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Biomedical subjects

K Fujii

Publications and source records attributed to K Fujii.

At least 361 records · Page 20Linked to original sources

Age-related changes in response of brain stem vessels to opening of ATP-sensitive potassium channels.

BACKGROUND AND PURPOSE: This study was designed to determine regional differences and age-related changes in the contribution of ATP-sensitive potassium (KATP) channels to vasodilator responses in the brain stem circulation in vivo. METHODS: Changes in diameter of the basilar artery (baseline diameter, 270 +/- 5 microns [mean +/- SEM]), its large branch (112 +/- 5 microns), and its small branch (49 +/- 2 microns) in response to KATP channel openers levcromakalim and Y-26763 were measured through a cranial window in anesthetized adult (4 to 6 months) and aged (24 to 26 months) Sprague-Dawley rats. RESULTS: Topical application of levcromakalim and Y-26763 produced concentration-dependent vasodilation that was similar among the three vessel groups in adult rats. In aged rats, dilator responses of the branches, but not of the basilar artery, to the KATP channel openers were smaller than those in adult rats (P < .05). Glibenclamide, a selective KATP channel blocker, almost abolished this vasodilation in both groups of rats. Vasodilator responses to sodium nitroprusside were preserved in aged rats. CONCLUSIONS: In adult rats, there is no regional heterogeneity in vasodilator response to KATP channel openers in the brain stem circulation in vivo. In aged rats, although KATP channels are also functional in the brain stem circulation, dilator response of the microvessels but not of the large arteries to direct activation of KATP channels is impaired.

Aging↗

Bronchial hyperreactivity in patients with familial amyloidotic polyneuropathy and autonomic neuropathy.

To investigate the role of autonomic regulation on airway reactivity, we performed bronchial inhalation tests of methacholine (MCh) and histamine (Hist) in Japanese patients with familial amyloidotic polyneuropathy (FAP) and autonomic neuropathy. First we examined the FEV1 and Raw in seven patients with FAP and in six normal subjects, then we administered aerosols of increasing concentrations of MCh (0.075 to 25 mg/ml) at about 5-min intervals via a nebulizer controlled by a dosimeter. We measured the FEV1 until either the concentration of MCh producing a 20% reduction from the basal value (PD20) or the maximal concentration was reached. Five of the seven patients with FAP showed bronchial hyperreactivity to MCh, and PD20 to MCh was significantly lower than that of the normal subjects (p < 0.01). Furthermore the PD20 tended to correlate inversely with the severity of autonomic neuropathy (p = 0.052). The bronchial hyperreactivity to MCh was completely blocked by pretreatment inhalation of ipratropium bromide, suggesting the muscarinic receptor-mediated mechanism. Of these five patients with hyperreactivity to MCh, three with low PD20 to MCh (< 50 units) did not respond to Hist, but two with high PD20 (> 50 units) to MCh did, suggesting different mechanisms of hyperreactivity to MCh and Hist in FAP. The PD20 to Hist significantly correlated inversely to the PD20 to MCh (p < 0.05). Histochemical examination revealed marked amyloid deposition in the vagus nerves and tracheal wall in an autopsied patient with FAP and severe autonomic symptoms. These data suggest that patients with FAP and advanced autonomic neuropathy have bronchial hyperreactivity to MCh and/or Hist, probably because of denervation supersensitivity resulting from amyloid deposition in the peripheral autonomic nerves of the airways.

Adult↗

High ratios of free to total insulin-like growth factor-I in early infancy.

Insulin-like growth factor-I (IGF-I) is a major effector of somatic growth and metabolism. In normal, nonpregnant plasma, most of the IGF-I is complexed to specific IGF-binding proteins (IGFBPs), particularly IGFBP-3; only a minor fraction of plasma IGF-I exists in a free form. Recently, we have reported that free IGF-I levels, as measured using a new immunoradiometric assay, are relatively high in maternal plasma during pregnancy because of increased IGFBP-3 proteolytic activity. These high free IGF-I levels are physiologically important for the growth of maternal tissues such as uterus and placenta, which are related to the fetal growth. Growth during early infancy may be a continuation of fetal growth. In the present study, we have analyzed free and total plasma IGF-I and IGFBP-3 proteolytic activity in early infancy. Although the levels of free and total IGF-I were not significantly different in early infancy as compared with prepubertal periods, the ratio of free to total IGF-I (mean = 2.04%) was relatively increased and was similar to the ratio in pregnancy plasma (1.86%). However, unlike in maternal plasma, the high ratios were not totally caused by increased IGFBP-3 proteolytic activity. Our results suggest that there may be an increased conversion of plasma IGF-I to a free form in early infancy. The resultant increase in IGF-I bioavailability could contribute to the rapid somatic growth in early infancy.

