Biomedical subjects

Y Nakashima

Publications and source records attributed to Y Nakashima.

At least 217 records · Page 12Linked to original sources

PubMed1997

Neurohumoral and hemodynamic mechanisms of diuresis during atrioventricular nodal reentrant tachycardia.

Thirty-two consecutive patients with paroxysmal supraventricular tachycardias, with previously defined mechanisms of the tachycardias, were interviewed by noninvestigators about whether they experienced symptoms of diuresis during or at the termination of the tachycardias, to test the hypothesis that patients with AV nodal reentrant tachycardia would have a feeling of diuresis, polyuria, or both during or at the termination of the tachycardia. Twelve of the 13 patients with AV nodal reentrant tachycardia (92%), two of the 15 patients with AV reentrant tachycardia (13%), and one of the 4 patients with atrial flutter associated with 2:1 AV conduction (25%) felt diuresis during or at the termination of the tachycardias (AV nodal reentrant tachycardia vs other forms of tachycardia; P < 0.001). In 14 of the 32 patients, the right atrial pressure and plasma atrial natriuretic peptide (ANP) concentration were measured during both the tachycardias and sinus rhythm. The mean right atrial pressure during AV nodal reentrant tachycardia was significantly elevated compared to that during other forms of tachycardia (P < 0.01). The plasma ANP concentration during AV nodal reentrant tachycardia was also elevated significantly compared to that during other forms of tachycardias (P < 0.001). There were no significant differences in the cycle lengths of the tachycardias, age, left atrial dimensions, or the left ventricular ejection fraction between the AV nodal reentrant tachycardia and the other forms of tachycardia. We concluded that the feeling of diuresis during or at the termination of tachycardia was a more common symptom in patients with AV nodal reentrant tachycardia. The higher secretion of plasma ANP from the right atrium might be involved in the mechanism of this symptom.

Atrial Natriuretic Factor↗

PubMed1997

Effects of an angiotensin II antagonist on reperfusion arrhythmias in dogs.

Losartan, an angiotensin II receptor antagonist with no bradykinin potentiating property, provides the opportunity to study the consequences of blocking angiotensin II. The objective of this study was to evaluate the antiarrhythmic responses of reperfusion arrhythmia to losartan in dogs. The effects of losartan on ventricular tachyarrhythmias induced during occlusion and reperfusion of the left anterior descending coronary artery were investigated in 30 dogs. The animals were randomized to receive either losartan (n = 15) or saline (n = 15). The VF inducing threshold was measured before occlusion and after reperfusion. Losartan (50 micrograms/kg per min) or saline was intravenously administered 5 minutes before occlusion and continued throughout the entire study period. The incidence of ventricular tachyarrhythmias during reperfusion was lower in the losartan group than in the control group (4/15 vs 6/15). There was no significant change in VF inducing threshold between the period before occlusion and during reperfusion in the losartan group [10.9 +/- 5.7 vs 11.1 +/- 5.7 mA, P = NS), whereas there was a significant decrease in the control group (15.5 +/- 4.4 vs 7.7 +/- 3.9 mA, P < 0.01). Blockade of the angiotensin II receptor has beneficial effects on reperfusion arrhythmias.

Aldosterone↗

PubMed1997

Effects of nisoldipine on cytosolic calcium, platelet aggregation, and coagulation/fibrinolysis in patients with coronary artery disease.

The effect of nisoldipine, a dihydropyridine Ca2+ antagonist, on the platelet cytosolic Ca2+ concentration ([Ca2+]i), platelet aggregation, and various coagulation and fibrinolysis parameters was assessed in normotensive patients with coronary artery disease (CAD). Eleven patients with angiographically confirmed CAD (4 men, 7 women aged 67.3 +/- 5.4 years) were administered nisoldipine at 10 mg/day for two weeks. The [Ca2+]i was determined by use of fura2-loaded platelets, platelet aggregation was measured with an aggregometer, and coagulation/fibrinolysis parameters were measured by standard methods. Nisoldipine did not significantly affect blood pressure or heart rate. However, the [Ca2+]i decreased significantly (P<0.05) and platelet aggregation was also significantly inhibited. Plasma D-dimer levels decreased significantly (P<0.01). Thus, nisoldipine not only suppressed platelet activation but also affected the coagulation system, suggesting that it is not only a vasodilator and platelet inhibitor but also an antithrombotic agent.

