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Mitsuo Iida

Publications and source records attributed to Mitsuo Iida.

At least 145 records · Page 8Linked to original sources
PubMed2003

Neural regulation of blood pressure by leptin and the related peptides.

Recent biological advances make it possible to discover new peptides associated with obesity. Leptin, neuropeptide Y, corticotrophin-releasing factor (CRF), alpha-melanocyte stimulating hormone (alpha-MSH), and cocaine- and amphetamine-regulated transcript (CART) peptides are known to participate in appetite and feeding behavior. Various lines of evidence suggest that these peptides participate not only in feeding behavior but also in cardiovascular and sympathetic regulations. Both leptin and ghrelin are secreted from the peripheral tissue; then they reach the brain to modulate sympathetic activity. These two peptides seem to play important roles to transmit peripheral metabolic information to the brain, and to convert it to cardiovascular and sympathetic information. Leptin activates neurons containing alpha-melanocyte stimulating hormone and cocaine- and amphetamine-regulated transcript peptides, resulting in increases in sympathetic activity and blood pressure. Cardiovascular action of alpha-melanocyte stimulating hormone is mediated through melanocortin-4 receptor, and agouti-related protein (AGRP) plays a role as an endogenous melanocortin-4 receptor antagonist. In contrast, ghrelin and neuropeptide Y in the brain suppress sympathetic activity and decrease blood pressure. Depressor and sympathoinhibitory effects of central neuropeptide Y are inhibited by leptin. Furthermore, central ghrelin modulates baroreflex control of renal sympathetic nerve activity and heart rate. Thus, leptin and the related peptides, which participate in appetite and feeding behavior, seem to function together to regulate cardiovascular system and sympathetic nerve activity, and may play a key role in the association between obesity and hypertension.

Agouti-Related Protein↗
PubMed2003

Primary gastrointestinal lymphoma in Japan: a clinicopathologic analysis of 455 patients with special reference to its time trends.

BACKGROUND: An optimal treatment modality for patients with primary gastrointestinal lymphoma has not yet been established. This study aimed to elucidate the clinicopathologic features of this disease and the influence of therapeutic modalities on the prognosis in Japanese patients METHODS: The clinicopathologic features of 455 patients with primary gastrointestinal lymphoma were investigated retrospectively regarding treatment modalities and time trends. RESULTS: This study comprised 342 patients (75%) with gastric lymphoma, 96 patients (22%) with intestinal lymphoma, and 17 patients (4%) with both gastric and intestinal lymphoma. Two hundred thirty-one (51%) patients were classified as having low-grade B-cell lymphoma including 200 marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) type, 185 (41%) patients were classified as having high-grade B-cell lymphoma including 76 diffuse large cell lymphoma plus MALT lymphoma, and 39 (9%) patients were classified as having T-cell lymphoma. The frequency of nonsurgical treatment, including Helicobacter pylori eradication, chemotherapy, and radiation, increased during the latest decade. Patients who received nonsurgical treatment showed a better overall survival than those treated by surgery, but event-free survival did not differ between two groups. Cox multivariate analysis revealed that early stage, younger age, gastric localization, B-cell phenotype, and absence of B symptoms were independent prognostic factors for better overall and event-free survivals. Mucosa-associated lymphoid tissue-derived lymphoma was also an independent prognostic factor for event-free survival, but not for overall survival. CONCLUSIONS: Nonsurgical treatment may be an optimal therapeutic modality for patients with primary gastrointestinal lymphoma.

Adolescent↗
PubMed2003

Antioxidant ameliorates cisplatin-induced renal tubular cell death through inhibition of death receptor-mediated pathways.

