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Biomedical subjects

H Ohnuma

Publications and source records attributed to H Ohnuma.

At least 37 records · Page 2Linked to original sources
PubMed1998

Effects of glucagon on glycogenolysis and gluconeogenesis are region-specific in periportal and perivenous hepatocytes.

It has been established, mainly by histochemical and immunohistochemical studies, that liver cells are functionally heterogeneous, with periportal hepatocytes (PPHs) being predominantly gluconeogenic and perivenous hepatocytes (PVHs) being glycolytic. We therefore investigated the region-specific functional effects of glucagon on glycogenolysis and gluconeogenesis in isolated PPHs and PVHs prepared by the digitonin-collagenase method. BB rats, a model of insulin-dependent diabetes, were used to study the region-specific heterogeneity of gluconeogenesis in the diabetic state. Although glycogen content was not different between PVHs and PPHs in rats fed the normal diet, basal glucose release was 1.37 times greater in PVHs than in PPHs (P <.05). The increase in glucose release stimulated by 0.01 to 0.1 nmol/L glucagon was 1.52 times greater in PVHs than in PPHs (P < .05), whereas no differences were seen in response to 1 to 100 nmol/L glucagon. Glucose release from gluconeogenic substrates was 1.57 times greater in the PPHs than in the PVHs of fasted normal rats (P < .05), whereas the increase in gluconeogenesis produced by glucagon was not different between PPHs and PVHs. The glucagon-binding capacity, the cAMP release, and the increase in intracellular Ca2+ stimulated by glucagon were not different between PPHs and PVHs in the fed or fasted states. Gluconeogenesis from gluconeogenic substrates was 1.52 times greater in the PPHs than in the PVHs of fasted nondiabetic BB rats (P < .05). After the development of diabetes, the gluconeogenic capacity in PVHs increased to the level observed in PPHs, but that in PPHs did not change. Thus there was no difference in gluconeogenesis between the PPHs and PVHs of diabetic BB rats. In both the PPHs and PVHs of diabetic BB rats, the 0.01 to 100 nmol/L glucagon-induced increase in gluconeogenesis was greater than that in PPHs from nondiabetic BB rats (2.30 and 3.07 times, P < .01, respectively). We conclude that PPHs and PVHs of normal rat liver express region-specific differences in their glycogenolytic and gluconeogenic responses to glucagon. In diabetic BB rats, the difference in the gluconeogenic capacity between PPHs and PVHs disappeared, whereas glucagon-induced gluconeogenesis was enhanced.

Animals↗
PubMed1998

Impaired vagus nerve-mediated control of insulin secretion in Wistar fatty rats.

It has been reported that hyperglycemia in the portal venous blood suppresses afferent activity of the hepatic branch of the vagus nerve, which in turn accelerates efferent activity of the pancreatic branch of the vagus nerve to stimulate insulin secretion. The present study examined this neural control mechanism in genetically obese diabetic male Wistar fatty (fa/fa) rats. Adult (aged 12 to 14 weeks) Wistar fatty rats were obese, hyperinsulinemic, and hyperglycemic. Young (aged 5 to 6 weeks) Wistar fatty rats were slightly obese and hyperinsulinemic, but were euglycemic compared with the lean littermates. In both adult and young lean littermates, the plasma insulin response after an intragastric glucose load (1 g/kg) was diminished by intracerebroventricular (i.c.v.) atropine methylbromide (methylatropine 10 nmol) pretreatment, and a transient increase in plasma insulin was observed after selective hepatic vagotomy, as reported in normal rats. In contrast, in both adult and young Wistar fatty rats, the plasma insulin response after an intragastric glucose load was not diminished by i.c.v. methylatropine pretreatment, and plasma insulin decreased slightly after selective hepatic vagotomy. Further, afferent discharges of the hepatic vagal branch decreased and efferent discharges of the celiac/pancreatic vagal branch increased when 10 mg glucose was infused into the portal vein in the 9-week-old lean littermates, as reported in normal rats. In 7-week-old Wistar fatty rats, afferent discharges of the hepatic vagal branch decreased but efferent discharges of the celiac/pancreatic vagal branch did not increase after intraportal glucose infusion. It is concluded that the vagus nerve-mediated regulation of insulin secretion is impaired from an early stage of life in Wistar fatty rats. Efferent discharges of the vagus nerve to the pancreas seem not to be suppressed by afferent discharges from the hepatic vagus branch, which may lead to insufficient insulin secretion in response to nutrient ingestion followed by a delayed peak. These abnormalities may thus lead to the insulin resistance and fasting hyperinsulinemia that characterize the Wistar fatty rat model.

