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Biomedical subjects

H Shinohara

Publications and source records attributed to H Shinohara.

At least 163 records · Page 9Linked to original sources
PubMed1996

Changes in glucose transporter 2 and carbohydrate-metabolizing enzymes in the liver during cold preservation and warm ischemia.

In order to examine glucose metabolism in liver grafts during cold preservation (24 and 48 hr), warm ischemia (60 and 120 min), a combination of the two and reperfusion, the amount of protein and mRNA of glucose transporter 2 and the activities of enzymes in glycolysis (glucokinase, phosphofructokinase, pyruvatekinase), gluconeogenesis (glucose 6-phosphatase, fructose 1,6-bisphosphatase), and the pentose phosphate pathway (glucose 6-phosphate dehydrogenase) were measured. It appeared that glucose transport, the pentose phosphate pathway, and gluconeogenesis were maintained during cold preservation and warm ischemia. The activity of glucokinase significantly decreased from the control value of 1.33 +/- 0.23 IU/g protein to 0.70 +/- 0.17 (24 hr, P<0.05) and 0.57 +/- 0.12 (48 hr, P<0.01) only during cold preservation. However, the activity of phosphofructokinase significantly decreased from the control value of 4.37 +/- 0.06 IU/g protein to 2.67 +/- 0.15 (60 min, P<0.0001) and 1.53 +/- 0.06 (120 min, P<0.0001) only during warm ischemia. This indicates that glycolysis deteriorates during both cold preservation and warm ischemia and demonstrates further that the balance between glycolysis and gluconeogenesis shifts to gluconeogenesis. Even when cold preservation was combined with warm ischemia, the activity of glucokinase decreased only during cold preservation and the activity of phosphofructokinase decreased only during warm ischemia. Furthermore, these changes were time-dependent. It is suggested that they can be used as a clock to measure the durations of cold preservation and warm ischemia separately and that the magnitude of an ischemic injury to a liver and a liver graft's viability can be indirectly estimated before transplantation.

Animals↗
PubMed1996

Extension of the indication for living related liver transplantation from children to adults based on resolution of graft size mismatch in relation to tissue oxygenation and metabolic load: a case report.

We extended the indication for living related partial liver transplantation from pediatric to adult cases. Our first case was a 49-year-old woman with primary biliary cirrhosis. Her sister's left lobe, weighing 280 g, was employed as a graft, and the graft weight/recipient's body weight ratio was calculated as 0.59%. To decrease the metabolic load to the relatively small graft, the total bilirubin was decreased from a maximum value of 75.0 mg/d1 to the most recent preoperative value of 36.2 mg/dl by plasma exchange. Intraoperative recovery of tissue oxygenation and its heterogeneity were satisfactory due to a relatively high blood supply. A postoperative decrease in bilirubin and increase in cholesterol esterification were facilitated, concomitant with regeneration of the graft, which weighed 280 g, to 860 cm3 at 3 weeks. Linear regression analysis with respect to tissue oxygenation and metabolic capacity obtained in pediatric cases were applied to this adult case.

Child↗
PubMed1996

Long-duration xenogeneic extracorporeal pig liver perfusion with human blood.

Hepatic xenografts can tolerate hyperacute rejection owing to their lower susceptibility to humorally mediated injury. We investigated the possibility of long-duration xenoperfusion without immunologically controlling natural antibodies or complements. Pig livers were perfused for 9 h with human blood (Group 1) or pig blood (Group 2). Physiological conditioning and administration of prostaglandin E1 and insulin was characteristic of our system. The portal vein and hepatic artery pressure and bile production did not significantly differ between the two groups. Despite a gradual decrease throughout the perfusion, overall oxygen consumption was significantly higher in Group 1. Liver enzymes were released at higher levels in Group 1. Histological examination revealed intact hepatic architecture in Group 2, while in Group 1 interlobular morphology was severely damaged by endothelial disruption, although hepatic sinusoidal architecture was preserved. It is concluded that, despite biochemically and histologically confirmed tissue injury, graft viability was well-maintained in xenoperfusion even without immunological manipulations.

Alprostadil↗
PubMed1996

Graft size-matching in living related partial liver transplantation in relation to tissue oxygenation and metabolic capacity.

