Biomedical subjects

Y Oka

Publications and source records attributed to Y Oka.

At least 271 records · Page 15Linked to original sources

PubMed1995

Immunocytochemical localization of sGnRH and cGnRH-II in the brain of goldfish, Carassius auratus.

The immunocytochemical distribution of salmon gonadotropin-releasing hormone (sGnRH) and chicken GnRH-II (cGnRH-II) neurons in the brain of goldfish was examined using respective antisera. Salmon GnRH-immunoreactive (ir) cell bodies were localized in the area between the olfactory nerve and the olfactory bulb (the terminal nerve ganglion), the ventral telencephalon, the preoptic area, and the hypothalamus. Chicken GnRH-II-ir cell bodies were observed in the same areas as were those of sGnRH, although the number of cell bodies were fewer than those of sGnRH. In addition, chicken GnRH-II-ir cell bodies were also observed in the midbrain tegmentum where no sGnRH-ir cell bodies were found. Both sGnRH-ir and cGnRH-II-ir fibers were distributed not only in the hypothalamus and the pituitary gland but also in various brain areas from the olfactory bulb to the spinal cord. The wide distribution of GnRH-ir fibers suggests that in the goldfish, sGnRH and cGnRH-II not only regulate gonadotropin release from the pituitary gland but also function as neuromodulators in various brain regions.

Animals↗

PubMed1995

Multiple gonadotropin-releasing hormone (GnRH)-immunoreactive systems in the brain of the dwarf gourami, Colisa lalia: immunohistochemistry and radioimmunoassay.

The present study characterizes gonadotropin-releasing hormone (GnRH) neuronal groups that are located in several different brain regions by investigating GnRH molecular species and projection patterns in an anabantid fish, Colisa lalia. First, we examined the molecular species of GnRHs in extracts of the brain and the pituitary by reverse-phase high-performance liquid chromatography followed by radioimmunoassays. We found salmon GnRH (sGnRH), chicken GnRH-II (cGnRH-II), and an unfamiliar GnRH-like substance. Next, to examine the distribution of each GnRH molecule in different GnRH neuronal groups, we performed immunohistochemistry using four kinds of antisera and an antibody. Furthermore, we performed brain lesioning experiments of terminal nerve (TN) cells, the most conspicuous GnRH-immunoreactive cells in Colisa lalia. Comparisons of immunoreactive structures between TN-lesioned fish and untreated fish elucidated the projection area of each neuronal group. Three major neuronal groups were observed. TN-GnRH cells, which are located in the transitional area between the olfactory bulb and the telencephalon, showed strong sGnRH and weaker cGnRH-II immunoreactivity. TN-GnRH cells projected to wide areas of the central nervous system from the olfactory bulb to the spinal cord. The second group, located in the preoptic area, showed only sGnRH immunoreactivity and projected only to the pituitary. The third one, located in the midbrain tegmentum, exhibited strong cGnRH-II and weaker sGnRH immunoreactivity. This cell group projected mainly to brain regions posterior to the hypothalamus and the spinal cord. These different projection patterns suggest functional differentiation of each GnRH neuronal group.

Animals↗

PubMed1995

Tetrodotoxin-resistant persistent Na+ current underlying pacemaker potentials of fish gonadotrophin-releasing hormone neurones.

1. Gonadotrophin-releasing hormone (GnRH)-immunoreactive terminal nerve (TN) cells show endogenous regular beating discharges, which may be related to their putative neuromodulator functions. The ionic mechanism underlying the pacemaker potential was studied using intracellular and patch-pipette current clamp recordings from a whole brain in vitro preparation of a small fish brain. 2. The pacemaker potentials were resistant to 1.5-3 microM tetrodotoxin (TTX) and were not affected by Ca2+ channel blockers (amiloride, Ni2+, Co2+, Cd2+) or in Ca(2+)-free solution. In contrast, the pacemaker potentials were readily blocked by substituting tetramethylammonium or choline for Na+ in the perfusing solution, and the resting membrane potential became more hyperpolarized than the control level. 3. The present results suggest that the TTX-resistant persistent Na+ current, INa(slow), supplies the persistent depolarizing drive and plays an important role in the generation of pacemaker potentials in TN GnRH cells.

