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Biomedical subjects

M Fujishima

Publications and source records attributed to M Fujishima.

At least 127 records · Page 7Linked to original sources
PubMed1999

Effect of hyperinsulinemia on renal function in a general Japanese population: the Hisayama study.

BACKGROUND: Insulin resistance and hyperinsulinemia induce glomerular hypertension and hyperfiltration, which may result in glomerulosclerosis. However, the relationship between hyperinsulinemia and renal function is uncertain. METHODS: To elucidate whether hyperinsulinemia plays a significant part in the initiation and development of renal dysfunction, we examined in 1988 the relationship between serum insulin and renal function on data from a cross-sectional community survey conducted among residents from Hisayama Town, Japan, who were aged 40 to 79 years old. A total of 1065 men (72.0% of the total population in the same age range) and 1381 women (79.0%) without renal failure (creatinine clearance of more than 30 ml/min) underwent a comprehensive examination, including a 75 g oral glucose tolerance test. RESULTS: The correlation analysis showed that serum insulin, blood pressure, total cholesterol, low-density lipoprotein cholesterol, triglycerides, and body mass index were all negatively correlated with the reciprocal of serum creatinine level (P < 0.01), and alcohol intake was positively correlated (P < 0.05) in both sexes. High-density lipoprotein cholesterol and smoking habits were positively correlated (P < 0.05) in men. When the subjects were divided into quartiles based on the sum of fasting and two-hour postloading insulin levels, the averages of the reciprocal of serum creatinine were significantly lower in the fourth quartile (0.90 +/- 0.10 for men and 1.10 +/- 0.14 for women) compared with the lowest quartile (0.95 +/- 0.12 and 1.13 +/- 0.13, respectively) in both sexes (P < 0.05). In multiple regression analysis, the correlation between the sum of insulin levels and the reciprocal of serum creatinine remained significant even after controlling for age, sex, body mass index, blood pressure, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, alcohol intake, and smoking habits. We could not find appropriate correlations of creatinine clearance calculated by the Cockcroft-Gault formula with the covariates including serum insulin. CONCLUSIONS: The findings of this study suggest that hyperinsulinemia is a significant relevant factor of renal function in the general population.

Adult↗
PubMed1999

Lysophosphatidylcholine molecular species in low density lipoprotein and high density lipoprotein in alloxan-induced diabetic rats: effect of probucol.

To elucidate the contribution of diabetic state toward the accumulation of lysophosphatidylcholine (LPC) in low density lipoprotein (LDL), the LPC molecular species in LDL and high density lipoprotein (HDL) obtained from alloxan-induced diabetic rats were determined by high performance liquid chromatography. The palmitoyl LPC (PLPC) per protein was increased in the LDL of diabetic rats (p < 0.05), whereas the stearoyl LPC (SLPC) decreased in both the LDL and HDL of diabetic rats (p < 0.001) in comparison to nondiabetic rats. After the dietary administration of probucol for 4 weeks, the concentrations of SLPC and PLPC in the LDL of diabetic rats and of SLPC in the LDL of nondiabetic rats all significantly decreased by probucol (all; p < 0.01), with a concomitant decrease of the plasma concentrations of total and HDL cholesterol, and phospholipid, compared with those without probucol. The level of TBARS per protein in LDL increased in diabetic rats, and decreased by probucol (p < 0.01). In conclusion, the oxidative stress is thought to be an important factor to accumulate LPC in LDL, although the paradoxical decrease of SLPC in diabetic LDL suggests a non-oxidative metabolism with a preference for the LPC molecular species. The reducing effect of probucol on LPC may not be solely attributed to its antioxidative effect.

Animals↗
PubMed1999

Lysophosphatidylcholine molecular species in low density lipoprotein of type 2 diabetes.

To reveal the importance of lysoposphatidylcholine (LPC) in patients with Type 2 diabetes (DM), LPC in low density lipoprotein (LDL) was determined by high performance liquid chromatography in 38 patients with Type 2 DM and 31 age and sex-matched non-diabetic controls. Stearoyl LPC (SLPC) and palmitoyl LPC (PLPC) were detected in LDL. The contents of both LPCs per gram protein in LDL were increased in diabetic patients compared with the non-diabetics (1.99+/-0.94mg SLPC and 3.02+/-1.81 mg PLPC vs 1.47+/-0.57 mg SLPC and 2.30+/-0.83 mg PLPC, mean +/- SD, p < 0.01 and p < 0.05, respectively). PLPC showed a weak correlation with the levels of fasting plasma glucose (FPG) and HbA1c (r=0.27 and r=0.33, p < 0.05 and p < 0.01, respectively). The diabetic patients with macroangiopathy showed higher levels of PLPC per gram protein compared to those without macroangiopathy (4.60+/-2.61 mg vs 2.53+/1.15 mg, respectively, p < 0.05). The LPC molecular species may participate in the atherogenicity of LDL in patients with Type 2 diabetes.