The influence of graft size-matching on tissue oxygenation and metabolic capability was studied in living related partial liver transplantations for 47 pediatric patients. Their age ranged from 4 months to 17 years 3 months, their body weight from 4.0 to 58.0 kg, graft weight from 191 to 440 g, and graft weight/recipient body weight ratio from 0.61% to 6.0%. Tissue oxygenation and its heterogeneity were investigated by measuring oxygen saturation of hemoglobin in the liver sinusoid (SO2), coefficient of variation of SO2, and arterial ketone body ratio. The metabolic capacity of the graft was investigated by measuring bilirubin clearance, recovery of cholesterol esterification, and ketone body production. In infants with a relatively large liver graft, both intra- and extracellular oxygenation remained low soon after reperfusion but recovered to the control value by the end of the operation. In adolescent recipients of a relatively small graft, by contrast, synthetic and detoxification capacities were relatively deficient; however, these improved with time. These results indicate that sufficient tissue oxygenation and liver regeneration are essential for successful liver transplantation with relatively large and small grafts, respectively.

Adolescent↗
PubMed1996

Ontogeny of GTP-binding proteins, Gi and G(o), in rat retina.

The distribution and the levels of Gi1 (plus Gi3), Gi2, and G(o) in rat retina were studied immunohistochemically and immunochemically during development. At embryonic day (E) 15, Gi1 alpha/Gi3 alpha was observed in the inner layer of the neural retina, the future nerve fiber layer (NFL), while Gi2 alpha was observed both in the inner and outer layers of the neural retina. No immunoreactivity for G(o) alpha was observed. At E18, Gi1 alpha/Gi3 alpha and Gi2 alpha appeared in the inner plexiform layer (IPL), while G(o) alpha was faintly immunoreactive only in the NFL. At birth, Gi2 alpha/Gi3 alpha and G(o) alpha appeared in the ganglion cell layer. Gi2 alpha was intensely immunoreactive in the NFL and IPL. At postnatal day (P) 10, the inner portions of the retina, from the NFL to the outer plexiform layer, were immunoreactive to Gi1 alpha/Gi3 alpha, Gi2 alpha, and G(o) alpha. Gi1 alpha/Gi3 alpha and G(o) alpha were distributed characteristically in a laminated pattern in the IPL, but Gi2 alpha was present homogeneously in the IPL. At P12, Gi2 alpha appeared in the outer nuclear layer. As the postnatal days advanced, the laminated pattern of immunoreactivity to G(o) alpha in the IPL became diffuse, but immunoreactivity to Gi1 alpha/Gi3 alpha remained. The results of enzyme immunoassays showed that the concentration of G(o) alpha increased rapidly from P10 to P15 and reached almost the adult level at P20-P30, while Gi2 alpha decreased until P15 and was almost constant thereafter. These results showed that the distribution of Gi1 alpha/Gi3 alpha, Gi2 alpha, and G(o) alpha differs during development, suggesting that each G protein in the developing retina has a unique function.

Animals↗
PubMed1996

Energy metabolism and regeneration in transgenic mouse liver expressing creatine kinase after major hepatectomy.

BACKGROUND & AIMS: The catalysis of a creatinine/phosphocreatine system by creatine kinase is not expressed in the liver. The aim of this study was to examine the energy energy metabolism and regeneration after hepatectomy using transgenic mouse liver expressing creatine kinase to clarify the effects of phosphocreatine on liver regeneration. METHODS: Transgenic mice were divided into two groups: group 1 was fed normal chow, and group 2 was fed 10% creatine chow for 5 days. Hepatic energy metabolism was evaluated before and after hepatectomies. Changes in remnant liver weight gain and bromodeoxyuridine labeling index were measured after 70% and 80% hepatectomies. RESULTS: Hepatic adenosine triphosphate level 24 hours after 70% hepatectomy was significantly higher in group 2 than group 1 (P<0.05). In group 2, mitochondrial adenosine triphosphate synthesis was enhanced because of elevated intramitochondrial adenine nucleotide content before hepatectomy, leading to sufficient adenosine triphosphate synthesis after a 70% hepatectomy. Bromodeoxyuridine DNA labeling index 24 hours after a 70% hepatectomy was significantly higher in group 2 than group 1. Rapid liver weight gain was observed in group 2 after a 70% hepatectomy. CONCLUSIONS: Abundant phosphocreatine promotes liver regeneration by reinforced hepatic energy metabolism. Gene transfer of creatine kinase to the liver may be a potential method in liver surgery.

Adenine Nucleotides↗
PubMed1996

Direct measurement of hepatic indocyanine green clearance with near-infrared spectroscopy: separate evaluation of uptake and removal.