Animals↗

PubMed1995

An interleukin-6 transgene expressed in B lymphocyte lineage cells overcomes the T cell-dependent establishment of normal levels of switched immunoglobulin isotypes.

Long-term proliferating, stromal cell/interleukin (IL)-7-reactive precursor B cell lines established from fetal liver and bone marrow of human IL-6-transgenic B6Ld46 mice produce and secrete human IL-6. When transplanted into severe-combined immunodeficient (SCID) or Rag2 knockout (Rag2-T) mice, these pre-B-cell lines establish a part of the B cell compartment but yield no T cells, as do pre-B cell lines from genetically matched non-transgenic mice. Within 2 to 3 months after transplantation, the serum of mice transplanted with pre-B cells from normal mice contains normal levels of IgM (200-600 micrograms/ml) but 10-100-fold lower levels of the IgG subclasses and of IgA. In contrast, the sera of mice transplanted with IL-6 transgenic pre-B cells contain not only IgM, but also IgG and IgA at nearly normal levels. The results indicate that at least a part of the plasmacytosis and elevated IgG production observed previously in the IL-6-transgenic mice appears to be due to a T cell-independent activation of IgG and IgA production by the IL-6-secreting pre-B cells and their differentiated progeny in the immunodeficient hosts.

Animals↗

PubMed1995

Mitochondrial diabetes mellitus--glucose-induced signaling defects and beta-cell loss.

Japanese diabetic patients whose mothers were also diabetic were screened, using peripheral leukocytes, for an A to G transition at nucleotide pair 3243 of the mitochondrial gene, a tRNA(Leu)(UUR) mutation. This mutation was identified in four pedigrees from among 300 unrelated patients. Diabetes mellitus cosegretated with the mutation, except in 1 young subject, and was maternally inherited. Long-term follow-up revealed that the underlying disorder in affected members is a progressive impairment of insulin secretion. In accord with this finding, this mutation was found to be highly prevalent in a subset of diabetes mellitus called slowly progressive IDDM; the mutation was identified in 3 of 27 Japanese patients enrolled in the prospective study of islet cell antibody (ICA)-positive, initially non-insulin-dependent diabetic patients, who are very likely to become insulin dependent in several years. The histologic characteristics of slowly progressive IDDM include loss, though incomplete, of pancreatic beta-cells. Mitochondrial gene defects in beta-cells could therefore cause glucose-induced signaling defects as well as beta-cell loss, which explains the wide range of diabetic phenotypes, from NIDDM phenotype to IDDM, in patients with this mitochondrial gene mutation.

Adolescent↗

PubMed1995

Malposition of a totally implantable venous access catheter in the azygous vein: report of a case.

We report herein the case of a 2-year-old girl with short bowel syndrome who developed chest pain 2 weeks after a totally implantable central venous access catheter had been surgically placed to facilitate total parenteral nutrition. A lateral chest X-ray and contrast flow study subsequently revealed that the catheter tip had been inserted into the azygous vein. Although this complication is very rare, it may be encountered more commonly with the increasing use of this type of venous access. Thus, we believe that a lateral chest X-ray should be routinely performed on all patients following catheter insertion to check for possible malposition of the tip in the azygous vein.

Catheters, Indwelling↗

PubMed1995

Possible mechanism to induce protein kinase C-dependent arterial smooth muscle contraction after subarachnoid haemorrhage.

