Search PubMed⌕ Search

Biomedical subjects

Hirofumi Makino

Publications and source records attributed to Hirofumi Makino.

At least 19 recordsLinked to original sources
PubMed2007

Comparison of ventilatory threshold and exercise habits between Japanese men with and without metabolic syndrome.

OBJECTIVE: We compared the levels of ventilatory threshold (VT) and exercise habits in subjects with metabolic syndrome with those in age, sex-matched subjects without metabolic syndrome. METHODS: We used data of 155 Japanese men (47.1+/-9.2 years) with metabolic syndrome; the diagnosis was given by the definition and the diagnostic standard for metabolic syndrome in Japan. The influence of metabolic syndrome on oxygen uptake, work rate and heart rate at VT, and exercise habits were evaluated. RESULTS: Oxygen uptake and work rate at VT in subjects with metabolic syndrome were significantly lower than those in subjects without metabolic syndrome even after adjusting for body mass index (BMI). The number of subjects with exercise habits was significantly lower in metabolic syndrome. The subjects with exercise habits were significantly older than that in subjects without exercise habits. Furthermore, oxygen uptake and work rate at VT were significantly higher in subjects with exercise habits than those in subjects without exercise habits. CONCLUSION: Lower level of VT was characteristic in subjects with metabolic syndrome. Promotion of exercise habits is necessary for preventing and improving metabolic syndrome in Japanese men.

Adult↗
PubMed2007

Apparent mineralocorticoid excess manifested in an elderly patient with hypothyroidism.

The syndrome of apparent mineralocorticoid excess (AME) is characterized by persistent hypertension and hypokalemia, which is caused by impaired inactivation of cortisol (F) to cortisone (E). The thyroid hormone has been known to influence the F to E conversion leading to efficacious inactivation of F into E. However, there have been no reports regarding the clinical manifestation of secondary AME due to hypothyroidism. Here we report an elderly patient who manifested AME, showing persistent hypertension with hypokalemia induced by primary hypothyroidism. Maintenance of euthyroid conditions ameliorated the concurrent AME and restored adrenal secretion of aldosterone after the recovery of the F to E shuttle. This case report would broaden our clinical recognition regarding acquired AME in relation to thyroid dysfunction.

Aged, 80 and over↗
PubMed2006

Thiazolidinedione ameliorates renal injury in experimental diabetic rats through anti-inflammatory effects mediated by inhibition of NF-kappaB activation.

Thiazolidinedione (TZD), a ligand for peroxisome proliferator-activated receptor-gamma (PPAR-gamma), exerts anti-inflammatory effects independently of the insulin-sensitizing effect. In the present study, we tested the hypothesis that TZD prevents the progression of diabetic nephropathy by modulating the inflammatory process. Five-week-old Sprague-Dawley rats were divided into three groups: 1) nondiabetic control rats (non-DM), 2) diabetic rats (DM), and 3) diabetic rats treated with pioglitazone (DM+pio). Diabetes was induced by injection with streptozotocin (STZ). The DM+pio group received 0.0002% pioglitazone mixed in chow for 8 wk after induction of diabetes. Blood glucose and HbA1c were elevated in diabetic rats but did not change by treatment with pioglitazone. Pioglitazone reduced urinary albumin excretion and glomerular hypertrophy, suppressed the expression of transforming growth factor (TGF)-beta, type IV collagen, and ICAM-1, and infiltration of macrophages in the kidneys of diabetic rats. Furthermore, renal NF-kappaB activity was increased in diabetic rats and reduced by pioglitazone. PPAR-gamma was expressed in glomerular endothelial cells in the diabetic kidney and in cultured glomerular endothelial cells. High-glucose conditions increased the expression of ICAM-1 and the activation of NF-kappaB in cultured glomerular endothelial cells. These changes were reduced by pioglitazone, ciglitazone, and pyrrolidine dithiocarbamate, an inhibitor of NF-kappaB. However, pioglitazone did not show the changes in the presence of PPAR-gamma antagonist GW9662. Our results suggest that the preventive effects of pioglitazone may be mediated by its anti-inflammatory actions, including inhibition of NF-kappaB activation, ICAM-1 expression, and macrophage infiltration in the diabetic kidney.

