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Biomedical subjects

H Katagiri

Publications and source records attributed to H Katagiri.

At least 91 records · Page 5Linked to original sources
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

Proliferating cell nuclear antigen staining as a prognostic indicator in soft-tissue malignant fibrous histiocytoma.

To determine the value of proliferating cell nuclear antigen (PCNA) staining as a prognostic indicator in soft-tissue malignant fibrous histiocytoma (MFH), we studied 27 patients who underwent resection including an adequately wide margin but without chemotherapy. The survival rate of patients with a lesion in which less than 70% of the cells was positively stained was significantly higher (P < 0.01) than of those with more than 70% positive staining. Twenty-two patients (81.5%) evidenced disease-free survival (mean follow-up period 4.6 years), 1 patient was alive with disease, and 4 (14.8%) died of the disease with lung or lymph node metastasis. In all 4 patients who died, PCNA staining was over 70% positive. In 2 of them, an increase in the number of PCNA-positive cells was observed after repeated recurrence. We conclude that PCNA is a useful prognostic indicator which provides a quantitative measure of the grade of malignancy in MFH patients who receive operative treatment without chemotherapy.

Adolescent↗
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

Effect of modified calm conditions on nuclear dispersion estimates.

When the definition of calm in atmospheric diffusion analyses is changed from 0.5 m s-1 to 0.1 m s-1, actual and more accurate low wind speeds and wind directions can be used to calculate the average air concentrations due to continuous releases of radionuclides at 10-m stack height more realistically and accurately. However, this modified calm condition has little affect on the calculated adult thyroid exposure for a postulated accident.

Adult↗
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

A case of diabetic amyotrophy associated with 3243 mitochondrial tRNA(leu; UUR) mutation and successful therapy with coenzyme Q10.

We report the case of 71-year-old male who was once diagnosed as having diabetic amyotrophy, because of pronounced wasting in proximal muscles, massive weight loss, and development of paresthesia in his legs. Afterwards, ragged red fibers and mitochondrial tRNA mutation at position 3243 were documented in muscle biopsy. He had diabetes mellitus associated with 3243 mitochondrial DNA mutation, suggesting that clinically, diabetic amyotrophy may be overlapped with mitochondria-related disease entities in some parts. Coenzyme Q10 administration was effective in relieving the symptoms in his legs, fatigue, and residual urine in his bladder. These were confirmed with the improvement in neurological parameters. In conclusion, this case gives important help in understanding myopathy in diabetes. It would be important to check on the 3243 mitochondrial tRNA mutation in patients with diabetic amyotrophy and/or diabetic neuropathic symptoms.

Animals↗
PubMed1995

Regulation of glucose transporter 1 (GLUT1) gene expression by epidermal growth factor in bovine corneal endothelial cells.

The regulation mechanism of glucose transporter 1 (GLUT1) gene expression was investigated in cultured bovine corneal endothelial cells. Epidermal growth factor (EGF) stimulated both GLUT1 mRNA expression and cell proliferation. Fetal bovine serum, in contrast, stimulated cell proliferation but did not increase GLUT1 mRNA. IGF-I, hyaluronic acid or fibronectin did not stimulate GLUT1 gene expression. These results suggest that GLUT1 gene expression is controlled, at least in part, by EGF and is related to neither cell proliferation, cell motility nor cell adhesion regulation. The EGF signal was transduced through a pathway including protein kinase C. GLUT1 is reported to work as a water transporter, and so EGF can be considered as one of the possible agent which stimulate water transport activity through the corneal endothelial cells. EGF could be useful in the therapy of corneal edema caused by endothelial dysfunction.

Animals↗
PubMed1994

Replacement of both tryptophan residues at 388 and 412 completely abolished cytochalasin B photolabelling of the GLUT1 glucose transporter.

A mutated GLUT1 glucose transporter, a Trp-388, 412 mutant whose tryptophans 388 and 412 were both replaced by leucines, was constructed by site-directed mutagenesis and expressed in Chinese hamster ovary cells. Glucose transport activity was decreased to approx. 30% in the Trp-388, 412 mutant compared with that in the wild type, a similar decrease in transport activity had been observed previously in the Trp-388 mutant and the Trp-412 mutant which had leucine at 388 and 412 respectively. Cytochalasin B labelling of the Trp-388 mutant was only decreased rather than abolished, a result similar to that obtained previously for the Trp-412 mutant. Cytochalasin B labelling was finally abolished completely in the Trp-388, 412 mutant, while cytochalasin B binding to this mutant was decreased to approx. 30% of that of the wild-type GLUT1 at the concentration used for photolabelling. This level of binding is thought to be adequate to detect labelling, assuming that the labelling efficiency of these transporters is similar. These findings suggest that cytochalasin B binds to the transmembrane domain of the glucose transporter in the vicinity of helix 10-11, and is inserted covalently by photoactivation at either the 388 or the 412 site.

