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Biomedical subjects

Y Sato

Publications and source records attributed to Y Sato.

At least 91 records · Page 5Linked to original sources

Insulin-nonspecific reduction in skeletal muscle glucose transport in high-fat-fed rats.

High-fat feeding diminishes insulin-stimulated glucose transport in skeletal muscle. However, conflicting results are reported regarding whether phosphatidylinositol (PI)-3 kinase-independent glucose transport is also impaired in insulin-resistant high-fat-fed rodents. The aim of the present study was to study whether non-insulin-dependent mechanisms for stimulation of glucose transport are defective in skeletal muscle from high-fat-fed rats. Rats were fed normal chow diet or high-fat diet for 4 weeks and isolated epitrochlearis muscles were used for measuring glucose transport. Insulin-stimulated glucose transport was significantly lower in rats fed the high-fat diet compared with chow-fed rats (P < .05). Hypoxia-stimulated glucose transport was also reduced in high-fat-fed rats (P < .05). Nevertheless, hypoxia-stimulated adenosine monophosphate-activated protein kinase (AMPK) phosphorylation (Thr172) level was not affected by high-fat feeding. Glucose transport by sodium nitroprusside stimulation was reduced in high-fat-fed rats (P < .05). Protein content of glucose transporter (GLUT)-4 and AMPK-alpha, and glycogen content were comparable between both groups. Our findings provide evidence that high-fat feeding can affect not only insulin but also non-insulin-stimulated glucose transport. A putative defect in common steps in glucose transport may play a role to account for impaired insulin-stimulated glucose transport in rats fed a high-fat diet.

Adenylate Kinase↗

Transforming growth factor-beta signaling is enhanced following mitomycin-C treatment of islet xenograft.

Mitomycin-C (MMC) is categorized as an agent that causes genotoxic stress by triggering various intracellular signaling pathways. We have previously shown that MMC pretreatment of highly immunogenic crude islets leads to significant prolongation of graft survival in a rat-to-mouse model. In the present study, we examined whether TH1/TH2 cytokine, including the inflammatory cytokines interferon-gamma and interleukin (IL)-2, or the Th2 group, IL-4, IL-10, TNF-alpha, IL-1 beta, IL-6, GM-CSF, and transforming growth factor (TGF)-beta were up-regulated or down-regulated following MMC treatment of islets. We found changes in TGF-beta messenger RNA (mRNA) transcription as the only events among the measured cytokines. TGF-beta concentration was elevated in blebs formed under the kidney capsule, but not in the serum or ascites among animals given MMC-treated islets than in animals given untreated islets, suggesting local processes induced by MMC might inhibit xenograft rejection.

Animals↗

A novel method for determination of ATP, ADP, and AMP contents of a single pancreatic islet before transplantation.

Assessment of islet viability before transplantation is mandatory for successful clinical transplantation. ATP content or energy charge (EC) of islets may represent a good parameter to assess viability. We have introduced a novel bioluminescent enzymatic cycling assay using synthetic firefly luciferase, pyruvate kinase) (PK), and pyruvate orthophosphate dikinase (PPDK) to determine adenine nucleotides (AN) in isolated islets. A complete assay requires several minutes. The ATP contents of 1, 3, 10, 30 or 100 islets each with a diameter of 150 microm were 9.95 +/- 0.03, 28.3 +/- 1.18, 89.5 +/- 1.48, 282 +/- 10.2, and 673 +/- 27.1 pmol, respectively, showing a relatively constant ATP content per 30 islets (9.95, 9.42, 8.95, and 9.41 pmol/IEQ). ECs of each group were 0.74 +/- 0.02, 0.74 +/- 0.02, 0.75 +/- 0.02, 0.74 +/- 0.02, and 0.65 +/- 0.01, respectively, a value that was quite constant up to 30 islets. The quantity of ATP and EC in a single islet can be measured quickly and reproducibly, offering a new method to determine viability of isolated islets prior to transplantation.

Adenosine Diphosphate↗

Decreased proteinuria following liver transplantation in a patient with type C liver cirrhosis complicated with nephrotic syndrome: a case report.

