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Biomedical subjects

H Sekihara

Publications and source records attributed to H Sekihara.

At least 55 records · Page 3Linked to original sources
PubMed1999

Hepatic arterial resistance after mixed-meal ingestion in healthy subjects and patients with chronic liver disease.

PURPOSE: This study investigated hemodynamic changes in the resistance index of the hepatic artery after mixed-meal ingestion. METHODS: We used color Doppler sonography to measure hemodynamic changes in the right hepatic artery in response to mixed-meal ingestion (225 ml, 69 g, 300 kcal) in 9 healthy subjects, 15 patients with chronic hepatitis with low-grade fibrosis (no bridging), 10 patients with chronic hepatitis with moderate-grade (bridging) fibrosis, and 18 patients with cirrhosis. RESULTS: After mixed-meal ingestion, the mean (+/-standard error) maximum increase in the resistance index of the right hepatic artery in healthy subjects was 31+/-2%. These changes were significantly greater than those in patients with chronic hepatitis with low-grade fibrosis (22+/-2%; p<0.05), patients with chronic hepatitis with moderate-grade fibrosis (11+/-2%; p<0.01), and cirrhotic patients (5+/-2%; p<0.01). Mixed-meal ingestion produced significantly smaller increases in the resistance index in cirrhotic patients than in patients with chronic hepatitis with low-grade fibrosis (p<0.01). A postprandial increase in the resistance index of 15% or less was associated with 100% sensitivity, 72% specificity, and 84% accuracy in distinguishing patients with cirrhosis from patients with chronic hepatitis. CONCLUSIONS: The response of the resistance index after mixed-meal ingestion decreases as the severity of hepatic fibrosis increases. Doppler evaluation of postprandial increases in the resistance index of the right hepatic artery may be useful in differentiating between patients with chronic hepatitis and those with cirrhosis.

Chronic Disease↗
PubMed1999

Nitric oxide increases hepatic arterial blood flow in rats with carbon tetrachloride-induced acute hepatic injury.

BACKGROUND & AIMS: Little is known about the changes in hepatic blood flow associated with acute hepatic injury. The aim of this study was to investigate the effect of nitric oxide (NO) on hepatic blood flow and the severity of hepatic injury in rats with carbon tetrachloride (CCl4)-induced acute hepatic injury. METHODS: Rats were pretreated with CCl4 to induce acute hepatic injury. Hepatic blood flow was measured using a radioactive microsphere method. The role of NO in the regulation of hepatic blood flow and the severity of hepatic injury was investigated by administering NG-nitro-L-arginine (L-NNA) and aminoguanidine (AG). Plasma nitrite/nitrate levels, hepatic NO synthase (NOS) activity, and expression of hepatic NOS messenger RNA (mRNA) were measured, and histological examinations were performed. RESULTS: Hepatic arterial and portal venous blood flow was increased significantly by CCl4, without any change in mean arterial pressure or cardiac output. L-NNA and AG dose-dependently decreased hepatic arterial blood flow, with the highest dose resulting in complete blockade of hepatic arterial dilation, but failed to change portal venous blood flow. Histologically, administration of AG aggravated the hepatic injury in CCl4-treated rats. Plasma nitrite/nitrate levels and hepatic NOS activity were increased significantly by CCl4 treatment. Inducible NOS mRNA was detected in CCl4-treated rats but not in the controls. CONCLUSIONS: The results of this study suggest that the increased hepatic arterial blood flow in CCl4-induced acute hepatic injury is mediated by excessive NO production and up-regulated by inducible NOS, which plays a role in reducing hepatic injury.

Acute Disease↗
PubMed1999

Dehydroepiandrosterone (DHEA) facilitates liver regeneration after partial hepatectomy in rats.

