Search PubMed⌕ Search

Biomedical subjects

K Fujimoto

Publications and source records attributed to K Fujimoto.

At least 433 records · Page 24Linked to original sources
PubMed1995

Epidermal growth factor enhances repair of rat intestinal mucosa damaged by oral administration of methotrexate.

To examine the trophic effect of epidermal growth factor on the rat small intestine, we measured diamine oxidase and ornithine decarboxylase activities in intestinal mucosa injured by methotrexate. Methotrexate was infused orally via a gastric tube at a dose of 10 mg/kg per day on 3 successive days (days 1-3). Epidermal growth factor was injected intraperitoneally at a dose of 40 micrograms/kg per day on 4 successive days following methotrexate infusion (days 4-7). Methotrexate caused a marked decrease in diamine oxidase activity; this decrease returned to a normal level on day 13 in controls. In rats injected with epidermal growth factor, diamine oxidase activity began to recover earlier than in the controls, and returned to a normal level on day 11. Epidermal growth factor enhanced the increase of ornithine decarboxylase activity in mucosa injured by methotrexate. When the increase of ornithine decarboxylase activity was suppressed by alpha-difluoromethylornithine, epidermal growth factor failed to facilitate the repair of intestinal mucosa. These results indicate that epidermal growth factor enhances intestinal repair following methotrexate infusion, and that this effect is mediated, at least in part, by ornithine decarboxylase. It is proposed that epidermal growth factor can be used clinically as a means to enhance mucosal repair of the intestine after chemotherapy with methotrexate.

Administration, Oral↗
PubMed1995

Chemiluminescence detection of mono-, bis-, and tris-hydroperoxy triacylglycerols present in vegetable oils.

A reliable method was needed to analyze molecular species of oxidized vegetable oils. In order to accomplish this goal, mono-, bis-, and tris-hydroperoxides (Mono-OOH, Bis-OOH, and Tris-OOH, respectively) of triacylglycerols formed during autoxidation and photosensitized oxidation of oils were determined by reversed-phase high-performance liquid chromatography in combination with chemiluminescence detection (CL-HPLC). Mono-OOH was the major species (96% of total hydroperoxides) in trioleoylglycerol [peroxide value (PV) 0.16 meg/kg], and Bis-OOH and Tris-OOH showed prolonged accumulation with photooxidation. This profile was confirmed in photooxidation of trilinoleoylglycerol and trilinoleoylglycerol. Soybean oil (PV 6 meq/kg) contained Mono-OOH oleoyl-linoleoylglycerol as the main peroxidic molecular species (50% of total hydroperoxides). Mono-OOH trilinoleoylglycerol was the principal species (61% of total hydroperoxides) in safflower oil (PV 5 meq/kg), and Mono-OOH oleoyl-oleoyl-linoleoylglycerol was the representative species (66% of total hydroperoxides) in olive oil (PV 3 meq/kg). The CL-HPLC method, which is specific for the detection of hydroperoxides, should prove useful in studies of triacylglycerol oxidation in foods and vegetable oils.

Chromatography, High Pressure Liquid↗
PubMed1995

Neutrophil elastase inhibitor reduces asthmatic responses in allergic sheep.

To determine the role of neutrophil elastase in asthmatic responses, we studied the effect of ONO-5046, a specific neutrophil elastase inhibitor, on antigen-induced asthmatic responses in allergic sheep. Pulmonary resistance (RL) was measured for 8 h after antigen challenge. Measurements of airway responsiveness to methacholine and bronchoalveolar lavage fluid (BALF) were obtained 8 h after challenge. Antigen challenge caused early and late increases in RL, airway hyperresponsiveness (AHR), and recruitment of neutrophils and eosinophils along with increases in TXB2 and LTB4 in BALF. ONO-5046 treatment significantly reduced both early and late bronchoconstriction, neutrophil recruitment, increases in LTB4 in BALF, and AHR. ONO-5046 post-treatment significantly reduced the increase in RL 8 h after antigen challenge. Another neutrophil elastase inhibitor, FR 134043, significantly reduced both early and late bronchoconstriction. ONO-5046 had little effect on calcium ionophore-induced LTB4 release from isolated neutrophils and whole blood obtained from drug-treated sheep. These findings suggest that neutrophil elastase is involved in antigen-induced bronchoconstriction and AHR mediated by neutrophil accumulation and 5-lipoxygenase products in allergic sheep.

