Effect of exogenously administered HGF activator in liver regeneration.
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Animals↗
Biomedical subjects
T Okumura
Publications and source records attributed to T Okumura.
Relationship of regional adiposity to serum leptin level in nonobese Japanese type 2 diabetic male patients.
BACKGROUND: The aim of the present study was to investigate the relationships between serum leptin levels and regional adipose fat area, BMI, and the measures of variables including serum insulin in nonobese Japanese type 2 diabetic patients. METHODS: A total of 121 nonobese Japanese type 2 diabetic patients [aged 35 to 83 years, body mass index (BMI) (15.4 to 26.8 kg/m(2))] were studied. They all were male patients. In conjunction with serum leptin level, BMI, glycosylated hemoglobin (HbA(1c)), and fasting concentrations of plasma glucose and serum insulin and lipids (triglycerides, total and HDL cholesterol) were measured. RESULTS: Univariate regression analysis showed that serum leptin levels were positively correlated to subcutaneous (r=0.566, P<0.0001) and visceral (r=0.481, P<0.001) fat area in our diabetic patients. Furthermore, serum leptin levels were positively correlated to serum insulin (r=0.517, P<0.0001), BMI (r=0.428, P<0.0001), serum triglycerides (r=0.279, P<0.005), and age (r=0.225, P<0.05). There was, however, no relationship between serum leptin levels and measures of other variables including total and HDL cholesterol. Multiple regression analyses showed that serum leptin levels were predicted by subcutaneous fat area (F=5.92, P<0.0001) and serum insulin level (F=5.60, P<0.0001), which explained 29.0% of the variability of serum leptin concentrations in our nonobese Japanese type 2 diabetic male patients. Visceral fat area, BMI, serum triglycerides, and age, however, were not independently associated with serum leptin levels in our patients. CONCLUSIONS: These results indicate that serum leptin levels are reflective of subcutaneous fat area in nonobese Japanese type 2 diabetic male patients.
Adipose Tissue↗
Comparison of one- and two-step procedures in a rat model of small bowel transplantation.
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Anastomosis, Surgical↗
Effect of short-term low-intensity exercise on insulin sensitivity, insulin secretion, and glucose and lipid metabolism in non-obese Japanese type 2 diabetic patients.
The aim of the present study was to investigate the effects of short-term physical exercise that did not change body mass on insulin sensitivity, insulin secretion, and glucose and lipid metabolism in 39 non-obese Japanese type 2 diabetic patients. Insulin sensitivity and insulin secretion were estimated with homeostasis model assessment insulin resistance (HOMA-IR) and HOMA-B-cell function proposed by Matthews et al., respectively. All patients were hospitalized and were engaged in low-intensity exercise that consisted of walking and dumbbell exercise for successive 7 days. There were no changes in hospital diet and the dose of any medications used throughout the study. Fasting glucose, insulin, and lipids were measured before and after exercise. After exercise, serum triglyceride levels significantly decreased, but no significant changes were observed in total and HDL cholesterol concentrations. Fasting glucose, insulin, and HOMA-IR levels significantly decreased after exercise, but HOMA-B-cell function did not change during the study. There was no significant difference between BMI levels before and after exercise. From these results, it can be concluded that short-term (7 days) low-intensity physical exercise combined with hospital diet reduces serum triglycerides, insulin resistance, and fasting glucose levels without affecting BMI in non-obese Japanese type 2 diabetic patients.
Adult↗
Effect of low or high dietary calcium on the morphology of the rat femur.