Type C liver cirrhosis is often associated with a nephrotic syndrome secondary to membranoproliferative glomerulonephritis. Liver transplantation in such patients may sometimes worsen viremia, causing renal dysfunction upon the introduction of immunosuppressive drugs. We present a case of a patient whose proteinuria decreased after liver transplantation. The patient was a 49-year-old male who had been followed due to chronic hepatitis type C from 1984. From 1999 he was diagnosed as having nephrotic syndrome. We performed a living related liver transplant on August 21, 2001. An intraoperative renal biopsy revealed the histology to show membranoproliferative glomerulonephritis. The volume of proteinuria was 2 to 11 g/day before surgery. After surgery it varied from 6 to 10 g/day, gradually decreasing to 1 to 2 g/day. One of the causes of reduced proteinuria may be alleviation of membranoproliferative glomerulonephritis by immunosuppression. But from the view that the recovery of the renal function followed the recovery of liver function, the major effect may have been alleviated hepatorenal syndrome.

Biopsy↗

Changes in serum LECT 2 levels during the early period of liver regeneration after adult living related donor liver transplantation.

We investigated changes in serum leukocyte cell-derived chemotaxin2 (LECT2) levels between donors and recipients in the early period during liver regeneration following adult living related donor liver transplantation (LRDLT). Five recipients (three women, two men; 37.0 +/- 15.8 years old), all of whom had end-stage liver failure, underwent LRDLT from healthy five donors (two women, three men; 41.6 +/- 14.3 years old) between June 2000 and February 2001. FK506 and methylprednisolone were used as immunosuppressants for recipients. Serum LECT2 levels decreased immediately after both the hepatectomy in all donors and the implantation of liver graft in all recipients. Donors showed a nadir at 3 to 12 hours, increasing at 24 to 48 hours. The nadir in recipients occurred several hours after the donors. The serum LECT2 levels of donors were significantly higher than those of recipients on day 5 (9.5 +/- 5.9 ng/mL vs 3.1 +/- 2.2 ng/mL, P = .04) and on day 7 (9.3 +/- 3.8 ng/mL vs 3.5 +/- 1.1 ng/mL, P = .04). Serum GPT and GOT levels were inversely proportionate to the serum LECT2 levels. The present studies suggest that LECT2 participates in liver regeneration and injury following hepatectomy.

Adult↗

Serum LECT2 level as a prognostic indicator in acute liver failure.

In the present study, we investigated the relationship between serum leukocyte cell-derived chemotaxin2 (LECT2) levels and liver function in patients with acute liver failure, and its use as a prognostic indicator. We studied six acute liver failure patients (two women, four men; 49.8 +/- 20.7 years old) admitted to our hospital in 2002. These patients had diagnoses of fulminant hepatitis due to acute liver failure (1) from congestive heart failure; (2) from portal venous gas, and (3) from postoperative disseminated intravascular coagulation (DIC). We measured serum LECT2, GOT, and GPT levels, the last two being inversely proportionate to the serum LECT2 levels. When the serum GPT levels peaked, the serum LECT2 levels were the lowest. When the liver function recovered, serum LECT2 levels increased. Three of four patients died due to liver failure, one to congestive heart failure. Maximum serum LECT2 levels among the expired group were significantly lower than those among the alive group (0.96 +/- 0.8 ng/mL vs 12.9 +/- 4.3 ng/mL). Serum LECT2 levels may be a prognostic indicator of recovery from liver failure. The present study suggests that in clinical medicine LECT2 participates in regeneration after injury of hepatocytes.

Adult↗

Rapid progressive hepatitis C after liver transplantation: a case report.

A 56-year-old man on hemodialysis for 3 years because of chronic renal failure underwent living related donor liver transplantation (LRDLT) and splenectomy using the right hepatic lobe for liver cirrhosis type C (genotype 1b) with hepatocellular carcinoma. At 69 postoperative days (POD), he displayed a high fever and his blood transaminase and total bilirubin were increased. Based on finding in his liver biopsy, we diagnosed rapid recurrence of progressive hepatitis C after LRDLT, so we administered IFNbeta. Thereafter his liver function returned to normal and his HCV-mRNA decreased to 1200 kcopy/mL. We inferred that hemodialysis and splenectomy decreased his immunity, allowing rapidly progressive hepatitis C recurrence after LRDLT.