Anilides↗
PubMed2006

Regulatory expression of bone morphogenetic protein-6 system in aldosterone production by human adrenocortical cells.

Bone morphogenetic protein-6 (BMP-6) enhances aldosterone production by upregulating angiotensin II (Ang II)-to-MAPK pathway. Here we investigated effects of Ang II and potassium on the BMP system in human adrenocortical H295R cells. BMP-6 transcription was transiently downregulated by treatments with Ang II and potassium. Aldosterone also decreased BMP-6 expression at a high concentration. Chemical inhibitions of transcription and translation abolished the transient reduction of BMP-6, suggesting that destabilization of BMP-6 mRNA was hardly involved while new protein synthesis was possibly mediated in this mechanism. However, BMP-6 protein was stably detected during the exposures of Ang II and potassium. Notably, Ang II, potassium and aldosterone decreased mRNA levels of follistatin that extracellularly neutralizes bioactivities of activins and BMPs although the BMP-6 receptor expression was unaffected. Given the maintenance of bioavailable BMP-6 protein and the receptor expression in adrenocortical cells, endogenous BMP-6 may be a key autocrine modulator for aldosterone production.

Adrenal Cortex↗
PubMed2006

Relationship between metabolic syndrome and cigarette smoking in the Japanese population.

OBJECTIVE: We investigated the link between metabolic syndrome and cigarette smoking in the Japanese population. METHODS: A total of 3,177 Japanese subjects aged 20-79 years were recruited in a cross-sectional clinical investigation study. Habits of cigarette smoking were obtained at interviews by well-trained staff. The diagnosis of metabolic syndrome was based on the new criterion in Japan. RESULTS: Four hundred and forty men (35.3%) and 142 women (7.4%) were current smokers. Three hundred thirty four men (26.8%) and 69 women (3.6%) were diagnosed as metabolic syndrome. The prevalence of current smoker in subjects with metabolic syndrome was significantly higher than in subjects with non-metabolic syndrome in men with and without adjustment for age. The prevalence of metabolic syndrome in men with Brinkman index > or = 600 was significantly higher than that in men with Brinkman index < 600. CONCLUSION: The present study indicated that cigarette smoking may be an important modifiable factor in Japanese men with metabolic syndrome.

Adult↗
PubMed2006

Differential regulation of steroidogenesis by bone morphogenetic proteins in granulosa cells: involvement of extracellularly regulated kinase signaling and oocyte actions in follicle-stimulating hormone-induced estrogen production.

In the present study, we investigated the cellular mechanism by which oocytes and bone morphogenetic proteins (BMPs) govern FSH-induced steroidogenesis using rat primary granulosa cells. BMP-6 and BMP-7 both inhibited FSH- and forskolin (FSK)-induced progesterone synthesis and reduced cAMP synthesis independent of the presence or absence of oocytes. BMP-7 also increased FSH-induced estradiol production, and the response was further augmented in the presence of oocytes. In contrast, BMP-6 had no impact on estradiol synthesis regardless of the presence of oocytes. Because BMP-7 changed neither FSK- nor cAMP-induced estradiol production, the BMP-7 action was mediated through a FSH receptor signaling mechanism that was independent of cAMP-protein kinase A pathway. Treatment with FSH but not cAMP activated ERK1/2 phosphorylation in granulosa cells, which was further accelerated by oocytes. A specific ERK inhibitor, U0126, increased estradiol production and decreased FSH- and FSK-induced progesterone production and cAMP synthesis. This suggests that ERK activation is directly linked to inhibition of estradiol synthesis and amplification of cAMP. Moreover, FSH-induced ERK1/2 phosphorylation was inhibited by BMP-7 but not influenced by BMP-6. In contrast, BMP signaling including Smad1/5/8 phosphorylation and Id-1 transcription was up-regulated by FSH and oocytes in granulosa cells through inhibition of Smad6/7 expression. Collectively, oocytes enhance FSH-induced MAPK activation and BMP signaling in granulosa cells, which leads to differential regulation of steroidogenesis elicited by BMPs in the presence of FSH in developing follicles.

Animals↗
PubMed2006

Urinary PGDS levels are associated with vascular injury in type 2 diabetes patients.