The present study compared the effect of a calcium deficit or surfeit on femurs. Young female rats were fed with the normal (1.18%), low (0.05%), or high (2.00%) calcium diet for 3, 7, 15 or 30 days. Two groups received the low calcium diet for the first 15 days and then were followed by the normal (L-N) or high calcium diets (L-H) for the sequential 15 days. The morphology of the femur was studied together with serum calcium, parathyroid hormone (PTH), calcitonin and bone mineral density (BMD). We did not find any significant changes in the serum PTH level and bone morphology in the high calcium group. In the low calcium group, the serum PTH level increased, BMD of the whole body, the femoral weight and the femoral trabecular bone decreased as compared with the normal calcium group. There was a greater proportion of resorbing surface, less resting surface and larger vascular canal openings in the femoral endosteal surfaces in the low calcium group. In the L-N or L-H group, the femoral trabecular bone increased and the femoral resorbing surface decreased as compared with those of the low calcium group. These findings suggest that high calcium intakes do not affect the bone mass, and low calcium intakes have a deleterious effect on bone status, which may be related to vascular alternations of the bone. Reversing the low income calcium intake by a higher calcium diet can partially improve the bone alternations induced by low calcium intake.
Animals↗
Estrogen decreases the responsiveness of subfornical organ neurons projecting to the hypothalamic paraventricular nucleus to angiotensin II in female rats.
Extracellular single-unit activity was recorded from subfornical organ (SFO) neurons antidromically identified as projecting to the hypothalamic paraventricular nucleus (PVN) in urethane-anesthetized ovariectomized female rats that were treated with either propylene glycol (PG) vehicle or estradiol benzoate (EB). No significant differences were observed between the PG- and EB-treated rats in the latency, conduction velocity, or threshold of antidromic activation. The mean spontaneous firing rate was significantly lower and the refractory period was significantly longer in the EB-treated rats. In the identified units that were activated by angiotensin II (ANG II) applied iontophoretically, the amount of excitatory response to intracarotid administration of ANG II was much greater in the PG-treated than in the EB-treated rats. These results suggest that estrogen may decrease the responsiveness of SFO neurons projecting to the PVN to circulating ANG II.
Action Potentials↗
FK506, but not cyclosporin A, prevents mitochondrial dysfunction during hypoxia in rat hepatocytes.
Hepatic ischemia/reperfusion injury occurs in the clinical situations including liver transplantation. FK506 and cyclosporin A (CsA) are reported to be hepatotrophic agents in addition to being a powerful immunosuppressive agent. Studies were performed to determine whether the drugs influence a mitochondrial dysfunction under the hypoxic conditions in primary culture model of rat hepatocytes. The Anaeropack system was used for cell culture to create a hypoxia. Cells were treated with FK506 or CsA under the normoxic and hypoxic conditions. Hypoxia markedly decreased intracellular adenosine 5'-triphosphate (ATP) contents and the ketone body ratio (KBR, acetoacetate/beta-hydroxybutyrate) in culture medium as compared with normoxia. FK506 prevented the decreases of ATP contents and the KBR. In contrast, CsA had no effect on either ATP contents or the KBR. FK506, but not CsA, increased the KBR under the normoxic conditions. Under the hypoxic conditions, heat shock protein 70 (Hsp70) was detected after reoxygenation. FK506 enhanced the induction of Hsp70, but CsA again had no effect on Hsp70 induction. These results indicate that FK506 protects the hypoxia injury in part by preventing the mitochondrial dysfunction in concert with the enhancement of heat shock response in hepatocytes.
Adenine Nucleotides↗
Activation of the subfornical organ enhances extracellular noradrenaline concentrations in the hypothalamic paraventricular nucleus in the rat.
Experiments were carried out to investigate whether angiotensinergic efferent pathways from the subfornical organ (SFO) regulate the noradrenergic system in the region of the hypothalamic paraventricular nucleus (PVN). Intracerebral microdialysis techniques were utilized to quantify the extracellular content of noradrenaline (NA) in the PVN area. In urethane-anaesthetized male rats, electrical stimulation (5-20 Hz, 600 microA) of the SFO significantly increased the NA concentration in the region of the PVN, and the increase was significantly prevented by pretreatment with the angiotensin II (ANG II) antagonist saralasin (Sar, 5 microg), into the third ventricle (3V). Injections of ANG II (5 microg) into the 3V significantly enhanced NA release in the PVN area. These results suggest that the angiotensinergic pathways from the SFO to the PVN may act to enhance NA release in the region of the PVN.
