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Biomedical subjects

Shigehiro Katayama

Publications and source records attributed to Shigehiro Katayama.

At least 37 records · Page 2Linked to original sources
PubMed2005

[Osteoporosis and intake of carbohydrates].

Adequate energy intake including carbohydrates is essential to maintain bone mass. Emaciation along with deficiency in nutrients, such as calcium, vitamin D, and protein is a significant risk factor for bone loss, and should be avoided. However, there is no clinical evidence that shows the direct effects of carbohydrate on bone mass. On the other hand, excessive intake of carbohydrates results in obesity, which causes other metabolic diseases such as diabetes mellitus (DM). Therefore, dietary regimen must be balanced in general, and complications and conditions of individual patients should be taken well into account. In addition, energy intake is a basis for adequate exercise in order to maintain physical activity and ideal body weight, which will further decrease the risk of bone fracture. Some indigestible carbohydrates, such as inulin and oligofructose, are shown to increase the availability of minerals from foods, and thus can be beneficial to bone mass.

Body Weight↗
PubMed2005

[Clinical significance of calcium channel blocker in patients with metabolic syndrome].

Diabetes mellitus, hyperlipidemia and hypertension are often coexisting, especially in obese subjects. Based on the close relationship between these abnormalities, the new definition of "Metabolic Syndrome" was established this April, in which "Metabolic Syndrome" was defined to have 2 of 3 abnormalities such as hypertriglyceridemia (>150 mg/dL) and/or low HDL-cholesterolemia (<40 mg/dL), hypertension (>130/85 mmHg) and high fasting glucose levels (>110 mg/dL) in addition to abdominal obesity (waist circumference >85 cm in men and >90 cm in women). It seems to be very important to select hypotensive agents which improve insulin sensitivity in hypertensive patients with "Metabolic Syndrome".

Antihypertensive Agents↗
PubMed2005

[Revised criteria for the early diagnosis of diabetic nephropathy].

The Diabetic Nephropathy Committee recommends the use of revised criteria for the early diagnosis of diabetic nephropathy in Japan. The new criteria are as follows: 1) Urinary albumin should be determined by immunoassay using a morning spot urine sample in diabetic patients without proteinuria or with dipstick-positive(+ 1) proteinuria. 2) A urinary albumin-to-creatinine ratio ranging from 30 to 299 mg/ gCr in 2 or more of 3 specimens may be diagnosed as microalbuminuria. 3) Two alternatives, i.e. the urinary albumin excretion rate of 30-299 mg/24hr in 24hr urine collection or 20-199 microg/min in timed urine collection can be used to detect microalbuminuria. 4) Renal hypertrophy and elevated urinary type IV collagen may indicate the existence of diabetic renal disease. 5) Microalbuminuria originating in non-diabetic diseases should be excluded.

Albuminuria↗
PubMed2004

Regulation of adiponectin receptor gene expression in diabetic mice.

Adiponectin is an adipocyte-derived factor that plays pivotal roles in lipid and glucose metabolism in muscle and liver. The following two adiponectin receptor types were recently identified: AdipoR1 is abundantly expressed in muscle, whereas AdipoR2 is predominantly expressed in the liver. To clarify the regulation of adiponectin receptor gene expression in diabetic states, we examined mRNA levels of AdipoR1 in the muscles of diabetic animals by Northern blotting. The level of AdipoR1 mRNA was increased approximately 2.5-fold in muscle of streptozotocin (STZ) diabetic mice, but the normal level was restored by insulin administration, indicating that insulin has an inhibitory effect on AdipoR1 expression. To confirm this inhibitory effect of insulin, we performed in vitro experiments using C2C12 skeletal muscle cells. Insulin treatment for 24 h decreased AdipoR1 expression by approximately 60% in C2C12 cells. In addition, this effect was mediated by the phosphatidylinositol 3-kinase-dependent pathway rather than the mitogen-activated protein kinase pathway. AdipoR1 expression in insulin-resistant diabetic mice was also investigated. AdipoR1 expression was decreased by 36% in type 2 diabetic obese db/db mice compared with lean mice. In contrast, hepatic AdipoR2 expression was not significantly changed in either STZ mice or genetically obese mice. Our results indicate that regulation of AdipoR1, but not that of AdipoR2, may be involved in glucose and lipid metabolism in diabetic states.

Animals↗
PubMed2004

Efficacy of glimepiride in Japanese type 2 diabetic subjects.