A possible mechanism for the induction of protein kinase C (PKC)-dependent vascular contraction independent to the increase of intracellular Ca++ was investigated in the pathogenesis of cerebral vasospasm in the double subarachnoid haemorrhage (SAH) model. The level of 1,2-diacylglycerol (DAG), which is an intrinsic PKC activator, significantly increased from days 4 to 7 in the basilar artery after the initial SAH, and the continuous administration of 1,2-bis(nicotinamido)-propane (AVS), a novel free radical scavenger, not only lowered the concentration of lipid peroxides in the CSF but also successfully suppressed the basilar arterial wall in the same model. It was suggested that lipid peroxides generated in the subarachnoid clot affect the DAG content of the cerebral artery. Analysis of hydroxy-eicosatetraenoic acids (HETEs) with high performance liquid chromatography (HPLC) revealed the production of relatively large amount of 12-HETE in the subarachnoid clot. To examine the potential effect of exogenous 12-HETE on the DAG content of the cerebral artery, the basilar artery was incubated with 12-HETE in vitro. 12-HETE induced a concentration-dependent slow increase in DAG content in the arterial wall after 6 hours of incubation. Under conditions in which DAG formation was facilitated by the Ca(++)-ionophore, DAG accumulation in the basilar artery was enhanced in the presence of 12-HETE. It was suggested that 12-HETE generated in the subarachnoid clot, induced DAG accumulation in the arterial wall by inhibition of DAG metabolism, resulting in the induction of prolonged PKC-dependent smooth muscle contraction in the pathogenesis of cerebral vasospasm.

12-Hydroxy-5,8,10,14-eicosatetraenoic Acid↗

PubMed1995

A patient with diabetes mellitus, cardiomyopathy, and a mitochondrial gene mutation: confirmation of a gene mutation in cardiac muscle.

A 44-year-old woman with diabetes mellitus, cardiomyopathy, and a mitochondrial gene mutation, was reported. She was diagnosed as having diabetes at 33 years of age and was treated with insulin. However, she stopped treatment 6 months later and had no medical care until she developed diabetic ketoacidosis at 41 years of age. She had diabetic foot, diabetic retinopathy, and nephropathy with low insulin secretory capacity, leading to insulin treatment. A point mutation of the mitochondrial tRNA(Leu(UUR)) gene was identified in peripheral leukocytes at 43 years of age, and sensorineural hearing impairment was detected at the same time. Her mother also suffered from diabetes mellitus with deafness and her son, who was not diabetic at age 19, had the same mitochondrial DNA (mtDNA) mutation. At 44 years of age, she developed congestive heart failure due to cardiomyopathy, and the same mtDNA mutation was identified in the cardiac muscle. Thus, it is very likely that in this patient, diabetes and cardiomyopathy was caused by the same abnormality, the point mutation of mitochondrial tRNA(Leu(UUR)) gene.

Adult↗

PubMed1995

Insulin edema in diabetes mellitus associated with the 3243 mitochondrial tRNA(Leu(UUR)) mutation; case reports.

We encountered a patient with diabetes mellitus due to the 3243 mitochondrial tRNA mutation(DM-Mt3243), who developed insulin edema and hepatic dysfunction after starting insulin. Such a rare phenomenon was unlikely to be a fortuitous coincidence in mitochondrial diabetes, as none in 197 non-mutant NIDDM patients had same episode. Moreover, similar leg edema was noticed in another DM-Mt3243 patient, and other two DM-Mt3243 patients had leg edema which responded to coenzyme Q10. These observations suggest further a role of mitochondrial function on leg edema. The mechanism of his insulin edema may involve vasomotor changes induced by the rapidly glycemic control, because our case of insulin edema had a prominent increase of strong succinate dehydrogenase reactive vessels. Alternatively, myocardial dysfunction might have produced leg edema and hepatic dysfunction, because he had subclinical myocardial dysfunction, judged by imaging with beta-methyl-p-(123I)-iodophenyl-pentadecanoic acid. The third explanation is that a rapid improvement of glycemic control might have induced hepatic reoxygenation and the production of reactive oxygen species in the liver that contributed to cell damage. Thus, although we cannot draw definite conclusion, our experiences here suggest that mitochondrial dysfunction is important in the etiology of insulin edema.

Aged↗

PubMed1995

HCV RNA monitoring for tailored regimens of interferon therapy in hepatitis C.

