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Biomedical subjects

G Tanabe

Publications and source records attributed to G Tanabe.

At least 37 records · Page 2Linked to original sources
PubMed1997

Comparison of p53 expression in proximal and distal gastric cancer: histopathologic correlation and prognostic significance.

BACKGROUND: The overexpression of p53 has been found to be correlated with prognosis of some carcinomas, including gastric cancer, but no studies have reported on its relationship to the location of gastric cancer. In the present study, we compared the p53 expression of proximal and distal gastric cancer concerning histopathology and prognosis. METHODS: A total of 170 tumors in the patients with proximal (80 cases) and distal (90 cases) gastric cancer were studied by immunohistochemical methods. RESULTS: p53 immunopositivity was detected in 28.8% of all tumors. The p53-positive expression in proximal gastric cancer was higher than in distal gastric cancer (38.8% vs. 20.0%, p < 0.05). A 5-year survival analysis showed that there is no significant difference between tumors that are p53 positive and p53 negative. No correlation was found between p53 expression and histopathology of gastric cancer. CONCLUSION: p53 nuclear staining is not useful as a prognostic indicator or as a parameter in gastric cancer.

Adult↗
PubMed1996

Induction of hepatocyte growth by intraportal infusion of HGF into beagle dogs.

Hepatocyte growth factor (HGF), originally identified as a potent mitogen for mature parenchymal hepatocytes, is a hepatotrophic factor involved in liver regeneration and is even essential for development of the liver. We report here that human recombinant HGF at a very low concentration and given intraportaly stimulated liver regeneration in dogs. In vitro, HGF dose-dependently stimulated DNA synthesis of primary cultured hepatocytes isolated from a dog. The maximal activity was twofold higher than that of epidermal growth factor, and insulin potentiated the mitogenic activity of HGF. When human recombinant HGF was infused through the portal vein into 30% partially hepatectomized dogs at 0.25 microg/kg body weight in order to directly target the liver, HGF stimulated DNA synthesis of hepatocytes and liver weight at 72 h after the operation; labeling indices in saline- and HGF-injected groups were 0.75 and 1.82%, respectively, and the liver weights in saline- and HGF-injected groups were 302 and 374 g, respectively. Since HGF exerts potent antihepatitis activity as well as mitogenic activity, these results indicate that intraportal administration of HGF may be particularly important to enhance liver regeneration and prevent the severe hepatic insufficiently after hepatic surgery.

Animals↗
PubMed1996

High serum alpha-fetoprotein concentration associated with pseudoinfarction of a cirrhotic liver: report of a case.

We report herein the case of a 65-year-old man with cirrhosis of the liver in whom a portal vein thrombus was found to be the cause of a marked elevation in serum alpha-fetoprotein (AFP). The patient presented with fever and abdominal pain, and a diagnostic work-up revealed a liver mass and an increased serum AFP concentration of 91,000 ng/ml. The mass gradually regressed, and the AFP concentration simultaneously decreased to 163 ng/ml. However, because hepatocellular carcinoma (HCC) could not be ruled out, a partial hepatectomy was performed. Histological examination of the resected specimen revealed a thrombus of the portal vein surrounded by the fibrosis associated with liver cirrhosis, but no neoplastic lesion was found. Thus, portal thrombus associated with liver cirrhosis might induce an extremely high level of AFP production.

Aged↗
PubMed1996

Exogenous hepatocyte growth factor markedly stimulates liver regeneration following portal branch ligation in dogs.