Animals↗
PubMed1998

Hyperglycemia is a factor for an increase in serum ceruloplasmin in type 2 diabetes.

OBJECTIVE: To examine if there is a correlation between high blood glucose and serum ceruloplasmin (Cp) levels. RESEARCH DESIGN AND METHODS: Serum Cp levels were measured in 637 patients with type 2 diabetes (all type 2 diabetes group). For the follow-up type 2 diabetes group, 161 patients who had not had any changes in their situation during the last year that are known to influence serum Cp levels were reexamined 1 year later. The control group was composed of 158 healthy individuals. Serum Cp and blood HbA1c levels were measured by radial immunodiffusion and high-performance liquid chromatography assays, respectively. RESULTS: Serum Cp levels in the all type 2 diabetes group were significantly higher than those in the control group (P < 0.0001), although the serum Cp levels did not correlate with the blood HbA1c levels in the all type 2 diabetes group (r = 0.055, P = 0.351). Then we evaluated those factors (delta-log Cp and delta-HbA1c) in the follow-up type 2 diabetes group to minimize changes from the genetic differences and to exclude any known factors influencing serum Cp levels. This indicated that the delta-HbA1c had a positive correlation to the delta-log Cp (r = 0.304, P < 0.0001). CONCLUSIONS: A persistent high blood glucose (namely HbA1c) is associated with an increase in serum Cp levels over 1 year.

Adult↗
PubMed1997

A monoclonal antibody against a hepatitis B e antigen epitope borne by six amino acids encoded by the precore region.

Hepatitis B e antigen (HBeAg) polypeptide in the circulation (p17e) is composed of ten amino acids (aa) coded for by the precore region and 149 aa by the core gene of hepatitis B virus. A monoclonal antibody (Y0583A) was raised against the N-terminal ten amino acids (SKLCLGWLWG) encoded by the precore region. The binding of Y0583A with a panel of 203 decapeptides on multipins, which covered the precursor of HBeAg polypeptide made of 212 aa shifting by one aa, recognized an epitope sequenced LGWLWG representing the C-terminal six aa coded for by the precore region. This HBeAg epitope was not readily accessible on HBeAg in serum, but it became exposed and bound with Y0583A by treatment with 0.2 N NaOH. Using Y0583A, an enzyme-linked immunosorbent assay was developed for specific determination of HBeAg. The test sample was incubated with the monoclonal antibody to an HBeAg determinant encoded by the core gene (904) that had been immobilized on a solid support. Captured HBeAg was treated with 0.2 N NaOH, neutralized and released into the fluid phase. The reactant was then tested for a sandwich between monoclonal antibody (C33) to the C-terminus of the HBeAg polypeptide immobilized on a solid support and Y0583A labeled with horseradish peroxidase.

Amino Acid Sequence↗
PubMed1997

Increased epinephrine-induced cAMP response in severely diabetic BB/W rat liver.

