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F Iwata

Publications and source records attributed to F Iwata.

At least 55 records · Page 3Linked to original sources
PubMed1996

Studies on the mechanism of early onset macular degeneration in cynomolgus monkeys. II. Suppression of metallothionein synthesis in the retina in oxidative stress.

Initial investigations done in this laboratory detected increased albumin and decreased glyceraldehyde 3-phosphate dehydrogenase concentrations in the retina of an animal model manifesting early onset macular degeneration. Both glyceraldehyde 3-phosphate dehydrogenase and albumin are markers of oxidative stress in cells. In this study, we used the same animal model to study further biochemical and physiological processes which may be involved in the pathogenesis of early onset macular degeneration in monkeys. We detected 60% lower catalase and glutathione peroxidase activities in the affected retinas suggesting lower antioxidant activities and oxidative stress. One of the consequences of oxidative stress is the production of metallothionein, a low molecular weight protein also induced by high concentrations of heavy metals such as zinc. Metallothionein was detected by RT-PCR in these monkey retinas. However initial quantitative PCR studies on this protein showed that the synthesis of metallothionein in affected retinas appears to be less than in normal controls. The affected retinas also showed a fourfold lower zinc concentration compared with the normal controls. No significant difference, however, could be detected in the zinc concentrations in plasma samples. Since induction of metallothionein synthesis is mediated by transcription factors which require heavy metals such as zinc for binding to specific sites in the DNA, the lowered zinc concentration may, thus, correlate with the lowered metallothionein expression. And since metallothionein is suggested to function as a free radical scavenger, the lowered metallothionein synthesis may consequently contribute to increased peroxidation reactions in the affected retinas. It appears therefore, that oxidative stress and the decreased metallothionein synthesis may be involved in the pathogenesis of early onset macular degeneration in this animal model.

Amino Acid Sequence↗
PubMed1996

Association of thyroid disease with retinitis pigmentosa and gyrate atrophy.

PURPOSE: To compare the prevalence of thyroid disease in patients with retinitis pigmentosa, in patients with gyrate atrophy of the choroid and retina, and in patients with no history of ocular disease. METHOD: Forty-four patients with retinitis pigmentosa, 34 patients with gyrate atrophy, and 30 normal control patients with no ocular disease were evaluated in a case-control study for the presence of thyroid disease. RESULTS: Thyroid disease was diagnosed in six of 44 patients with retinitis pigmentosa and seven of 34 patients with gyrate atrophy but in only one of 30 control patients. Compared with control patients, the odds ratio for the occurrence of thyroid disease was 6.2 for patients with retinitis pigmentosa and 12.7 for patients with gyrate atrophy. CONCLUSION: These data suggest an increased occurrence of thyroid disease in patients with retinitis pigmentosa and gyrate atrophy.

Adolescent↗
PubMed1996

Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter.

Maintenance of fluid and electrolyte homeostasis is critical for normal neuromuscular function. Bartter's syndrome is an autosomal recessive disease characterized by diverse abnormalities in electrolyte homeostasis including hypokalaemic metabolic alkalosis; Gitelman's syndrome represents the predominant subset of Bartter's patients having hypomagnesemia and hypocalciuria. We now demonstrate complete linkage of Gitelman's syndrome to the locus encoding the renal thiazide-sensitive Na-Cl cotransporter, and identify a wide variety of non-conservative mutations, consistent with loss of function alleles, in affected subjects. These findings demonstrate the molecular basis of Gitelman's syndrome. We speculate that these mutant alleles lead to reduced sodium chloride reabsorption in the more common heterozygotes, potentially protecting against development of hypertension.

Amino Acid Sequence↗
PubMed1996

Ocular manifestations of metabolic disorders.