We investigated the efficacy of glimepiride, a third-generation sulfonylurea (SU), in Japanese type 2 diabetic patients in whom glycemic control had been inadequate with a conventional SU, gliclazide or glibenclamide. A total of 172 Japanese type 2 diabetic patients (HbA1C > or = 7.0%), maintained on a conventional SU, were randomly assigned to the 3rd SU group (SU treatments switched to glimepiride) or the 2nd SU group (treatments not changed). The conventional SU was switched to the indicated doses of glimepiride (gliclazide 40 mg = glimepiride 1 mg, glibenclamide 2.5 mg = glimepiride 2 mg). After 6 months, glycemic control (HbA1C and fasting plasma glucose) had not changed significantly in either the 2nd or the 3rd SU group. The homeostasis assessment model of insulin resistance (HOMA-IR) in the 3rd SU group was decreased by more than 10% (p = 0.015), whereas no change was observed in the 2nd SU group. The triglyceride level was decreased by approximately 10% in the 3rd SU group, not a significant change (p = 0.080). Patients who had been treated with only SU, or treated with SU for a short time (less than 5 years), and who were also obese (BMI > or = 25) or had a high HOMA-IR (HOMA-IR > or = 3), showed significantly reduced insulin resistance. According to logistic regression analysis, high BMI ( > or = 25) was the only variable predicting that glimepiride would more effectively improve HbA1C than conventional SU treatment. In conclusion, switching conventional SUs to glimepiride reduced insulin resistance without improving glycemic control. A notable finding of this study is that glimepiride was more beneficial in obese than in non-obese Japanese type 2 diabetic patients.

Aged↗
PubMed2004

Essential role of p38 mitogen-activated protein kinase in cathepsin K gene expression during osteoclastogenesis through association of NFATc1 and PU.1.

The receptor activator of NF-kappaB ligand (RANKL) induces various osteoclast-specific marker genes during osteoclast differentiation mediated by mitogen-activated protein (MAP) kinase cascades. However, the results of transcriptional programming of an osteoclast-specific cathepsin K gene are inconclusive. Here we report the regulatory mechanisms of RANKL-induced cathepsin K gene expression during osteoclastogenesis in a p38 MAP kinase-dependent manner. The reporter gene analysis with sequential 5'-deletion constructs of the cathepsin K gene promoter indicates that limited sets of the transcription factors such as NFATc1, PU.1, and microphthalmia transcription factor indeed enhance synergistically the gene expression when overexpressed in RAW264 cells. In addition, the activation of p38 MAP kinase is required for the maximum enhancement of the gene expression. RANKL-induced NFATc1 forms a complex with PU.1 in nuclei of osteoclasts following the nuclear accumulation of NFATc1 phosphorylated by the activated p38 MAP kinase. These results suggest that the RANKL-induced cathepsin K gene expression is cooperatively regulated by the combination of the transcription factors and p38 MAP kinase in a gradual manner.

Animals↗
PubMed2004

ANGPTL3 is increased in both insulin-deficient and -resistant diabetic states.

Angiopoietin-like protein 3 (ANGPTL3) is secreted by the liver and was recently postulated to be an important hormone regulating serum triglyceride levels. In the present study, in order to clarify the regulation of ANGPTL3 gene expression in diabetic states, we examined mRNA and protein levels of ANGPTL3 in the livers of diabetic animals. The level of ANGPTL3 mRNA was increased approximately 2.2-fold in the livers of streptozotocin (STZ) diabetic mice, and this effect was reversed by administration of insulin. Furthermore, the level of ANGPTL3 mRNA was increased more than 3.0-fold in type 2 diabetic obese mice, db/db mice, as compared with age matched lean littermates. The hepatic level of ANGPTL3 protein was also increased in these diabetic mice to an extent similar to that of ANGPTL3 mRNA. Thus, the expression of ANGPTL3 was enhanced in both insulin-deficient and -resistant diabetic states. These results strongly suggest ANGPTL3 to play an important role in hyperlipidemia in diabetes.

Angiopoietin-Like Protein 3↗
PubMed2004

Interaction between 3' untranslated region of calcitonin receptor messenger ribonucleic acid (RNA) and adenylate/uridylate (AU)-rich element binding proteins (AU-rich RNA-binding factor 1 and Hu antigen R).