In this study we investigated whether or not liver regeneration is facilitated by dehydroepiandrosterone (DHEA) after partial (70%) hepatectomy in rats. Treatment with DHEA (300 mg/kg body weight) did not cause any significant increase in the expression ratio of proliferating cell nuclear antigen (PCNA) in sham-operated controls; however, in partially hepatectomized rats it caused a significant increase in the ratio in hepatocytes 24 and 36 hr after hepatectomy. In partially hepatectomized rats, DHEA treatment significantly accelerated the restoration of liver 48, 60, and 72 hr after partial hepatectomy. The restoration rate in DHEA-treated hepatectomized rats at 72 hr was 1.3-fold greater than in partially hepatectomized controls. Treatment with androstenedione (300 mg/kg body weight), the first metabolite of DHEA, did not cause any significant increase in the expression of PCNA in either sham-operated controls or partially hepatectomized rats. These results indicate that DHEA itself promotes the liver regenerative process after partial hepatectomy in rats.

Androstenedione↗
PubMed1999

PPAR gamma mediates high-fat diet-induced adipocyte hypertrophy and insulin resistance.

Agonist-induced activation of peroxisome proliferator-activated receptor gamma (PPAR gamma) is known to cause adipocyte differentiation and insulin sensitivity. The biological role of PPAR gamma was investigated by gene targeting. Homozygous PPAR gamma-deficient embryos died at 10.5-11.5 dpc due to placental dysfunction. Quite unexpectedly, heterozygous PPAR gamma-deficient mice were protected from the development of insulin resistance due to adipocyte hypertrophy under a high-fat diet. These phenotypes were abrogated by PPAR gamma agonist treatment. Heterozygous PPAR gamma-deficient mice showed overexpression and hypersecretion of leptin despite the smaller size of adipocytes and decreased fat mass, which may explain these phenotypes at least in part. This study reveals a hitherto unpredicted role for PPAR gamma in high-fat diet-induced obesity due to adipocyte hypertrophy and insulin resistance, which requires both alleles of PPAR gamma.

Adipocytes↗
PubMed1999

Increased insulin sensitivity and hypoglycaemia in mice lacking the p85 alpha subunit of phosphoinositide 3-kinase.

The hallmark of type 2 diabetes, the most common metabolic disorder, is a defect in insulin-stimulated glucose transport in peripheral tissues. Although a role for phosphoinositide-3-kinase (PI3K) activity in insulin-stimulated glucose transport and glucose transporter isoform 4 (Glut4) translocation has been suggested in vitro, its role in vivo and the molecular link between activation of PI3K and translocation has not yet been elucidated. To determine the role of PI3K in glucose homeostasis, we generated mice with a targeted disruption of the gene encoding the p85alpha regulatory subunit of PI3K (Pik3r1; refs 3-5). Pik3r1-/- mice showed increased insulin sensitivity and hypoglycaemia due to increased glucose transport in skeletal muscle and adipocytes. Insulin-stimulated PI3K activity associated with insulin receptor substrates (IRSs) was mediated via full-length p85 alpha in wild-type mice, but via the p50 alpha alternative splicing isoform of the same gene in Pik3r1-/- mice. This isoform switch was associated with an increase in insulin-induced generation of phosphatidylinositol(3,4,5)triphosphate (PtdIns(3,4,5)P3) in Pik3r1-/- adipocytes and facilitation of Glut4 translocation from the low-density microsome (LDM) fraction to the plasma membrane (PM). This mechanism seems to be responsible for the phenotype of Pik3r1-/- mice, namely increased glucose transport and hypoglycaemia. Our work provides the first direct evidence that PI3K and its regulatory subunit have a role in glucose homeostasis in vivo.

Animals↗
PubMed1999

Correlation between hepatic tumor index on color Doppler sonography and tumor vessels on arteriography in large hepatocellular carcinomas.