Angiotensin II↗
Requirement of intact disulfide bonds in orexin-A-induced stimulation of gastric acid secretion that is mediated by OX1 receptor activation.
Orexin-A is a neuropeptide consisting of 33 amino acids with two intrachain disulfide bonds, namely Cys6-Cys12 and Cys7-Cys14, and is a potent stimulator of food consumption and gastric acid secretion. In contrast, orexin-B, a peptide containing 28 amino acids without disulfide bond, which has no stimulatory action of gastric acid. The objective of the present study was to characterize the receptor-mediated mechanism of orexin-A-induced stimulation of gastric acid secretion using orexin-A-related peptides with modification of disulfide bonds. Intracisternal injection of orexin-A, but not orexin-B or orexin-A (15-33), that does not contain both disulfide bonds stimulated gastric acid secretion in pylorus-ligated conscious rats. The ability of the stimulation of gastric acid output was less in three alanine-substituted orexin-A, [Ala(6,12)]orexin-A, [Ala(7,14)]orexin-A, and [Ala(6,7,12,14)]orexin-A, than orexin-A. Orexins-induced calcium increase was measured in CHO-K1 cells expressing OX1R or OX2R. Orexin-A induced a transient increase in [Ca(2+)]i in CHO-K1/OX1R cells in a dose-dependent manner. EC50 values for OX1R of orexin-A, orexin-B, or orexin-A (15-33) was 0.068, 0.69 or 4.1 nM, respectively, suggesting that peptides containing no disulfide bonds have lower potency for the receptor. Agonistic activity for OX1R of the three orexin-A analogues with modification of one or both disulfide bonds was significantly reduced as compared with that of orexin-A. EC50 values for OX2R of orexin-A and orexin-B was almost equal but potency for the receptor of orexin-A (15-33) and three alanine substituted orexin-A was less than that of orexin-A. A significant inverse relationship between gastric acid output and EC50 values for OX1R, but not OX2R, was observed. These results suggested that the orexin-A-induced acid stimulation requires OX1R activation and that disulfide bonds in orexin-A may have a key role in the receptor activation.
Amino Acid Sequence↗
High density O-glycosylation of the MUC2 tandem repeat unit by N-acetylgalactosaminyltransferase-3 in colonic adenocarcinoma extracts.
A synthetic peptide corresponding to the human MUC2 tandem repeat unit was glycosylated in vitro using UDP-GalNAc and extracts of colonic adenocarcinoma and paired normal mucosa, followed by fractionation of the products by reverse phase high-performance liquid chromatography. Several peaks of glycopeptides with different numbers of GalNAc residues attached were detected. It is notable that the adenocarcinoma extract was capable of glycosylating peptides to a much greater extent than was normal mucosa. The levels of mRNA for N-acetylgalactosaminyltransferases-1, -2, and -3 were determined by reverse transcription-PCR. Only N-acetylgalactosaminyltransferase-3 mRNA was expressed at a higher level in the adenocarcinoma than in the normal tissue. When the MUC2 tandem repeat peptide was glycosylated with a mixture of the normal mucosa extract and recombinant N-acetylgalactosaminyltransferase-3, larger amounts of glycopeptides with higher contents of GalNAc residues were produced. The MUC2 tandem repeat peptides glycosylated extensively by recombinant N-acetylgalactosaminyltransferase-1, -2, or -3 were prepared and characterized. Substitution at each Thr residue, as revealed by Edman degradation sequencing, in conjunction with evidence obtained on mass spectrometry indicated a heterogeneous pattern of site-specific glycosylation within the MUC2 tandem repeat. It was found that maximum numbers of 6, 8, and 11 GalNAc residues were incorporated by N-acetylgalactosaminyltransferases-1, -2, and -3, respectively, and that only N-acetylgalactosaminyltransferase-3 could completely glycosylate both consecutive sequences composed of three and five Thr residues in the MUC2 tandem repeat unit. These results suggest that O-glycosylation of the clustered Thr residues is a selective process controlled by N-acetylgalactosaminyltransferase-3 in the synthesis of clustered carbohydrate antigens.