Adult↗
PubMed1999

Polymorphism of heat-shock protein gene HSP70-2 in Crohn disease: possible genetic marker for two forms of Crohn disease.

BACKGROUND: Previous reports have shown that heat-shock protein 70 (HSP70) may be associated with Crohn disease. However, genetic analysis of the HSP70 gene in Crohn disease has not been done. The aim of this study is to investigate whether HSP70-2 gene polymorphism is involved in susceptibility to Crohn disease in the Japanese population and whether it correlates with clinical manifestation of the disease. METHODS: A total of 108 genetically unrelated patients with Crohn disease and 108 healthy controls were typed for HSP70-2 PstI polymorphism by restriction fragment length polymorphism analysis (alleles A and B). Patients with Crohn disease were classified into two types: either perforating or non-perforating. RESULTS: Genotype and allele frequency did not differ between patients and controls. In patients with Crohn disease, allele A frequency was significantly higher in the non-perforating than in the perforating type (P = 0.02). When patients with Crohn disease of more than 6.7 years' duration were assessed, the differences in genotype and allele frequency between the two groups became more significant (P < 0.001 and P < 0.001, respectively). CONCLUSIONS: These data suggest that HSP70-2 gene polymorphic allele A is a possible genetic marker of less severe clinical phenotype in Japanese patients with Crohn disease.

Adolescent↗
PubMed1999

Eicosanoids and membrane properties in arteries of aged spontaneously hypertensive rats.

OBJECTIVE: The arteries of aged spontaneously hypertensive rats (SHR) exhibit spontaneous electrical activity together with membrane depolarization. Vascular eicosanoid production is increased in SHR, which is further accelerated with aging. We tested the hypothesis that eicosanoids are involved in spontaneous electrical activity, membrane depolarization or both in mesenteric arteries of aged SHR. DESIGN AND METHODS: Membrane potentials were recorded with microelectrodes from the mesenteric arteries of aged (24 months and older) SHR, aged Wistar-Kyoto (WKY) rats and adult (6- to 8-month-old) SHR. RESULTS: The membrane potential was less negative in aged SHR (-38.5 +/- 0.9 mV) than in either aged WKY rats or adult SHR (-49.8 +/- 0.5 and -47.2 +/- 0.6 mV, respectively; P < 0.05 for both). Spontaneous electrical activity (5-20 mV, 1-7/min) was present only in arteries of aged SHR. Spontaneous electrical activity was not affected by phentolamine, atropine or tetrodotoxin, but was abolished by indomethacin, a cyclooxygenase inhibitor, and ONO-3708, a thromboxane A2/prostaglandin H2 receptor antagonist. Furthermore, indomethacin and ONO-3708 hyperpolarized the membrane by about 5 mV in aged SHR but not in the other two groups. Spontaneous electrical activity was enhanced by a thromboxane A2 analog and prostaglandin H2, and was abolished by a Ca2+ antagonist, nicardipine, and Ca(2+)-free solution. CONCLUSIONS: These findings suggest that cyclooxygenase-dependent eicosanoids contribute importantly to both spontaneous electrical activity and membrane depolarization, presumably through activation of the thromboxane A2/prostaglandin H2 receptor, in mesenteric arteries of aged SHR, and that spontaneous electrical activity is mediated by a Ca2+ influx through voltage-dependent Ca2+ channels.

Aging↗
PubMed1999

Effects of chronic oral treatment with imidapril and TCV-116 on the responsiveness to angiotensin II in ventrolateral medulla of SHR.