Adult↗

Living related donor liver transplantation for primary sclerosing cholangitis with hepatocellular carcinoma and Crohn's disease: a case report.

INTRODUCTION: Primary sclerosing cholangitis (PSC) is a premalignant condition associated with a risk of developing cholangiocarcinoma in 10% to 20% of patients. However, the prevalence of hepatocellular carcinoma (HCC) in patients with PSC is estimated to be only 2%. In addition, PSC often occurs in association with inflammatory bowel disease. Ulcerative colitis occurs in 60% of PSC patients and Crohn's disease occurs in about 10%. We diagnosed a patient as having PSC with HCC and concomitant Crohn's disease prior to living related donor liver transplantation (LRDLT). PATIENTS AND METHODS: A 63-year-old woman was diagnosed as having PSC with solitary HCC. Preoperative liver condition was Child-Pugh grade C. Colonoscopic findings showed an active longitudinal ulcer in the terminal ileum and clinically diagnosed Crohn's disease. The medical treatment was 5'-aminosalicylates. She received a left lobe graft from her daughter. The immunosuppressants were tacrolimus and azathioprine, which was changed to predonisolone because of leukopenia and moderate acute cellular rejection, after which the postoperative course was uneventful. Colonoscopic findings revealed disappearance of the longitudinal ulcer in the terminal ileum at 15 months after LRDLT. There was no evidence of PSC or HCC recurrence. CONCLUSIONS: Generally, PSC with HCC is rare with a poor prognosis; however, LRDLT may be a treatments option although the patient with PSC had a combined HCC. Moreover, aminosalicylates together with the immunosuppressants may be effective for the clinical management of concomitant Crohn's disease.

Cholangitis, Sclerosing↗

Inferior mesenteric venous left renal vein shunting for decompression of excessive portal hypertension in adult living related liver transplantation.

In the present study, we investigated the effect of decompression of excessive portal hypertension by inferior mesenteric venous (IMV) left renal vein shunting in 7 cirrhotic patients with esophago-gastric varices and 2 patients who underwent adult living related donor liver transplantation (ALRDLT). The portal pressure remarkably decreased after shunting in all patients with esophago-gastric varices (388 +/- 42 mm H2O vs. 247 +/- 57 mm H2O; P < .05). It also decreased after a shunt operation in patients who had undergone liver transplantation. We report that the excessive shear stress by portal hypertension after small-for-size LRDLT induces a liver injury and the decompression of portal hypertension by splenic arterial ligation or splenectomy prevents postoperative liver injury following massive hepatectomy and small-for-size LRDLT. Our present studies suggested that IMV left renal vein shunting might prevent postoperative liver injury by partial decompression of excessive portal hypertension following small-for-size LRDLT.

Angiography↗

Inactivation of srtA gene of Streptococcus mutans inhibits dextran-dependent aggregation by glucan-binding protein C.

A sortase-deficient mutant of Streptococcus mutans was prepared by insertional inactivation of a sortase gene (srtA). The srtA mutant was defective in cell wall-anchoring of two surface proteins 200 and 75 kDa in size. A previous study has shown that the 200 kDa protein is a surface protein antigen PAc and that the sortase catalyzes cell wall-anchoring of PAc in S. mutans. In this study another surface protein 75 kDa in size was examined by immunologic and physiologic methods. Western blot analysis with a specific antiserum showed that the 75 kDa protein was a surface protein, glucan-binding protein C. The protein was overexpressed under a stress condition including a sublethal concentration of tetracycline. The srtA mutant cells also lost the ability of dextran-dependent aggregation. These results suggest that the S. mutans sortase mediates cell wall-anchoring of the glucan-binding protein C and dextran-dependent aggregation of this organism.

Adhesins, Bacterial↗

Effects of imidapril, an angiotensin-converting enzyme inhibitor, on insulin sensitivity and responsiveness in streptozotocin-induced diabetic rats.