BACKGROUND: The presence of metabolic syndrome has been shown to be predictors of cardiovascular morbidity and mortality in patients with type 2 diabetes. In a cross-sectional clinical study, we investigated the association of metabolic syndrome with asymptomatic lacunar strokes and cardiovascular disease (CVD) and we compared its significance with urinary protein markers. METHODS: We studied Japanese type 2 diabetes patients (n=233, men=124, women=109). The diagnosis of metabolic syndrome was made according to WHO and International Diabetes Federation (IDF) criteria. Cardiovascular events were recorded and asymptomatic lacunar lesions were evaluated with magnetic resonance imaging (MRI). We also measured urinary levels of albumin, type IV collagen, beta2-microglobulin (beta2MG), N-acetyl-beta-d-glucosaminidase (NAG) and lipocalin-type prostaglandin D synthase (PGDS). RESULTS: The prevalence of metabolic syndrome is 31.3% (IDF) and 52% (WHO) in 233 patients and microalbuminuria was present in 62 subjects (26.6%). Metabolic syndrome (WHO) significantly associated with asymptomatic lacunar lesions (p=0.035, OR=2.854, CI 1.075-7.579), while metabolic syndrome (IDF) or urinary markers failed to associate with presence of asymptomatic lacunar lesions. The presence of metabolic syndrome or microalbuminuria did not show significant association with CVD; however, the elevation of beta2MG, NAG and PGDS showed significant association with CVD. By a logistic regression analysis using urinary proteins as independent variables, the presence of higher PGDS excretion independently associated with history of CVD (p=0.025, OR=3.847, CI 1.180-12.545). CONCLUSIONS: In type 2 diabetes patients, the elevation of urinary PGDS secretion closely associated with cardiovascular events and may be a supplemental or additional marker to the criteria of metabolic syndrome.

Albuminuria↗
PubMed2006

Steroid pulse therapy impaired endothelial function while increasing plasma high molecule adiponectin concentration in patients with IgA nephropathy.

BACKGROUND: Decreased plasma adiponectin is associated with impaired endothelial function and, thereby, increased risk for cardiovascular events. Glucocorticoid (GC) affects vascular endothelial cells either favourably or harmfully depending upon the dosages and duration. We examined the effect of GC pulse therapy on vascular endothelial function. METHODS: Fourteen young patients with IgA nephropathy were evaluated for flow-mediated vasodilation (FMD), plasma levels of adiponectin both in high molecular weight (HMW adiponectin) form and in single molecular form (total adiponectin), hepatocyte growth factor (HGF), asymmetric dimethylarginine (ADMA), and high-sensitive C-reactive protein, before and after a course of GC pulse therapy. RESULTS: GC pulse therapy significantly decreased FMD (from 7.2 +/- 2.6 to 5.7 +/- 2.5%, P < 0.01). Meanwhile, plasma adiponectin levels were significantly augmented (total adiponectin: from 10.2 +/- 4.0 to 12.1 +/- 6.3 microg/ml, P < 0.05; HMW: from 6.5 +/- 3.2 to 7.7 +/- 3.3 microg/ml, P < 0.05). In parallel, elevated concentrations of serum HGF (from 0.28 +/- 0.12 to 0.63 +/- 0.38 ng/ml, P < 0.01) and plasma ADMA (from 0.45 +/- 0.07 to 0.53 +/- 0.04 nmol/ml, P < 0.05) were observed. CONCLUSIONS: GC pulse therapy impaired endothelial function while increasing plasma adiponectin levels, which may in turn restore the endothelial function in patients with IgA nephropathy.

Adiponectin↗
PubMed2006

Manifestation of rheumatoid arthritis after transsphenoidal surgery in a patient with acromegaly.

Acromegalic arthropathy is one of the most frequent manifestations occurring in acromegaly patients. In contrast, rheumatoid arthritis (RA) is a rare clinical complication in acromegaly patients. Here, we report a 70-year-old Japanese woman with acromegaly, who complained of bilateral finger stiffness and polyarthralgia two months after transsphenoidal surgery of a growth hormone (GH)-secreting pituitary adenoma. Postoperative levels of serum GH and insulin-like growth factor-1 (IGF-1) were markedly decreased without any secretory deficiency of other anterior pituitary hormones. Hand X-ray did not show typical RA changes; however, erosive changes in carpal bones were clearly detected by magnetic resonance imaging with gadolinium enhancement. Based on the levels of serological markers in the patient following surgery including C-reactive protein, rheumatoid factor and matrix metalloproteinase-3, anti-rheumatic therapy was subsequently commenced. Regardless of the levels of GH and IGF-1, acromegaly patients frequently complain about joint-related symptoms even after remission. Therefore, careful observation of bone erosive changes and immunological activity in acromegaly patients is required when joint-related symptoms persist.