Animals↗
PubMed1994

Overexpression of hexokinase I but not GLUT1 glucose transporter alters concentration dependence of glucose-stimulated insulin secretion in pancreatic beta-cell line MIN6.

The recently established pancreatic beta-cell line MIN6 retains the ability to secrete insulin in response to physiological glucose concentrations. To investigate the role of glucose transport and phosphorylation in glucose-stimulated insulin secretion by beta-cells, MIN6 cells were stably transfected with a rabbit GLUT1 glucose transporter cDNA or a rat hexokinase I cDNA cloned in an expression vector. Overexpression of GLUT1 increased 3-O-methylglucose uptake, but did not alter either glucose utilization or glucose-stimulated insulin secretion. In contrast, clones overexpressing hexokinase I exhibited enhanced glucose-stimulated insulin secretion at glucose concentrations below 10 mM with a concomitant increase in glucose utilization. Maximal insulin secretion as well as the maximal rate of glucose utilization were not altered in these clones. Insulin secretion stimulated by 2-ketoisocaproate, a non-glucose secretagogue, was not affected by hexokinase I expression. These results strongly suggest that the glucose phosphorylating step, but not glucose transport step, regulates glucose-stimulated insulin secretion by modulating the glycolytic rate in the beta-cell.

3-O-Methylglucose↗
PubMed1994

Mitochondrial diabetes mellitus: prevalence and clinical characterization of diabetes due to mitochondrial tRNA(Leu(UUR)) gene mutation in Japanese patients.

Mutations in the mitochondrial gene were recently identified in a large pedigree of diabetes mellitus and deafness. As the mitochondrial gene is materially inherited, Japanese diabetic patients whose mothers were also diabetic were screened, using peripheral leucocytes, 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 who were screened. Diabetes co-segregated with the mutation, except in one young subject, and was maternally inherited. The apparent onset of disease occurred between 11 and 68 years of age. Some of the affected members developed hearing impairment and congestive heart failure due to cardiomyopathy, though generally long after the onset of diabetes, and these patients had therefore not been diagnosed as having a specific form of diabetes. The duration of sulphonyl-urea treatment was not more than 8 years in these pedigrees and affected members were prone to progression to insulin-requiring diabetes. Thus, these patients were secondary sulphonylurea failures. Long-term follow-up revealed that the underlying disorder in affected members is a progressive impairment of insulin secretion. Some were initially diagnosed as having IDDM based on an apparent acute onset in youth and the clinical severity of their diabetes. Others were regarded as having MODY with an aggressive course. The mitochondrial gene mutation or diabetes is not transmitted to all offspring of the affected mothers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

[Bone mineral measurement of the calcaneus by single X-ray absorptiometry].

The bone mineral content (BMC) of the calcaneus was evaluated using single X-ray absorptiometry (SXA) with respect to reproducibility of bone mineral measurement, age-related bone loss in healthy Japanese, the spine fracture threshold in osteoporotic women, and the effect of non-weight bearing on bone mass in patients after hip arthroplasty. The mean reproducibilities using this method in vitro and in vivo were 0.81% and 0.59%. In 264 healthy men aged between 21 and 79 years and 328 healthy women aged between 20 and 79 years, the calcaneus BMC reached a peak in their twenties and thereafter decreased linearly with age by 0.57% per year in men and 1.32% per year in women. Body height and weight were well correlated with the calcaneus BMC in healthy men and women (p < 0.001). The bone mineral density (BMD) of the lumbar spine was measured using dual X-ray absorptiometry (DXA) and was significantly correlated with the calcaneus BMC in both men (r = 0.727, p < 0.001) and women (r = 0.703, p < 0.001). The fracture threshold, defined as the 90th percentile for calcaneus BMC in a woman with a vertebral fracture, was 313.31 mg/cm2 and 70.2% of the peak bone mass in the calcaneus. In 30 patients with hip implant arthroplasty, the bone mass in the calcaneus, lumbar spine and the distal radius was evaluated longitudinally during a follow-up period of one year. Only the calcaneus BMC in the treated leg changed significantly during this period. In the first four months, the calcaneus BMC in the treated leg diminished by approximately 21%, but had recovered by one year after surgery. We concluded that bone mineral measurement in the calcaneus was useful for evaluating age-related bone mass changes in healthy men and women, bone loss in osteoporotic patients, and the effect of non-weight bearing on bone mass in patients after hip arthroplasty.