Articles published during the past year on the ocular manifestations of metabolic disorders and related issues are reviewed. Fewer articles on this topic were available this year than previous years. Ornithine-delta-amino transferase-deficient mice were produced by gene targeting in the hope of creating an animal model for gyrate atrophy. The mice developed unexpected hypoornithinemia in the neonatal period and died 24 to 48 hours after birth. One human infant also had hypoornithnemia without serious symptoms. Both mice and human develop hyperornithinemia later. Arginine supplementation rescued the mice, but they developed central retinal degeneration by 7 months. Coexistence of autosomal dominant congenital or early onset cataract and hyperferritinemia, not related to iron overload, was discovered in three pedigrees, two Italian and one not mentioned, by two different groups. Mutations of the ferritin L-subunit gene in the iron-responsive element were identified, with autosomal dominant inherited cataract associated with hyperferritinemia.

Animals↗
PubMed1995

Tobacco cigarette smoke attenuates duodenal ulcer margin hyperemia in the rat. Comparison of IAP clearance and hydrogen gas clearance techniques for measurements of gastrointestinal blood flow.

The hyperemia at the duodenal ulcer margin is important for ulcer healing. We studied the effect of tobacco cigarette smoke on the hyperemia at the margin of mepirizole-induced duodenal ulcer. Duodenal mucosal blood flow values measured by iodo[14C]antipyrine (IAP) autoradiography and hydrogen gas clearance (HGC) were compared. Twenty-four hours after rats were injected with an ulcerogenic dose of mepirizole, they were exposed to tobacco cigarette smoke and duodenal mucosal blood flow was measured by IAP autoradiography. There is a significant correlation between the blood flow measurements by HGC and IAP autoradiography. The hyperemia at the ulcer margin previously demonstrated in our laboratory is absent after exposure of the rats to tobacco cigarette smoke. We speculate that the inhibition of ulcer margin hyperemia could explain the aggravation of duodenal ulcer by tobacco cigarette smoke.

Animals↗
PubMed1995

Aggravation of gastric mucosal lesions in rat stomach by tobacco cigarette smoke.

In the model of gastric mucosal injury induced by 2 mol/liter hypertonic saline in rats, we tested the hypothesis that tobacco cigarette smoke aggravates gastric mucosal lesions by inhibition of injury-induced gastric mucosal hyperemia. Experimental rats were treated with tobacco cigarette smoke or nicotine-free smoke from nontobacco cigarettes, and controls breathed room air. Gastric mucosal blood flow was measured by hydrogen gas clearance before and during the intragastric administration of hypertonic saline. Tobacco cigarette smoke 3 and 18 ml/min, but not nicotine-free smoke, significantly attenuated the hyperemia and aggravated the hypertonic saline-induced lesion in a dose-dependent manner. We then tested the hypothesis that 18 ml/min of tobacco cigarette smoke, and the dose of intravenous nicotine previously shown to block injury-induced hyperemia and aggravate 2 mol/liter saline-induced gastric damage, will also adversely affect gastric lesions induced by acidified aspirin or acidified ethanol. The results confirm that tobacco cigarette smoke and intravenous nicotine indeed aggravate gastric mucosal damage in these two models. Taken together, the data suggest that the inhibition of injury-induced hyperemia by nicotine and tobacco cigarette smoke is an important predictor of their ability to increase the susceptibility of the gastric mucosa to noxious damage. Although limited in their experimental nature, these data provide one plausible explanation for the adverse effect of tobacco cigarette smoke on peptic ulcer disease.

Animals↗
PubMed1995

Inhibition of endogenous nitric oxide reduces basal mesenteric vascular tone but does not alter intraduodenal hydrochloric acid-induced intestinal hyperemia in rats.