We have recently demonstrated the direct involvement of the death receptor-mediated apoptotic pathways in cisplatin-induced renal tubular cell (RTC) death. Reactive oxygen species are thought to be a major cause of cellular damage in such injury. The aim of this study was to examine the mechanism through which antioxidants ameliorate cisplatin-induced RTC death, with special emphasis on death receptor-mediated apoptotic pathways. Cisplatin was added to cultures of normal rat kidney (NRK52E) cells or injected in rats. NRK52E cells and rats were also treated with dimethylthiourea (DMTU), a hydroxyl radical scavenger. We then examined the mRNA levels of death ligands and receptors, caspase-8 activity, cell viability, cell death, renal function, and histological alterations. RT-PCR indicated cisplatin-induced upregulation of Fas, Fas ligand, and TNF-alpha mRNAs and complete inhibition by DMTU in vitro and in vivo. Cisplatin increased caspase-8 activity of NRK52E cells, and DMTU prevented such activation. Exposure to cisplatin reduced viability of NRK52E cells, examined by WST-1 assay, and increased apoptosis and necrosis of the cells, examined by terminal deoxynucleotidyl transferase dUTP nick-end labeling assay and fluorescence-activated cell sorter analysis. DMTU abrogated cisplatin-induced changes in cell viability and apoptosis and/or necrosis. Cisplatin-induced renal dysfunction and histological damage were also prevented by DMTU. DMTU did not hinder cisplatin incorporation into RTCs. Our results suggest that antioxidants can ameliorate cisplatin-induced acute renal failure through inactivation of the death receptor-mediated apoptotic pathways.

Animals↗
PubMed2003

ATP-sensitive potassium channels mediate dilatation of basilar artery in response to intracellular acidification in vivo.

BACKGROUND AND PURPOSE: During cerebral ischemia, both hypoxia and hypercapnia appear to produce marked dilatation of the cerebral arteries. Hypercapnia and hypoxia may be accompanied by extracellular and intracellular acidosis, which is another potent dilator of cerebral arteries. However, the precise mechanism by which acidosis produces dilatation of the cerebral arteries is not fully understood. The objective of the present study was to examine the mechanisms by which intracellular acidosis produces dilatation of the basilar artery in vivo. METHODS: Using a cranial window in anesthetized rats, we examined responses of the basilar artery to sodium propionate, which was used to cause intracellular acidosis specifically. Expression of subunits of potassium channels was determined by reverse transcription and polymerase chain reaction (RT-PCR). RESULTS: Topical application of propionate increased diameter of the basilar artery in a concentration-related manner. Propionate-induced dilatation of the artery was attenuated by glibenclamide, an inhibitor of ATP-sensitive potassium channels. However, inhibitors of nitric oxide synthase (N(G)-nitro-L-arginine), large-conductance calcium-activated potassium channels (iberiotoxin), and cyclooxygenase (indomethacin) did not affect the vasodilatation. Expression of mRNA for SUR2B and Kir6.1 was detected, with the use of RT-PCR, in the cultured basilar arterial muscle cells. CONCLUSIONS: The findings suggest that intracellular acidification may produce dilatation of the basilar artery through activation of ATP-sensitive potassium channels in vivo. Kir6.1/SUR2B may be the major potassium channels that mediate propionate-induced dilatation of the artery.

ATP-Binding Cassette Transporters↗
PubMed2003

Validity of the JNC VI recommendations for the management of hypertension in a general population of Japanese elderly: the Hisayama study.

BACKGROUND: It is not known whether the treatment recommendations presented in the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure are applicable to the Japanese elderly population. METHODS: We followed up 588 cardiovascular disease-free residents of a Japanese community who were 60 years or older from November 1, 1961, through October 31, 1993. Treated hypertensive patients were excluded from the analysis. During this period, CVD occurred in 179 subjects. The incidences were estimated by the pooling of repeated observations method. RESULTS: The age- and sex-adjusted incidences of cardiovascular disease significantly increased with elevated blood pressure levels. The hazard ratio for stage 3 hypertension was 5.34 (95% confidence interval, 2.66-10.71; P<.001) compared with optimal blood pressure after adjustment for other covariates. Among subjects aged 60 to 79 years, the incidences for stages 1 through 3 hypertension were significantly higher than for those with optimal and normal blood pressure. In comparison, among those 80 years or older, the incidence was significantly higher only in patients with stage 3 hypertension. We further estimated the incidences according to the risk stratification system. In the younger elderly subjects, the incidences increased with rising blood pressure levels in each risk stratum. Similar relationships were not observed among the older elderly subjects. CONCLUSIONS: Our findings demonstrate that the recommendations of the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure were potentially applicable to the Japanese elderly subjects 79 years or younger. Based on our findings, however, hypertension might not be a risk factor for cardiovascular disease among very old hypertensive patients with advanced atherosclerosis.