Adult↗

Ultrasonographic assessment of regional differences in atherosclerotic lesions in patients with hypertension, diabetes mellitus, or both.

We evaluated risk factors involved in regional differences in atherosclerotic lesions in patients with hypertension, diabetes mellitus, or both. Using ultrasonography, we examined the brachial, common carotid, and common femoral arteries in 65 hospitalized Japanese patients (15 controls, 18 patients with hypertension, 16 with diabetes mellitus, and 16 with both hypertension and diabetes mellitus). They ranged in age from 39 to 81 yr, mean 60.3 yr. The thickness of the intima-media complex of the far wall was measured, and the severity of atherosclerotic plaques was graded according to maximal lumen stenosis. The intima-media thickness in the carotid and femoral arteries was significantly greater in the hypertensive patients and the hypertensive patients with diabetes than in the controls. Severity of plaque was greater in the hypertensive patients with diabetes than in the controls. Plaque grades were higher in the carotid and femoral arteries than in the brachial artery. Multiple regression analysis revealed that age and mean blood pressure were strongly associated with the intima-media thickness in all three arteries. In the femoral artery, cigarette smoking and hyperglycemia also significantly correlated with the intima-media thickness. Plaque grades increased with age in the carotid and brachial arteries, while in the femoral artery the grade increased with cigarette smoking and serum cholesterol concentration. These findings suggest that the extent of atherosclerosis and its underlying risk factors differ among arterial sites. In addition, risk factors may partly differ according to the stage of atherosclerosis. To prevent or reverse atherosclerosis, the above differences should be taken into account.

Adult↗

Idiopathic renal hematuria in a dog; the usefulness of a method of partial occlusion of the renal artery.

Exploratory laparotomy was performed on a dog suspected of having idiopathic renal hematuria. Two catheters were inserted into the bilateral ureters, and hematuria from the left kidney was confirmed. The blood flow was occluded in the ventral and dorsal rami of the left renal artery in order to localize the site of hemorrhage. As hematuria disappeared when the dorsal ramus was occluded, the site of renal hematuria was localized to the area dominated by the dorsal ramus of the renal artery. As a result of ligating the dorsal ramus of the left renal artery in this dog, renal hematuria subsided, and the dog has shown a favorable course, to date, one year after surgery.

Animals↗

A clinical evaluation of blood pressure through non-invasive measurement using the oscillometric procedure in conscious dogs.

The oscillometric procedure was used to measure the heart rate as well as the systolic, mean, and diastolic blood pressures of 152 dogs (102 in the control group, 13 in the group with renal disease, 37 in the group with heart disease) who were brought to Azabu University of Veterinary Teaching Hospital. It was demonstrated that the blood pressure and heart rate of the control group lowered and tended to become stable as the number of measurements increased. No appreciable difference was identified in the measurements of either blood pressure or heart rate in the forelimbs and tail head. With regard to gender, males showed a significantly higher value than females (p < 0.05). No interaction was identified between age and blood pressure. No difference was identified in the heart rate in all groups. In an investigation of blood pressure in all groups, the renal disease group showed significantly higher values (p < 0.05) than either the control or the heart disease group in all values of systolic, mean and diastolic pressures. These results indicated that dogs with renal disease can manifest hypertension.

Aging↗

Preventive effect of isoflurane on destruction of cytochrome P450 during reductive dehalogenation of carbon tetrachloride in guinea-pig liver microsomes.

Effects of isoflurane on cytochrome P450 loss during anaerobic dechlorination of carbon tetrachloride in guinea pig liver microsomes were examined. Under anaerobic conditions, chloroform was produced from carbon tetrachloride by the microsomes in the presence of NADPH, and production of chloroform was increased 1.80 times by the addition of isoflurane. The concentration of microsomal cytochrome P450 decreased to 71.6% after 7 minutes incubation with carbon tetrachloride and NADPH. With the addition of isoflurane in the same incubation system, the decrease in cytochrome P450 was to 84.9%. The essential components for the loss of cytochrome P450 during the dechlorination of carbon tetrachloride were microsomes, NADPH and carbon tetrachloride. Addition of carbon monoxide reduced the cytochrome P450 loss to negligible. These findings indicate that isoflurane interacts with cytochrome P450 to prevent the cytochrome P450 destruction during the anaerobic dechlorination of carbon tetrachloride in guinea-pig liver microsomes. These results also suggest that the destruction of cytochrome P450 during anaerobic dechlorination of carbon tetrachloride in microsomes was caused by direct attack by the trichloromethyl radical, rather than by carbon tetrachloride-induced lipid peroxidation.