Portal branch ligation (PBL) or embolization prior to extensive hepatectomy has been employed to increase the functional reserve of the remaining liver. This study investigated the effects of human recombinant hepatocyte growth factor (rh-HGF) on liver regeneration following PBL in dogs. Beagle dogs were subjected to PBL and were divided into two groups, a control group (n = 11) without rh-HGF and a treated group (n = 12) receiving postoperative rh-HGF at 250 ng/kg via the portal vein. Dogs were killed 72 h or 14 days following PBL. We studied the changes in serum HGF level, DNA synthesis of the liver, hepatocyte size, liver weight, and liver function tests. In the HGF group, the ratio of whole liver weight to body weight increased significantly, and both ligated and nonligated lobes showed marked increases in weight. The nonligated lobes in the HGF group showed significant increases in both DNA synthesis and hepatocyte size. Moreover, ligated lobes in the HGF group showed an increase in DNA synthesis without hypertrophy compared with the control group. Administration of rh-HGF did not significantly affect liver function tests. Ligation of the portal branch supplying the portion of liver to be resected, coupled with the administration of rh-HGF, is a useful strategy to increase hepatic reserve in advance of major hepatectomy.

Animals↗
PubMed1996

Pharmacokinetics of indomethacin ester prodrugs: gastrointestinal and hepatic toxicity and the hydrolytic capacity of various tissues in rats.

In order to develop a potential prodrug of indomethacin (IM) which causes less irritation to the gastrointestinal mucosa, the ester prodrugs [butyl ester (IM-BE) and octyl ester (IM-OE)] of IM were synthesized and evaluated for their ulcerogenic activity and hepatic injury after oral administration in rats. Additionally, the kinetics of hydrolysis of the prodrugs were examined to characterize the tissues or organs capable of hydrolyzing the ester bonds. The plasma levels of IM after the oral administration of IM-OE and IM-BE were comparatively low compared with those after IM, with a small bioavailability (2.1 and 15.0%, respectively). Ulcerogenic activity and hepatic injury, expressed by decreased hepatic microsomal enzyme activities, were hardly seen after repeated oral administration of the prodrugs, in contrast with the severely irritating effects of IM alone. Hydrolysis of the prodrugs was adequately described by first-order kinetics. IM-BE was relatively rapidly hydrolyzed in plasma, skin and whole blood, but the hydrolysis in the intestinal mucosa and liver was very slow. The hydrolytic rates for IM-OE were exceedingly small or negligible. These results indicate that the main part of IM-BE and IM-OE administered orally might not be hydrolyzed to IM in the gastrointestinal tract, and that the ester prodrugs themselves were absorbed through the mucosa; also, that the hydrolysis of ester bonds would be carried out mainly in the circulatory system. Consequently, IM-BE seems to be an ideal prodrug of IM.

Administration, Oral↗
PubMed1996

Hepatic hemodynamics in a patient with nodular regenerative hyperplasia.

Nodular regenerative hyperplasia of the liver is an uncommon condition. Approximately 50% of these patients develop portal hypertension. Few previous reports document the site of increased resistance to blood flow within the liver in this disorder. We measured Doppler waveform patterns of the right hepatic vein by pulsed Doppler ultrasonography and portal, wedged hepatic, and free hepatic venous pressure by intravenous catheter before and after splenectomy in a 47-yr-old woman with nodular regenerative hyperplasia who presented with portal hypertension and pancytopenia. Nodular regenerative hyperplasia was histologically confirmed. Pre- and postoperative measures indicated a marked difference between wedged hepatic venous pressure and free hepatic venous pressure, whereas there was little difference between portal venous pressure and wedged hepatic venous pressure. Doppler waveform patterns of the right hepatic vein showed an unclear pulsatile flow pattern with a decreasing reversed phase. The above data suggest that portal hypertension in nodular regenerative hyperplasia is primarily sinusoidal, similar to that seen with cirrhosis.

Female↗
PubMed1995

Intraoperative risk factors associated with hepatic resection.

Risk factors associated with complications following hepatic resection were investigated retrospectively in 121 patients between January 1987 and April 1992. Fifty-seven patients recovered uneventfully, but 64 suffered post-operative complications and 15 died within 3 months. All those who died had suffered from hyperbilirubinaemia or bleeding and/or coagulopathy, which were considered critical complications after hepatic resection. Risk factors following hepatic resection were investigated statistically. Stepwise logistic regression analysis showed that serum levels of cholinesterase, the histology of the remaining liver and the volume of intraoperative blood loss were significantly associated with major complications (odds ratio 0.02, 5.14 and 4.97 respectively). Coexisting liver cirrhosis, deterioration of liver protein synthesis and massive intraoperative blood loss are important risk factors following hepatic resection.