We continuously measured hepatic absorbance of indocyanine green (ICG) using near-infrared (NIR) spectroscopy after intravenous bolus injection in rabbits. Hepatic ICG concentration was obtained by subtracting out the absorbance of hemoglobin and other pigments within the liver. Two exponential rate constants, the first reflecting the dye uptake from plasma to the hepatocytes, and the second representing the dye removal from the liver by cytoplasmic transport and biliary excretion, were determined by fitting the time-course curve of hepatic ICG concentration to a two-compartment model with irreversible transfer between the two compartments, as defined by the double-exponential equation: [ICG]liver(t) = -A exp(-alpha t) + B exp(-beta t). The results showed that treatment with bilirubin, a competitive inhibitor of ICG uptake, caused a decrease in alpha. Treatment with either colchicine, which is toxic to microtubules, or with ouabain, an inhibitor of Na+,K(+)-ATPase, caused a decrease in beta. These results were compatible with the kinetic model. This new method was then used in liver-injured rabbits inflicted with hemorrhagic shock and ischemia-reperfusion, to show that the first rate constant is primarily affected by hepatic microcirculatory condition, and the second refers closely to parenchymal liver damage. In another series of partial liver ischemia-reperfusions, it was possible to simultaneously and separately monitor the ICG profiles of post-ischemic and nonischemic areas. Thus, the kinetic analysis of hepatic ICG concentration curves, as directly measured by NIR spectroscopy, led to the separate evaluation of different clearance process of ICG in the liver, suggesting the advanced utility as a comprehensive liver function test.

Adenine Nucleotides↗
PubMed1996

Induction of endotoxin tolerance in transgenic mouse liver expressing creatine kinase.

The liver plays an important role in maintaining homeostasis during endotoxin-triggered systemic inflammatory response. To study the effects of phosphocreatine on hepatic energy metabolism after endotoxin administration, we used transgenic mice whose livers express creatine kinase (CK). CK catalyzes a phosphocreatine/creatine reaction, that is, an adenosine triphosphate (ATP) reservoir system. Because dietary supplementation with creatine leads to an accumulation of creatine and phosphocreatine in transgenic livers, we compared the CK transgenic mice fed with creatine with the normally fed CK transgenic mice. In the creatine-fed mice, hepatic ATP, energy charge ([ATP + 0.5 adenosine diphosphate (ADP)]/[ATP + ADP + adenosine monophosphate (AMP)]), and mitochondrial oxidative phosphorylation activities remained at high levels after injection of 10 mg/kg of lipopolysaccharide (LPS) as compared with those in normally fed mice. Furthermore, there were beneficial effects on the functional reserve for ATP synthesis and work-cost performance, as calculated by free cytoplasmic ADP and the Michaelis constant (Km). Interestingly, a reduction of tissue necrosis factor alpha and interleukin-lalpha (IL-lalpha), and suppression of the decrease in glucose levels after LPS injection were observed in the creatine fed mice. Survival rates at 72 hours after injection of 10 mg/kg of LPS significantly increased in the creatine fed mice compared with the normally fed mice (80% vs. 24%, P < .001). Therefore, we concluded that the presence of phosphocreatine in the liver maintains energy metabolism and attenuates cytokine response, resulting in endotoxin tolerance.

Adenine Nucleotides↗
PubMed1996

Application of agar-fill method to estimate compartment capacity of gastrointestinal tract in Syrian hamsters (Mesocricetus auretus).

In the present study we have developed the agar-fill method for the measurement of gastrointestinal-tract capacity (GTC) to replace the in vitro water-fill method. This would estimate GTC without using complex equipment and techniques, and can be applied to the measurement of GTC for small laboratory animals. We attempted to confirm the efficiency of the agar-fill method by investigating the relationship between dietary neutral-detergent fibre (NDF) content and GTC. The digestion trials were carried out using the Syrian hamster (Mesocricetus auretus). The trials were conducted using both sexes, two age-groups and three levels of dietary NDF with a cross-classified design. The size of each gastrointestinal organ was determined as tissue weight (TW) and GTC. The DM intake, digestible DM intake, DM digestibility, NDF digestibility, acid-detergent fibre (ADF) digestibility and digesta transit time were also measured. GTC increased with increasing NDF content of the diets. TW responded similarly to increasing NDF content, but the response was smaller than that of GTC. DM digestibility decreased with increasing NDF content of the diet. The digestible DM intake did not decrease with increasing NDF because DM intake increased with NDF content. Digesta transit time was not shorter of the high-NDF diet group but DM intake increased with increasing NDF content. NDF digestibility did not differ significantly between low- and medium-NDF diets. ADF digestibility was low in the low-NDF-diet group. The digestion characteristics were highly correlated with TW and GTC, except for TW of small intestine. These correlations were higher with GTC than with TW. The results of the present study confirm previous findings suggesting that the agar-fill method is a useful means of estimating GTC for small laboratory animals.