There are conflicting reports on the role of endogenous nitric oxide (NO) in the regulation of basal intestinal blood flow. The effect of inhibition of NO in intraduodenal hydrochloric acid (HCl) induced intestinal hyperemia remains to be confirmed. We investigated the effect of inhibition of endogenous NO on basal intestinal blood flow, HCl-induced intestinal hyperemia, and duodenal villous injury. Superior mesenteric artery blood flow in rats was measured by pulsed Doppler flowmetry and duodenal villous injury evaluated by histology. Intravenous NG-nitro-L-arginine methyl ester (L-NAME), or L-arginine or D-arginine followed by L-NAME, was given to show inhibition, reversal of inhibition of endogenous NO synthase, and stereospecificity, respectively. An intraduodenal 2 ml/kg bolus or perfusion for 30 min of 0.1 N HCl was given 15 min after L-NAME or vehicle. Mean arterial blood pressure was increased by L-NAME, which also significantly reduced intestinal blood flow under basal condition and after intraduodenal HCl. Basal mesenteric blood flow was not altered by L- or D- arginine. The L-NAME-induced increase in blood pressure and decrease in basal blood flow was attenuated by L- but not D-arginine. The villous damage and the magnitude of the peak hyperemia was unchanged by L-NAME, L- or D-arginine. Inhibition of endogenous NO by L-NAME is suggested by the significant rise in blood pressure. The rise in blood pressure and reduction in blood flow are attenuated by L- but not D-arginine, indicating stereospecificity. Inhibition of endogenous NO reduces basal mesenteric vascular tone but does not alter intraduodenal HCl-induced intestinal hyperemia.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Ocular manifestations of metabolic disorders.

Major advances in the molecular basis of oculocutaneous and ocular albinism have been published. In addition to mutations of the P gene, some patients, with so-called autosomal recessive ocular albinism, were found to have a tyrosinase gene mutation in one allele and a nucleotide substitution of the same gene, which was considered as a polymorphism, in another allele. This finding has great impact on the diagnosis and genetic counseling of albinism. Flash visually evoked potentials may be a useful tool to show the asymmetry pattern in albino patients especially in infants. Some reports suggested that there may be an overlap between corneal amyloidosis and other forms of corneal dystrophy. Lattice dystrophy, granular dystrophy, and Avellino (granular-lattice) dystrophy were mapped on the same locus of chromosome 5q. Histopathologic findings supported that these different phenotypes were derived from defects of the same gene. Gelatinous droplike dystrophy and spheroidal band-shaped degeneration were also suggested to be allelic disorders by clinical and histopathological findings.

Eye Diseases↗
PubMed1995

Lipoprotein (a) and apolipoprotein A-1 and B in schoolchildren whose grandparents had coronary and cerebrovascular events: a preliminary study of 12-13 year old Japanese children.

The aim of this study was to evaluate the relationship between the serum levels of lipoprotein (a) [Lp (a)] and apolipoproteins (apo A-1 and apo B) in schoolchildren with a history of coronary and cerebrovascular events in their grandparents. We measured serum concentrations of Lp (a) and apoliproteins immunochemically in 289 schoolchildren aged 12-13 years and questioned parents about coronary and cerebrovascular events in the children's grandparents. In boys and girls, mean +/- s.d. levels of apo A-1, apo B and Lp (a) were 134 +/- 20.3 and 136 +/- 17.4 mg/dL, 61 +/- 16 and 66 +/- 15 mg/dL and 12.5 +/- 15.3 and 12.5 +/- 15.1 mg/dL, respectively. There were no significant sex differences in the levels of apo A-1, apo B, and Lp (a). The Lp (a) levels (mean +/- s.d., 12.5 +/- 15.2 mg/dL; median 7.5 mg/dL, n = 289) were not affected by other variables. The Lp (a) distribution was strongly positively skewed and 75% of schoolchildren had very low levels. In the total 289 schoolchildren, thirty-two grandparents who had had coronary vascular events (21 myocardial infarction, 11 angina pectoris) and twenty-three grandparents who had had cerebrovascular events were recorded. By the boxplot statistical analysis, no difference was found in Lp (a) levels in children whose grandparents had myocardial infarction compared with those whose grandparents had no such history, or compared with those whose grandparents had suffered cerebrovascular events.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Intra-abdominal fat in obese children.

We investigated the distribution of abdominal fat accumulation in obese children to know whether a clustering of coronary risk factors was demonstrated in visceral fat obesity as reported in adults. The relative indicator of intra-abdominal fat accumulation was obtained from computed tomography scans at the umbilicus level in 36 obese subjects (24 males, 12 females). There was no visceral fat obesity in this study by reported criteria. All metabolic variables except triglyceride did not correlate significantly with intra-abdominal fat accumulation. We conclude that visceral fat obesity is a rare status and has no close relationship to coronary risk factors in childhood.