The effect of prolonged diabetes on epinephrine-induced adenosine 3',5'-monophosphate (cAMP) response in the liver was examined in diabetes-prone BB/W rats. Basal and 1 microM epinephrine-induced cAMP release from isolated perfused liver was similar in non-diabetic and diabetic BB/W rats with preserved adipose tissue. In adipose tissue-absent diabetic rats losing intra- and retro-peritoneal adipose tissue completely, both basal and 1 microM epinephrine-induced cAMP release from the liver were enhanced (P<0.01, each case). Plasma epinephrine and norepinephrine were similar in non-diabetic, adipose tissue-preserved and -absent diabetic BB/W rats. The plasma free thyroxine level was similar in non-diabetic and adipose tissue-preserved diabetic BB/W rats, but was lower in adipose tissue-absent diabetic BB/W rats than in non-diabetic rats (P<0.01), but the frequency of lymphocytic thyroiditis was similar in these three groups, although plasma corticosterone was lower in adipose tissue-preserved diabetic BB/W rats (P<0.05) and the lowest in adipose tissue-absent diabetic BB/W rats (P<0.01). Lymphocytic infiltration was not observed in the adrenal or pituitary glands in any group. Plasma total protein and albumin were low in adipose tissue-absent diabetic BB/W rats (P<0.01, each case). In adipose tissue-absent diabetic BB/W rats, liver dysfunction and hepatomegaly, but no apparent histological change in the liver, were observed. Plasma glucose was higher (P<0.01) and plasma insulin lower (P<0.05) in adipose tissue-absent diabetic BB/W rats than in adipose tissue-preserved diabetic BB/W rats. In conclusion, epinephrine-induced cAMP response in the liver was enhanced only in adipose tissue-absent diabetic BB/W rats. Denervation supersensitivity was not likely to be responsible for the enhanced beta-adrenergic response. The observed reductions in plasma thyroxine and corticosterone seemed to result from severe diabetes. Although the severity of diabetes can vary continuously, severe diabetes with loss of adipose tissue appeared to cause significant changes in the metabolism and enhanced beta-adrenergic response in the liver.

Alanine Transaminase↗
PubMed1996

Intracerebroventricular injection of methylatropine suppresses insulin response to oral glucose load in rats.

Hepatic glucoreceptor-vagal afferent inputs to the central nervous system and pancreatic vagal efferent stimuli are important for insulin secretion. In the present study, we examined the effect of intracerebroventricular (i.c.v.) injection of atropine methyl bromide (methylatropine) on the insulin response following glucose ingestion in rats. When rats were injected with methylatropine i.c.v., the plasma glucose concentration increased, the insulin response reduced, and glucagon-like peptide-1 (7-36) amide (tGLP-1) was unchanged following an oral glucose load, compared with the controls. The plasma insulin response following an intravenous glucose load was not affected by i.c.v. or intraperitoneal injection of methylatropine. A transient increase in plasma insulin after selective hepatic vagotomy was inhibited by i.c.v. injection of methylatropine. Arterial blood pressure or pulse rate was not changed by i.c.v. injection of methylatropine. These results show that the central nervous system plays an important role in the vagal control of the insulin response to glucose ingestion. In rats, for the insulin response soon after glucose ingestion (early phase insulin response), direct neural control (hepatic vagal afferent-central nervous system-pancreatic vagal efferent) of the islet B cells seems more important than the intestinal insulinotropic hormone, tGLP-1.

Administration, Oral↗
PubMed1996

Crohn's disease in a 92-year-old male.

A case of Crohn's disease in an extremely elderly man (92-years-old) is reported. He was admitted for abdominal pain and was operated on under a diagnosis of ischemic colitis. At the mucosal surface, many linear and irregularly shaped shallow ulcers were found on the mesenteric side. Microscopically, transmural inflammatory cell infiltration, bead-like lymphoid aggregates around the propriate muscle, small epithelioid cell granulomas, fissure, and volcano-like streamers of inflammatory cells were found. Nerve fibers in Meissner's and Auerbach's plexi seemed to be increased in number, and some were hyperplastic. There was no feature of ischemic colitis or Yersinia enteritis. Serially sectioned tissue specimens did not show dysplastic mucosal change. Many cases of Crohn's disease in the elderly have been reported but an extremely elderly patient such as the present one is very rare, especially in Japan. Characteristics of elderly patients with Crohn's disease are discussed.

Age of Onset↗
PubMed1995

[Prognostic diagnosis of facial palsy with electroneuronography].

We examined the accuracy of electroneuronography (ENoG) as a prognostic indicator in 58 patients with facial palsy: 47 patients with Bell's palsy and 11 patients with Ramsay-Hunt syndrome over a period of one year. For surface recording, the active electrodes were placed over the orbicularis oculi, orbicularis oris, quadratus labii, nasal alae or nasolabial fold, and the indifferent electrode over the same muscle in the opposite side. ENoG over nasal alae showed the most reliable value and the next was orbicularis oris. All other muscles were less reliable. We found that in 87.2% of cases, recovery was satisfactory in Bell's palsy and 63.6% cases in Ramsay-Hunt syndrome. Of the 47 Bell's palsy patients, 38 patients (80.9%) had a response to ENoG over nasal alae of 10% or greater, while 5 patients (45.5%) of the 11 patients with Ramsay-Hunt syndrome. All these patients recovered satisfactorily within four months. Nine of 47 patients (19.1%) with Bell's palsy and 6 of 11 patients (54.5%) with Ramsay-Hunt syndrome had a response of 10% or less. Satisfactory recovery rate among these patients was 33.3%. In conclusion, ENoG over nasal alae and orbicularis oris shows reliable values among other muscles. Patients with responses to ENoG over nasal alae of 10% or greater showed satisfactory recovery.