Acromegaly↗
PubMed2006

Relationship between metabolic syndrome and proteinuria in the Japanese population.

OBJECTIVE: We investigated the link between metabolic syndrome and proteinuria in Japanese. METHODS: A total of 12,023 Japanese subjects, aged 20-79 years, were recruited in a cross-sectional clinical investigation study. From this group, we used data of 2,121 subjects for further investigation. Proteinuria was measured by using urine strip devices. The diagnosis of metabolic syndrome was based on the new criterion in Japan. RESULTS: In the first analysis, 224 men (6.0%) and 359 women (4.3%) were diagnosed as trace positive (+/-) and 155 men (4.1%) and 147 women (1.8%) were diagnosed as positive (+< or =) with proteinuria. In the second analysis, 264 men (29.7%) and 45 women (3.7%) were diagnosed as metabolic syndrome. Prevalence of proteinuria in subjects with metabolic syndrome was significantly higher than that in subjects with non metabolic syndrome in both sexes. In addition, the atherogenic index was significantly higher in subjects with metabolic syndrome than in subjects with non-metabolic syndrome. CONCLUSION: The present study indicated that metabolic syndrome might be an important factor in the etiology of proteinuria in Japanese.

Adult↗
PubMed2006

The S100A8/A9 heterodimer amplifies proinflammatory cytokine production by macrophages via activation of nuclear factor kappa B and p38 mitogen-activated protein kinase in rheumatoid arthritis.

S100A8 and S100A9, two Ca2+-binding proteins of the S100 family, are secreted as a heterodimeric complex (S100A8/A9) from neutrophils and monocytes/macrophages. Serum and synovial fluid levels of S100A8, S100A9, and S100A8/A9 were all higher in patients with rheumatoid arthritis (RA) than in patients with osteoarthritis (OA), with the S100A8/A9 heterodimer being prevalent. By two-color immunofluorescence labeling, S100A8/A9 antigens were found to be expressed mainly by infiltrating CD68+ macrophages in RA synovial tissue (ST). Isolated ST cells from patients with RA spontaneously released larger amounts of S100A8/A9 protein than did the cells from patients with OA. S100A8/A9 complexes, as well as S100A9 homodimers, stimulated the production of proinflammatory cytokines, such as tumor necrosis factor alpha, by purified monocytes and in vitro-differentiated macrophages. S100A8/A9-mediated cytokine production was suppressed significantly by p38 mitogen-activated protein kinase (MAPK) inhibitors and almost completely by nuclear factor kappa B (NF-kappaB) inhibitors. NF-kappaB activation was induced in S100A8/A9-stimulated monocytes, but this activity was not inhibited by p38 MAPK inhibitors. These results indicate that the S100A8/A9 heterodimer, secreted extracellularly from activated tissue macrophages, may amplify proinflammatory cytokine responses through activation of NF-kappaB and p38 MAPK pathways in RA.

Aged↗
PubMed2006

Involvement of bone morphogenetic protein-6 in differential regulation of aldosterone production by angiotensin II and potassium in human adrenocortical cells.

