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Biomedical subjects

Yuzuru Kato

Publications and source records attributed to Yuzuru Kato.

At least 19 recordsLinked to original sources
PubMed2005

Imprinting and looping: epigenetic marks control interactions between regulatory elements.

Gene regulation involves various cis-regulatory elements that can act at a distance. They may physically interact each other or with their target genes to exert their effects. Such interactions are beginning to be uncovered in the imprinted Igf2/H19 domain.(1) The differentially methylated regions (DMRs), containing insulators, silencers and activators, were shown to have physical contacts between them. The interactions were changeable depending on their epigenetic state, presumably enabling Igf2 to move between an active and a silent chromatin domain. The study gives us a novel view on how regulatory elements influence gene expression and how epigenetic modifications modulate their long-range effects.

Alleles↗
PubMed2005

Effect of recombinant human GH on circulating granulocyte colony-stimulating factor and neutrophils in patients with adult GH deficiency.

BACKGROUND: We previously reported that short-term continuous subcutaneous infusion (CSI) of recombinant human growth hormone (rhGH) increased plasma erythropoietin levels and hemoglobin concentrations in patients with adult GH deficiency. In the present study, we investigated the effect of rhGH on plasma granulocyte colony-stimulating factor (G-CSF) levels and neutrophil counts in patients with adult GH deficiency. METHODS: rhGH was administrated for 1 year in six patients with adult GH deficiency (age range, 24-69 years; mean +/- S.E.M., 51.7 +/- 5.8 years; two males and four females) by means of CSI at a rate of 0.25 U/kg per week. Blood samples were obtained in the morning after overnight fasting every month before and after the start of rhGH administration. Plasma GH, insulin-like growth factor I (IGF-I) and G-CSF levels, and neutrophil counts, were measured. RESULTS: Mean ( +/- S.E.M.) plasma GH levels increased from 0.26 +/- 0.14 to 2.28 +/- 0.20 microg/l 1 month after the start of rhGH administration. An increase of the plasma GH levels was accompanied by an increase in the plasma IGF-I levels from 64.7 +/- 8.5 to 293.3 +/- 80.6 microg/l. Plasma G-CSF levels increased at 2, 3, 8, 9 and 10 months after the start of rhGH administration compared with 28.6 +/- 11.0 ng/l at time 0. The neutrophil counts increased at 2, 3, 7, 8, 9, 11 and 12 months after the start of rhGH administration compared with 2822 +/- 377 neutrophils/microl at time 0. CONCLUSION: rhGH administration increased plasma G-CSF levels and neutrophil counts. GH and/or IGF-I might stimulate neutrophil production and/or release via G-CSF.

Adult↗
PubMed2005

An individualized GH dose regimen for long-term GH treatment in Japanese patients with adult GH deficiency.

OBJECTIVES: To investigate the effects of growth hormone (GH) treatment, using a dose-adjustment regimen based on serum insulin-like growth factor (IGF)-I concentrations, in adult Japanese hypopituitary patients with GH deficiency. STUDY DESIGN: Japanese patients who had initially been administered GH (n = 31) or placebo (n = 28) in a 24-week double-blind study received individualized GH treatment in an open-label study for 48 weeks. Body composition from dual-energy X-ray absorptiometry (DXA) and serum IGF-I, IGF-binding protein 3 (IGFBP-3) and lipid levels were determined centrally. RESULTS: Significant increases in lean body mass (4.5%) and decreases in fat mass (-10.5%) were observed in the group that received individualized GH doses in the present open-label study following placebo in the double-blind study. This was comparable with the changes observed in these parameters (4.7 and -9.2%, respectively) with fixed-dose GH treatment in the double-blind study; this latter group maintained these improvements throughout the open-label study. Individualized dose adjustment allowed for more moderate dose increases than the fixed-dose titration method. Individualized dosing also resulted in a lower mean dose for adult-onset compared with childhood-onset GH-deficient patients (0.032+/-0.019 versus 0.061+/-0.023 mg/kg per week for patients treated with GH for 48 weeks in the open-label study following placebo in the double-blind study). Dosing patterns in the two groups were paralleled by the changes in IGF-I and IGFBP-3. The incidence of oedema and cases with high IGF-I level were less frequent under the IGF-I controlled regimen compared with those during the fixed-dose titration method. CONCLUSION: Individualized GH administration based on IGF-I levels was safe and effective. This regimen demonstrated differences in dose requirements between adult- and childhood-onset patients. An individualized dose regimen is recommended in adult Japanese GH-deficient patients.