OBJECTIVE: To examine whether chronic oral treatment with an angiotensin-converting enzyme inhibitor imidapril and an angiotensin II type 1 receptor antagonist TCV-116 would alter the response to angiotensin II in the rostral ventrolateral medulla. METHODS: Twelve-week-old spontaneously hypertensive rats (SHR) were treated with imidapril (20 mg/kg per day, n = 7), TCV-116 (5 mg/kg per day, n = 8) or vehicle (n = 8) for 4 weeks. Wistar- Kyoto rats (WKY) (n = 8) served as normotensive controls. At 16 weeks of age, angiotensin II (100 pmol) was microinjected into the rostral ventrolateral medulla of anaesthetized rats. RESULTS: Blood pressure decreased significantly in the rats treated with either imidapril or TCV-116. Pressor responses to angiotensin II microinjected into the rostral ventrolateral medulla were comparable in the untreated SHR, the imidapril-treated SHR and WKY (12 +/- 2, 15 +/- 4 and 10 +/- 1 mmHg, respectively), but were abolished in SHR treated with TCV-116 (0 +/- 2 mmHg, P< 0.01). Angiotensin-converting enzyme activity in the brain stem was significantly lower in SHR treated with imidapril (0.70 +/- 0.06 nmol/mg per h), but significantly higher in SHR treated with TCV-116 (1.62 +/- 0.04 nmol/mg per h) than in the untreated SHR (1.37 +/- 0.05 nmol/mg per h). CONCLUSIONS: Chronic oral treatment with imidapril and TCV-116 may have divergent influences on the renin-angiotensin system within the brain stem. TCV-116, but not imidapril, abolishes the pressor effect of angiotensin II in the rostral ventrolateral medulla.

Administration, Oral↗
PubMed1999

In vivo observation of the ileal microadenoma in familial adenomatous polyposis.

Microadenomas or aberrant crypt foci (ACFs) are regarded as early neoplastic lesions that precede the development of macroscopic adenomas. The aim of this study was to characterize surface features of ileal microadenomas in patients with familial adenomatous polyposis (FAP). Magnifying ileoscopy was performed in 19 patients with FAP. A histologically verified adenomatous tubule, the existence of which was suggested by magnified observation, was regarded as a microadenoma. Magnifying ileoscopy detected microadenoma in five patients. In four of the five cases, the ileal microadenomas were identified as areas with tiny crypt openings or serrated surfaces, which were distinctive of nonneoplastic, diminutive protrusions. Magnifying ileoscopy seems to be useful in the detection of ileal microadenomas.

Adenoma↗
PubMed1999

Monoclonality of infiltrating plasma cells in primary pulmonary nodular amyloidosis: detection with polymerase chain reaction.

AIMS: To investigate the relation between localised amyloidosis and immunocytic dyscrasia. METHODS: Open lung biopsy specimens from a 72 year old man with multiple nodules in the right middle and lower lung were stained with haematoxylin-eosin, Congo red, and antibodies against IgG, IgA, IgM, and kappa and lambda light chains. Semi-nested PCR amplification for the immunoglobulin heavy chain (IgH) gene was performed using consensus primers for the VDJ region of the IgH gene, FR3A, LJH, and VLJH. RESULTS: The biopsy specimens contained eosinophilic amorphous material stained with Congro red and anti-kappa light chain, and surrounded by inflammatory cells intermingled with plasma cells. Plasma cells in the adjacent amorphous material showed cytoplasmic staining with anti-kappa. Polymerase chain reaction revealed a discrete amplified band of apparently uniform size with background smear. CONCLUSIONS: Primary AL type localised amyloidosis involves local accumulation of monoclonal plasma cells and their secreted products, as in nodular cutaneous amyloidosis. Localised AL type nodular amyloidosis is a separate entity in amyloidosis.

Aged↗
PubMed1999

Decreased plasma tryptophan associated with deep white matter lesions in elderly subjects.

The aim was to identify potentially treatable risk factors for cerebral white matter lesions often found on MRI in elderly persons. findings were assessed on 1.0 T MRI of 178 subjects living in the community and aged 60 years or older. Participants underwent standardised evaluations including standard questionnaires, a physical and neurological examination, cognitive function tests, electrocardiogram, a complete blood chemistry panel, and plasma amino acid measurements. Brain MRI infarcts, deep white matter lesions (DWMLs), and periventricular hyperintensities were found in 26%, 43%, and 29% of the 178 participants, respectively. Subjects with DWMLs were significantly older and had a higher frequency of hypertension, higher systolic blood pressure, and more brain infarcts, but lower plasma concentrations of tryptophan. In the multivariate model, greater age and lower plasma tryptophan concentrations were independently associated with DWMLs. Tryptophan concentrations were inversely related to DWML grading, whereas hypertension and brain infarction were more common in subjects with higher extents of DWMLs. The present study suggests that greater age and lower plasma tryptophan concentrations were important in producing DWMLs in elderly subjects.