Acetylgalactosamine↗
Angiotensinergic and noradrenergic mechanisms in the hypothalamic paraventricular nucleus participate in the drinking response induced by activation of the subfornical organ in rats.
The present study was done to investigate the contribution of the hypothalamic paraventricular nucleus (PVN) to the drinking response caused by activation of the subfornical organ (SFO) following angiotensin II (ANG II) injections in the awake rat. Microinjection of ANG II into the SFO elicited the drinking response. Previous injections of either saralasin, an ANG II antagonist, or phentolamine, an alpha-adrenoceptor antagonist, bilaterally into the PVN resulted in the significant attenuation of the drinking response to ANG II. Similar injections of any of the beta-adrenoceptor antagonist timolol, the muscarinic antagonist atropine, or saline vehicle into the PVN had no significant effect on the drinking response. In an attempt to clarify the neural mechanisms in the PVN involved in the drinking response to ANG II injected into the SFO, the effect of microinjection of ANG II into the SFO on noradrenaline (NA) release in the PVN was examined using intracerebral microdialysis techniques. The injection of the ANG II, but not saline vehicle, significantly enhanced the NA release in the region of the PVN. These results indicate the involvement of both the angiotensinergic and alpha-adrenergic systems in the PVN in the drinking response caused by angiotensinergic activation of the SFO, and imply that the angiotensinergic projections from the SFO to the PVN may serve to increase NA release which results in mediating water intake.
Adrenergic alpha-Antagonists↗
GABAergic modulation of neurons in the nucleus of the solitary tract with ascending projections to the subfornical organ in the rat.
Twenty-five neurons in the region of the nucleus of the solitary tract (NTS) were antidromically activated by electrical stimulation of the subfornical organ (SFO) in male rats under urethane anesthesia. Microiontophoretically applied bicuculline, a gamma-aminobutyric acid (GABA)(A) antagonist, but not phaclofen, a GABA(B) antagonist, attenuated the post-antidromic inhibitory response evoked by SFO stimulation of approximately two-third (n=17) of identified neurons, indicating the existence of recurrent inhibitory systems through GABA(A) receptors. Iontophoretically applied GABA decreased the spontaneous activity of all identified neurons, and the GABA-induced inhibition was prevented by simultaneously applied bicuculline, but not by phaclofen. Activation of peripheral baroreceptors, achieved by rising arterial blood pressure with an intravenous infusions of phenylepherine, suppressed the activity of the majority (n=20) of identified neurons. The inhibitory response of identified neurons (n=7) to baroreceptor activation was partially antagonized by iontophoretically applied bicuculline, but not by phaclofen. These results imply that GABAergic mechanisms may modulate the baroreceptor reflex acting on GABA(A) receptors of NTS neurons with ascending projections to the SFO in the region of the NTS.
Animals↗
Activation of serotonergic pathways from the midbrain raphe system to the subfornical organ by hemorrhage in the rat.
The role of serotonergic neural pathways from the midbrain raphe nuclei to the subfornical organ (SFO) in the central regulation of cardiovascular function and body fluid balance was investigated in adult male rats under urethane anesthesia. Eleven neurons in the dorsal raphe nucleus (DR) were antidromically activated by electrical stimulation of the SFO. Of these neurons, 6 displayed an excitatory response following hemorrhage (10 ml/kg bwt) while the remaining 5 neurons were unresponsive. Ninety-four neurons in the SFO were tested for a response to electrical stimulation of the DR or hemorrhage. Electrical stimulation of the DR caused orthodromic excitation (19%) or inhibition (5%) of the activity of SFO neurons. In 14 of 18 SFO neurons that displayed the excitation to the stimulation of the DR, hemorrhage (30 to 50 mm Hg suppression in mean arterial pressure) produced an increase of their discharge, while the stimulus was without effect in the remaining neurons responsive to the stimulation of the DR. The effects of hemorrhage on serotonin (5-HT) release in the region of the SFO were examined using intracerebral microdialysis techniques. Hemorrhage significantly increased 5-HT and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the region of the SFO. The present data suggest that the serotonergic pathways from the DR to the SFO may relay activation of the peripheral baroreceptors to SFO neurons which result in enhanced excitability, indicating the involvement of the pathways in the regulation of cardiovascular function.