Adult↗
PubMed2005

Human growth hormone and insulin-like growth factor-I inhibit erythropoietin secretion from the kidneys of adult rats.

Growth hormone (GH) and insulin-like growth factor-I (IGF-I) play important roles in erythropoiesis and erythro-poietin (EPO) secretion. We examined the effects of GH and IGF-I on EPO production in adult rat kidney and liver in vivo and in vitro. Male Wistar rats aged 8-10 weeks were used. Recombinant human GH (hGH) was continuously infused (20 mug/kg per h) subcutaneously for 48 h using a micro-osmotic infusion pump. Octreotide (10 mug/kg) was subcutaneously injected every 12 h beginning 12 h before the hGH treatment. GH increased plasma EPO levels earlier than it increased plasma IGF-I levels. At 24 h, the IGF-I content in the liver and kidney was increased from 172.8+/-14.6 to 232.6+/-17.8 ng/g tissue (means+/-S.E.) and from 53.8+/-3.1 to 112.8+/-7.2 ng/g tissue, respectively. The EPO content in the liver was increased from 7.5+/-1.2 to 15.1+/-1.4 mIU/g tissue at 48 h, whereas the EPO content in the kidney was decreased at 12, 24, and 48 h after the start of hGH treatment. When the kidneys were organ-cultured, hGH considerably decreased EPO levels in the culture medium in a dose-related manner. The addition of anti-hGH IgG blunted the GH-induced inhibition of EPO secretion from the kidneys. IGF-I also decreased EPO levels in the medium in a dose-related manner. The addition of anti-IGF-I IgG blunted the IGF-I-induced inhibition of EPO secretion from the kidneys, whereas the GH-induced inhibition of EPO secretion was not affected. These findings suggest that both hGH and IGF-I have direct inhibitory effects on EPO secretion from adult rat kidneys.

Animals↗
PubMed2004

Increased resting metabolic rate in patients with type 2 diabetes mellitus accompanied by advanced diabetic nephropathy.

Thirty-three patients with type 2 diabetes mellitus (16 men, 17 women) were divided into 3 groups based on urinary excretion of albumin (U-Alb)--group A: U-Alb < 30 mg/d; group B: 30 mg/d < or = U-Alb < or = 300 mg/d; and group C: 300 mg/d < U-Alb. Serum creatinine levels were lower than 2.0 mg/dL in all the subjects. There was no difference in age, sex, therapy, body weight, body mass index (BMI), lean body mass (LBM), or hemoglobin A(1c) (HbA(1c)) levels among the 3 groups. Resting metabolic rate (RMR) (kJ/h/m(2)) and adjusted RMR for lean body mass (kJ/h/m(2)) were significantly increased in group C compared with groups A and B. Hb concentrations, serum albumin levels, and creatinine clearance were much lower in group C than in groups A and B (P < .001). There were no difference in serum urea nitrogen, total cholesterol, cholinesterase and free thyroxine, or plasma insulin-like growth factor I (IGF-I) levels among the 3 groups. Linear regression analysis revealed an inverse correlation between RMR and serum albumin levels, correlation between RMR and U-Alb, and inverse correlation between RMR and Hb concentrations, respectively, in these patients. In conclusion, RMR in diabetic patients correlated directly with U-Alb and inversely with serum albumin and Hb concentration. These findings suggest that RMR is related with urinary albumin loss and anemia in patients with type 2 diabetes mellitus accompanied by diabetic nephropathy.

Adult↗
PubMed2004

Effect of tetrahydrobiopterin on nitric oxide synthase-containing cells in the rat hippocampus.