Sustained non-viraemia is prerequisite for a virological cure of hepatitis C virus (HCV) disease. We monitored serum HCV RNA in our patients during interferon therapy and for 6 months of follow-up. The rate of sustained responders (RNA-negative at the end of follow-up) differed significantly by whether or not RNA became sero-negative within 24 weeks of the initiation of therapy (71% vs 7%); and also by whether or not the RNA-seronegativity lasted for 12 weeks during therapy (88% vs 11%). Thus, by monitoring viraemia in individual patients, we can tailor the duration of therapy and minimize waste of interferon.

Follow-Up Studies↗

PubMed1995

Evaluation of hepatic venous flow using transesophageal echocardiography in coronary artery bypass surgery: an index of right ventricular function.

Hepatic venous flows (HVFs) were evaluated to assess right-heart function by transesophageal Doppler echocardiography in 45 patients undergoing coronary artery bypass graft (CABG) surgery. Peak velocity and time velocity integral of A-wave (reverse flow in end diastole), S-wave (forward flow in systole), V-wave (reverse flow in late systole), and D-wave (forward flow in diastole) of biphasic HVF were examined. Peak systolic-diastolic ratio (S/D) of biphasic HVF and reverse flow ratio (% reversal flow/forward flow [RF/FF]) of both biphasic and monophasic HVF also were examined. Tricuspid regurgitation (TR) was assessed by color Doppler image. All data were obtained after performing the following: induction of anesthesia (stage 1); pericardiectomy (stage 2); cardiopulmonary bypass (CPB) (stage 3); and closure of sternum (stage 4). HVFs at stage 1 were obtained in all 45 patients, and the peak S/D in patients with a history of inferior wall myocardial infarction (MI) was significantly less than that in patients without a history of MI (p < 0.05). HVFs of 35 patients were recorded successfully at all stages. In 5 of these 35 patients, HVF patterns became monophasic after CPB, and only one of those patients had severe TR. In the rest of the 30 patients with biphasic patterns throughout the operation, peak A and D velocities increased (p < 0.01), whereas peak S and V velocities decreased (p < 0.01) after CPB compared with those before CPB. Consequently, peak S/D was reduced (p < 0.01), and %RF/FF increased (p < 0.05). These post-CPB changes were associated with increased (p < 0.01) pulmonary artery diastolic and right atrial pressures.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1995

An infection-resistant PTFE vascular graft; spiral coiling of the graft with ofloxacin-bonded PTFE thread.

OBJECTIVE: To develop an infection-resistant polytetrafluoroethylene (PTFE) vascular graft for potential clinical use in grafting in sites of bacterial contamination and in replacement of the infected grafts. SETTING: Experimental study in rabbits. MATERIALS AND METHODS: An antibiotic ofloxacin (OFLX) was bonded to a sheet of PTFE by impregnation, which was cut and twisted into fine threads. The in-vitro antibacterial activity of OFLX-PTFE thread was determined by measuring the zone of growth inhibition against Escherichia coli. The thread was spirally coiled around a ridged outerwall PTFE to make the OFLX-PTFE graft. OFLX-PTFE graft or control graft was interposed in the inferior vena cava (IVC) of rabbits and the entire graft was covered with fibrin containing a fixed number of E. coli. Three or 7 days after the grafting, the grafts with perigraft tissue were harvested and subjected to bacteriological studies. RESULTS: In spite of early phase rapid elution of OFLX, a significant antibacterial activity was retained for more than 2 weeks. The antibacterial activity of OFLX-PTFE threads implanted in the subcutaneous space of rabbits decreased to 48% after 24 h and to approximately 1% after a week. The swab culture of all the control grafts was positive, while only one of 13 PTFE-OFLX grafts was positive. The number of viable bacteria in the perigraft tissue of OFLX-PTFE grafts was remarkably low in comparison with that of control grafts. Thus, the OFLX-PTFE grafts exhibited a marked in-vivo antibacterial activity. CONCLUSION: By a unique method, it was possible to furnish PTFE graft with an excellent infection-resistant property, without affecting the original biological behaviour.

Animals↗

PubMed1995

Clearance of serum hepatitis C virus RNA after interferon therapy in relation to virus genotype.