Age Factors↗
PubMed2003

Accumulation of 8-oxoguanine in the cellular DNA and the alteration of the OGG1 expression during ischemia-reperfusion injury in the rat kidney.

During ischemia-reperfusion (I/R) injury in the rat kidney, apoptosis was observed in the distal tubules of the cortico-medullary region and outer medulla (OM) while severe necrosis was seen in the proximal straight tubules of the OM. The majority of these changes disappeared within 2 weeks. We examined the contents of 8-oxo-2'-deoxyguanosine (8-oxo-dG), which is a major type of oxidative damage in DNA, in the rat kidney during I/R injury, and also investigated the expression level of the OGG1 gene encoding the 8-oxoguanine DNA glycosylase. High-performance liquid chromatography with an MS/MS analysis of the nuclear DNA revealed an immediate accumulation of 8-oxo-dG in the nuclear DNA prepared from the cortex and OM of the kidney 1h after I/R, and an immunohistochemical analysis demonstrated the immediate accumulation of 8-oxo-dG in the nuclei of renal tubular cells both in the cortex and OM. A delayed increase of cytoplasmic staining with anti-8-oxo-dG was observed only in the cortico-medulla and OM, where the cytoplasmic staining in the proximal tubular cells is higher than in the distal tubular cells. The level of cytoplasmic staining representing 8-oxo-dG in mitochondrial DNA, peaked at 6h after I/R and preceded the necrosis of proximal tubular cells in the OM. An RNase protection assay showed a high level of OGG1 mRNA in the normal kidney, and the level decreased within 3h only in the OM, and increased thereafter 1-7 days of I/R both in the cortex and OM. In situ hybridization showed higher levels of OGG1 mRNA expression in the renal tubules in the OM than in the cortex of the normal kidney, which decreased rapidly within 3h of I/R. Thus, the accumulation of 8-oxo-dG in the mitochondrial DNA rather than in nuclear DNA is likely to be involved in the pathogenic responses such as necrosis of renal tubular cells during I/R injury of the kidney, together with an altered level of OGG1 expression.

Animals↗
PubMed2003

Infusion of radiocontrast agents induces exaggerated release of urinary endothelin in patients with impaired renal function.

BACKGROUND: The aim of the study was to examine the role of endothelin in radiocontrast-induced nephropathy (RCN) in patients with chronic renal failure. METHODS: We measured plasma endothelin-1 (ET) and the urinary excretion of endothelin-like immunoreactivity before and after infusion of radio contrast medium (CM) in patients with normal renal function (group N; n = 6; mean serum creatinine concentration, 0.8 +/- 0.1 (SEM) mg/dl), and in another group, with renal dysfunction (group R; n = 6; 2.7 +/- 0.5 mg/dl). Half-normal saline (0.45% NaCl solution) was continuously infused in all patients for 25 h, at a rate of 100 ml/h; starting from 5 h before the infusion of CM. RESULTS: Plasma ET in group R (5.2 +/- 1.4 pg/ml) was significantly higher than in group N (0.9 +/- 0.3; P << 0.01). Urinary endothelin excretion corrected by creatinine concentration (uET/Cr) in group R (7.9 +/- 2.4 mg/g Cr) was significantly higher than in group N (1.5 +/- 0.4 mg/g Cr; P << 0.05). Urinary excretion levels of N-acetyl-Beta- d-glucosaminidase (NAG) and Beta2-microglobulin (Beta2M) were also significantly higher in group R (0.8 +/- 0.2 mU/g Cr and 670 +/- 400 mg/g Cr, respectively) than in group N (0.3 +/- 0.1 and 7.5 +/- 2.2, respectively). After CM infusion, uET/Cr in group R significantly increased, to 10.7 +/- 2.6 mg/g Cr on the next day and returned to baseline level on the third day. NAG and Beta2M showed a similar pattern, but a significant change in NAG was observed on the second day in group R. In group N, uET/Cr, NAG, and Beta2M did not change after CM infusion. Plasma ET remained unchanged throughout the observation period of 4 days in both groups. No patient developed pulmonary edema or a significant rise in serum creatinine (more than 0.5 mg/dl), caused by infusion of the amount of half-normal saline used. CONCLUSIONS: In the present study, uET/Cr increased after the administration of CM only in the patients with renal impairment. This difference in endothelin reaction may be a causal one, in that patients with renal insufficiency readily develop RCN. The infusion of half-normal saline starting before CM infusion causes no side effects and is safe for the prevention of CM-induced acute renal failure. The aim of the study was to examine the role of endothelin in radiocontrast-induced nephropathy (RCN) in patients with chronic renal failure.