Aged↗
PubMed1995

Expression of HGF and TGF-beta 1 mRNA after partial hepatectomy in rats with liver cirrhosis.

Hepatocyte growth factor (HGF) is a potent mitogen for the maturation of hepatocytes in vitro which plays a role in liver regeneration in vivo. In addition, transforming growth factor-beta 1 (TGF-beta 1) is also a potent regulator of liver regeneration. In attempting to clarify the mechanisms related to liver regeneration after partial hepatectomy, we investigated the expression of HGF and TGF-beta 1 in rats with liver cirrhosis (LC). A rat model of LC was prepared using carbon tetrachloride (CCl4). The expression of HGF mRNA in both the LC and control groups showed a similar time-course with the highest expression seen at 18h after a 70% hepatectomy. The expression of TGF-beta 1 mRNA peaked at 18h after partial hepatectomy in the LC group and at 48h in the control group. The 5-bromo-2'-deoxyuridine (BrdU) labeling index for the LC group at 24, 48, and 72 h after partial hepatectomy was 9.2%, 5.9%, and 1.8%, while for the control group it was 7.0%, 11.7%, and 6.8%, respectively. The BrdU labeling index in the LC group was thus suppressed earlier than that in the control group. We therefore postulate that regeneration of the remnant liver in the presence of LC accelerates immediately after partial hepatectomy, but the extent of regeneration is insufficient because of an early cessation due to an early expression of TGF-beta 1.

Animals↗
PubMed1995

Effect of prior portosystemic shunt on early hepatic hemodynamics and sinusoids following 84% hepatectomy in dogs.

The effects of a prior portosystemic shunt (PSS) on the hepatic hemodynamics and sinusoids shortly after an 84% hepatectomy (Hx) were investigated in dogs. Fifteen mongrel dogs were divided into three groups, a 70% Hx group (n = 5), an 84% Hx group (n = 5) and an 84% Hx+PSS group (n = 5). In the last group, a shunt was inserted between the splenic and femoral veins prior to the hepatectomy. The systemic and hepatic hemodynamics were measured, before and 180 min after the hepatectomy, and the remaining liver tissue was then examined immunohistochemically by light microscopy using the thrombomodulin (TM) staining method. The postoperative portal vein pressure and the vascular resistance were significantly lower in the PSS group than in the 84% non-PSS group. The total postoperative hepatic blood flow was higher in the 84% non-PSS group than in the other two groups. Immunohistochemical observation after TM staining indicated that the sinusoidal endothelial cells in the 84% non-PSS group were markedly damaged 3 h after surgery. We conclude that a prior PSS improves the hepatic hemodynamics and is beneficial to the sinusoids within the first few hours of an 84% hepatectomy in dogs.

Animals↗
PubMed1994

Inhibition of the increase of intrahepatic Ca2+ by diltiazem in rats with liver ischemia.

The effects of a continuous infusion of a calcium entry blocker, 1, 5-benzothiazepine derivative (diltiazem), on ischemic liver cell damage were studied using quantitative 45Ca-autoradiographic and liquid scintillation techniques. The drug was administered to male Wistar rats as a continuous infusion for 3 h, beginning 30 min before ischemia. Autoradiographic studies showed that 45Ca accumulated in the liver lobuli after 1 h of liver ischemia and 3 h of reperfusion, but the level of 45Ca accumulation was significantly lower in drug-treated rats than in untreated animals. In addition, liquid scintillation studies showed significant differences in the intrahepatic 45Ca contents. These results suggest that diltiazem may inhibit the rise of intracellular Ca2+ due to the flow of extracellular Ca2+ into the cytosol, and may protect the ischemic liver from damage.

Animals↗
PubMed1994

Physicochemical and hydrolytic characteristics of phenytoin derivatives.