We assessed a possible correlation between the hepatic tumor index (as the ratio of the tumoral peak systolic velocity to the peak systolic velocity of the right or left hepatic artery) and grade of tumor vessel in large hepatocellular carcinomas (HCCs). Color Doppler sonographic findings were evaluated and compared with selective hepatic arteriographic findings in 78 patients with 93 hepatocellular carcinomas larger than 2.0 cm in diameter. Pulsatile color flow images were obtained in 78 of 93 lesions. The hepatic tumor index was equal to or greater than 1.0 in 57 of 78 lesions. These lesions were revealed arteriographically to have distinct tumor vessels and/or arteriovenous shunting. When this index was 1.0 or greater, we calculated 90% accuracy in distinguishing HCCs with distinct tumor vessels from those without distinct tumor vessels. The hepatic tumor index correlated with the grade of tumor vessels and the presence of arteriovenous shunting.

Adult↗
PubMed1999

Lactoferrin inhibits hepatitis C virus viremia in patients with chronic hepatitis C: a pilot study.

Hepatitis C virus (HCV) is associated with the development of cirrhosis and hepatocellular carcinoma. We recently found that bovine lactoferrin, a milk protein belonging to the iron transporter family, effectively prevented HCV infection in cultured human hepatocytes (PH5CH8). We tested the hypothesis that lactoferrin inhibits HCV viremia in patients with chronic hepatitis C. Eleven patients with chronic hepatitis C received an 8-week course of bovine lactoferrin (1.8 or 3.6 g/day). At the end of lactoferrin treatment, a decrease in serum alanine transaminase and HCV RNA concentrations was apparent in 3 (75%) of 4 patients with low pretreatment serum concentrations of HCV RNA. However, 7 patients with high pretreatment concentrations showed no significant changes in these indices. This pilot study suggests that lactoferrin is one potential candidate as an anti-HCV reagent that may be effective for the treatment of patients with chronic hepatitis.

Adult↗
PubMed1999

Medullary thyroid carcinoma with multiple hepatic metastases: treatment with transcatheter arterial embolization and percutaneous ethanol injection.

A 54-year-old man with medullary thyroid carcinoma in the thyroid gland was unable to undergo total thyroidectomy because the tumor had invaded the mediastinum. Radiation therapy and chemotherapy were given. Seven years later, intractable diarrhea and abdominal pain appeared, and computed tomography demonstrated hypervascular tumors in the thyroid gland and in the liver. The tumors were successfully treated with percutaneous ethanol injection to a lesion in the thyroid gland and transcatheter arterial embolization followed by percutaneous ethanol injection to tumors in the liver. Transcatheter arterial embolization and percutaneous ethanol injection may be valuable in treating medullary thyroid carcinoma.

Angiography↗
PubMed1999

Dehydroepiandrosterone suppresses the elevated hepatic glucose-6-phosphatase and fructose-1,6-bisphosphatase activities in C57BL/Ksj-db/db mice: comparison with troglitazone.

The effect of dehydroepiandrosterone (DHEA) on the hepatic and muscle glucose metabolizing enzymes and on blood glucose were investigated in insulin-resistant diabetic C57BL/KsJ-db/db mice and their heterozygote littermates (db/+m). The results were compared with those after troglitazone administration under the same conditions. Despite hyperinsulinemia, hepatic glucose-6-phosphatase (G6Pase) and fructose-1,6-bisphosphatase (FBPase) activities are higher in db/db than in db/+m mice. Dietary administration of DHEA and that of troglitazone for 15 days to respective groups of five mice each significantly decreased blood glucose in db/db mice and hepatic G6Pase and FBPase activities in both db/db and db/+m mice. Hepatic G6Pase and FBPase activities showed a linear relationship with blood glucose in all groups of mice, suggesting that the activities of G6Pase and FBPase are closely related to blood glucose levels. Because androstenedione, a DHEA metabolite, barely affected either of these enzyme activities or blood glucose in db/db mice, the actions of DHEA, which are similar to those of troglitazone, are presumed to be caused by DHEA itself. DHEA is considered to be a modulating agent for the activities of hepatic gluconeogenic enzymes in db/db mice.

Androstenedione↗
PubMed1998

Lactoferrin markedly inhibits hepatitis C virus infection in cultured human hepatocytes.