Our previous results in mouse osteoclasts suggested that calcitonin (CT) alters CT receptor (CTR) mRNA stability. The CTR mRNA transcript contains several adenylate/uridylate (AU)-rich destabilizing elements in the 3' untranslated region (3'UTR). When the 3'UTR of mouse CTR mRNA was labeled by [alpha-(32)P]-uridine 5-triphosphate, interactions were observed between the transcript and several cell extracts, including those from the osteoclast progenitor monocyte/macrophage cell line, RAW 264.7. The molecular masses of the interacting proteins ranged from approximately 35 to 50 kDa, similar to AU-rich RNA-binding factor 1 (AUF1) and Hu antigen R (HuR). Radiolabeled 3'UTR transcripts bound with a 40-kDa protein, which could be extracted from cells transfected with AUF1 p40. To confirm the binding specificity, a pSG5 vector construct, containing the AUF1 p40 with an hemagglutinin tag, was transiently transfected into NIH3T3 cells. The extracts were incubated with poly(A)-added CTR3'UTR. The reaction mixture was immunoprecipitated using an antihemagglutinin antibody and precipitated mRNA species were extracted and reverse transcribed using oligo-dT primers. It was found that PCR primers specific for the 3'UTR of CTR mRNA sequence generated a PCR signal. No signal was observed when mutated AUF1 p40 was transfected. In a manner similar to the AUF1 binding, HuR was also found to bind to the 3'UTR. Specific binding of AUF1 p40 and HuR was also found with RNA extracted from mouse osteoclasts. Treatment of osteoclasts with CT did not significantly affect the expression of AUF1 but decreased the levels of HuR and its mRNA. The role of CTR3'UTR in mRNA stability was further tested by expressing luciferase reporter constructs that did, or did not, contain the CTR3'UTR, under the control of the tetracycline-regulatory system. The results showed that the addition of 3'UTR considerably shortened the mRNA half-life of the luciferase reporter gene. These results suggest that AUF1 p40, HuR, and the 3'UTR of the CTR mRNA transcript could be involved in posttranscriptional regulation of CTR mRNA expression.

3' Untranslated Regions↗
PubMed2004

Pro12Ala substitution in peroxisome proliferator-activated receptor gamma 2 is associated with low adiponectin concentrations in young Japanese men.

Peroxisome proliferator-activated receptor gamma (PPAR gamma) has been shown to play an important role in adipocyte differentiation. A Pro12Ala substitution in PPAR gamma 2 has been reported to decrease receptor activity in vitro and to be associated with a decreased risk of type 2 diabetes in the general population. Recently, a PPAR response element (PPRE) was identified in the adiponectin promoter, suggesting that decreased PPAR gamma activity may lead to lower adiponectin levels. In the present study, serum adiponectin concentrations and the PPAR gamma Pro12Ala polymorphism were analyzed to determine whether this polymorphism is associated with lower serum adiponectin concentrations in young healthy Japanese subjects. Serum adiponectin concentrations were significantly lower in men with than in those without the Ala12 allele, whereas body mass index (BMI), homeostasis model assessment (HOMA)-beta, HOMA-IR, the insulin sensitivity index during oral glucose tolerance test (ISI [composite]), and serum leptin did not differ significantly between subjects with and without the Ala12 allele. Stepwise regression demonstrated BMI and the Ala12 allele to be independent predictors of serum adiponectin concentrations in men. In conclusion, the Pro12Ala substitution in PPAR gamma 2 may reduce serum adiponectin concentrations in young Japanese men.

Adiponectin↗
PubMed2004

Stimulation of thyroid-stimulating hormone (TSH) receptor antibody production following painless thyroiditis.

OBJECTIVE: Development or recurrence of Graves' disease (GD) following painless thyroiditis (PT) has been documented. Therefore, we measured titres of TSH receptor antibodies (TSHR Ab) using a novel sensitive TSHR Ab assay in patients with PT to determine whether PT enhances TSHR Ab production, possibly triggering the development or recurrence of GD. DESIGN AND MEASUREMENTS: Ninety-two patients who developed PT were studied. Group G consisted of 40 patients with a history of GD (19 patients in remission, 21 who had stopped taking antithyroid drugs during pregnancy). Group P consisted of 52 patients with no history of GD. Serum thyroid hormone levels, thyroid autoantibodies including TSHR Ab, and 123I uptake at 24 h (RAIU) were measured in these patients at the time of PT onset. TSHR Abs were measured by radioreceptor assay using porcine TSH receptors (pTBII) or human TSH receptors (hTBII). RESULTS: There were no significant differences in serum thyroid hormone levels or pTBII values between groups G and P. Nor was there any significant difference between p- and h-TBII values in group P. There was also no significant difference in pTBII levels before, compared to at the time of PT onset in group G patients. However, hTBII values at the PT onset were significantly higher in the group G than in the group P (7.7 +/- 9.8%vs. 1.4 +/- 5.4%, P = 0.0014). The rate of hTBII positivity was also significantly higher in group G than in group P (12/40 vs. 3/52, P = 0.002). Furthermore, the RAIU in group G patients was significantly higher than that in group P patients (2.8 +/- 2.4%vs. 1.3 +/- 0.9%, P = 0.0002). GD recurrence was observed in seven patients in group G, whose hTBII levels were significantly higher than those of other patients in this group (17.0 +/- 11.8%vs. 5.7 +/- 8.2%, P = 0.02). Of these seven with relapses, five had hTBII values exceeding 15%. CONCLUSIONS: TBII elevation at the onset of PT in patients with a history of GD was detected by a sensitive hTBII assay. Destruction of the thyroid by PT may trigger GD recurrence in patients with a history of GD.