Absorptiometry, Photon↗
PubMed1994

Superoxide dismutase in developing mouse retina.

Superoxide dismutase (SOD) activity and the production site of H2O2 were studied in the developing mouse retina. The H2O2 production site moved from the inner to the outer region within the outer nuclear layer between the ages of 4 days through 12 days. This shift occurred in parallel with the development of the inner segments of the photoreceptor layer. SOD activity increased significantly at the age of 2-3 weeks. Both manganese-SOD (Mn-SOD) and copper-zinc SOD (Cu,Zn-SOD) activities (combined mean) in the retina of mice older than 2 weeks of age were 1.9 times greater in comparison with those of mice at the age of 2 weeks and younger. The mRNA of Cu,Zn-SOD did not change during these periods, suggesting that the translational efficiency of the mRNA and/or the stability of the SOD enzyme might increase, or the active form of the enzyme might increase during the development of the retina. The results of this study indicate that the localization and production of active oxygen change during the development of the mouse retina, and that SOD activity does exist in the retina from birth, increasing as its role in the protective system against active oxygen increases in the maturing mouse retina.

Animals↗
PubMed1994

[Evaluation of plasma prothrombin fragment 1+2 in healthy donors and thrombotic diseases].

We have evaluated plasma F1+2 values by enzyme immunoassay (Enzygnost F1+2; Behringwerke) in 80 healthy blood donors in various ages and compared to that from patients with DIC, thrombosis and oral anticoagulant therapy. The reference range of F1+2 from 35 donors with 20 to 29 age-group, was found 0.82 +/- 0.39 nM, whereas the range from 20 donors with 30 to 39 age-group showed higher F1+2 levels with 1.46 +/- 0.56nM (p < 0.001). F1+2 values from 15 donors with 40 to 49 age-group revealed similar with 30 to 39 age-group, while the range from 10 donors with 50 to 59 age-group was found much higher F1+2 levels with 2.16 +/- 0.80nM (p < 0.001). In patients with DIC, F1+2 levels were significantly higher than those in all healthy subjects (p < 0.01). In patients under stable oral anticoagulant therapy, F1+2 values were significantly lower than in healthy donors with any age-group (p < 0.001). On the contrary, in patients with thrombosis including 9 AMI and 4 DVT, the determination of F1+2 values appeared controversial. They were significantly higher than those in 20 age-group donors (p < 0.001), however, when compared with those in all healthy donors, it showed no statistical significance. These results suggest that evaluation of reference range of plasma F1+2 values is very important from the viewpoint of aging. In addition, F1+2 determination is clinically useful for monitoring of DIC and anticoagulant therapy.

Adult↗
PubMed1994

[The importance of dose intensity in preoperative chemotherapy for osteosarcoma--retrospective analysis of a short intensive chemotherapy regimen preoperatively using high-dose methotrexate and cisplatinum].

A retrospective investigation was performed on the significance of dose intensity in preoperative chemotherapy for osteosarcoma. In this paper, we studied 29 patients, who had classical stage II-B osteosarcoma and received preoperative treatment consisting of high dose methotrexate (HD-MTX) and/or cisplatinum (CDDP) between 1985 and 1991. Preoperative dose intensity was calculated in the following two ways. 1. Total dose of MTX and CDDP administered during initial five weeks: MTX (g)/10/m2 + CDDP(mg)/100/m2 2. Dose intensity of MTX and CDDP from initiation of treatment (I) to resumption of postoperative chemotherapy (R): MTX (g)/10/m2 + CDDP (mg)/100/m2 / days from (I) to (R)/ideal period of new regimen (63 days) Continuous disease free survival rate (CDFR) was significantly higher in the group receiving preoperative chemotherapy at higher dose intensity (> 3.0). Supplementary administration of adriamycin (ADR) to CDDP/MTX was not favorable in the preoperative stage, because it put off the following therapy and diminished the dose intensity. Since July 1989, we have tried a short intensive preoperative chemotherapy regimen: weekly two cycles of CDDP 100 mg/m2 intravenously, followed by weekly two cycles of HD-MTX 10g/m2. Surgery was scheduled six weeks after beginning treatment, and postoperative chemotherapy was started three weeks after surgery. Twenty patients have been treated by this regimen to date. All patients remain disease free, and six are CDF beyond 24 months.

Antineoplastic Combined Chemotherapy Protocols↗