Acetylglucosaminidase↗
PubMed2003

Brain ischemia augments exo-focal transgene expression of adenovirus-mediated gene transfer to ependyma in hypertensive rats.

The ependyma is one of the feasible targets for gene transfer to the brain. Using two different replication-deficient recombinant adenoviral vectors, AdCMVbetaGal or AdRSVIL10, we examined effects of cortical brain ischemia on transgene expression in the ependyma after administration of the vector into the lateral ventricle of spontaneously hypertensive rats (SHR). Expression of the reporter gene lacZ at the lateral ventricle was detected by histochemistry for semiquantitative scoring or by biochemical assay for quantitative analysis. Ependymal cells in the ventricles expressed the transgene as early as 6 h after gene transfer in both sham treatment and ischemia treatment. In the sham treatment, the expression peaked at 12 h and slowly decreased toward day 4 and day 7. However, transgene expressions in the ischemic brain on day 4 and day 7 were significantly higher than sham treatment. In the biochemical assay, beta-galactosidase activity detected on day 4 at the periventricular area of the ischemic group (37 +/- 9 mU/mg protein) was significantly greater than that of the sham group (12 +/- 4, P < 0.01). In the enzyme-linked immunosorbent assay for gene transfer of interleukin-10 (IL-10), IL-10 in the cerebrospinal fluid (CSF) of the ischemic group (11,633 +/- 4322 pg/ml) was significantly greater than that in the sham group (2460 +/- 1486, P < 0.05) on day 5. These results suggest that transgene expression in the exo-focal remote area of ependyma is augmented by cortical ischemia, and the ependyma may be a promising target of gene transfer of brain ischemia.

Adenoviridae↗
PubMed2003

Adenovirus-mediated gene transfer to ischemic brain is augmented in aged rats.

Gene therapy may be a promising approach for the treatment of brain ischemia. Because older populations are susceptible to ischemic stroke, we examined the effects of aging on adenovirus-mediated gene transfer to the ischemic brain of rats. Brain ischemia was produced by photochemical occlusion of the distal middle cerebral artery of aged and adult spontaneously hypertensive rats. Ninety minutes after ischemia, an adenoviral vector encoding beta-galactosidase was injected into the contralateral (C) and ipsilateral [peri-ischemic (I-p) and ischemic core (I-c)] parietal cortices. Cerebral blood flow (CBF) was measured by laser Doppler flowmetry. Transgene expression was scored semiquantitatively as an expression score by histochemistry and also quantitatively analyzed by chemiluminescence assay. Changes in CBF after ischemia in aged rats were not significantly different from those in adult rats, although the infarct rim in the older rats tended to be closer to the midline than in the younger rats. beta-galactosidase was detected in both neurons and non-neuronal cells at C and I-p, and was primarily present in non-neuronal cells at I-c. The expression scores 1 and 4 days after ischemia in the aged rats were similar to those in the adult rats. However, the score for the I-c at 7 days after injection was significantly greater in the older rats than in the younger adult rats. beta-galactosidase activity at I-c 7 days after ischemia in the aged rats (8.0+/-1.7mU/mg protein) was significantly greater than that in the adult rats (1.3+/-0.4, p<0.01). Adenovirus-mediated gene transfer to the ischemic brain may thus be more effective in aged rats than in adult rats.

Adenoviridae↗
PubMed2003

Histological and immunological features of appendix in patients with ulcerative colitis.

Patients with ulcerative colitis (UC) have a less frequent prior history of appendectomy than the general population. The aim of the present investigation was to elucidate histological and immunological characteristics of the appendix in UC and to assess the effect of appendectomy on the disease. Nine subjects with mildly active UC were treated by surgical appendectomy. In four subjects, the histological findings of the appendix were compatible with ulcerative appendicitis. CD3+CD4+CD25+, CD3+CD4+CD45RO+, and CD3+CD8+CD45RO+ appendiceal mononuclear cells were significantly higher in UC than in acute appendicitis and in normal appendix. There was a trend towards higher mRNA transcripts of IFN-gamma in the appendix of UC than those in other two groups. Clinical activity index decreased significantly four weeks after the appendectomy, although the effect was transient. The appendix is a site of involvement in UC, where mononuclear cells are presumed to be at a state of basal activation.