The effect of recombinant interferon-alfa on serum HCV RNA levels in Japanese patients with chronic hepatitis C was investigated. At 24 weeks of treatment, 41 (32.5%) of 126 patients lost HCV RNA from serum, and aminotransferases were normalized in 31 (75.6%) of these 41 cases. HCV genotypes were categorized into four types (Type I, II, III, IV); the frequencies among the patients were: Type I: 0%, Type II: 70.6%, Type III: 20.6%, and Type IV: 6.3%. At the end of the 24-week treatment, HCV RNA levels were remarkably decreased in Type III patients and became undetectable in 18 (69.2%) of 26. In contrast, only 18 (20.2%) of 89 patients with Type II and two of eight with Type IV lost HCV RNA from sera. The relation between HCV genotype (Type III) and response to IFN therapy was also confirmed using a logistic regression model. HCV genotype seems to be an important factor in determining the response to IFN in patients with chronic hepatitis C.

Alanine Transaminase↗

PubMed1995

Human GLUT-2 overexpression does not affect glucose-stimulated insulin secretion in MIN6 cells.

Accumulated evidence suggests that GLUT-2, in addition to its role in glucose transport, may also have other functions in glucose-stimulated insulin secretion. As a first step in addressing this possibility, we have engineered MIN6 cells overexpressing human GLUT-2 by transfection with human GLUT-2 cDNA. Stable transformants harboring human GLUT-2 cDNA exhibited an approximately twofold increase in 3-O-methyl-D-glucose uptake at 0.5 and 15 mM. Glucokinase activity or glucose utilization measured by conversion of [5-3H]glucose to [3H]H2O was not, however, altered in the MIN6 cells overexpressing human GLUT-2. Furthermore, glucose-stimulated insulin secretion was not affected by over-expression of human GLUT-2. An abundance of GLUT-2, therefore, does not correlate with the glucose responsiveness of cells in which glycolysis is regulated at the glucose phosphorylating step. These data suggest that GLUT-2 by itself does not have significant functions other than its role in glucose transport in glucose sensing by MIN6 cells.

3-O-Methylglucose↗

PubMed1995

Desensitization of endothelin-1 binding by vasopressin via a cAMP-mediated pathway in rat CCD.

In renal collecting ducts, endothelin-1 (ET-1) inhibits Na+ reabsorption and antagonizes the effects of arginine vasopressin (AVP). Whether AVP may affect ET-1 action in the collecting ducts that mainly express the ETB receptor subtype, however, remains unknown. Since ETB, but not ETA, possesses a consensus amino acid sequence for possible phosphorylation by protein kinase A (PKA), we hypothesized that AVP may influence ET-1 binding to the ETB receptor via PKA. In microdissected rat cortical collecting ducts, the specific ET-1 binding decreased by 35% (15.6 +/- 4.4 vs. 24.0 +/- 3.6 amol/mm in control) following 20-min preincubation with 10(-7) M AVP. This decrease in ET-1 binding was mimicked by 10(-5) M forskolin and by 10(-4) M dibutyryl (DB) adenosine 3',5'-cyclic monophosphate (cAMP), indicating that this heterologous desensitization may be caused by a cAMP-dependent mechanism. Moreover, N-(2([3-(4-bromophenyl)-2-propenyl]-amino]-ethyl)-5- isoquinolinesulfonamide (H-89) and the Rp diastereoisomer of cAMP, Rp-cAMPS, which are both PKA-specific inhibitors, eliminated AVP-induced ETB receptor desensitization. The reduction in ET-1 binding was characterized by a decrease in binding affinity [dissociation constant (Kd) = 4 vs. 2 nM in control] with no change in maximal binding capacity. In contrast, forskolin and DBcAMP had no effect on ET-1 binding in endothelium-denuded aortic strips, which mainly express ETA subtype. These results showed that AVP rapidly downregulates the ETB receptor by reducing Kd through a PKA-dependent pathway. Thus ET-1 and AVP may act in a mutually antagonizing manner in the renal collecting ducts.

Amino Acid Sequence↗

PubMed1995

Characterization of rat GLUT5 and functional analysis of chimeric proteins of GLUT1 glucose transporter and GLUT5 fructose transporter.