Anesthetics, Inhalation↗

Enhanced electrical activity in mesenteric arteries from salt-loaded Dahl salt-sensitive rats: actions of prostaglandin H2 on membrane channels.

Salt loading increases blood pressure in Dahl salt-sensitive (Dahl S) rats. We have previously shown that the mesenteric artery of salt-loaded Dahl S rats exhibits enhanced electrical activity that is corrected by a cycloxygenase inhibitor, indomethacin. Prostaglandin H2 (PGH2) is a product of cycloxygenase that is known as an intrinsic vasoconstricting factor in spontaneously hypertensive rats. Our hypothesis is that tissue production of PGH2 would be involved in the enhanced electrical activity of arteries from salt-loaded Dahl S rats. In the present study, to clarify this possibility, we evaluated the actions of PGH2 on membrane channels in arterial cells from Dahl S rats. Membrane currents were recorded by whole-cell voltage clamp technique in single smooth muscle cells from the mesenteric artery. Application of PGH2 evoked an inward current that was mainly dependent on extracellular Na+ in the physiological extracellular solution. When high Ba2+ solution was used for the extracellular solution, PGH2 also evoked the inward current, suggesting that a divalent cation, such as Ba2+ or Ca2+, could permeate the PGH2-activated channels. In contrast, the L-type Ca2+ channel currents were not enhanced by the application of PGH2. The present results suggest that production of PGH2 contributes to the enhanced electrical activity by activating cation-permeable channels and depolarizing the membrane potential. PGH2 also directly stimulates the Ca2+ influx by activating Ca2+ permeable channels.

Animals↗

[A family of dentatorubral-pallidoluysian atrophy: clinical and neuroradiologic studies].

We described a family of dentatorubral-pallidoluysian atrophy (DRPLA). The mother presented with cerebellar ataxia at 35 years of age and thereafter her neurological symptoms became exacerbated. Her daughter had mental retardation during the preschool period and epilepsy at 10 years. Her son presented with epilepsy at 14 years. Their clinical phenotypes demonstrated maternal anticipation in this family. Genetical analysis of their DNA revealed CAG repeat expansion of the DRPLA gene, the number of which was 51 (mother), 65 (her daughter), and 53 (her son). MR imaging showed disappearance of T, shortening of the red nucleus in the mother and her daughter in contrast to the normal appearance in her son. MR imaging was effective in evaluating neuropathological changes in the DRPLA patients.

Adolescent↗

[Evaluation of 5-fluorouracil concentration in peripheral blood and side effects in continuous hepatic arterial infusion chemotherapy for patients with unresectable liver cancer].

Fourteen patients with unresectable primary or metastatic liver cancer were divided into two groups: group A, continuous hepatic arterial infusion of 5-FU in 10 cases; group V, continuous intravenous infusion of 5-FU in 4 cases. In group A, 5-FU (360 mg/m2/day x 5 days/week x 4 weeks) was continuously infused into the hepatic artery via femoral or gastroduodenal artery through Infuse A Port. In group V, 5-FU (360 mg/m2/day x 2 weeks) was continuously infused into the subclavian vein through IVH route. On day 1, the concentration of 5-FU in peripheral blood in group A (12.1 +/- 12.8 ng/ml) was significantly lower than in group V (43.8 +/- 19.8 ng/ml, p = 0.004). On day 5, it was also decreased in group A (24.6 +/- 24.1 ng/ml) compared with that in group V (61.8 +/- 34.4 ng/ml, p = 0.039). Side effects of 5-FU like nausea, abdominal discomfort and stomatitis were recognized in 4 out of 10 patients in group A (40%) and 3 out of 4 patients in group V (75%). In group A, a complete response was obtained in one patient with synchronous multiple liver metastases of sigmoid colon cancer. These results suggest that systemic toxicity of 5-FU is alleviated by continuous hepatic arterial infusion in the patients with unresectable liver cancer because of its low concentration in peripheral blood.