We have observed that tetrahydrobiopterin (BH4), a cofactor of nitric oxide synthase (NOS), acts as a self-protection factor against nitric oxide (NO) toxicity in PC12 cells. To further investigate the self-protection action of BH4 in vivo, the effect of deletion of endogenous BH4 on NO-producing cells was examined in the rat hippocampus. Following the peripheral infusion of 50 mM 2,4-diamino-6-hydroxypyrimidine (DAHP), an inhibitor of GTP cyclohydrolase I, using a miniosmotic pump for 14 days, BH4 content in the hippocampus decreased as compared with the control group administered with vehicle solution, which had no effect on brain BH4 content. When the rats were administered with 50 mM DAHP and 10 mM BH4, the DAHP-induced decrease in BH4 content was prevented. The extracellular concentration of NO metabolites remained unchanged following DAHP administration, suggesting that DAHP-induced decrease in BH4 content had no effect on NO production. The number of NOS-positive cells decreased following DAHP administration in the hippocampal regions, while the number of NOS-negative cells remained unchanged. The DAHP-induced decrease in the NOS-positive cell number was prevented by the administration of 10 mM BH4 and DAHP. These results suggest that endogenous BH4 may affect NOS-positive cell number in the rat hippocampus.

Animals↗
PubMed2004

A new device to introduce self-injection of insulin by his non-dominant hand in a patient with hemiplegia.

Dominant hand dysfunction due to cerebrovascular accident or fracture makes it more difficult to self-inject insulin. This would likely lead to diminishing a patient's quality of life. We made a new device to introduce self-injection of insulin by a patient's non-dominant hand and tested it. This device was built into a 600-g block of wood 11.5 cm x 8 cm x 8 cm, to be used with the InnoLet insulin kit system (Novo Nordisk Pharmaceuticals Inc., Bagsvaerd, Denmark). It had an insulin injector clamp on the front and a needle holder on the top. The bottom and the back were covered with silicon rubber, which allows the device's own weight to affix it on a table. The insulin injector is placed upright in a holder and fastened with a bar. A needle is installed on the insulin injector with a needle cap. After this cap was removed, the patient could remove any air bubbles by pushing 2 units of insulin through the needle. After the insulin injector was unfastened from the device, the patient injected the insulin subcutaneously into his abdomen or thigh. Then, the insulin injector was removed from the device. We introduced this device in a 59-year-old man with type 2 diabetes mellitus who had suffered from ischemic cerebral infarction in the left middle cerebral artery distribution, resulting in complete right hemiparesis. Our patient mastered this procedure within a few days. At the time of discharge, he could self-inject regular human insulin in a dose of 16 units in the morning, 6 units at noon, and 8 units in the evening. Two weeks after he was admitted to our hospital, he continued independent insulin self-injection three times per day without any help. His hemoglobin A(1c) level gradually decreased until it reached 5.7%. The self-injection of insulin may be introduced with a new device by the non-dominant hand in a patient with diabetes having a disabled dominant hand.

Diabetes Complications↗
PubMed2004

Metabolic effects of 20-kilodalton human growth hormone (20K-hGH) for adults with growth hormone deficiency: results of an exploratory uncontrolled multicenter clinical trial of 20K-hGH.

The biological effects of 20-kDa human GH (20K-hGH), which is produced in the pituitary by alternative splicing of GH mRNA and comprises approximately 6% of all GH in serum, have not been reported. We have investigated the metabolic effects of recombinant 20K-hGH in adult patients with GH deficiency in an exploratory study. Three doses of 20K-hGH (0.006, 0.012, and 0.024 mg/kg.d), were administered for 16 wk to three groups (consisting of 18 or 19 subjects), respectively. The 20K-hGH dose-dependently increased serum IGF-I and IGFBP-3 levels, and the lowest dose (0.006 mg/kg) was enough to normalize both hormones by wk 4. Serum osteocalcin levels and urinary deoxypyridinoline excretion were also dose-dependently increased. There was a significant decrease in body fat mass with an increase of lean body mass at the lowest dose of 0.006 mg/kg.d. Blood glucose and serum insulin were increased significantly at 4 wk only in the high-dose group (0.024 mg/kg). Glucose tolerance was slightly impaired in 26-39% of patients in all treatment groups as judged by oral glucose tolerance tests, but there was no development of overt diabetes. The major adverse event in the 20K-hGH treatment was peripheral edema, similar to the incidence reported for 22K-hGH. The data demonstrated that 20K-hGH had metabolic effects comparable to those of 22K-hGH in humans. The results suggest that 20K-hGH could be used to treat GH-deficient patients, although further studies may be required to investigate the optimum dose and superiority of 20K-hGH over 22K-hGH in a comparative study.