We have studied the effect of imidapril, an angiotensin-converting enzyme inhibitor, on streptozotocin-induced diabetic rats. A sequential euglycemic hyperinsulinemic clamp procedure was used (insulin infusion rates: 3 and 30 mU/kg BW/min) in 30 diabetic rats. The rats were divided in 6 groups: a control group, a control group with N-monomethyl-L-arginine (L-NMMA, 1 mg/kg/min, a nitric oxide synthase inhibitor) infusion, a streptozotocin-induced diabetic group, a diabetic group with L-NMMA infusion, a diabetic group involving imidapril infusion (5 microg/kg/min), and a diabetic group involving simultaneous imidapril and L-NMMA infusion. Glucose concentrations were maintained around 140 mg/dl during the clamp studies. Plasma insulin levels during the 3 and 30 mU/kg BW/min insulin infusions were 30 and 400 microU/ml, respectively. Glucose infusion rates (GIR) in STZ-induced diabetic rats showed a significant decrease compared to controls. At both insulin infusion rates, imidapril-infused diabetic rats showed an increased GIR, compared with the saline infused ones. There was no significant difference in GIR between L-NMMA and saline infusion in diabetic rats. Simultaneous infusion of imidapril and L-NMMA did not significantly decrease GIR with low-dose insulin infusion, but the increase in GIR induced by imidapril with high-dose insulin infusion was impaired by 100 % by L-NMMA infusion in diabetic rats. These results suggest that imidapril may improve insulin action, in part, via nitric oxide.

Angiotensin-Converting Enzyme Inhibitors↗

Cinnamon extract prevents the insulin resistance induced by a high-fructose diet.

The aim of this study was to determine whether cinnamon extract (CE) would improve the glucose utilization in normal male Wistar rats fed a high-fructose diet (HFD) for three weeks with or without CE added to the drinking water (300 mg/kg/day). In vivo glucose utilization was measured by the euglycemic clamp technique. Further analyses on the possible changes in insulin signaling occurring in skeletal muscle were performed afterwards by Western blotting. At 3 mU/kg/min insulin infusions, the decreased glucose infusion rate (GIR) in HFD-fed rats (60 % of controls, p < 0.01) was improved by CE administration to the same level of controls (normal chow diet) and the improving effect of CE on the GIR of HFD-fed rats was blocked by approximately 50 % by N-monometyl-L-arginine. The same tendency was found during the 30 mU/kg/min insulin infusions. There were no differences in skeletal muscle insulin receptor (IR)-beta, IR substrate (IRS)-1, or phosphatidylinositol (PI) 3-kinase protein content in any groups. However, the muscular insulin-stimulated IR-beta and IRS-1 tyrosine phosphorylation levels and IRS-1 associated with PI 3-kinase in HFD-fed rats were only 70 +/- 9 %, 76 +/- 5 %, and 72 +/- 6 % of controls (p < 0.05), respectively, and these decreases were significantly improved by CE treatment. These results suggest that early CE administration to HFD-fed rats would prevent the development of insulin resistance at least in part by enhancing insulin signaling and possibly via the NO pathway in skeletal muscle.

Animals↗

Expression of protein gene product 9.5 (PGP9.5)/ubiquitin-C-terminal hydrolase 1 (UCHL-1) in human myeloma cells.

The neuron cytoplasmic protein gene product 9.5 (PGP9.5)/ubiquitin-C-terminal hydrolase 1 (UCHL-1) protein is a thiol protease that recognizes and hydrolyzes a peptide bond at the C-terminal of ubiquitin, and is involved in the processing of ubiquitin precursors and ubiquinated proteins. Although this molecule is known as a specific tissue marker for the neuroendocrine system, many reports have indicated that PGP9.5 is a marker for certain tumour types, such as cancer of the lung, colon, and pancreas. The expression of PGP9.5 in myeloma cells was examined. PGP9.5 seemed to be expressed specifically in myeloma cells as compared with other haematological malignant cells. In addition, in myeloma cells subjected to growth-factor starvation, the upregulation of PGP9.5 was observed in association with that of p27(Kip1), a cyclin-dependent-kinase inhibitor, although the upregulation caused by irradiation was milder. In contrast, the hypoxic culture of myeloma cells induced down-regulation of PGP9.5. These results suggested that PGP9.5 may be a good marker for myeloma among haematological malignancies. In addition, it may indicate certain cellular features of myeloma cells, such as sensitivity to proteasome inhibitors.