Abdomen↗
PubMed1995

Tobacco cigarette smoke aggravates gastric ulcer in rats by attenuation of ulcer margin hyperemia.

We tested the hypothesis that attenuation of the hyperemia at the margin of acetic acid-induced gastric ulcer in rats by tobacco cigarette smoke will increase the size of the ulcer in the acute and the healing stages. Compared with the adjacent mucosa, blood flow measured by hydrogen gas clearance at the ulcer margin was significantly higher (ulcer margin hyperemia). Tobacco cigarette smoke and subcutaneous nicotine but not nicotine-free smoke from non-tobacco cigarettes significantly attenuated the ulcer margin hyperemia in a dose-related fashion. Repeated exposure of the rats to tobacco cigarette smoke increases ulcer size in the acute and the healing stages. Subcutaneous nicotine but not nicotine-free smoke also increased the size of ulcers in the acute stage. These results indicate that the nicotine in tobacco cigarette smoke may be responsible in part for its adverse effects. We conclude that attenuation of the hyperemia at the ulcer margin is a plausible explanation for the mechanism of the adverse effect of the tobacco cigarette smoke on experimental gastric ulcers in rats.

Acetates↗
PubMed1995

Misoprostol reverses the inhibition of gastric hyperemia and aggravation of gastric damage by tobacco cigarette smoke in the rat.

BACKGROUND: Tobacco cigarette smoke attenuates injury-induced hyperemia, aggravates hypertonic saline-induced mucosal damage, inhibits ulcer margin hyperemia, and increases the size of the acetic acid-induced ulcer in the rat stomach. The inhibitory effect of tobacco cigarette smoke on gastric prostaglandin metabolism may be the basis for these observations. We have tested the hypothesis that exogenous prostaglandin (misoprostol) treatment will reverse these effects. METHODS: Rats with these two types of gastric injury were treated with tobacco cigarette smoke or breathed room air and were given intragastric misoprostol or vehicle. Gastric mucosal blood flow was measured by hydrogen gas clearance, and lesion score or ulcer size was measured by image analysis. RESULTS: Tobacco cigarette smoke attenuated the hyperemia and significantly aggravated the mucosal lesions and increased ulcer size. Treatment with intragastric misoprostol preserved the hyperemia and significantly attenuated the exacerbation of mucosal damage or increase in ulcer size produced by tobacco cigarette smoke. CONCLUSION: These data are consistent with the hypothesis that the attenuation of injury-induced or ulcer margin hyperemia by tobacco cigarette smoke is mediated by the inhibition of endogenous prostaglandins.

Acetates↗
PubMed1995

Anti-neutrophil serum attenuates dextran sulfate sodium-induced colonic damage in the rat.

BACKGROUND: The role of neutrophils in experimental colonic damage induced by dextran sulfate sodium is uncertain. We test the hypothesis that neutrophils are of pathogenic significance and anti-neutrophil serum will attenuate the colonic damage induced by oral dextran sulfate sodium in rats. METHODS: Rabbit anti-rat neutrophil serum (anti-neutrophil serum) or control rabbit serum was administered to, and circulating neutrophil count was monitored in, rats before and during feeding of dextran sulfate sodium or regular rat diet for 2 weeks. Histologic features of mucosal damage were evaluated in hematoxylin and eosin-stained proximal and distal colonic sections by a blinded observer. RESULTS: Oral dextran sulfate sodium induces weight loss, diarrhea, peripheral neutrophilia, and colonic damage. Anti-neutrophil serum induced neutropenia and significantly attenuated the weight loss, the neutrophil infiltration in the colon, and the mucosal necrosis and pathologic index in the distal colon. CONCLUSION: The data showing that anti-neutrophil serum attenuates distal colonic mucosal injury induced by dextran sulfate sodium support the hypothesis that neutrophils play a pathogenic role in this model of colonic mucosal damage.

Animals↗
PubMed1995

[A study on the rhodopsin gene in Japanese retinitis pigmentosa--screening of mutation by restriction endonucreases and frequencies of DNA polymorphisms].