To further clarify the pharmacokinetic characteristics of phenytoin (DPH) and its derivatives, DPH-1-methylnicotininate (MNDPH), valeroyl DPH (VADPH) and valproyl DPH (VPDPH), in plasma and brain, we have investigated their physicochemical properties and protein binding characteristics. Additionally, the hydrolytic conversion of these derivatives to DPH was also studied using small intestine, liver and brain tissues, as well as rat plasma. The log partition coefficient (PC) values of all derivatives were much higher than that of DPH. Judging from their pKa values (5.68 and 5.91 for VADPH and VPDPH, respectively) and pH-solubilities, VADPH and VPDPH were acidic compounds, while MNDPH was basic. These data indicated that most fractions of VADPH and VPDPH existed as an ionized form (these fractions existed in an ionized form, 0.98 and 0.97, respectively) at physiological pH, whereas MNDPH existed as a unionized form under the same conditions. Rosenthal or Scatchard plots of the binding data of DPH and its derivatives to both rat plasma protein and bovine serum albumin (BSA) exhibited straight lines over their concentration ranges used, indicating that DPH and its derivatives have a single binding site on the protein. The binding potencies (K or n.Pt value) of the derivatives to both proteins were much greater than that of DPH. No DPH produced from VADPH and VPDPH was found in the biological fluids over a period of 24 h. However, the hydrolysis of MNDPH to DPH was observed in plasma and the tissues used, with the most rapid hydrolysis in the small intestine, and the hydrolysis rate constant in plasma was ca. 20-fold greater than that in the brain.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1993

Hepatocellular carcinoma coexistent with adenomatous hyperplasia: report of a case.

We would like to draw attention to hepatic tumor-like lesions which frequently complicate the differential diagnosis of hepatocellular carcinoma (HCC), while considering their pathology and diagnosis by radiographic imaging. In particular, adenomatous hyperplasia is recognized as a precancerous lesion of HCC, and the relationship between adenomatous hyperplasia and the multicentric development of HCC is recognized. We observed a patient who demonstrated hyperplastic changes in both the liver cells and a well-differentiated HCC lesion adjacent to the adenomatous hyperplasia, suggesting a multicentric development of the HCC. The histopathological features of adenomatous hyperplasia are also described.

Carcinoma, Hepatocellular↗
PubMed1993

Ischemic liver cell damage and calcium accumulation in rats.

Regions of calcium accumulation were studied by 45Ca-autoradiography and microdensitometry during liver ischemia and reperfusion in rats. In autoradiographic studies 45Ca accumulated in all zones of the liver lobuli after 1-2 h of liver ischemia and 1, 3 and 6 h of reperfusion, but did not accumulate in non-ischemic liver lobes. Significant 45Ca accumulation occurred only with reperfusion after 1 or 2 h of liver ischemia. In the presence of reperfusion, 45Ca accumulation correlated with the length of ischemia. In histopathologic studies, liver necrosis was absent in lobuli after 1-h reperfusion. Some liver necrosis was observed in the group reperfused for 3 h and widespread liver necrosis appeared after 6-h reperfusion. Regions of 45Ca accumulation coincided with sites of microscopic liver cell damage and necrosis. These results suggested that calcium accumulation might be responsible for the liver cell damage induced by ischemia with reperfusion, that the intensity of calcium accumulation in 45Ca-autoradiograms indicates the degree of ischemia damage, and that the primary event leading to hepatocellular necrosis might be calcium accumulation and subsequent liver cell death.

Animals↗
PubMed1993

Pharmacokinetic analysis of phenytoin and its derivatives in plasma and brain in rats.