Airway Resistance↗
PubMed1995

Lipid profiles of cerebral gray matter and livers of macaque monkeys Macaca fascicularis and Macaca fuscata fuscata: a comparative study during development.

The lipid and fatty acid profiles in cerebral gray matter and livers were studied in macaque monkeys (Macaca fascicularis and M. fuscata fuscata) of different ages. In cerebral gray matter, the phosphatidylcholine/phosphatidylethanolamine (PC/PE) ratio decreased in animals more than 3 years old, while the cholesterol/lipid-phosphorus ratios and the unsaturation indices increased, as compared with those in fetuses and newborns. The level of 22:6n-3 in PE of cerebral gray matter increased up to 3 years old, mainly by replacing 20:4n-6, whereas the level in phosphatidylserine did not change significantly with age. The hepatic lipid-phosphorus levels and PC/PE ratios were lower in newborns than in animals more than 3 years old. The level of 22:6n-3 in liver phospholipid did not change, while that of 20:4n-6 was lower in animals more than 3 years old than in newborns.

Aging↗
PubMed1995

Effects of fatty acids and fatty acyl CoA esters on Cu(2+)-induced conversion of xanthine dehydrogenase to oxidase in rabbit liver.

Effects of various fatty acids and fatty acyl CoA esters on Cu(2+)-induced conversion of xanthine dehydrogenase to oxidase in rabbit liver were examined. Cu2+ (2-10 microM) brought about the conversion of xanthine dehydrogenase to oxidase in a dose-dependent manner. Oleic, arachidonic, eicosapentaenoic, and docosahexaenoic acids (50-200 microM) prevented the conversion of xanthine dehydrogenase to oxidase catalyzed by 6 microM-Cu2+. The effect of these four fatty acids was concentration-dependent, whereas palmitic, stearic, and linoleic acids had no effect on the conversion of xanthine dehydrogenase to oxidase at the same concentration range. On the other hand, palmitoyl, linoleoyl, and arachidonoyl CoAs elicited the inhibition of 6 microM-Cu(2+)-induced conversion of xanthine dehydrogenase to oxidase at concentrations of 50, 100, and 200 microM. These results suggest that oleic, arachidonic, eicosapentaenoic and docosahexaenoic acids, and fatty acyl CoAs have the potential to inhibit the conversion of xanthine dehydrogenase to oxidase in rabbit liver.

Acyl Coenzyme A↗
PubMed1995

Mice devoid of the glial fibrillary acidic protein develop normally and are susceptible to scrapie prions.

Glial fibrillary acidic protein (GFAP) is an intermediate filament protein specifically expressed in astrocytes in the CNS. To examine the function of GFAP in vivo, the Gfap gene was disrupted by gene targeting in embryonic stem cells. Mice homozygous for the mutation were completely devoid of GFAP but exhibited normal development and showed no obvious anatomical abnormalities in the CNS. When inoculated with infectious scrapie prions, the mutant mice exhibited neuropathological changes typical of prion diseases. Infectious prions accumulated in brains of the mutant mice to a degree similar to that in control littermates. These results suggest that GFAP is not essential for the morphogenesis of the CNS or for astrocytic responses against neuronal injury. The results argue against the hypothesis that GFAP plays a crucial role in the pathogenesis of prion diseases.

Animals↗
PubMed1995

Prevention of recurrent bleeding from gastric ulcer with a nonbleeding visible vessel by endoscopic injection of absolute ethanol: a prospective, controlled trial.

We performed a prospective, randomized trial to assess the efficacy of endoscopic injection therapy with absolute ethanol in preventing recurrent bleeding in patients with nonbleeding visible vessels in gastric ulcers. During the period of 1990 to 1993, 62 patients who bled were found to have gastric ulcers with nonbleeding visible vessels; all of them were enrolled for this trial. The 62 patients were randomly divided into two groups, which were comparable at entry. In group I (33 patients), we performed endoscopic injection therapy with absolute ethanol. In group II (29 patients), we sprayed the ulcers with 0.1% epinephrine and thrombin. Endoscopic injection therapy with ethanol was performed at the second endoscopy in the patients in both groups who had recurrent bleeding. Among the 33 patients in group I, 4 patients (12.1%) rebled after the initial ethanol injection therapy, whereas 10 of 29 patients (34.5%) rebled in the control group (p < .05). No patients in group I required surgical intervention, and ultimate hemostasis was achieved in all 33 group I patients (100%), indicating that endoscopic ethanol injection therapy achieves ultimate hemostasis and prevents recurrent bleeding in patients with gastric ulcers and nonbleeding visible vessels.