Agar↗
PubMed1996

Absorbable and nonabsorbable buried sutures for primary cleft lip repair.

Absorbable and nonabsorbable buried sutures were studied in primary cleft lip repair. Group 1 (N = 56) consisted of patients repaired with buried nonabsorbable material (monofilament nylon). Group 2 (N = 47) consisted of patients repaired with absorbable materials (polyglyconate, polydioxanone). All patients were monitored for 12 months. There were stitch abscesses in Group 1 (14%). There were no abscesses in Group 2. This difference was significant (p = 0.007). Abscesses were located in the suture line with no identifiable distribution. There was no significant difference in the cosmetic appearance of the scars in Groups 1 and 2. These results support the view that absorbable sutures are preferable to nonabsorbable sutures for primary cleft lip repair.

Abscess↗
PubMed1996

Immunohistochemical study of 28-kD heat shock protein in the lens of young human embryos.

The localization of 28-kD heat shock protein (HSP28) in the lenses of human embryos (Carnegie stages 13-21) was studied immunohistochemically using antibodies for HSP28. At stage 13, HSP28 was observed in the lens placode. At stage 15, when the lens vesicle is formed by the invagination of the lens placode, HSP28 was observed in the posterior portion of the lens vesicle. From stages 16 to 18, when the posterior portion of the lens epithelium elongates toward the anterior lens epithelium and forms the primary lens fiber, HSP28 was observed in the apical and basal sides of the primary lens fiber. At stage 19, when the primary lens fiber attaches to the anterior lens epithelium, immunoreactivity to HSP28 appeared in the anterior lens epithelium. At stage 21, the anterior lens epithelium and the equator portion of the lens, where the secondary lens fiber is formed, were intensely immunoreactive to HSP28. Although alpha B-crystallin is thought to be one of the small HSPs, the distribution of HSP28 in the lenses of human embryos was different from that of alpha B-crystallin which we previously reported.

Gestational Age↗
PubMed1996

Epidermal growth factor delays gastric emptying and small intestinal transit in suckling rats.

Suckling (12-d-old) rats that were fasted for 15 h received epidermal growth factor (EGF) s.c. (0.5 and 1.0 microgram per rat, i.e. approximately 2 and 4 micrograms/100 g of body weight), together with motility markers 51Cr-EDTA or Poly R-478, and were killed 45 min later. Counts were measured separately in the stomach and the small intestine, which was divided into 12 segments. Administration of EGF delayed gastric emptying. In controls, the stomach contained 26.1 +/- 1.6% (mean +/- SEM); in EGF-treated rats the stomach contained 75.9 +/- 10.2% and 75.7 +/- 2.5% of the total 51Cr-EDTA counts given. EGF had the maximum effect (1.0 microgram) when given simultaneously with 51Cr-EDTA. Significant, but lower, effects of EGF were seen with the administration of EGF preceded by 10 min or followed by 10 and 20 min with the administration of 51Cr-EDTA (65.8 +/- 5.8%, 60.0 +/- 6.4%, and 54.1 +/- 4.2%, respectively). Small intestinal transit was also delayed. Administration of anti-EGF antiserum did not affect gastric emptying, but accelerated small intestinal transit as determined 30 min after administration of 51Cr-EDTA. These studies are the first to demonstrate the effect of EGF on gastrointestinal motility in vivo in suckling mammals.

Animals↗
PubMed1996

Does the nerve supply to both the superficial and deep surfaces of pectoralis major imply two separate developmental origins?

The nature of the nerve supply to the "pocket' of pectoralis major was examined on 7 randomly selected sides of 5 embalmed cadavers. The pocket was a U-shaped muscular fold, opening cranially. The anterior limb and inner surface of the fold were supplied by nerve branches that originated from the middle segment of the pectoral nerve loop and penetrated pectoralis minor. The outer surface of the posterior limb was supplied by one or two branches that extended from the caudal segment of the pectoral nerve loop. If the muscular U-shaped fold is unfolded, it becomes obvious that the posterior wall of the pocket forms the most caudal part of pectoralis major and is supplied from both the superficial (anterior) and deep (posterior) surfaces. This dual surface supply does not suggest any aspect of the developmental origin of the pocket but may simply be due to the relative positions of the pectoralis major and its nerve.

Aged↗