Abdomen↗
PubMed2004

Serum levels of 20 kilodalton human growth hormone (20K-hGH) in patients with acromegaly before and after treatment with octreotide and transsphenoidal surgery.

Circulating human GH (hGH) consists of several molecular isoforms. It was previously reported that the proportion of 20 kilodalton hGH (20K-hGH) was elevated in the serum of patients with active acromegaly. In this study, we investigated the effects of octreotide and transsphenoidal adenomectomy on the proportion of 20K-hGH in the serum of 7 acromegalic patients. To achieve an acute effect, octreotide (100 microg) was subcutaneously injected as a bolus. To observe the chronic effects of octreotide therapy and surgery, serum samples were obtained by repetitive blood sampling before and 3 to 8 weeks after treatment. Serum levels of 20K-hGH and 22 kilodalton hGH (22K-hGH) were determined by specific enzyme-linked immunosorbent assay. A bolus injection of octreotide elicited a parallel decrease in serum 22K-hGH and 20K-hGH, resulting in an unchanged proportion of 20K-hGH to total circulating hGH. The proportion of 20K-hGH was decreased in 4 of 4 patients 4 to 7 weeks after surgery and in 2 of 4 patients after chronic treatment with octreotide for 3 to 8 weeks. The proportion of serum 20K-hGH was positively related to mean serum 20K-hGH as well as serum total hGH levels, but not with serum IGF-I levels. These findings suggest that high serum levels of 20K-hGH or total hGH per se might elicit a chronic change in the clearance kinetics of 20K-hGH and increase the proportion of 20K-hGH in acromegalic patients.

Acromegaly↗
PubMed2004

Adult GH deficiency in Japanese patients: effects of GH treatment in a randomised, placebo-controlled trial.

OBJECTIVE: To evaluate the influence of factors intrinsic to the Japanese population on consequences of growth hormone deficiency (GHD) and effects of GH treatment in adult Japanese hypopituitary patients with GHD. STUDY DESIGN: A 24-week, randomised, placebo-controlled, double-blind study in 64 patients in Japan, with GHD onset during adulthood (AO; n=27) or childhood (CO; n=37). Body composition measured by dual-energy X-ray absorptiometry (DXA) was evaluated centrally. Serum IGF-I, IGF binding protein-3 (IGFBP-3) and lipid levels were determined centrally. RESULTS: In contrast to Caucasian patients, there were no significant differences before treatment between AO and CO patients for body mass index (BMI), lean body mass (LBM) and fat mass (FM). Baseline BMI was >/=25 kg/m(2) for 32.8% of patients. For all patients combined, a significant increase in LBM and decrease in FM (P<0.001 for each) was seen with GH treatment. Serum IGF-I and IGFBP-3 were significantly lower at baseline in CO compared with AO patients, similar to Caucasian patients, and were increased in both onsets following GH treatment. Serum total and low-density lipoprotein (LDL)-cholesterol concentrations did not differ between AO and CO patients at baseline and were elevated compared with normal ranges. GH-induced decreases were significant compared with placebo for both total (P=0.036) and LDL-cholesterol (P=0.040). Glycosylated haemoglobin was increased with GH compared with placebo treatment (P=0.016) but remained within the upper limit of normal for all patients at endpoint. CONCLUSIONS: Adult Japanese hypopituitary patients with GHD demonstrated obesity relative to healthy Japanese subjects but the clinical presentation differed from that of Caucasian patients. GH treatment improved body composition and serum cholesterol profiles of adult Japanese hypopituitary patients with GHD.