Adolescent↗
PubMed1995

A point mutation, C to T, in exon 8 of the porphobilinogen deaminase gene in a Japanese family with acute intermittent porphyria.

Acute intermittent porphyria (AIP) is an autosomal dominant disease characterized by a deficiency of porphobilinogen deaminase (PBGD). To date, only two mutations have been reported in Japanese patients. We report here another mutation of the gene in a Japanese patient. Analysis of the PCR amplified DNA fragments of the gene by direct-sequencing method revealed the gene abnormality responsible for the disease. The mutation found was a point mutation, C to T, in exon 8 of the gene at position 346 of the housekeeping cDNA from the translation codon ATG. This mutation resulted in an Arg116 to Trp substitution. Four carriers in the family were successfully diagnosed by detecting the mutation using restriction analysis of PCR products.

Adult↗
PubMed1995

Peutz-Jeghers syndrome with osseous metaplasia of the intestinal polyps.

A case of Peutz-Jeghers syndrome (PJS) with osseous metaplasia in three of 15 hamartomatous polyps of the small intestine is reported. At 35 years of age, the patient was diagnosed as having PJS by cutaneous pigmentation around the mouth and polyposis of the stomach, duodenum and intestine. Fifty-two polys of the large intestine were resected, which were characteristic of those of PJS. Three of them showed adenomatous and carcinomatous changes, but there was no osseous metaplasia in any of the resected polyps. At age 40, he had surgery under the diagnosis of intestinal obstruction. There were 15 polyps in the resected jejunum. These polyps were also characteristic of those of PJS. Additionally, three of these polyps were accompanied by osseous metaplasia. Histologically, mature bone formation and calcification were found close to the hyperplastic glands in the submucosa or in the propriate muscle. Malignant transformation was not observed. Osseous metaplasia is extremely rare in benign polyps, and it has not been reported in hamartomatous polyps of PJS to date. The knowledge of this association may be helpful in the clinical diagnosis of this benign lesion in PJS.

Adult↗
PubMed1994

Ubiquitin expression in atherosclerotic lesions of wistar fatty and wistar lean rats.

To clarify whether ubiquitin is expressed in atherosclerotic lesions, and, if so, the expression is influenced by diabetes mellitus, we examined atherosclerotic (AS) lesions from Wistar fatty (WF) and Wistar lean (WL) rats immunohistochemically using an antibody against ubiquitin (AUb). Ten-week-old male WF and WL rats were treated to cannulize a silicon tube from the left carotid artery (LCA) to the descending aorta under chloral hydrate anesthesia and the tube was fixed. Age-matched WF and WL rats without cannulization were served as controls. Eight weeks after operation, 1 ml of 0.1% Evans blue solution was injected to all rats from the tail vein. 15 min latter, the aortae were removed, fixed with 4% paraformaldehyde and embedded in paraffin. Immunohistochemical staining with AUb by the ABC method, hematoxylin and eosin (HE) and elastica-Goldner (EG) stains were performed. In the cannulized group, focal areas of the luminal surface of the aorta were stained blue with Evans blue and these areas were microscopically confirmed as AS lesions in all WF and WL rats. In the control group, no Evans blue staining or AS lesions were observed. The destruction of the internal elastic lamina in AS lesions were seen with EG stain in the cannulized aorta of both WF and WL rats. No significant difference of the area ratio of intima/media was present between WF and WL rats in the cannulized group. Ubiquitin immunoreactivity was observed in the nucleus and cytoplasm of cells in AS lesions of both WF and WL rats. The present study suggests that ubiquitin plays a role in the formation of AS, and the condition of diabetes mellitus has little influence on ubiquitin expression and AS formation in this experimental model.

Animals↗
PubMed1993

Allelic subtypic determinants of hepatitis B surface antigen (i and t) that are distinct from d/y or w/r.