Abdominal Pain↗

Stimulatory effect of anesthetics on dechlorination of carbon tetrachloride in guinea-pig liver microsomes.

Effects of the anesthetics isoflurane, enflurane, halothane and sevoflurane on the dechlorination of carbon tetrachloride to produce chloroform were investigated using guinea pig liver microsomes. Under anaerobic conditions, chloroform is produced from carbon tetrachloride by the microsomes in the presence of NADPH, and chloroform production from 86 microM carbon tetrachloride was enhanced to 146%, 133%, 123% and 115% by the addition of isoflurane, enflurane, halothane and sevoflurane, respectively. The half-life of oxidized cytochrome P450 which remained during the reduction by the addition of NADPH was shortened to 51%, 54%, 60% and 80% by isoflurane, enflurane, halothane and sevoflurane, respectively, without alteration of NADPH-cytochrome c reductase activity. These anesthetics hastened the onset of the 445 nm absorption band formation which was shown by microsomes with carbon tetrachloride in the presence of NADPH under anaerobic conditions. These results indicate that the anesthetics isoflurane, enflurane, sevoflurane and halothane stimulate the reduction of cytochrome P450 results in the acceleration of the carbon tetrachloride dechlorination. These results may have implications for other type II drugs that are administered during anesthesia.

Anesthetics, Inhalation↗

Multiple early gastric carcinomas. Clinicopathologic features and histogenesis.

BACKGROUND: Multiple early gastric carcinomas were found in 5-15% of patients with early gastric carcinoma. The goals of this study were to clarify the clinicopathologic features of multiple early gastric carcinomas and to investigate their histogenesis. METHODS: Of 724 patients with early gastric carcinoma, there were 65 with multiple (159) gastric carcinomas. Investigation of the histogenesis of multiple gastric carcinomas was conducted using serial sections of the stomach of 33 patients with multiple early gastric carcinomas (MEGC) and 33 patients with solitary early gastric carcinoma (SEGC). The cancerous and epithelial dysplastic lesions were examined by hematoxylin and eosin staining and immunohistochemical staining of p53 protein with anti-p53 monoclonal antibody (BP53-12). RESULTS: The macroscopically depressed type was common. The flat type was observed only in accessory lesions, most of which were diagnosed postoperatively. There were 126 differentiated type lesions, and 33 poorly differentiated type lesions. In most cases both the main and accessory lesions were differentiated. The average number of epithelial dysplastic lesions (18.3) in the stomach of patients with differentiated MEGC was significantly higher than that in the stomach of patients with differentiated SEGC (7), poorly differentiated MEGC (2.1), and SEGC (2). Moreover, severe dysplastic lesions were frequently observed in the stomach of patients with differentiated MEGC. p53 protein expression was detected in 0.9% of mildly atypical epithelial dysplastic lesions, 3.7% of moderately atypical dysplastic lesions, and 18.2% of severely dysplastic lesions. CONCLUSIONS: In cases of early gastric carcinoma, small depressed type and flat type accessory lesions of multiple gastric carcinomas should be detected preoperatively. Epithelial dysplastic lesions probably are significant in the histogenesis of differentiated multiple gastric carcinomas.

Adenocarcinoma↗

Proton magnetic resonance spectroscopy of the basal ganglia in patients with schizophrenia: a preliminary report.

To examine metabolic changes in the left basal ganglia in chronic schizophrenia, we performed proton magnetic resonance spectroscopy (1H-MRS) in 21 medicated schizophrenic patients and 21 gender and age-matched normal controls. Compared to the normal subjects, the schizophrenic patients showed a significantly increased level of choline containing compounds (Cho) (t = 2.60, p < 0.05) and ratio of Cho to N-acetylaspartate (NAA) (t = 2.46, p < 0.05) in the left basal ganglia. No significant correlation was observed between the 1H-MRS measurements in the left basal ganglia and clinical symptom scores as evaluated using the Brief Psychiatric Rating Scale (BPRS). The chlorpromazine equivalent neuroleptic dosage was positively correlated with the level of NAA (r = 0.38, p < 0.05) and negatively correlated with the Cho/NAA ratio (r = -0.34, p < 0.05). These findings suggest that these changes in metabolites in the left basal ganglia may reflect some of the functional and morphological abnormalities reported previously for the brain in schizophrenia.

Adolescent↗

Alternation in the coronary blood flow velocity pattern in patients with no reflow and reperfused acute myocardial infarction.