6-Ketoprostaglandin F1 alpha↗

PubMed1997

Eosinophilic myocarditis complicated by acute myocardial infarction--a case report.

The authors report a patient with eosinophilic myocarditis who developed severe chest pain with marked elevation of the ST segment on the electrocardiogram, which led them to suspect the presence of acute myocardial infarction. Emergency coronary angiography showed numerous occlusions and stenoses at the distal right and left coronary arteries, especially affecting the latter, owing probably to thrombus. The angiographic findings in this case demonstrate the formation and obstruction of thrombus in the small coronary arteries in a patient in the acute necrotic stage of eosinophilic myocarditis, believed to be the first such case reported.

Adult↗

PubMed1997

Tissue distribution and subcellular localization of rabbit liver metalloendopeptidase.

We have previously isolated rabbit liver microsomal metalloendopeptidase (MEP) as a candidate for the processing enzyme of vitamin K-dependent plasma proteins. A cDNA coding for MEP has revealed that it is structurally related to metalloendopeptidase-24.15, which catalyzes the proteolytic processing of several bioactive peptides. In this study we examined the tissue distribution and subcellular localization of MEP by light and electron microscopic immunohistochemical methods, in addition to Northern blot analysis. Chicken polyclonal antibodies were raised by using synthetic peptides AG1 (Met31-Asn46) and AG3 (Asp537-Gly551) derived from the sequence of MEP. Both anti-AG1 and anti-AG3 antibodies reacted specifically with MEP, as judged by Western blotting and immunohistochemical methods. Both antibodies gave an identical staining distribution, which was localized on the luminal cell surfaces and in the cytoplasm of the following organs: liver, brain, lungs, kidneys, esophagus, stomach, duodenum, pancreas, placenta, epididymis, uterus, ovary, and oviduct. Northern blot analysis revealed that the expression of MEP mRNA is similar to its immunohistochemical distribution except in the heart. These results suggest that MEP may participate more closely in a degradation role in peptide metabolism in various tissues than in a processing role of the proprotein, like metalloendopeptidase-24.15.

Amino Acid Sequence↗

PubMed1997

Effectiveness of fructose-modified chitosan as a scaffold for hepatocyte attachment.

Free amino groups of chitosan, a substance which has previously been shown to be a good scaffold for hepatocyte attachment, were covalently modified with fructose. The modification significantly increased the number of cells that could be attached on the surface of chitosan gel. Rat hepatocytes cultivated on fructose-chitosan behaved similarly to those on unmodified chitosan, i.e., they retained the spherical shape they have in vivo, and released much less lactate dehydrogenase than cells attached on a collagen-coated surface. The modification with fructose did not alter the important characteristics of chitosan for hepatocyte culture: liver-specific functions such as urea synthesis and drug metabolism were stably maintained for 5 d in the hepatocytes cultured on fructose-chitosan. In sharp contrast, hepatocytes attached on a collagen-coated surface underwent a severe morphological change, from spherical to flat, and lost almost all their lidocaine-removal activity within 5d. A very thin fructose-chitosan layer was also applied onto the collagen-coated surfaces of polystyrene plates and a dextran microcarrier by crosslinking free amino groups in the chitosan and collagen with glutaraldehyde to fix the thin layer. Hepatocytes on the fructose-chitosan-coated surface retained their spherical shape, masking the cell-flattening effect of the collagen layer. Perfusion culture was then carried out using a hollow-fiber cartridge in which hepatocytes attached on fructose-chitosan-coated microcarriers were suspended in the extracapillary space: the liver-specific functions were stably maintained during 4d of the culture. A fructose-chitosan-coated surface thus appears to be a very promising scaffold for hepatocyte attachment which can be used in cellular biological studies of liver functions, especially in relation to cytochrome P450, as well as in bioartificial liver support systems.