Adult↗
PubMed2004

Characterization of the epitopes specific for the monoclonal antibody 9F5-3a and quantification of oxidized HDL in human plasma.

BACKGROUND: We previously isolated a monoclonal antibody, 9F5-3a, that is specific for HDL oxidized by CuSO(4). METHODS: We examined the characteristics of the 9F5-3a epitope by Western blot and measured the concentration of oxidized HDL in human plasma by enzyme-linked immunosorbent assay using this antibody. RESULTS: The monoclonal antibody specifically reacted with oxidized HDL in a mixture of HDL, LDL and modified lipoproteins. Oxidation of the HDL particles accelerated cross-linkage of apolipoproteins caused by lipid peroxidation, and the cross-linked apolipoprotein AI selectively reacted with the 9F5-3a antibody. Mean (standard deviation) plasma concentrations of oxidized HDL were 127 (50) microg/L in 23 healthy controls, 191 (65) microg/L in 30 patients with non-insulin-dependent diabetes mellitus (P < 0.01 versus healthy controls) and 200 (87) microg/L in 25 patients with coronary artery disease (P < 0.01 versus healthy controls). The concentrations of oxidized HDL did not correlate with the concentrations of thiobarbituric acid-reactive substances. CONCLUSIONS: The results indicate that determination of oxidized HDL concentration may be useful for identifying patients with atherosclerotic disease.

Adult↗
PubMed2004

Combined treatment with an AT1 receptor blocker and angiotensin converting enzyme inhibitor has an additive effect on inhibiting neointima formation via improvement of nitric oxide production and suppression of oxidative stress.

Accumulating evidence shows that inhibition of the vascular renin-angiotensin system results in suppression of injury-elicited neointima formation. We attempted to determine whether or not combined treatment with an angiotensin II type 1 receptor blocker (ARB) and angiotensin converting enzyme inhibitor (ACEI) has an additive inhibitory effect on balloon-injury-elicited neointima formation in the carotid artery. Male Sprague-Dawley rats were treated with an ARB (valsartan: 3 mg/kg/day) and/or an ACEI (benazepril: 0.3 mg/kg/day) from 1 week before until 2 weeks after balloon injury. Experiments were also conducted with one-third of the dose combination used in the original experiments. Both ARB and ACEI inhibited neointima formation without any blood pressure changes. The full-dose combination lowered blood pressure and suppressed neointima formation significantly compared with the levels in the groups treated with either ACEI or ARB alone. The low-dose combination without blood pressure reduction also inhibited neointima formation to a similar extent as the full-dose combination. We measured 8-iso-prostaglandin F2alpha (8-iso-PGF2alpha), a marker of oxidative stress, and nitrite and nitrate (NOx), an index of nitric monoxide production, in media conditioned by the injured artery. NOx production was lower and 8-iso-PGF2alpha was higher in the media of the injured artery, compared with those in the normal artery. ACEI restored NOx production more dramatically than ARB, and ARB suppressed 8-iso-PGF2alpha markedly compared with ACEI. These results suggest that the combination of an ARB and an ACEI exerts an additive inhibitory effect, presumably through an increase in production and bioavailability of NO from the endothelium.

Angioplasty, Balloon↗
PubMed2004

Effects of a low dose of indapamide, a diuretic, given daily or every-other-day on blood pressure and metabolic parameters.