Aldosterone production is modified by several growth factors that reside in the adrenal. We have recently reported the existence of a bone morphogenetic protein (BMP) system in human adrenocortical cells, in which BMP-6 augments aldosterone synthesis. Here, we investigated functional roles of BMP-6, focusing on the differential regulation of aldosterone synthesis induced by angiotensin (Ang) II and potassium (K). In human adrenocortical H295R cells, BMP-6 augmented Ang II-induced CYP11B2 transcription and mRNA and aldosterone production but had no effect on K-induced aldosterone production. Inhibition of endogenous BMP-6 action by neutralizing antibodies impaired aldosterone production induced by Ang II but not that induced by K. Blockage of ligand-receptor binding using extracellular domain (ECD) of BMP type I receptors revealed that ECDs to activin receptor-like kinase (ALK)-2 and ALK-3 significantly reduced the aldosterone production induced by Ang II. None of the type I-receptor ECDs tested had any effect on K-induced aldosterone levels. Overexpression of a dominant negative-activin type II receptor construct selectively decreased Ang II-induced aldosterone production without having any effect on K-induced aldosterone production. BMP type II receptor-dominant negative had no effect on aldosterone induced by either Ang II or K. These results infer that BMP-6 acts through ALK-2, ALK-3, and activin type II receptor receptors in adrenocortical cells. BMP-6 pretreatment extends the induction of ERK1/2 phosphorylation by Ang II and treatment with ECDs to ALK-2 and ALK-3 impaired Ang II-induced ERK phosphorylation. The specific inhibitor of ERK activation, U0126, suppressed the activation of CYP11B2 transcription induced by BMP-6 without affecting Smad phosphorylation and Tlx2-Luc activity. Collectively, the endogenous BMP-6 system plays critical roles in aldosterone production between Ang II and K through ERK signaling pathway.

Adrenal Cortex↗
PubMed2006

Therapeutic approach for diabetic nephropathy using gene delivery of translocase of inner mitochondrial membrane 44 by reducing mitochondrial superoxide production.

Hyperglycemia-induced overproduction of mitochondrial reactive oxygen species has emerged as a major player in diabetic vascular complications. Mammalian translocase of inner mitochondrial membrane 44 (TIM44) was identified by upregulation in diabetic mouse kidneys. TIM44 functions as a membrane anchor of mitochondrial heat-shock protein 70 (mtHsp70) to TIM23 complex and is involved in the import of mitochondria-targeted preproteins into mitochondrial matrix. The process is dependent on inner membrane potential and ATP hydrolysis on ATPase domain of mitochondrial heat-shock protein 70. Hemagglutination virus of Japan-envelope vector that carries pcDNA3.1 plasmid that contains the full-length cDNA of TIM44 and control plasmid were injected weekly into the tail vein of uninephrectomized streptozotocin-induced diabetic CD-1 mice. The gene delivery alleviated proteinuria and renal hypertrophy at 8 wk after the injection, inhibited renal cell proliferation and apoptosis, and suppressed superoxide production. In vitro experiments, using human proximal tubular (HK2) cells, revealed that the gene delivery of TIM44 reversed high glucose-induced metabolic and cellular abnormalities such as enhanced reactive oxygen species production, increased ATP contents, alterations in inner membrane potential, increased cell proliferation, and apoptosis. Transfection with siRNA and expressing vector of TIM44 revealed that TIM44 facilitates import of antioxidative enzymes such as superoxide dismutase and glutathione peroxidase into mitochondria. The gene delivery of TIM44 therefore seems to be beneficial for the maintenance of mitochondrial function and is a novel therapeutic approach for diabetic nephropathy.

Adenosine Triphosphate↗
PubMed2006

An elderly patient with severe acute renal failure due to sodium bromate intoxication.

Accidental or deliberate ingestion of bromate solution has been reported in pediatric as well as adult cases; however there have been no reports of such intoxication in the elderly. We report a 78-year-old woman who suffered severe acute renal failure due to the accidental ingestion of sodium bromate solution. The patient was successfully treated with hemodialysis therapy and renal function recovered without hearing loss. This case suggests that emergency therapeutic measures, including hemodialysis, should be taken as soon as possible, and the rapid removal of bromate is essential to prevent severe intoxication and its sequelae. To the best of our knowledge this is the first report of an elderly patient that demonstrates the clinical benefit of hemodialysis therapy for bromate intoxication.

Acute Kidney Injury↗
PubMed2006

Mutual regulation of follicle-stimulating hormone signaling and bone morphogenetic protein system in human granulosa cells.