Animals↗

PubMed1997

Application of glutaraldehyde-crosslinked chitosan as a scaffold for hepatocyte attachment.

The effectiveness of chitosan, a biocompatible polymer derived by the deacetylation of chitin, as a scaffold of hepatocyte attachment, was examined. Since chitosan gel was too fragile to use for cell culture, its free amino groups were crosslinked by glutaraldehyde to increase its strength. Rat hepatocytes seeded onto glutaraldehyde-crosslinked chitosan (GA-chitosan) gel could stably attach to the surface, retaining its spherical form, the same as in vivo, and then release a very small amount of lactate dehydrogenase during the 5 d culture period. By contrast, hepatocytes on a collagen-coated surface spread flat, and they released much more lactate dehydrogenase than those on the GA-chitosan gel. Hepatocytes on GA-chitosan also retained higher urea synthesis activity, a liver-specific function, than those on the collagen-coated surface. These results indicate that chitosan is a promising biopolymer as a scaffold of hepatocyte attachment, which can be applied to an effective bioartificial liver support system.

Animals↗

PubMed1997

Effects of ischemic preconditioning on ventricular arrhythmias during ischemia and reperfusion using a retrograde blood flow model in dogs.

We examined the effects of ischemic preconditioning on ventricular arrhythmias during ischemia and reperfusion from the electrophysiologic point of view by using the retrograde blood flow (RBF) model, which causes severe ischemia. A total of 51 anesthetized dogs were divided into 3 groups. Group 1 (10-min simple occlusion) consisted of 15 dogs; group 2 (10-min RBF) consisted of 20 dogs; and group 3 (10-min RBF with preconditioning) consisted of 16 dogs. Preconditioning consisted of 5 cycles of 2 min of ischemia (RBF) and 5 min of reperfusion. In the subepicardium, myocardial blood flow (MBF) in group 2 was significantly lower than in group 1 or group 3 [group 2 (4.7 +/- 2.3 ml/min per 100 g) vs group 1 (35.0 +/- 5.8) or group 3 (22.0 +/- 4.6); p < 0.01 and p < 0.05 respectively]. However, there were no differences in MBF in the subendocardium between the 3 groups. The incidence of conduction block in the subepicardium was significantly higher in group 2 than in group 1 or group 3 [group 2 (85%) vs group 1 (33%), p < 0.01; vs group 3 (38%), p < 0.01]. There were no differences in the incidence of conduction block in the subendocardium between the 3 groups. During 10-min ischemia, the incidences of ventricular fibrillation (VF) were 7% in group 1, 35% in group 2, and 6% in group 3 (group 2 vs group 1, p < 0.05; and group 2 vs group 3, p < 0.05). During 10-min reperfusion, the incidences of VF were 29% in group 1, 77% in group 2, and 33% in group 3 (group 2 vs group 1, p < 0.05; and group 2 vs group 3, p < 0.05). Ventricular arrhythmias were reduced during both 10-min ischemia and 10-min reperfusion as a result of the improvement in the conduction components by ischemic preconditioning which increased MBF in the subepicardium.

Animals↗

PubMed1997

Exercise-induced neurally mediated syncope.

We describe a 16-year-old female referred for evaluation of syncope associated with competitive long distance running. She had experienced 4 episodes of syncope during competitive long distance racing. The syncope associated with marked bradycardia and asystole was demonstrated by head-up tilt testing without isoproterenol infusion. Oral propranolol therapy failed to prevent the syncope. Oral disopyramide therapy, however, prevented the syncope induced by both head-up tilt testing and competitive long distance racing. Caution should be urged in evaluating athletes with syncope, especially in the pediatric age group, because the cause of the syncope may result from life-threatening disorders such as cardiomyopathy, long QT syndrome, or exercise-induced arrhythmias. The head-up tilt test is an important diagnostic tool for the evaluation of exercise-associated syncope.

Adolescent↗

PubMed1997

[Progression of renal disease in patients with reflux nephropathy. Follow-up study].

