 1 diarrhea were observed, these adverse reactions did not interrupt the treatment schedule and CPT-11 was administered without interruption for a total of 12 weeks. Despite the dose reduction, the area under the concentration-time curve of SN-38, the active metabolite of CPT-11, was nearly equal to the values reported in phase I and II studies of CPT-11. The patient's ratio of SN-38 to the SN-38 glucuronide (SN-38G) was low, suggesting a low risk of diarrhea. The optimal dose modification provided a sufficient amount of the active metabolite. Supportive therapy managed therapy-related toxicities and resulted in a stable treatment schedule. This is a rare case of a patient successfully treated with CPT-11 after a 4th relapse, in which the agent was administered at the total dose of 960 mg/m2, despite the patient's advanced age.

Aged↗
PubMed1999

[Present situation of medical care for foreigners at medical facilities in Chiba City].

OBJECTIVE: The number of foreigners residing in Japan has increased during the past decade. The aim of this survey was to clarify the present situation and the disadvantages in the medical care for foreigners. METHODS: In October 1997, we mailed a questionnaire to all clinics and hospitals in Chiba City. The questionnaire included questions regarding the number of foreign patients who visited during the past three months, the proportion of patients who have any health insurance, procedures for handling foreign patients, and the disadvantages in medical care for them. RESULTS: Of the 210 respondents (183 clinics and 27 hospitals), 133 facilities (63.3%) provided medical care for foreign patients during the past three months, and 187 (89.0%) during the past year. In 102 facilities (76.7%), the number of foreign patients was fewer than 10 during the past three months. The mean number of foreign patients was 13.8 per facility (12.2 per clinic, and 23.5 per hospital). Of these foreign patients, 68.6% had any health insurance. In 172 facilities (81.9%), foreign patients were accepted in the same way as the Japanese. The main disadvantages in medical care for foreigners were difficulty in understanding because of communication problems, and default in payment of medical expenses for the foreigners with no health insurance. In 154 facilities (73.3%), no special preparation to communicate with foreign patients was provided, and few facilities could understand foreign languages except for English. In 20 facilities, fees for medical care had been left unpaid by foreign patients during the past year, and the total outstanding amount was about 23,800,000 yen. CONCLUSION: In Chiba City, many medical facilities provide medical care for foreign patients. This study suggests that support for communication with foreigners and compensation for default in medical expenses are necessary.

Communication↗
PubMed1999

[Minimum intensity projection image and curved reformation image of the main pancreatic duct obtained by helical CT in patients with main pancreatic duct dilation].

Contrast enhanced CT was performed in seven patients with pancreatic disease (chronic pancreatitis, n = 3; pancreatic head cancer, n = 2; mucin-producing pancreatic tumor, n = 2) who showed dilation of the main pancreatic duct (MPD) Minimum intensity projection (Min-IP) images of the pancreas were obtained using multi-projection volume reconstruction (MPVR) software by selecting an oblique slab that contained the entire MPD. Curved reformation (CR) images were obtained using multiplanar reformation (MPR) software by tracing the MPD on the Min-IP image. Both Min-IP images and CR images clearly showed the dilated main pancreatic duct in all seven patients. In three of the seven, obstruction of the MPD in the pancreatic head and the cause of obstruction (tumor mass, n = 2; caliculus, n = 1) were also clearly seen. Min-IP and CR images seem to be useful for the diagnosis of pancreatic diseases.

Chronic Disease↗
PubMed1999

[Development of the quantification method of TTV-DNA and clinical application].

We developed a method to measure the quantity of TTV-DNA. This measurement is based on the principle of the real time PCR method using the TaqMan probe. By measuring the change of the fluorescent intensity caused by FRET, we could detect the amount of TTV-DNA. This method has the characteristics that the possibility of the contamination is very rare when it is compared with the usual PCR method, because the reaction system contains UNG and dUTP. This quantification method is useful for the future research of TTV to study the relationship between this virus and diseases.

Biomarkers↗
PubMed1999

[Virological response to interferon therapy in patients dually infected with TT virus and hepatitis C virus].

In 30 chronic hepatitis C patients co-infected with TTV, TTV DNA in the sera immediately after cessation of IFN and 6 months after the end of IFN was examined. Sustained loss of TTV DNA was observed in 12 of 30 (40.0%) patients. In 7 of 30 (23.3%) patients, TTV DNA re-appeared 6 months after becoming undetectable at the end of IFN therapy. In the remaining 11 patients (36.7%), TTV DNA remained detectable during the entire follow-up period. The ALT values correlated only with the presence of HCV RNA regardless of the effect of IFN on TTV replication. This study indicates that IFN therapy is effective against TTV.

Adult↗