Bone morphogenetic proteins (BMPs) play critical roles in folliculogenesis by modulating the actions of follicle-stimulating hormone (FSH) in the ovary. However, the effects of FSH on the BMP system remain unknown. Here, we have investigated the effects of FSH on BMP signaling using the human granulosa-like tumor cell line KGN. KGN cells express BMP type I and type II receptors and the BMP signaling molecules SMADs. FSH administration upregulated BMP type IA (BMPR1A) and IB (BMPR1B) receptors, activin type II receptor (ACVR2), and BMP type II receptor (BMPR2). FSH also augmented SMAD1 and SMAD5 expression, and conversely, FSH suppressed the expression of the inhibitory SMADs, SMAD6 and SMAD7. Bioassays revealed that FSH enhances BMP-induced SMAD1/5/8 phosphorylation and cellular DNA synthesis induced by BMP6 and BMP7. Since overexpression of BMPR1A and BMPR1B, but not SMADs, significantly enhanced the BMP responses, these type I receptors were revealed to be limiting factors for BMP signaling in KGN cells. BMPs significantly suppressed progesterone synthesis induced by forskolin and dibutyryl-cAMP (BtcAMP) but had no effect on estradiol induced by the same factors. KGN cAMP levels induced by forskolin were not altered by BMPs, suggesting that BMPs regulate steroidogenesis at a level downstream of cAMP synthesis in KGN cells. In this regard, BMPs specifically reduced the STAR transcription, whereas the levels of CYP11A, HSD3B2, and CYP19 stimulated by forskolin as well as BtcAMP were not altered. Collectively, the two major factors, FSH-cAMP pathway and BMP system, are reciprocally and functionally linked. Given that BMPs downregulate FSH receptors in KGN cells, this interaction may contribute to fine-tuning of the mutual sensitivity toward BMP ligands and FSH.

Bone Morphogenetic Protein Receptors, Type I↗
PubMed2006

Increased expression of receptor for advanced glycation end products by synovial tissue macrophages in rheumatoid arthritis.

OBJECTIVE: The accumulation of advanced glycation end products (AGEs), S100A12, and high mobility group box chromosomal protein 1 has been associated with joint inflammation in rheumatoid arthritis (RA). This study was undertaken to determine the induction of the receptor for these proteins, termed receptor for AGEs (RAGE), in synovial tissue (ST) macrophages from RA patients. METHODS: RAGE and CD68 expression in ST were determined by 2-color immunofluorescence labeling. Cell surface and messenger RNA (mRNA) expression of RAGE were examined by flow cytometry and reverse transcriptase-polymerase chain reaction (PCR) or real-time PCR, respectively. RESULTS: CD68+ lining macrophages, like the vasculature, expressed high levels of RAGE in inflamed ST from RA patients. RAGE mRNA expression was significantly higher in RA ST than in ST from patients with osteoarthritis. RAGE mRNA levels were significantly higher in ST macrophages and normal endothelial cells than in ST CD4+ T cells and synovial fibroblasts stimulated with tumor necrosis factor alpha and interleukin-1beta (IL-1beta). Cell surface RAGE was highly induced on normal monocytes after a 24-hour incubation with a 20% concentration of RA ST cell culture supernatants. RAGE mRNA expression in adherent monocytes was augmented by various cytokines, most potently by IL-1beta. CONCLUSION: These results indicate that RAGE overexpression in lining macrophages may be induced, at least in part, by cytokines such as IL-1, leading to the amplification of inflammatory responses mediated by RAGE ligands that are abundant in RA joints.

Arthritis, Rheumatoid↗
PubMed2006

Hypokalemic paralysis and osteomalacia secondary to renal tubular acidosis in a case with primary Sjögren's syndrome.

A 39-year-old Japanese woman was admitted to our hospital for severe weakness owing to potassium deficiency caused by type 1 renal tubular acidosis (RTA1). Sicca complex, serological tests, and lip biopsy revealed that she had Sjögren's syndrome (SS). Acidosis was corrected by alkali supplement treatment. She also had an impaired renal function with proteinuria, and high absorbance on Ga scintigram was recognized in both kidneys. She was taking warfarin potassium after aortic valve substitution due to aortic regurgitation, therefore renal biopsy was not performed. Prednisone (20 mg/day) was administered for renal inflammation. One month later, she suffered severe chest wall pains with some local tender points over the costae of both sides, which was presumed to be due to pseudo-fractures based on osteomalacia. Hypokalemic paralysis and osteomalacia should be taken into consideration in the diagnosis of SS with RTA1.

Acidosis, Renal Tubular↗