To investigate the effects of the diuretic, indapamide, on blood pressure (BP) and metabolic parameters, thirty hypertensive patients were treated with 1 mg of indapamide either every day or every other day. BP, fasting plasma glucose, lipids, serum potassium and uric acid were determined at baseline and after 3 months of a stable regimen of the drug. At the termination of the study, 48-h ambulatory blood pressure monitoring (ABPM) was performed. Three patients received only indapamide, while other patients were treated in combination with additional antihypertensive medications. Patients treated with daily indapamide showed a BP reduction from 162 +/- 2.9/85 +/- 2.4 mmHg to 134 +/- 2.4/71 +/-2.6 mmHg (p < 0.001). The BP reduction was similar in those patients receiving the drug every other day (137 +/- 3.4/71 +/- 3.6 mmHg). While plasma lipids and serum potassium did not differ significantly with the intervention, uric acid increased significantly with daily treatment and normalized with every-other-day treatment. Glycosylated hemoglobin A1c (HbA1c) was not altered (5.6 +/- 0.1% vs. 5.4 +/- 0.2%), and did not differ between patients with and without diabetes mellitus. ABPM revealed an average 24-h BP of 134 +/- 3.3/75 +/- 1.7 mmHg on days in which patients received the medication and 139 +/- 4.9/78 +/- 2.6 mmHg on the intervening day without indapamide (no significant difference). These results suggest that a low dose of indapamide given every day or every other day is effective in lowering BP and does not result in metabolic derangements.

Aged↗
PubMed2004

Erectile dysfunction in hypertensive rats results from impairment of the relaxation evoked by neurogenic carbon monoxide and nitric oxide.

Erectile dysfunction (ED) with aging and diabetes mellitus is caused by impairment of the relaxation evoked by nitric oxide (NO) of penile cavernous smooth muscles and arterioles. However, the mechanism of ED in hypertension is unknown. Carbon monoxide (CO), which is produced by heme oxygenase (HO)-2 in the neuronal system is a neurotransmitter and a vasodilator. We examined the neurogenic role of CO in penile erection and the neurogenic mechanisms of ED in hypertension, using spontaneously hypertensive rats (SHR) or Wistar-Kyoto rats (WKY). The isometric tension of corpus cavernosum tissues from both strains was recorded after guanethidine and atropine treatment. Relaxation in response to electrical field stimulation (EFS) in WKY was suppressed dose-dependently by HO inhibitors both in the absence and presence of an NO synthase (NOS) inhibitor. Reverse transcription-polymerase chain reaction (RT-PCR) showed that the HO-2 gene was expressed in the corpus cavernosum. CO-saturated solution induced a concentration-dependent relaxation in WKY. The neurogenic relaxation to EFS in SHR was impaired as compared with that in WKY after the age of 5 weeks, when blood pressure began to be elevated, due to the attenuated relaxation in response to neurogenic NO and CO. In the corpus cavernosum of SHR, expression of the HO-2 and nNOS genes was similar, and NOx levels after EFS were similar to those of WKY. cGMP levels after EFS and the relaxation evoked by the NO donor was lower in SHR than WKY. Thiobarbituric acid-reacting substance (TBARS) levels were increased, and superoxide dismutase (SOD) activity was suppressed in SHR, as compared with those in WKY, suggesting that the increasing oxidative stress partially causes the impairment of NO-dependent relaxation. These findings suggest that CO regulates the relaxation evoked by EFS in the rat corpus cavernosum, and that ED in hypertension in rats results from an impairment of the relaxation induced by neurogenic CO and NO.

Animals↗
PubMed2004

The possible therapeutic actions of peroxisome proliferator-activated receptor alpha (PPAR alpha) agonists, PPAR gamma agonists, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors, angiotensin converting enzyme (ACE) inhibitors and calcium (Ca)-antagonists on vascular endothelial cells.

Several intervention studies have shown that some hypolipidemic and hypotensive drugs such as fibrates, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors, angiotensin converting enzyme (ACE) inhibitors and calcium (Ca)-antagonists prevent atherosclerosis. The main pathological findings in atherosclerosis include abnormal reactions of neutrophils, lymphocytes and monocytes/ macrophages, vascular smooth muscle cells and vascular endothelial cells, and the accumulation of cholesterol ester in the arterial wall. Therefore, investigating the effects of these drugs on the arterial wall may improve understanding of the mechanisms underlying atherosclerosis. Here, based on recent studies including our own, we describe the relationships between risk factors for atherosclerosis, especially hyperlipidemia and hypertension, and the molecular mechanisms that govern lipid metabolism in the arteries.

Angiotensin-Converting Enzyme Inhibitors↗