Aged↗
PubMed1999

Experimental enteropathy in athymic and euthymic rats: synergistic role of lipopolysaccharide and indomethacin.

The aim of this study was to investigate the immunologic and microbiological bases of indomethacin enteropathy. Athymic nude and euthymic specific pathogen-free (SPF) rats were reared under conventional or SPF conditions. In each group, indomethacin was given intrarectally for 2 days. Indomethacin enteropathy was evaluated using a previously described ulcer index and tissue myeloperoxidase activity. Both euthymic and athymic nude rats developed intestinal ulcers to the same degree under conventional conditions but no or minimal ulcer under SPF conditions. Pretreatment of conventional rats with intragastric kanamycin sulfate, an aminoglycoside antibiotic, attenuated indomethacin enteropathy in a dose-dependent fashion. Interestingly, when lipopolysaccharide was injected intraperitoneally in kanamycin-pretreated rats, it fully restored enteropathy in these rats in a dose-dependent manner. We confirmed that kanamycin decreased the number of gram-negative bacteria and endotoxin concentration of the small intestine in a dose-dependent fashion. These results indicate that indomethacin enteropathy is bacteria dependent and does not require a T cell function. Synergy between indomethacin and bacterial lipopolysaccharide may play a major role in this enteropathy.

Animals↗
PubMed1999

Central adrenomedullin augments the baroreceptor reflex in conscious rabbits.

We examined the roles of central adrenomedullin, proadrenomedullin N-terminal 20 peptide (PAMP), and calcitonin gene-related peptide (CGRP) on the baroreceptor reflex in conscious rabbits. Intracerebroventricular injection of adrenomedullin (0.2 and 1 nmol/80 microL) elicited dose-related increases in arterial pressure and renal sympathetic nerve activity. On the other hand, a subpressor dose of intracerebroventricular infusion of adrenomedullin (1 nmol/300 microL per hour) caused significant increases in baroreflex sensitivities assessed by renal sympathetic nerve activity and heart rate compared with vehicle infusion (Gmax; -14.9+/-1.7 versus -8.0+/-0.7%/mm Hg, P<0.01, and -8.1+/-0.8 versus -5.1+/-0.5 bpm/mm Hg, P<0.01, respectively). Intracerebroventricular infusion of CGRP (1 nmol/300 microL per hour), which is structurally homologous to adrenomedullin, also enhanced the baroreflex controls of renal sympathetic nerve activity and heart rate. However, the intracerebroventricular infusion of PAMP (30 nmol/300 microL per hour) failed to alter the baseline levels of arterial pressure and baroreflex sensitivities. These results suggest that central adrenomedullin and CGRP, but not PAMP, participate in cardiovascular regulation to augment the baroreflex controls of renal sympathetic nerve activity and heart rate in conscious rabbits.

Adrenomedullin↗
PubMed1999

Impaired isoproterenol-induced hyperpolarization in isolated mesenteric arteries of aged rats.

Stimulation of vascular beta-adrenoceptors leads to membrane hyperpolarization, presumably via the beta-adrenoceptor/G(s) protein/adenylate cyclase signaling cascade; the ionic mechanisms of this phenomenon remain unclear. beta-Adrenoceptor-mediated vascular relaxation is impaired with aging; however, little is known concerning whether beta-adrenoceptor-mediated hyperpolarization is altered with aging. We sought to determine the ionic mechanisms of isoproterenol-induced hyperpolarization in the rat mesenteric resistance artery, as well as the age-related changes in isoproterenol-induced hyperpolarization and their underlying mechanisms. Isoproterenol-induced hyperpolarization was inhibited by high-K(+) solution and glibenclamide (10(-6) mol/L), an inhibitor of ATP-sensitive K(+) channels (K(ATP)), but not by apamin, iberiotoxin, or charybdotoxin, inhibitors of Ca(2+)-activated K(+) channels. Isoproterenol-induced hyperpolarization was markedly less in aged rats (>/=24 months) than in adults rats (12 to 20 weeks) (3x10(-6) mol/L; -3.1 versus -9.9 mV; P<0.001; n=8 to 9). Cholera toxin (10(-9) g/mL), an activator of G(s), evoked hyperpolarization only in adult rats. Hyperpolarization to forskolin, a direct activator of adenylate cyclase, was also reduced to some extent in aged rats (10(-5) mol/L; -8.8 versus -13 mV; P<0.05; n=6), whereas hyperpolarization to levcromakalim, a K(ATP) opener, was comparable in both groups. These findings suggest that isoproterenol elicits hyperpolarization via an opening of K(ATP) in the rat resistance artery and that isoproterenol-induced hyperpolarization is attenuated in aged rats mainly because of a defective coupling of beta-adrenoceptors to adenylate cyclase and partly because of a defect at the level of adenylate cyclase, but not because of an alteration of K(ATP) per se.