We analyzed 11 sites of the rhodopsin gene using polymerase chain reaction (PCR) amplification and restriction endonucleases in 30 unrelated Japanese patients with autosomal dominant retinitis pigmentosa (ADRP). No point mutation was found in any patient. The frequencies of the single nucleotide (nt) substitution at nt 269, nt 5145 and nt 5321 were examined in three groups, 38 unrelated patients with ADRP, 23 patients with autosomal recessive retinitis pigmentosa (ARRP), and 67 normal controls. There was no significant difference in the frequencies of substitution among these three groups. The frequencies of A269G, G5145A, and C5321A were 52%, 36%, and 5%, respectively. These values were different from those of the American population. The polymorphisms, A269G and G5145A, are useful as DNA makers for linkage analysis.

Asian People↗
PubMed1994

Intragastric nicotine protects against 40% ethanol-induced gastric injury despite pretreatment with NG-nitro-L-arginine methyl ester or adrenal medullectomy in rats.

We tested the hypotheses that the protective effect of intragastric nicotine against ethanol-induced gastric mucosal injury is dependent on endogenous nitric oxide or peripheral sympathoadrenal mechanisms. Rats were pretreated with NG-nitro-L-arginine methyl ester (3 mg/kg subcutaneous, 1 h prior to study) to block endogenous nitric oxide synthesis or with adrenal medullectomy (three weeks prior to study) to ablate the effect of the adrenal medulla. At 1-h intervals, vehicle or nicotine (4 mg/kg) and 40% ethanol were then given intragastrically. The total lengths of the linear gastric corpus mucosal lesions were measured unbiasedly. The protective effect of intragastric nicotine was not modified by either pretreatment. We conclude that the mechanism mediating intragastric nicotine protection against 40% ethanol-induced gastric mucosal injury is independent of endogenous nitric oxide or the adrenal medulla.

Administration, Oral↗
PubMed1994

Ocular manifestations of metabolic disorders.

Articles published during the past year on the ocular manifestations of metabolic diseases and related issues are reviewed. The focus is on clarifying the genetic or molecular basis of various metabolic disorders. Mutations of the P gene were reported in tyrosinase-positive oculocutaneous albinism and autosomal recessive ocular albinism, and were associated with a wide range of clinical phenotypes. This finding should aid in more accurate diagnosis and facilitate genetic counseling. There is no consensus but the horizontal supranuclear gaze palsy in Gaucher's disease may aid in subtyping. The report of a family with Morquio syndrome suggests that lenticular opacities should be considered as an additional finding in this syndrome. Patients with nephropathic cystinosis, which had been a fatal disease in childhood, are now surviving to adulthood. Serious ocular complications were described in adults.

Amino Acids↗
PubMed1994

Gastric epithelial damage induced by local ischemia-reperfusion with or without exogenous acid.

We evaluated the damage to the gastric epithelium produced by local ischemia-reperfusion (IR) with or without luminal perfusion with 0.1 N HCl. Local gastric ischemia was induced by clamping the left gastric artery. Use of radioactive microsphere technique revealed a significant reduction in blood flow induced only in the corpus (67% reduction). Because no measurable gross lesion was observed in this model, the blood-to-lumen clearance of 51Cr-labeled EDTA (51Cr-EDTA) served as an index of epithelial damage. In the absence of exogenous acid, the histological damage was minimum and could not be quantified. However, a significant increase in 51Cr-EDTA clearance was observed shortly after reperfusion in a manner that depended on the duration of ischemia. This increase in clearance reached a maximum approximately 10 min after reperfusion and returned rapidly toward control levels within 40-50 min after reperfusion. In the presence of exogenous acid, EDTA clearance increased significantly during ischemia, increased further during reperfusion, and did not recover for at least 60 min after reperfusion. The acid infused after reperfusion (no acid before reperfusion) did not significantly aggravate the mucosal damage that followed reperfusion. However, the acid infused before reperfusion (no acid after reperfusion) showed an effect on EDTA clearance similar to that induced by continuous acid perfusion.(ABSTRACT TRUNCATED AT 250 WORDS)

Allopurinol↗