Biomarkers, Tumor↗

Biochemical markers of myocyte injury in heart failure.

This review discusses the role of biochemical markers of myocyte injury in patients with chronic congestive heart failure. Heart specific assays have been developed for the measurement of cardiac troponin T (cTnT), cardiac troponin I (cTnI), heart type fatty acid binding protein (H-FABP), and myosin light chain 1 (MLC-1). Concentrations of these biochemical markers increase in the absence of ischaemic events in the subset of patients with heart failure whose long term outcomes are most adverse. The markers are easy to measure serially and it is therefore easy to follow patients without inter-observer variability. The serial clinical use of these markers, separately or in combination, will sharpen our understanding of the state of heart failure.

Biomarkers↗

Streptococcus mutans strains harboring collagen-binding adhesin.

A previously unidentified 120-kDa protein was detected in Streptococcus mutans strain Z1 and was involved in the cold-agglutination of the strain. We have identified the gene, designated cnm, as being involved in the agglutination of strain Z1 following random mutagenesis. The amino acid sequence of the deduced Cnm protein exhibited high similarity to those of collagen-binding adhesins from staphylococci and other organisms. To confirm whether the protein is involved in collagen-binding, we cloned a cnm gene fragment, overexpressed it in E.coli, and prepared crude extracts. The extracts containing recombinant protein exhibited binding to immobilized collagen and laminin but not to fibronectin. Compared with the parental strain Z1, the cold-agglutination-negative mutant 05A02 exhibited reduced binding to collagen and laminin but retained that to fibronectin. This gene was detected in some strains of S. mutans. Therefore, the cnm gene encoded a new strain-specific member of the collagen-binding adhesin family.

Adhesins, Bacterial↗

[Clinicopathologic features of small-sized peripheral lung cancer; is intentional limited resection appropriate for selected patients?].

We sought to determine the eligibility of patients with early peripheral lung cancer for intentional limited resection. The clinicopathologic features of 103 patients who underwent lobectomy and mediastinal nodal dissection for early stage peripheral lung cancer measuring 2 cm or less in maximum dimension between 1992 and 2002 were examined retrospectively. The lymph node metastasis and residual cancer after thoracoscopic partial resection were analyzed by the following categories. Three groups were divided by maximum dimension of the primary lesion in the resected specimen; 10 mm or less (n = 11), 15 mm or less (n = 33), and 20 mm or less (n = 59). Two groups were divided by lesion histology; bronchioloalveolar adenocarcinoma (BAC) [n = 42] and invasive lung cancer (n = 61). Residual cancer was found in the residual lobe after thoracoscopic partial resection in 3 of 43 patients who had no diagnosis preoperatively. Their maximum dimensions were 15 mm or less. No lymph node metastasis was detected in the patients with tumor measuring 10 mm or less, and BAC. Intentional limited resection without mediastinal nodal dissection is appropriate for patients with tumor measuring 10 mm or less and BAC. Further investigation associated with partial resection is necessary.

Adenocarcinoma, Bronchiolo-Alveolar↗

[Total removal of infected pacemaker lead with cardiopulmonary bypass; report of a case].

The incidence of infection after pacemaker implant has been reported to occur rarely but it's one of the severe complication. Pacemaker lead sometimes imbedded in the right atrial and ventricular wall, and it seemed to be difficult to remove the pacemaker lead by closed techniques. The optimal treatment is total removal generator and pacing lead, therefore, it is necessary to remove with cardiopulmonary bypass. Septicemia caused by infections retained pacemaker lead developed in an 87-year-old man. Following antibiotic therapy, the lead was successfully removed by cardiotomy on cardiopulmonary bypass. Total removal with cardiopulmonary bypass would be recommended.

Aged↗