BACKGROUND: We previously estimated the turning point of reflux nephropathy irreversibly deteriorating to end stage renal disease, mainly based on findings in renal biopsy (Eur. Urol., 26: 153-159, 1994). In this study, we aim to evaluate clinical parameters which may be closely associated with progression of reflux nephropathy to end stage renal disease. SUBJECTS AND METHODS: Ninety five patients (84 children and 11 adults; 41 men and 54 women) with renal scar and/or reflux (>/ = grade 3), mean aged 9.4 +/- 9.1 years (3 months-53 years) were followed up for 3.7 years +/- 2.7 (6 months-18 years). Vesicoureteral reflux was bilateral in 64 and unilateral in 31; primary in 85 and secondary in 10 patients. Clinical parameters including body weight, height, blood pressure, 24 hour urinary protein excretion, serum creatinine, 99m Tc-DTPA GFR and 99 m Tc-DMSA uptake were monitored over time. All patients underwent antireflux surgery (with or without other reconstructive surgery) and open renal biopsy. Three patients progressing to end stage renal disease underwent subsequent biopsy. RESULTS: Over-5 year observation period, the prevalence of new scare formation and further extension in scar was significantly higher in the group of renal functional deterioration (35%) than in the group of stable renal function (6.0%). Over the same period DMSA uptake decreased significantly (< 0.05) in the group of scar b (Smellie's classification), suggesting most kidneys of scar b eventually resulting in atrophic kidney (scar c). Proteinuria more than 100 mg/day appeared to be a critical level for predicting irreversible deterioration in renal function. Glomerular hypertrophy was closely related to the increase in urinary protein excretion and serum creatinine, contrary to the decrease in DTPA-GFR. In addition, bilateral renal scar b, glomerular hypertrophy (> 2 SD), proteinuria (> 300 mg/day), low GFR (mean: 49 ml/min), and diastolic hypertension seemed to be implicated in the genesis of ESRD. CONCLUSION: Glomerular damage due to either reflux nephropathy or dysplasia may cause proteinuria. Proteinuria of 100 mg/day was significantly (p < 0.01) associated with 2 SD of glomerular hypertrophy on histology and clinical observation (suggesting hyperfiltration). Thereafter, a rapid increase in proteinuria followed by diastolic hypertension appears be significant for predicting ESRD.

Adult↗

PubMed1997

Polymerase chain reaction-based approaches for detection of allelic loss in the p53 tumor suppressor gene in colon neoplasms.

OBJECTIVES: Inactivation of the p53 tumor suppressor gene is considered to be a late event involved in the malignant transformation of colorectal adenoma to cancer. Thus, its detection is thought to provide useful information for the clinical management of colorectal neoplasms. We devised a rapid screening test for allelic loss of the p53 gene by non-radioisotopic single-strand conformation polymorphism analysis. METHODS: Biopsy materials from 119 colorectal tumors obtained at endoscopy were examined. Three intragenic polymorphic sites were amplified by polymerase chain reaction using DNA extracted from these materials, and amplified DNA fragments were subjected to non-radioisotopic single-strand conformation polymorphism. RESULTS: This method can detect a loss of heterozygosity (LOH) of the p53 locus from samples containing over 40% tumor derived DNA, and the combination of the three polymorphic markers encompassed 62.4% of Japanese patients as informative. In adenocarcinoma, an LOH was detected in 51.5% (17 of 33) of the samples and in 12.2% (4 of 33) of tubular and/or tubulovillous adenomas. The p53 gene was mutated only in samples carrying an LOH, that is 64.7% (11 of 17) of carcinomas and 25.0% (1 of 4) of adenomas, but there were no mutation in samples retaining both alleles. The presence of an LOH was statistically correlated both with p53 mutation and malignant histology (chi 2 test, p < 0.05). CONCLUSIONS: This method can detect LOH from biopsy material obtained at endoscopy. LOH in the p53 locus precedes mutation of the p53 gene, and its detection provides useful information of malignancy in colorectal tumors.

Adenocarcinoma↗

PubMed1996

Simvastatin increases plasma NO2- and NO3- levels in patients with hypercholesterolemia.