Action Potentials↗
Intrahepatic cholangiojejunostomy for unresectable malignant biliary tumors with obstructive jaundice.
We reviewed our experience with intrahepatic cholangiojejunostomy as a palliative therapy for patients with unresectable malignant diseases involving the ductal confluence or the common hepatic duct. Fifteen patients with malignant biliary obstruction were treated by cholangiojejunostomy at our hospital. Two patients had intrahepatic cholangiocarcinoma, 7 had gallbladder carcinoma, 5 had bile duct carcionoma, and 1 had pancreatic carcinoma. Segment III cholangiojejunostomies were performed in 14 patients and segment V cholangiojejunostomy in 1. Contraindications for surgical resection were locoregional invasion of tumors involving the proper and/or common hepatic artery and portal vein in 15 patients and the presence of hepatic metastases in 6 patients. Liver metastases were detected in 5 of the 7 patients with gallbladder carcinoma. Postoperative complications occurred in 2 patients (13%), but there was no leakage of the cholangioenteric anastomosis in our series. There was no operative mortality after cholangiojejunostomy. Of the 9 patients who survived for more than 6 months after surgery, 7 showed a significant improvement in performance status (PS) (82 +/- 10%) 3 months after the surgery compared with the preoperative PS (70 +/- 7%). Four of the 9 patients had recurrent cholangitis as a late complication, but 4 were completely free from jaundice. Median survival after cholangioenteric bypass was 9 months (range, 2-25 months). With respect to tumor location, the median survival time was 4 months (range, 2-25 months) in patients with gallbladder carcinoma and 15.5 months (range, 12-22 months) in those with bile duct carcinoma. While the median survival period after surgery was only 3 months (range, 2 to 8 months) in the 5 patients with hepatic metastases from gallbladder carcinoma, 2 patients without liver metastasis survived for 9 and 25 months after segment III cholangioenteric bypass. In conclusion, cholangiojejunostomy can provide useful palliation for malignant biliary obstruction when combined with careful patient selection.
Bile Duct Neoplasms↗
Fluoroscopy-assisted thoracoscopic surgery after computed tomography-guided bronchoscopic barium marking.
BACKGROUND: Small lesions of the peripheral lung have been detected more frequently with the recent prevalence of computed tomography (CT). Identification of these lesions is indispensable for wedge resection performed by video-assisted thoracic surgery. Previous reports of marking techniques showed some failure and complications. We have developed a new marking technique and herein describe the efficacy of this technique: fluoroscopy-assisted thoracoscopic surgery after computed tomography-guided bronchoscopic barium marking. METHODS: Twenty patients underwent this procedure for 21 small peripheral pulmonary lesions approximately 10 mm in size. RESULTS: All the lesions were successfully marked and identified during fluoroscopy-assisted thoracoscopy. They were resected with sufficient margins. There were no complications related to this procedure. The pathologic examination of these 21 lesions revealed primary lung cancer in 14, atypical adenomatous hyperplasia in four, a metastatic tumor in one, and a benign tumor in two. CONCLUSIONS: This procedure is both a reliable and minimally invasive technique in thoracoscopic wedge resection for small peripheral pulmonary lesions.
Adult↗
Recurrent hepatocellular carcinoma versus radiation-induced hepatic injury: differential diagnosis with MR imaging.