The derivatives of phenytoin (DPH) were synthesized by the reaction at 3 position of hydantoin ring with valproic acid and valeric acid, producing valproyl DPH (VPDPH) and valeroyl DPH (VADPH), respectively. These derivatives showed much higher lipid solubilities than that of DPH. Their distribution and elimination were compared to those of DPH. Additionally, the concentration profiles of the drugs in brain and plasma were analyzed with a modified 2-compartment model. DPH and its derivatives, without hydrolysis to DPH in blood, were found rapidly distributed into brain, although the distribution of derivatives was much less, probably due to the high protein binding capacities. The distribution of DPH and its derivatives into brain regions was similar to that into the cortex cerebri. VPDPH and VADPH were more rapidly eliminated from plasma and brain than DPH, giving smaller mean residence time (MRT) values (0.92 and 0.85 h) and much smaller cortex/plasma concentration ratio than those of DPH. The VPDPH and VADPH concentrations in the cerebrospinal fluid (CSF) were also much lower than that of DPH. The time course of plasma and brain concentrations of DPH and its derivatives after i.v. administration was successfully described by the modified 2-compartment models presented.

Animals↗
PubMed1992

A correlation between arterial ketone body ratio and concentration of beta-hydroxybutyrate as an indicator of hepatic functional reserve.

We have investigated the correlation between the arterial blood ketone body ratio (AKBR) and beta-hydroxybutyric acid (HBAC) in the course of a 75 g glucose tolerance test. The correlation was revealed to be represented by an equation of Y = A + BX [X = log(HBAC), Y = log(AKBR)] with high significance. This expression existed in both normal individuals and patients with liver, biliary tract or pancreas disease. The postoperative course was unsatisfactory because of liver dysfunction in cases whose value B was more than -0.6 in bisegmentectomy and more than -0.45 in uni- or subsegmentectomy. The coefficient B in the equation was suggested to contribute to the evaluation of hepatic functional reserve.

3-Hydroxybutyric Acid↗
PubMed1992

[A case of hepatoma patient who showed an abnormally high level of serum IRI with the beads method].

A fifty four years old hepatoma patient admitted to the hospital for a surgical operation. Preoperative laboratory examination demonstrated that his serum IRI level was very high (423 microU/ml) when measured with a beads method, however RIA or a microplate method demonstrated normal values. We studied the mechanism of the discrepancy of IRI values. 1) Both the beads and microplate methods demonstrated the same IRI values when the patient's serum insulin was roughly purified with Sep-Pak. The beads method showed high IRI values in serum which passed through Sep-Pak, therefore contained no insulin. 2) The similar results were observed when the patient's serum fractionated by a gel-chromatography (Biogel P-30). The beads method demonstrated high IRI values in both insulin fractions and the fractions containing serum proteins bigger than 40,000 molecular weight. The microplate method demonstrated only one large peak of insulin. 3) When non-specific IgG of guinea pig was used as a fixed antibody instead of human insulin antibody of guinea pig that was used in the beads method, the patient's serum showed the similar values as that obtained with the beads method. We thereby concluded that the abnormal level of IRI by the beads method was derived from the unknown substance reacting with IgG of guinea pig in the patient's serum. After the surgical resection of hepatoma, the levels of IRI measured by the beads method decreased significantly, suggesting that the substance is related to hepatoma cells.

Animals↗
PubMed1990

A new open reduction treatment for congenital hip dislocation: long-term follow-up of the extensive anterolateral approach.

Congenital hip dislocation, which is conservatively unmanageable, has usually been treated using open reduction. However, a long-term follow-up study of the results suggests that this procedure is unsatisfactory. Since 1973, Tanabe has used a new open reduction procedure that circumferentially dissects the joint capsule and produces sufficient concentric reduction of the femoral head in the acetabulum immediately after the surgery. Fifty-six children (65 hips) from the age of 1 to 3 years were treated by this procedure, and fifty-one of them were clinically and roentgenographically followed up from 6.3 to 12.4 years after the surgery. At the final follow-up session, all children had grown to be over 9 years of age, and no patient had clinically significant symptoms. According to Severin's classification, 33 hips were rated in Group I, and 14 hips in Group II. Another 10 hips were in Group III, and one hip was in Group IV. The incidence of avascular necrosis was 5.2 per cent. These data suggest that our procedure is more useful than the previous ones.

Child, Preschool↗