To investigate the biological and biochemical properties of GLUT5, rat GLUT5 complementary DNA was transfected into Chinese hamster ovary cells. Rat GLUT5 was exclusively targeted to the plasma membrane and exhibited a transport activity, not for glucose, but for fructose. The affinity for fructose (Km = 11.6mM) was much higher than that of GLUT2, the other glucose transporter with fructose transport activity. Interestingly, rat GLUT5 was not photolabeled with 0.5 microM cytochalasin B, whereas a similar amount of GLUT1 was adequately photolabeled under the same experimental conditions. Next, to investigate the domains required for transport of glucose/fructose in GLUT1 and/or GLUT5, several chimeric GLUT1/GLUT5 proteins were expressed, and their glucose and/or fructose transport activities were studied. The intracellular middle loop and the region encompassing the membrane spanning domains 7-12 were observed to have crucial roles in GLUT1 glucose transport, whereas replacement of the N-terminal half or the intracellular C-terminal region with the corresponding region of GLUT5 produced no marked effects on glucose transport activity. In contrast, both the N-terminal half encompassing the region from the N-terminus through the 6th membrane spanning domain and the intracellular C-terminal region were mandatory for GLUT5 fructose transport. In conclusion, GLUT5 is a transporter exclusively for fructose and the structural requirements for fructose transport are more stringent than those for glucose transport among hexose transporter proteins.

Affinity Labels↗

PubMed1995

Colocalization of vascular endothelial growth factor (vascular permeability factor) and insulin in pancreatic islet cells.

Previously, we found that the islet of pancreas stained with a antibody against the vascular permeability factor (VPF; also known as vascular endothelial growth factor, VEGF) protein. To determine how common this reaction was and whether it was a specific reaction for the islet, we examined its expression and specific cellular localization. Two different antibodies directed against VPF/VEGF peptide revealed an intense reaction for beta-cells in the human islets of Langerhans, and several human beta-cell tumors (insulinomas), but no reaction, were detectable in the vascular endothelium. In the fetal pancreas (second and third trimesters), the VPF/VEGF peptide was detected in immature islets. Northern blot analysis of cell lines derived from rodent insulinomas revealed expression of VPF/VEGF messenger ribonucleic acid. Western blot analysis of conditioned medium from one of these cell lines showed the presence of the released VPF/VEGF protein. These findings indicate that beta-cells have a specific role other than endocrine function in the pancreas. VPF/VEGF in beta-cells may be involved in the maintenance and control of permeability within the islet capillary system.

Adult↗

PubMed1995

Modeling of controlled release of aspirin derivatives from human erythrocytes.

The transport of aspirin (ASP) and its derivatives (m- or p-acetoxybenzoic acid (m- or p-AcOHBA), o-propionyloxybenzoic acid (PrOHBA), o-butyryloxybenzoic acid (BuOHBA), o-acetoxyhippuric acid (AcOHPA), and o-acetoxy-N-benzoyl-beta-alanine (AcONBA)) through human erythrocyte membrane was investigated. ASP derivatives were transported into the erythrocytes where they were hydrolyzed and then released, although the derivatives varied in the rate of transport. In different binding positions, the hydrolyzed derivatives were released rapidly in the order of p- > m- > o-AcOHBA (ASP). The rates of derivatives were accelerated by lengthening of the side chain of the acetoxyl group (BuOHBA > PrOHBA > ASP). The rate of release of o-, m- or p-AcOHBA, BuOHBA and PrOHBA was related to hydrolysis rate in erythrocytes but not to partition coefficient (log P). In different amino acids in a carboxyl group of ASP, the release of AcONBA was slower and about 2 h was required to attain equilibrium. The release of AcOHPA was also slower and increased gradually during an incubation of 3 h. The rate of release of AcOHPA and AcONBA was not related to hydrolysis rate in the erythrocytes. The rates were equivalent values with the predicted values calculated by log P of tested drugs. It was suggested from these results that ASP derivatives were able to control the release from human erythrocytes.

Aspirin↗