Adult↗
PubMed2003

Direct involvement of the receptor-mediated apoptotic pathways in cisplatin-induced renal tubular cell death.

BACKGROUND: Tumor necrosis factor (TNF) receptor family members, such as Fas and TNF receptor 1 (TNFR1), are thought to induce apoptosis in a variety of cells and organs. Although a number of potential scenarios have been postulated for the involvement of these receptors in the pathogenesis of acute renal failure (ARF), direct evidence for their involvement in death of renal tubular cells (RTCs) and renal dysfunction is preliminary. METHODS: This study examined the roles of these receptors in RTC death in two systems: (1). in vivo murine and rat models of cisplatin-induced ARF, and (2). murine proximal tubular cells (PTCs), which were isolated from C57BL/6 (B6) mice, Fas-mutant B6-lpr/lpr mice and TNFR1-deficient mice, and normal rat kidney (NRK52E) cells in vitro. RESULTS: Reverse transcription-polymerase chain reaction indicated cisplatin-induced up-regulation of Fas, Fas ligand and TNF-alpha mRNAs in the kidney in vivo and in RTCs in vitro, both in mice and rats. In contrast, the level of TNFR1 mRNA was substantial but did not change in response to cisplatin. TNF-alpha production in cell culture medium determined by enzyme-linked immunosorbent assay (ELISA) and Fas expression determined by fluorescence-activated cell sorter (FACS) analysis increased following incubation with cisplatin in B6 PTCs. In order to examine whether Fas and TNFR1 are directly involved in RTC death and renal dysfunction, we compared cell resistance to cisplatin using a cell viability assay and FACS analysis with fluorescein isothiocyanate-conjugated annexin V and propidium iodide staining. The ratios of cell viability loss and cell death, both from apoptosis and necrosis, were higher in B6 PTCs than in other cells, while the ratios were comparable between Fas-mutant PTCs and TNFR1-deficient PTCs. Caspase-8 activity was increased in B6 PTCs, but not in Fas-mutant PTCs and TNFR1-deficient PTCs. Furthermore, the renal dysfunction and RTC death, both apoptosis and necrosis, induced by cisplatin were more severe in B6 mice in vivo. CONCLUSION: Based on these data, we conclude that the Fas- and TNFR1-mediated apoptotic pathways are directly involved in the pathogenesis of cisplatin-induced RTC death process.

Acute Kidney Injury↗
PubMed2003

Risk factors for renal glomerular and vascular changes in an autopsy-based population survey: the Hisayama study.

BACKGROUND: Information of the effect of cardiovascular risk factors on renal glomerular and vascular changes is scarce in the general population. METHOD: Between 1962 and 1994, 1394 autopsies were performed in Hisayama, for a total autopsy rate of 80%. Of these, 839 individuals who preserved adequate renal tissues and had recent health examinations data before death were eligible for the present study. We examined the degree of glomerular sclerosis, renal arteriolar hyalinosis, and arteriosclerosis, and evaluated their risk factors by means of a logistic regression model. RESULTS: The development of glomerular sclerosis, arteriolar hyalinosis, and arteriosclerosis were 16%, 16%, and 18% in men, respectively, and 27%, 15%, and 24% in women, respectively. All these frequencies increased linearly with advancing age. In the multivariate analysis, both age and systolic blood pressure were significant independent risk factors for almost all these glomerular and vascular changes. In addition, glucose intolerance and proteinuria for men were found to be significant risk factors for glomerular sclerosis. Elevated total cholesterol levels significantly increased the risk of arteriolar hyalinosis in men. Electrocardiogram (ECG) abnormalities were an independent risk factor for arteriosclerosis in both men and women, and proteinuria was an additional risk factor in women. Alcohol intake tended to have a protective effect on glomerular sclerosis and arteriosclerosis in women. CONCLUSION: Our data confirmed that age and systolic blood pressure are common risk factors for all glomerular and renal vascular changes in the general population. In addition, glucose intolerance, total cholesterol, ECG abnormalities, and proteinuria affect either glomerular or vascular changes.