Adenylyl Cyclases↗
PubMed1999

Prevalence of intracranial saccular aneurysms in a Japanese community based on a consecutive autopsy series during a 30-year observation period. The Hisayama study.

BACKGROUND AND PURPOSE: Subarachnoid hemorrhage is a life-threatening disease that occurs mostly because of the rupture of intracranial saccular aneurysms. However, little is known about the prevalence of ruptured and unruptured aneurysms in the general population. The aim of the present study was to examine the prevalence of intracranial aneurysms on the basis of a consecutive autopsy series over a 30-year observation period in a general Japanese population in Hisayama. METHODS: We evaluated 1230 consecutive autopsy cases with craniotomy among the total deaths of Hisayama residents during 1962 through 1991 (overall autopsy rate, 80.1%). RESULTS: A total of 73 intracranial saccular aneurysms were found in 57 cases (4.6%). The prevalence of aneurysms for women was 2.4 times higher than that for men (7.1% versus 2.9%). Among men, the prevalence of aneurysms remained unchanged across the range of age groups. In contrast, there were 2 peaks in the prevalence of aneurysms for women falling in the 40- to 49-year (14.3%) and 60- to 69-year age groups (14.5%). The most common site of the aneurysms was the middle cerebral artery (31.5%), followed by the anterior communicating artery (30.1%), anterior cerebral artery (15.1%), vertebrobasilar artery (12.3%), and internal carotid artery (11.0%). Among these 73 aneurysms, 29 (39.7%) were ruptured. Ruptured aneurysms were common in subjects <80 years of age, whereas unruptured aneurysms were prevalent in those >/=80 years of age. The frequency of ruptured aneurysms was highest in the vertebrobasilar system (66.7%) and lowest in the middle cerebral artery (13.0%). CONCLUSIONS: Our data suggest that intracranial aneurysms are more frequent in women in the general Japanese population. Aneurysms are more prevalent in the middle cerebral artery, but the risk of rupture is highest in the vertebrobasilar system.

Adolescent↗
PubMed1999

Effects of salt-loading on membrane potentials in mesenteric arteries of spontaneously hypertensive rats.

Although salt intake and blood pressure are correlated, with hypertensives tending to exhibit higher blood pressure sensitivity to salt than normotensives, the precise mechanisms underlying this relationship remain unclear. This study aimed to determine whether salt-loading affects arterial membrane properties of spontaneously hypertensive rats (SHR). SHR and age-matched Wistar Kyoto rats (WKY) received either an 8% high salt diet or standard rat chow from 6 to 16 wk of age. Systolic blood pressure was significantly higher in salt-loaded SHR than in control SHR (267+/-7 vs. 235 +/- 5 mmHg, p < 0.05). The membrane potential of isolated conduit and resistance arteries of the superior mesenteric vascular bed, measured with microelectrodes, was less negative in salt-loaded SHR than in control SHR or salt-loaded WKY (conduit arteries, -39.9 +/- 0.3 vs. -44.5 +/- 0.4 or -47.4 +/- 0.4 mV, respectively, p < 0.05 for each; resistance arteries, -55.5 +/- 0.5 vs. -62.5 +/- 0.5 or -67.0 +/- 0.5 mV, respectively, p < 0.05 for each). Furthermore, conduit arteries of salt-loaded SHR exhibited spontaneous electrical activity (4-13 mV, 1-3/min), which was sensitive to ONO-3708, a thromboxane A2/prostaglandin H2 receptor antagonist. These findings suggest that salt-loading in SHR leads to a membrane depolarization in both conduit and resistance arteries, as well as to spontaneous electrical activity, presumably mediated by eicosanoids, in conduit arteries. These alterations in membrane properties might contribute to the exacerbation of hypertension and/or the target organ damage after salt loading in SHR.

Animals↗