The objective of this study was to assess the value of MR imaging in the differentiation between a recurrent hepatocellular carcinoma (HCC) and a radiation-induced hepatic injury. Nine male patients with suspected recurrence after radiotherapy for HCC underwent T(2)-, T(1)-weighted imaging and Gd-DTPA enhanced dynamic studies. T(2) relaxation times, signal intensity ratios in T(1)-weighted images (WI) and the relative enhancement of the dynamic study were calculated. Recurrent tumors and the irradiated area showed similar image characteristics: hypointense in T(1)-WI and hyperintense in T(2)-WI. T(2) values and signal intensity ratios in the T(1)-WI were not significantly different. In the gadolinium-enhanced dynamic study, a recurrent HCC showed early enhancement, followed by a rapid washout. However, the irradiated liver parenchyma showed hyperintensity from an early phase, and contrast enhancement tended to be more prominent and prolonged at the end of the dynamic studies. The characteristic findings of the dynamic MR study enable us to distinguish between a recurrent HCC and a radiation-induced hepatic injury.
Aged↗
Negotiation behavior when cultures collide: the United States and Japan.
This study compared the negotiation behaviors of Japanese and U.S. managers in intra- and intercultural settings. Transcripts from an integrative bargaining task were coded and analyzed with logistic and linear regression. U.S. negotiators exchanged information directly and avoided influence when negotiating intra- and interculturally. Japanese negotiators exchanged information indirectly and used influence when negotiating intraculturally but adapted their behaviors when negotiating interculturally. Culturally normative negotiation behaviors partially account for the lower joint gains generated by intercultural, relative to intracultural, dyads. The behavioral data inform motivational and skill-based explanations for elusive joint gains when cultures clash.
Adult↗
Effects of bezafibrate on insulin sensitivity and insulin secretion in non-obese Japanese type 2 diabetic patients.
The aim of the present study was to investigate the effect of bezafibrate on insulin sensitivity and insulin secretion in 30 non-obese Japanese type 2 diabetic patients with hypertriglyceridemia (serum triglycerides > 150 mg/dL). Insulin sensitivity was measured with homeostasis model assessment insulin resistance (HOMA-IR) proposed by Matthews et al. HOMA-B-cell function, proposed by Matthews et al validated against minimal model-derived insulin secretion, was used to assess pancreatic insulin function. Twenty-two patients were treated with glibenclimide and the rest were treated with diet alone. All patients were treated with bezafibrate (400 mg/d) for 3 months. There were no changes in diet and the dose of any medications used throughout the study. Fasting glucose, insulin, triglycerides, HDL cholesterol, and total cholesterol levels were measured before and after treatment of bezafibrate. After treatment of bezafibrate for 3 months, serum triglyceride levels significantly decreased from 277 +/- 30 to 139 +/- 9 mg/dL (P <.001) and serum HDL cholesterol levels increased significantly from 45 +/- 2 to 52 +/- 2 mg/dL (P =.003). Serum cholesterol level was unchanged during the study (198 +/- 7 v 201 +/- 7 mg/dL, P =.383). Fasting glucose (163 +/- 8 v 139 +/- 6 mg/dL, P =.006) significantly decreased after the treatment with bezafibrate. HbA1c levels decreased, although not statistically significant (7.50 +/- 0.25 v 7.17% +/- 0.19%, P =.147). On the other hand, fasting insulin (9.3 +/- 0.7 v 7.3 +/- 0.5 microU/mL, P =.010) and HOMA-IR (3.61 +/- 0.24 to 2.53 +/- 0.20, P <.001) levels decreased significantly after the treatment with bezafibrate. In contrast, HOMA-B-cell function did not change during the study (41.4 +/- 5.5 v 41.8 +/- 4.7, P =.478). There was no significant difference in body mass index (BMI) levels before and after the therapy (23.0 +/- 0.4 v 23.1 +/- 0.4 kg/m(2), P =.483). From these results, it can be concluded that bezafibrate reduces serum triglycerides, insulin resistance, and fasting blood glucose levels in non-obese Japanese type 2 diabetic patients.
Adult↗