Age Distribution↗
PubMed2003

Impact of interferon-gamma and interleukin-4 gene polymorphisms on development and progression of IgA nephropathy in Japanese patients.

BACKGROUND: Cytokines have an important role in the pathogenesis and disease progression of immunoglobulin A (IgA) nephropathy. The aim of this study is to investigate the impact of gene polymorphisms of T helper cell subtype 1 (T(H)1)/T(H)2 cytokines, interferon-gamma (IFN-gamma), and interleukin-4 (IL-4) on IgA nephropathy in Japanese patients. METHODS: We investigated IFN-gamma gene (IFNG) and IL-4 gene (IL4) polymorphisms in 96 patients with biopsy-confirmed IgA nephropathy who were followed-up for more than 3 years in our outpatient clinic and 61 healthy controls by polymerase chain reaction and direct sequencing methods. IFNG polymorphism was characterized as a microsatellite of intron 1. Four alleles were identified and designated IFNG 112, 114, 116, and 118, corresponding to 12, 13, 14, and 15 repeats, respectively. A variable number of tandem repeat (VNTR) polymorphisms of IL4 also were studied, and alleles were designated IL4 B1 and B2, corresponding to 2 and 3 repeats, respectively. RESULTS: In patients with IgA nephropathy, IFNG 114 allele and IFNG 114(+/+) genotype frequencies were significantly greater than in the healthy control group (60% versus 45%; P < 0.01 and 43% versus 23%; P < 0.05, respectively), but there was no difference between the IgA nephropathy and healthy control groups in frequencies of both IL4 VNTR allele and genotype. However, frequencies of IL4 B1 allele and B1/B1 genotype in patients with progressive IgA nephropathy (end-stage renal disease or doubling of serum creatinine level; n = 34) were significantly greater than corresponding values in the nonprogression group (n = 62; 79% versus 61%; P < 0.01 and 59% versus 34%; P < 0.05, respectively). We could not confirm an association between IgA nephropathy and polymorphisms of genes involved in the renin-angiotensin system. CONCLUSION: Our results suggest that IFN-gamma and IL-4 gene polymorphisms could influence disease susceptibility and disease progression in IgA nephropathy in Japanese patients. Am J Kidney Dis 41:371-379.

Adolescent↗
PubMed2003

Atherogenic role of lysophosphatidylcholine in low-density lipoprotein modified by phospholipase A2 and in diabetic patients: protection by nitric oxide donor.

The aim of our study was to investigate the atherogenic role of lysophosphatidylcholine (lyso-PC) in low-density lipoprotein (LDL) under diabetic environment. Expression of monocyte chemoattractant protein-1 (MCP-1) mRNA and nuclear factor-kappa B (NF-kappaB)-DNA binding activity were determined in human umbilical vein endothelial cells (HUVEC) incubated with native or glycoxidized LDL, LDL modified by phospholipase A2 (PLA2) and LDL isolated from diabetic patients. Lyso-PC contents in LDL were measured using electrospray ionization-liquid chromatography/mass spectrometry (ESI-LC/MS). Lyso-PC contents were higher in glycoxidized LDL and PLA2-treated LDL compared with native LDL. Glycoxidized LDL and enrichment of lyso-PC by PLA2 treatment resulted in upregulation of MCP-1 mRNA expression through increased NF-kappaB activity in HUVEC. Moreover, LDL isolated from diabetics contained more lyso-PC than that from nondiabetic subjects, and induced higher MCP-1 mRNA expression and NF-kappaB activity in HUVEC. In both in vitro and human studies, palmitoyl- and stearoyl-lyso-PC contents correlated with MCP-1 expression and NF-kappaB activity. Preincubation with 4-ethyl-2-hydroxyimino-5-nitro-3-hexenamide, a NO donor, abrogated increased expression of MCP-1 mRNA and high NF-kappaB activity induced by PLA2-treated LDL and by LDL isolated from diabetic patients. Our results suggest that lyso-PC contents in LDL play an important role in atherogenesis under diabetic condition, which could be prevented by increased availability of vascular NO.

Arteriosclerosis↗