We found that bovine lactoferrin (bLF), a milk protein belonging to the iron transporter family, effectively prevented hepatitis C virus (HCV) infection in cultured human hepatocytes (PH5CH8), a cell line susceptible to HCV infection and supportive of HCV replication. Because preincubation of HCV with bLF was required to prevent the infection of HCV to the cells, and preincubation of bLF with the cells showed no inhibitory effect on HCV infection, we demonstrated that the anti-HCV activity of bLF was due to the interaction of bLF with HCV, but not due to the interaction of bLF with the cells. We further found that human lactoferrin also had anti-HCV activity, but bovine transferrin, the other member of the iron transporter family, did not have anti-HCV activity. Our findings suggest that lactoferrin is one of candidates for an anti-HCV reagent that will be well-tolerated and effective in the treatment of patients with chronic hepatitis.

Animals↗
PubMed1998

The long term efficacy of combined transcatheter arterial embolization and percutaneous ethanol injection in the treatment of patients with large hepatocellular carcinoma and cirrhosis.

BACKGROUND: The long term efficacy of combination therapy with transcatheter arterial embolization (TAE) followed by percutaneous ethanol injection (PEI) was studied in patients with large primary hepatocellular carcinoma (HCC) tumors and cirrhosis. METHODS: The series included 83 patients with large unresectable HCC lesions, the largest of which was greater than 3 cm in largest dimension. Fifty-five had a solitary lesion and 28 had multiple (2 or 3) lesions. All patients were treated with both TAE and PEI and their survival rates were determined. RESULTS: The 3-, 5-, and 7-year calculated survival rates for the patients were be 68%, 35%, and 14%, respectively. The number of lesions (solitary vs. multiple), the stage of cirrhosis (Child's Class A vs. Class B or C), and the size of the largest lesion (3-5 cm in largest dimension compared with > 5 cm) significantly affected the survival rate (P < 0.05 to P < 0.01, log rank test). The 3-, 5-, and 7-year survival rates of the Child's Class A patients who had a 3-5 cm solitary lesion (n = 22) were 100%, 75%, and 27%, respectively. The Cox proportional hazards model showed the stage of cirrhosis and size of the largest lesion to be independently associated with survival. No serious complications occurred during or after treatment. CONCLUSIONS: Combination therapy with TAE and PEI is an effective and safe treatment that may improve the long term survival of patients with cirrhosis associated with large HCC lesions, and survival after this combination therapy may be comparable to that after surgery.

Adult↗
PubMed1998

T lymphopenia in genetically obese rats.

Although obese animals are more susceptible to infection, the underlying causes are not fully known. In this study, long-term measurements were made of lymphocyte subsets in peripheral blood, spleen, and thymus in genetically obese Zucker (fa/fa) rats. Blastogenic response of splenocytes to mitogens was also examined. fa/fa rats developed obesity, hyperlipidemia, and hyperinsulinemia after 5 weeks of age. Flow cytometric analysis revealed that T cells in peripheral blood, spleen, and thymus were all reduced significantly in obese rats after 8 weeks of age compared to nonobese (Fa/-) littermates. All T-cell subsets examined, including CD4+ and CD8+ T cells, were similarly reduced in spleen and thymus as well as in peripheral blood with advance in age. In addition, proliferative responses of splenocytes to mitogens were significantly low in obese rats. These results indicate that long-term obesity may reduce the size of the T-cell pool and impair the responsiveness of splenocytes in rats.

Animals↗
PubMed1998

Use of balloon-occluded retrograde transvenous obliteration with ethanolamine oleate for the treatment of hepatic encephalopathy in a cirrhotic patient with a large spontaneous splenorenal shunt.

We describe a technique for the treatment of hepatic encephalopathy in a cirrhotic patient with a large spontaneous splenorenal shunt. This large shunt was successfully occluded without severe complications by retrograde transrenal venous obliteration with ethanolamine oleate after balloon occlusion. This procedure may be an effective method to occlude a large spontaneous splenorenal shunt for the treatment of hepatic encephalopathy.