In this study, plasma NO2- and NO3- (NOx-) levels were studied after lowering cholesterol with simvastatin in 26 outpatients with hypercholesterolemia (male, 9; female, 17; mean age, 59 +/- 12 years; cholesterol level > 220 mg/dl). Simvastatin (5 mg) was orally administered once daily, and blood samples were collected before, and after 4 and 12 weeks of treatment. Total, very-low-density lipoprotein (VLDL), and low-density lipoprotein (LDL) cholesterol were lowered (total, 254 +/- 44 mg/dl to 209 +/- 34 mg/dl; VLDL, 48 mg/dl [5-126 mg/dl] to 34 mg/dl [10-67 mg/dl]; LDL, 171 +/- 41 mg/dl to 133 +/- 37 mg/dl), but high-density lipoprotein (HDL) cholesterol was elevated (33 +/- 9.5 mg/dl to 39 +/- 11 mg/dl) at 12 weeks after starting simvastatin. Although the effects of simvastatin on the lipid levels nearly reached their maximum levels at 4 weeks, NOx- was elevated in a linear fashion with simvastatin (before; 8 +/- 17 mumol/l, at 12 weeks; 57 +/- 32 mumol/l). The % changes in the NOx- correlated directly with those in HDL-cholesterol at 12 weeks (P < 0.002) but not with other lipoprotein cholesterol fractions. These results suggest that simvastatin lowers cholesterol levels and elevates HDL while increasing the plasma NOx- levels.

Administration, Oral↗

PubMed1996

Detection of respiratory frequency in the recordings of electrocardiogram, blood pressure or sympathetic nerve activity in the conscious rat.

We extracted the respiratory frequency in conscious rats from variations of blood pressure, electrocardiogram, or renal sympathetic nerve activity by means of a band-pass filter. The frequency derived from any one of these parameters corresponded to directly recorded respiratory chest movements. The method may be useful when respiration and cardiovascular parameters have to be recorded in small animals during steady state when minimal surgical intervention is crucial.

Action Potentials↗

PubMed1996

Three-dimensional structure of a DNA repair enzyme, 3-methyladenine DNA glycosylase II, from Escherichia coli.

The three-dimensional structure of Escherichia coli 3-methyladenine DNA glycosylase II, which removes numerous alkylated bases from DNA, was solved at 2.3 A resolution. The enzyme consists of three domains: one alpha + beta fold domain with a similarity to one-half of the eukaryotic TATA box-binding protein, and two all alpha-helical domains similar to those of Escherichia coli endonuclease III with combined N-glycosylase/abasic lyase activity. Mutagenesis and model-building studies suggest that the active site is located in a cleft between the two helical domains and that the enzyme flips the target base out of the DNA duplex into the active-site cleft. The structure of the active site implies broad substrate specificity and simple N-glycosylase activity.

Amino Acid Sequence↗

PubMed1996

Sensitive detection of loss of heterozygosity in the TP53 gene in pancreatic adenocarcinoma by fluorescence-based single-strand conformation polymorphism analysis using blunt-end DNA fragments.

We have developed a fluorescence-based single-strand conformation polymorphism analysis to detect Haelil-sensitive polymorphic sites in intron 1 of the TP53 gene. It is important to treat the PCR products with Klenow fragment to remove a 3'-protruding nucleotide from the amplified DNA fragments added during the reaction in order to obtain a single peak for each allele. A comparison of the signal profiles of two alleles with those of normal heterozygotes by data processing using computer software has enabled sensitive detection of loss of heterozygosity (LOH) from clinical materials with a fraction of tumor cells below 10%. In analysis of 14 pancreatic carcinomas in which the proportion of the tumor cells is usually low due to the abundance of the stromal component, 7 samples (50%) were informative and 5 of the 7 (71.4 %) were positive for LOH at the TP53 locus. This approach would be useful for allelotyping tumors with low cellularity, as well as other clinical samples such as biopsied specimens and paraffin embedded tissues.

Adenocarcinoma↗

PubMed1996

[11C]beta-CIT-FE, a radioligand for quantitation of the dopamine transporter in the living brain using positron emission tomography.