Epinephrine↗
PubMed1995

Snake-strike--induced ischemic colitis with colonic stricture complicated by disseminated intravascular coagulation.

A 57-year-old farmer was struck on the right thumb by a pit viper (Agkistrodon blomhoffü). Subsequently, he had acute renal failure and disseminated intravascular coagulation (DIC), associated with melanotic stools and abdominal pain. Renal failure caused by renal cortical necrosis was successfully treated with hemodialysis. A double-contrast barium enema examination revealed multiple stenoses of the colon, regional edema, and longitudinal ulcer. Histologic examination of the stenotic lesions after laparotomy revealed fibrosis of both submucosa and proper muscle layer, with fibrotic thickness in the small arteries of the colonic wall, indicating that ischemic colitis was associated with DIC. In this case, DIC from viper toxins played an etiologic role in the development of ischemic colitis with stricture, as well as acute renal failure.

Acute Kidney Injury↗
PubMed1995

Basic fibroblast growth factor as a candidate tumor marker for renal cell carcinoma.

The present investigation was conducted to determine serum levels of basic fibroblast growth factor (FGF) by enzyme immunoassay in patients with various urogenital tumors. Renal cell carcinoma had a higher tendency (28 of 52, 53.8%) toward increased serum levels of basic FGF than any of the other urogenital tumors, and increased serum basic FGF was detected more frequently in patients with advanced renal cell carcinoma. Analysis of histological pattern indicated that renal cell carcinoma with a solid or tubular component is more likely to produce basic FGF. However, no significant difference was seen between the percentage of clear cell type tumor patients with increased serum basic FGF (50.0%) and the percentage of granular cell type tumor patients with increased serum basic FGF (66.7%). Five of 8 patients with renal cell carcinoma who underwent selective renal venous sampling before nephrectomy showed increased serum basic FGF in the renal vein from the affected kidney. After resection of the affected kidney to remove the cancer, serum basic FGF disappeared within 2 weeks. However, residual huge tumor or postoperative disease prolonged the increased levels of basic FGF in 2 patients, indicating that basic FGF is produced from and secreted by tumor tissue itself. These findings suggest that serum basic FGF can be useful in the diagnosis, and in evaluating the prognosis, of patients with renal cell carcinoma.

Biomarkers, Tumor↗
PubMed1995

Role of nitric oxide in the control of blood pressure in young and adult spontaneously hypertensive rats.

1. The depressor response to sodium nitroprusside (SNP) and the pressor response to Nomega-nitro-L-arginine methyl ester (L-NAME) were investigated in anaesthetized and ganglion-blocked 6 week old (young) and 20 week old (adult) spontaneously hypertensive rats (SHR), and the results were compared with those in age-matched normotensive Wistar-Kyoto (WKY) rats. 2. SNP produced a dose-dependent decrease of the mean blood pressure (BP) in both strains, and no differences in vascular sensitivity to SNP were observed between the strains. 3. L-NAME caused dose-dependent pressor responses in both strains. The sensitivity and the maximal response to L-NAME in SHR were significantly greater than those in age-matched WKY (P< 0.05 or 0.01; t-test, 13 d.f. in both ages). However, there were no significant differences in the responses between ages in each strain. 4. Acute reduction of BP induced by 7-O-ethylfangchinoline did not affect the responses to SNP and L-NAME in the adult SHR. 5. These results indicate that a greater amount of NO is tonically released in SHR and that its contribution to BP control is greater in SHR than in WKY, whereas vascular sensitivity to NO does not differ between the strains. In addition, acute changes in BP do not affect the degree of dependency on NO for BP control.

Aging↗
PubMed1995

Antihypertensive effects, determined by a telemetry method, of trichloromethiazide and 7-O-ethylfangchinoline, a derivative of tetrandrine, in spontaneously hypertensive rats.