A monoclonal antibody (I-18) was raised against an enneapeptide representing amino acids 125 to 133 of the product of the S gene of hepatitis B virus DNA [S(125-133) segment] with a sequence of Thr-Ile-126-Pro-Ala-Gln-Gly-Thr-Ser-Met. Another monoclonal antibody (T-7) was raised against an S(125-133) segment in which Ile-126 was replaced by Thr-126. In a panel of 16 samples of hepatitis B surface antigen (HBsAg) with known S gene sequences, I-18 reacted with 5 with Ile-126. T-7 reacted with 10 HBsAg samples with Thr-126; it did not, however, react with the remaining one of subtype ayw with Thr-126 flanked by Met-125 and Thr-127. The two allelic subtypic determinants, specified by Ile-126 and Thr-126 and distinct from d/y or w/r, were named i and t after isoleucine and threonine, which regulate them. They were expressed in a mutually exclusive fashion in 216 (83%) of 260 HBsAg samples from asymptomatic carriers. They were not detected in 36 (14%) samples; the failure to detect an i or t determinant was particularly common in HBsAg samples of subtype ayw (26 [79%] of 33). A part of the S gene sequence was determined for eight HBsAg samples without a detectable i or t determinant. They had an Ile-126 or Thr-126 residue that was flanked by Thr-127, not the Pro-127 commonly possessed by HBsAg samples displaying an i or t determinant. Expression of the i/t allele, therefore, would require Pro-127. In eight (3%) of the samples, both i and t determinants were detected; the presence of i and t on the selfsame HBsAg particles was verified by sandwiching the particles between I-18 and T-7. A point mutation from thymine to cytosine at nucleotide 377 in the S gene, contributing different second letters to codon 126 (ATT for Ile and ACT for Thr), would have been responsible for the assembly of HBsAg particles with both i and t determinants by means of phenotypic mixing.

Alleles↗
PubMed1993

Effect of acidosis on insulin binding and glucose uptake in isolated rat adipocytes.

To assess the mechanism of insulin resistance in metabolic acidosis, we investigated insulin receptor binding and glucose uptake in isolated rat epididymal adipocytes at three pHs, acidic (pH 6.8), neutral (pH 7.4) and alkaline (pH 8.0) groups. After male Sprague-Dawley rats weighing 220-240 g were submitted under chloral hydrate anesthesia, epididymal fat pads were dissected and isolated. [125I]-insulin binding rate was not different between alkaline and neutral groups, but that of acidic group was markedly decreased to approximately 30% of neutral group at maximum specific insulin binding rate. Scatchard analysis showed that numbers of insulin receptors were not different among three groups, but values of binding affinity in acidic group was significantly lower than those of the others. 2-[3H]deoxy-D-glucose uptake of alkaline and neutral groups were increased to reach steady state immediately, but that of acidic group increased slowly and reached at maximum which was lower than the other two groups. Furthermore, 2-deoxy-D-glucose uptake against amount of bound insulin was lower in acidic group than other two groups. From these results, it is suggested that insulin resistance in metabolic acidosis resulted from the combined defects in binding affinity and post-binding process in the insulin receptor.

Acidosis↗
PubMed1993

Prevalence of diabetes and impaired glucose tolerance in Funagata area, Japan.

OBJECTIVE: To determine the prevalence of diabetes mellitus and IGT in the Funagata area of Japan. RESEARCH DESIGN AND METHODS: The total eligible subjects was 1163, all were > or = 45 yr of age, and 52 were known diabetic patients. Data collected included body height, weight, and answers to medical questionnaires. A 75-g OGTT was done in the morning. WHO criteria were used to classify the current diabetes status of study participants. RESULTS: Of the 1111 scheduled for the OGTT, 868 took the test; the participation rate was 77.8%. The prevalence of diabetes was 10.5 and 12.9%, and the prevalence of IGT was 14.7 and 18.0% for men and women, respectively. The prevalence of undiagnosed diabetes (4.9%) was almost equal to that of previously diagnosed diabetes (4.5%). CONCLUSIONS: The prevalence of diabetes in the Funagata area was two to four times higher than that of previous reports in Japan, in which many investigators used a urinary glucose test as a preliminary test. This difference is attributed to the method of determining the prevalence of diabetes.

Age Factors↗