The cocaine analogue beta-CIT-FE (N-(2-fluoroethyl)-2 beta-carbomethoxy-3 beta-(4-iodophenyl)nortropane) was labeled with 11C for positron emission tomography (PET) studies of the dopamine transporter. After intravenous administration to a cynomolgus monkey, [11C]beta-CIT-FE accumulated in the striatum with a striatum-to-cerebellum ratio of about 9 after 60 min. Pseudoequilibrium of specific [11C]beta-CIT-FE binding in the striatum was obtained within 30-50 min. The radioactivity ratios of the thalamus to the cerebellum and the neocortex to the cerebellum were about 2 and 1.5, respectively. In displacement and pretreatment experiments, radioactivity in the striatum but not in the cerebellum was reduced after injection of beta-CIT or the dopamine transporter inhibitor GBR 12909, indicating that striatal radioactivity following injection of [11C]beta-CIT-FE represents reversible binding to dopamine transporter sites. After displacement or pretreatment with cocaine there was a marked effect not only in the striatum but also in the thalamus and neocortex. [11C]beta-CIT-FE has potential as a useful PET radioligand for quantitation of the dopamine transporter in the primate brain in vivo.

Animals↗

PubMed1996

Effects of some calcium-related agents on the protoplast transfection of Lactobacillus casei with phage PL-1 DNA.

To clarify the mechanism of Ca2+ involvement in the DNA transfer through cell membrane, we studied the effects of Ca2+-chelator, Ca2+-ionophore, and Ca2+-channel blocker on the protoplast transfection of Lactobacillus casei ATCC 27092 by PL-1 phage DNA in the presence of Ca2+. Ca2+-chelators, citrate, EDTA, and dipicolinic acid, inhibited the transfection probably by compensating the effect of Ca2+. Ca2+-ionophores, A23187 and N,N,N', N'-tetracyclohexyl-3-oxapentanediamide, which were expected to accelerate transfection by introducing Ca2+ into cells, inhibited the transfection. This fact indicated the absence of correlation between the entry of Ca2+ and the transport of DNA into protoplasts. Verapamil, which blocks voltage-dependent Ca2+-channel besides beta-adrenergic receptor, inhibited the transfection with little effect on the survival of the protoplasts. Both flunarizine and vinpocetine, voltage-dependent Ca2+-channel blockers, did not show the selective toxicity. D-alpha-Aminoadipic acid, a glutamate receptor-operated Ca2+-channel blocker, had no effect. Propranolol, which blocks beta-adrenergic receptor as does verapamil, inhibited the transfection without severely damaging the protoplasts. These results suggested that a kind of receptor-operated Ca2+-channel was involved in the transport of PL-1 phage DNA into the cells and that the cell membrane might have a receptor structure somewhat similar to the beta-adrenergic receptor found in mammalian cells.

Adrenergic Antagonists↗

PubMed1996

Quantitative analysis of ferrochelatase mRNA in blood cells of erythropoietic protoporphyria patients.

Ferrochelatase (FC; heme synthetase, EC 4.99.1.1.) catalyses the synthesis of heme from protoporphyrin IX, the final step in the heme synthetic pathway. The hereditary deficiency of this enzyme gives rise to erythropoietic protoporphyria (EPP). We developed a rapid, non-radioactive means of measuring human FC mRNA levels in the EPP patients. It is based on the reverse transcriptase-polymerase chain reaction (RT-PCR) performed on the RNA obtained from peripheral blood. The amplified DNA was detected by agarose gel electrophoresis with ethidium bromide staining and the fluorescent intensity was measured by scanning densitometry applied directly to Polaroid 665 negative film. The relative expression level of FC mRNA, compared with that of glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA, was estimated at several points in the exponential phase of PCR cycles or at a point in the exponential phase of PCR performed on serially diluted the cDNA samples. The estimate of the FC mRNA by this method correlated well with the level of the FC mRNA measured by Northern blotting in the EB virus-transformed lymphocytes of the same patients. The level of the FC mRNA appeared to vary among the patients in whom a decreased level of enzymatic activity was indicated.

Adolescent↗