BACKGROUND: Experimental and clinical evidence indicates that myocardial ischemia often damages the coronary microvasculature ("no-reflow" phenomenon). In this study, we examined the effect of this phenomenon on the coronary blood flow velocity pattern in patients with reperfused acute myocardial infarction. METHODS AND RESULTS: We measured coronary blood flow velocity after coronary angioplasty in 42 patients with acute myocardial infarction using a Doppler guidewire. Myocardial contrast echocardiography (MCE) was also performed before and after angioplasty. Thirty-one patients showed good contrast reperfusion (MCE reflow), whereas the other 11 showed no reflow (MCE no reflow). Peak velocity and duration of systolic coronary flow were significantly less in patients with MCE no reflow than in those with MCE reflow (8 +/- 4 versus 17 +/- 10 cm/s and 207 +/- 79 versus 289 +/- 55 ms, respectively; P < .01). Early systolic retrograde flow was frequently observed in patients with MCE no reflow, whereas it was observed in only 1 patient among those with MCE reflow (95% versus 3%; P < .001). Although peak diastolic flow velocity was similar between the two subsets, diastolic deceleration rate was significantly higher in patients with MCE no reflow than in those with MCE reflow (107 +/- 76 versus 56 +/- 31 cm/s2; P < .01). CONCLUSIONS: The coronary flow velocity pattern in patients with the no-reflow phenomenon was characterized by the appearance of systolic retrograde flow, diminished systolic antegrade flow, and rapid deceleration of diastolic flow. Thus, the Doppler guidewire allows us to assess the presence of microvascular dysfunction in AMI.

Aged↗

Differential selectivity of M1 and M3 type muscarinic acetylcholine receptors in coupling with a G protein G01 alpha examined in Xenopus oocytes.

The coupling specificities between muscarinic acetylcholine receptors (porcine M1 and M3 subtypes) and a heterotrimeric GTP binding protein (bovine G01) were examined by analysing receptor-stimulated, phospholipase C (PLC)-mediated chloride current responses in Xenopus oocyte expression system. M1-stimulated responses were suppressed by G01 alpha, and this suppression was reversed by expressing exogenous G beta and G gamma, whereas M3-stimulated responses were enhanced by G01 alpha in the presence or absence of G beta and G gamma. G01 alpha itself, when activated directly by intracellular fluoride injection, efficiently activated PLC and stimulated chloride current responses. The results indicate that M1 receptor does not couple with G01, while M3 receptor activates G01 effectively.

Animals↗

Studies on factor XII in porcine plasma: purification and its conversion to activated form by porcine plasma kallikrein.

When porcine plasma was subjected to four steps of ion-exchange column chromatographies, factor XII (F. XII) was separated into two fractions, F. XII-1 and F.XII-2, and about 8.5 mg of F. XII-1 and 2.3 mg of F. XII-2 were obtained from 675 ml of the plasma. The purified proteins were found to give a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). The molecular masses of F. XII-1 and XII-2 were estimated to be about 84 kDa by SDS-PAGE, and consisted of a single polypeptide chain. However, F. XII-1 converted to active form after removing Polybrene, but F. XII-2 was not activated. Activation of F. XII-2 took place on incubation with porcine plasma kallikrein, and the activation rate was increased only in the presence of negatively charged surfaces, such as sulfatide. When the preparation was incubated with sulfatide, spontaneous activation was not observed on the condition that we used. Activation of porcine F. XII-2 by porcine plasma kallikrein was found to involve the cleavage of the peptide bond on the disulfide-bridged polypeptide chain, and further fragmentation of activated form was observed during prolonged incubation time.

Amino Acids↗

Differences in hypervariable region 1 quasispecies of hepatitis C virus between human serum and peripheral blood mononuclear cells.

The complexity of hypervariable region 1 (HVR1) quasispecies of hepatitis C virus (HCV) in serum and peripheral blood mononuclear cells (PBMCs) was assessed at several time points in 11 patients with chronic hepatitis C. Polymerase chain reaction and single-strand conformation polymorphism analysis revealed that four patients (36%) showed serial changes in the complexity of HVR1 quasispecies, which were identical in both serum and PBMCs; two patients (18%) showed both serial changes in quasispecies and differences in quasispecies between serum and PBMCs; and five patients (45%) showed neither serial changes in nor quasispecies differences between serum and PBMCs. These results demonstrate both the existence of different quasispecies between serum and PBMCs and the infection of PBMCs by HCV.

Adult↗