Adult↗
PubMed2003

Echocardiographic investigation of pericardial effusion in a case of anorexia nervosa.

OBJECTIVE: Pericardial effusion has recently been reported as a complication of anorexia nervosa. A distinct pathophysiological cause of it could not be revealed. In some reports, there was a probable correlation between weight gain and reduction of pericardial effusion in anorexia nervosa cases. We encountered a case in which pericardial effusion remitted completely along with body weight increase and normalization of low T3 syndrome. These findings suggest that the reduction of pericardial effusion may correlate with both weight gain and low T3 normalization. Plasma brain natriuretic peptide (BNP) levels were increased in this case despite heart failure, and plasma BNP decreased as pericardial effusion remitted. The measurement of serum BNP level may be a clinical parameter in such a case of pericardial effusion.

Adult↗
PubMed2003

Effect of high concentration of glucose on dopamine release from pheochromocytoma-12 cells.

To investigate the mechanism of the action of high concentration of glucose on transmitter release from neuronal cells, we examined the effect of high concentration of glucose on dopamine release from pheochromocytoma-12 (PC12) cells. When the cells were incubated with 9.0 or 13.5 mg/mL glucose (2- or 3-fold of the optimum glucose concentration for PC12 cells), dopamine release was increased in a dose-related manner. Glucose-induced increase in dopamine release was blunted by nicardipine, a Ca2+ channel blocker. Following addition of 13.5 mg/mL glucose, intracellular Ca2+ concentration was increased, which was eliminated by nicardipine. Administration of 9.0 or 13.5 mg/mL glucose induced membrane depolarization in a dose-related manner. Glucose-induced dopamine release was inhibited by pinacidil or diazoxide, adenosine triphosphate (ATP)-sensitive K+ channel (KATP channel) openers. These results suggest that a high concentration of glucose induced ATP production, which blocked the KATP channel to induce membrane depolarization, and increased intracellular Ca2+ concentration and dopamine release. When the cells were cultured with 9.0 or 13.5 mg/mL glucose for 7 days, high potassium chloride (KCl)-induced dopamine release and 45Ca2+ uptake were increased. These results suggest that long-term incubation with a high concentration of glucose increased the capacity of Ca2+ uptake to enhance depolarization-induced dopamine release from PC12 cells. These data taken together suggest that a high concentration of glucose induced activation of the Ca2+ channel to stimulate dopamine release from PC12 cells.

Adenosine Triphosphate↗
PubMed2003

Frequent appearance of autoantibodies against prohormone convertase 1/3 and neuroendocrine protein 7B2 in patients with nonfunctioning pituitary macroadenoma.

Among pituitary disorders having mass effect of the pituitary gland, nonfunctioning pituitary macroadenoma and lymphocytic hypophysitis are difficult to differentiate without histological examination. In order to efficiently distinguish lymphocytic hypophysitis and pituitary tumors, we studied the presence of autoantibodies against prohormone-processing enzymes, prohormone convertase (PC) 1/3, PC2, carboxypeptidase E (CPE), and PC2 regulatory protein, 7B2, by radioligand assay using recombinant human 35S-labeled protein in patients with clinically nonfunctioning pituitary macroadenoma, lymphocytic hypophysitis, and other pituitary diseases. The indexes for anti-PC1/3 antibodies (Ab) were significantly higher in patients with nonfunctioning pituitary macroadenoma than in patients with lymphocytic hypophysitis. Patients positive for either anti-PC1/3 or anti-7B2 Ab were significantly frequent among patients with nonfunctioning pituitary macroadenoma than in other pituitary diseases and healthy controls. None of the patients was positive for anti-PC2 Ab or anti-CPE Ab. These results suggest that autoantibodies against PC1/3 and 7B2 are novel tumor-associated autoantibodies and can be helpful in the diagnosis of clinically nonfunctioning pituitary macroadenoma.

Adenoma↗