1. The antihypertensive effects of 10 mg/kg trichloromethiazide (TCM), 10 mg/kg 7-O-ethylfangchinoline (7-O-EFC) and the combination of these drugs given orally once daily for 2 weeks were investigated by measuring the blood pressure (BP), heart rate (HR) and activity in conscious, freely moving spontaneously hypertensive rats (SHR) fitted with a telemetry device. 2. Clear diurnal rhythms of the HR and activity in synchrony with the light/dark cycle were observed during therapy, whereas the BP rhythm was obscure. 3. Alone, TCM and 7-O-EFC produced slight and insignificant reductions of 24h mean BP, whereas in combination they produced an additive and significant BP reduction, compared with the vehicle-treated controls, from the third day of therapy. The BP reduction induced by the combination of these drugs during the dark phase was more marked than that during the light phase. 4. None of the drug therapies affected the HR and activity diurnal rhythms. 5. The results of the present study demonstrate that the telemetry method is useful for monitoring the antihypertensive effects of drugs in SHR under physiological conditions with minimal stress.

Alkaloids↗
PubMed1995

Cytoplasmic calcium level and membrane fluidity of platelets contacting poly(acrylamide-co-methacrylic acid) particles with different surface properties.

Changes in cytoplasmic free calcium levels and membrane fluidity of platelets in contact with poly(acrylamide-co-methacrylic acid) (PAAmMAc) particles were examined to analyze the mechanistic aspect of regulating platelet function. Our previous studies demonstrated interesting features of PAAmMAc particles during interaction with platelets: (1) PAAmMAc particles induce no calcium increase but enhance membrane fluidity of platelets: (2) thrombin induces no calcium increase in platelets when the platelets were mixed previously with PAAmMAc particles; and (3) PAAmMAc particles induce a calcium increase in platelets when they were treated previously with sodium azide (NaN3). These results suggest the possibility that PAAmMAc surfaces may regulate the calcium level by influencing platelet metabolism. In this study, non-cross-linked PAAmMAc solution with the same chemical composition as the particles showed a suppressive effect on thrombin-induced calcium increase, but, no influence on membrane fluidity. This result indicates that aggregated macromolecular surface assemblies of PAAmMAc may dominate the increase in membrane fluidity of platelets although the calcium change is induced by discrete molecular level interaction between the PAAmMAc and platelet membranes. It was also revealed that the suppression of thrombin-induced calcium increase and the membrane fluidity increase in platelets by PAAmMAc particles were reduced by albumin-treatment of the particles. This result suggests that such phenomena may be due to a decrease in any physicochemical interaction of PAAmMAc surfaces with albumin, rather than platelet metabolic change. PAAmMAc particle surfaces with higher carboxyl groups exhibited a more suppressive effect on thrombin-induced calcium increase, whereas those with lower carboxyl groups derived a higher calcium increase when the platelets were treated previously with NaN3. These results suggest the importance of electrostatic and any other physicochemical interaction of PAAmMAc chains on regulating cytoplasmic calcium levels.

Acrylic Resins↗
PubMed1995

Three novel mutations of thyroid hormone receptor beta gene in unrelated patients with resistance to thyroid hormone: two mutations of the same codon (H435L and H435Q) produce separate subtypes of resistance.

We report three novel mutations of the thyroid hormone receptor beta (TR beta) gene in three unrelated Japanese patients with resistance to thyroid hormone (RTH). Patients A and B exhibited generalized resistance phenotype, while patient C displayed more pituitary-selective unresponsiveness. Direct sequencing of TR beta gene exon 10 disclosed novel point mutations in all three patients. A Phe to Ile (TTC-->ATC) substitution at codon 451, a His to Leu (CAT-->CTT) substitution at codon 435, and a His to Gln (CAT-->CAA) substitution at codon 435 were identified in patients A, B, and C, respectively. Sequencing of TR beta gene exons 5-9 as well as TR alpha gene exons 4-9 failed to detect any additional mutations. All three patients were heterozygous for respective mutations. The unaffected parents of patients A and B, having normal thyroid function, possessed no mutations of TR beta gene exon 10, indicating that the F451I and H435L mutations occurred de novo. The F451I mutation is located near the most frequent mutation site in the ligand 2 subdomain. The identical codon mutations H435L and H435Q, which lie at the extreme carboxyl-terminus of the dimerization subdomain near the 9th heptad, were found in clinically different subtypes of RTH: patient B with generalized resistance and patient C with pituitary-selective resistance, respectively. The mutations broaden the growing catalogue of the TR beta gene mutations that could cause different phenotypes, despite the defects at the same codon.