Aged↗
PubMed1998

Hepatocyte proliferation in rats after ventromedial hypothalamic lesions: immunoreactivity patterns of proliferating cell nuclear antigen (PCNA).

Ventromedial hypothalamic (VMH) lesions result in increased DNA content in the rat liver. However, little information is available concerning the proliferative activity and lobular distribution of different cell populations in VMH-lesioned rat liver. The aim of the present study was to quantitatively assess these parameters in VMH-lesioned rat liver by measuring proliferating cell nuclear antigen (PCNA) reactivity. We investigated to determine whether this mitotic response involves acinar zones 1, 2, or 3. Changes in immunohistochemical labeling indices in rat liver were measured with an antibody against PCNA until 7 days after VMH lesioning. The effects of hepatic vagotomy on proliferation were also examined. Proliferation of hepatocytes in acinar zones 1-3 began to increase on day 1, and reached a maximum at 3 days. The area of most intense proliferation progressively shifted from acinar zone 1 to zone 3 in several days. The proliferation was completely inhibited by hepatic vagotomy, indicating that VMH lesions induce cell proliferation in rat liver via hepatic vagus nerve activity. This study implicates the information available on neural factors which initiate hepatocyte proliferation.

Animals↗
PubMed1998

Effects of a 7-day infusion of glucose on insulin secretion in vivo and in vitro in ventromedial hypothalamic-lesioned obese rats.

Excessive stimulation of insulin secretion may be one cause of the beta-cell dysfunction induced by hyperglycemia. We investigated a possible link between the prior endogenous hypersecretion of insulin and this dysfunction by performing a 7-day glucose infusion (50% wt/vol, 1.2 ml/h) on ventromedial hypothalamic VMH-lesioned hyperinsulinemic rats. Intravenous glucose tolerance tests (i.v.GTT 1.0 g/kg) revealed that a 3-day glucose infusion enhanced the insulin responses in both the sham- and VMH-lesioned rats compared with saline infusions. A similar 7-day glucose infusion enhanced the insulin response to glucose in sham-lesioned rats but not in VMH-lesioned rats. Batch-incubation of islets isolated from sham-lesioned rats showed an enhanced insulin response to glucose after 7 days of glucose treatment compared with the saline infusions. Conversely, the glucose infusion in VMH-lesioned rats markedly suppressed the in vitro insulin response. In sham- and VMH-lesioned rats, similar islet insulin contents were produced by saline and glucose treatments. Electron microscopy revealed that glucose infusions impaired the granule-releasing function of the beta-cells in VMH-lesioned rats, while insulin synthesis was accelerated in either group. These findings support the notion that excessive secretion is partly responsible for the beta-cell dysfunction induced by hyperglycemia without signs of exhaustion.

Animals↗
PubMed1998

T lymphopenia in obese diabetic (db/db) mice is non-selective and thymus independent.

Although C57BL/KsJ db/db mice, an animal model of non-insulin-dependent diabetes mellitus (NIDDM), develop T lymphopenia in association with the progression of NIDDM, the T lymphopenia has not been fully investigated. In this study, to elucidate how and why T lymphopenia develops in db/db mice, T-lymphocyte subsets in spleen and thymus were longitudinally examined by flow cytometry and the effects of thymectomy and dietary restriction on the development of T lymphopenia were evaluated. After 8 weeks of age, when obese diabetes progresses, T lymphopenia in both spleen and thymus developed and all T-lymphocyte subsets examined were similarly reduced compared to lean (-/X) littermates, indicating non-selective T lymphopenia in db/db mice. Thymectomy performed at 5 wk of age, when neither T lymphopenia nor NIDDM yet presents, had no significant effect on the development of T lymphopenia. Furthermore, pair feeding until 30 weeks of age produced normal body weight and normoglycemia with still marked hyperinsulinemia, but failed to correct T lymphopenia in db/db mice. In conclusion, our results suggest that T lymphopenia may develop non-selectively and independently of either thymic dysfunction or obese diabetes in db/db mice.

Animals↗