Adult↗
PubMed1995

Freeze-fracture replica electron microscopy combined with SDS digestion for cytochemical labeling of integral membrane proteins. Application to the immunogold labeling of intercellular junctional complexes.

We propose a new electron microscopic method, the sodium dodecylsulphate (SDS)-digested freeze-fracture replica labeling technique, to study the two-dimensional distribution of integral membrane proteins in cellular membranes. Unfixed tissue slices were frozen with liquid helium, freeze-fractured, and replicated in a platinum/carbon evaporator. They were digested with 2.5% SDS to solubilize unfractured membranes and cytoplasm. While the detergent dissolved unfractured membranes and cytoplasm, it did not extract fractured membrane halves. After SDS-digestion, the platinum/carbon replicas, along with attached cytoplasmic and exoplasmic membrane halves, were processed for cytochemical labeling, followed by electron microscopic observation. As an initial screening, we applied this technique to the immunogold labeling of intercellular junction proteins: connexins (gap junction proteins), occludin (tight junction protein), desmoglein (desmosome protein), and E-cadherin (adherens junction protein). The immunogold labeling was seen superimposed on the image of a fracture face visualized by platinum/carbon shadowing. The immunoreaction was specific, and only the structures where the proteins were expected were labeled. For instance, anti-occludin immunogold complexes were observed immediately adjacent to the tight junction strands on the protoplasmic and exoplasmic fracture faces. No significant levels of gold label were associated with non-tight-junctional regions of plasma membranes. The procedures of the SDS-digested freeze-fracture replica labeling and its potential significance are discussed.

Animals↗
PubMed1995

Effect of the initial bolus volume of recombinant tissue-type plasminogen activator on coronary recanalization and infarct size in Japanese acute myocardial infarction patients. Kumamoto University Myocardial Infarction Study (KUMIS) Group.

Coronary recanalization rate and infarct size were compared between 2 different methods of intravenously administering recombinant tissue-type plasminogen activator (rt-PA) 41.4 mg; 1) an initial bolus dose of 30% followed by infusion of the remainder over 60 min (30% group), and an initial bolus dose of 10% followed by infusion of the remainder over 60 min (10% group). Thirty min after beginning rt-PA infusion, the coronary recanalization rate was higher in the 30% group than in the 10% group (82.9% (34/41) vs 53.7% (22/41), p < 0.01). The peak creatine kinase and peak creatine kinase-MB levels were lower in the 30% group than in the 10% group. We conclude that a higher initial bolus dose of rt-PA gives a higher rate of recanalization of the infarct-related artery at the very early phase, and probably leads to a smaller infarct size.

Aged↗
PubMed1995

Antihypertensive effect of chronic KT3-671, a structurally new nonpeptide angiotensin AT1-receptor antagonist, in stroke-prone spontaneously hypertensive rats.

KT3-671 (2-propyl-8-oxo-1-[(2'-(1H-tetrazole-5-yl)biphenyl-4-yl)methyl]-4,5,6, 7-tetrahydrocycloheptimidazole), a structurally new nonpeptide angiotensin AT1-receptor antagonist, was administered orally and repeatedly to 15-week-old stroke-prone spontaneously hypertensive rats for 7 weeks; and its effects on blood pressure, heart rate, renal function, plasma renin concentration (PRC), plasma aldosterone concentration (PAC) and hypertension-related tissue damage in the brain, heart, kidney and mesenteric artery were investigated. KT3-671 at a dose of 3 or 10 mg/kg, p.o. per day prevented development of hypertension and produced a significant and consistent reduction of blood pressure in a dose-dependent manner. Enalapril at a dose of 10 mg/kg per day produced cardiovascular effects similar to those of KT3-671 at 10 mg/kg. Despite marked reduction in blood pressure, neither KT3-671 nor enalapril affected the heart rate. KT3-671 at 10 mg/kg produced a transient and significant reduction of urinary sodium excretion in the second week, but did not affect renal function at any other time during the experimental period. Both KT3-671 at 10 mg/kg and enalapril at 10 mg/kg produced a significant increase in PRC and showed a tendency to decrease PAC. Repeated administration of KT3-671 reduced the severity of the pathological changes in the kidney. These results suggest that KT3-671 is a potentially useful antihypertensive drug.

Aldosterone↗