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Biomedical subjects

E Tanaka

Publications and source records attributed to E Tanaka.

At least 307 records · Page 17Linked to original sources

[Oscillatory changes in the intracellular Ca2+ concentration in cardiac muscles].

Contraction of cardiac muscle is regulated by intracellular Ca2+ concentration ([Ca2+]i) change. The Ca2+ increased by the action potential is removed by Ca2+ removal mechanisms (sarcoplasmic reticulum, Na-Ca exchanger and Ca pump of the surface membrane) and is also bound to troponin. However, under some specific conditions which induced an overload of Ca2+, oscillatory changes in [Ca2+]i, which are considered to be due to regenerative Ca2+ release from the sarcoplasmic reticulum, appear. In Ca2+ overload, a transient increase in [Ca2+]i is observed after the falling phase of the Ca2+ transient which is induced by electrical stimulation. In accordance with the transient increase in [Ca2+¿i, the membrane transiently depolarizes (delayed after-depolarization). This membrane depolarization is considered to be due to the inward currents through the Na-Ca exchanger and non-specific cation channels. If the depolarization is large enough to reach the threshold, the action potentials are triggered (triggered activity). Thus, an increase in [Ca2+]i is one of possible factors in triggering of arrhythmia.

Action Potentials↗

Serum thrombopoietin (c-Mpl ligand) levels in patients with liver cirrhosis.

To clarify the role of c-Mpl ligand (thrombopoietin: TPO) in liver cirrhosis (LC), we examined serum TPO levels (sTPO) in patients with LC (N = 44), chronic hepatitis (CH; N = 13) and healthy controls (N = 41) by an enzyme-linked immunosorbent assay. Although platelet counts of all LC patients (89 +/- 59 x 10(9)/l; mean +/- SD) were lower than those of controls and CH patients, sTPO levels in LC patients (1.23 +/- 0.51 fmol/ml) were the same as those in controls (1.22 +/- 0.37) and CH patients (1.18 +/- 0.36). Platelet counts were significantly higher in splenectomized patients than in unsplenectomized patients, but the sTPO level did not differ between these two groups. In LC patients, the sTPO level was not correlated with the platelet count, but was correlated with prothrombin time, activated partial thromboplastin time, and total bilirubin, indicating that production of TPO in the liver decreases slightly with the development of liver dysfunction. Our findings suggest that production of TPO is maintained in LC patients and their thrombocytopenia is not due to a defect in platelet production.

Case-Control Studies↗

[Coagulation and fibrinolytic parameters as predictors for small-vessel disease revealed by magnetic resonance imaging of the brain].

We correlated coagulation and fibrinolytic parameters with small-vessel disease revealed by magnetic resonance imaging (MRI) of the brain. One hundred and eleven patients with asymptomatic or symptomatic cerebral infarction were randomly selected for the study; 57 males and 54 females with an average age of 66.6 +/- 9.6, age range 40 to 85, years old. Among them, 76 patients had a history of symptomatic cerebral infarction; 38 patients hypertension; and 24 patients diabetes mellitus. Patients with large cortical infarction, cerebral hemorrhage, demyelinating disease or mass lesions were excluded from the present study. The MRI scans were reviewed for areas with increased signal intensity on T2-weighted images. The small infarction was defined as a lesion less than 10mm in diameter. The activity of von Willebrand factor (vWF) correlated significantly with the grade of caps at the anterior and posterior horns of the lateral ventricle, and the number of small infarctions in the subcortical white matter and basal ganglia, suggesting vWF could be a predictor for these small-vessel disease. The grade of caps at posterior horn of the lateral ventricle and the number of small infarctions in the subcortical white matter were associated significantly with the concentration of plasma fibrinogen and reversely with the activity of antithrombin III, an inhibitory factor in coagulation system. These results indicate that hypercoagulable state may causatively relate with small-vessel disease in the territory of medullary artery branching from cortical artery. On the contrary, these coagulation parameters did not correlate significantly with small ischemic lesions in the territory of perforating artery. No correlation was observed between the level of marker proteins for platelet activation and the degree of small-vessel disease, indicating the activation of platelet could not associate with the etiology of small-vessel disease.

Adult↗

Investigation of normal bacterial flora in the upper respiratory tract.

To study the bacterial flora in the upper respiratory tract we examined bacteria obtained from the larynx, posterior pharyngeal wall, palatine tonsil and nasal cavity to identify the constitutent strains and check for the existence of beta-lactamase in 37 subjects without infectious otolaryngological disease who underwent surgery with general anesthesia. A tendency toward a decrease with aging in aerobes and an increase in anaerobes was observed. The influence of fibronectin was considered to be one of the reasons for this tendency. beta-lactamase production strains showed a tendency to increase in the age group from 20-49 years and decrease in subjects 50 years and older. The number of constitutent strains in the nasal cavity was less than that in the pharynx, which was considered the result of the mucociliary function as a biophylactic function. Comparing the constitutent strain types in the larynx with those in other areas, the posterior pharyngeal wall showed the highest coincident rate of 70%, Notably, the coincident rate was more than 80% among aerobes. This suggests that causative bacteria can be estimated from pharyngeal culture.

Adolescent↗

Simultaneous determination of plasma phenytoin and its primary hydroxylated metabolites in carbon tetrachloride-intoxicated rats by high-performance liquid chromatography.

We have developed a simple and sensitive method for the simultaneous determination of phenytoin (PHT), 5-(p-hydroxyphenyl)-5-phenylhydantoin (p-HPPH) and 5-(m-hydroxyphenyl)-5-phenylhydantoin (m-HPPH) in rat plasma by high-performance liquid chromatography. The three substances were separated on a reversed-phase column (5 microns TSK gel ODS-80TM, 250 mm x 4.6 mm I.D.) using acetonitrile-0.008 M NaH2PO4 (pH 6) (35:65, v/v) as a mobile phase at a flow-rate of 0.8 ml/min. Absorbance was monitored at 215 nm. The quantification limit was 50 ng/ml for each of PHT, m-HPPH and p-HPPH. The mean recoveries for DPH, m-HPPH and p-HPPH from plasma were 95.6 +/- 3.6, 94.5 +/- 4.2 and 98.6 +/- 2.9%, respectively.

Animals↗

Usefulness of simple assays for serum concentration of hepatitis C virus RNA and HCV genotype in predicting the response of patients with chronic hepatitis C to interferon alpha 2a therapy.

The use of two new assays was evaluated for predicting the response to interferon (IFN) therapy in patients with chronic hepatitis C. The genotype of hepatitis C virus (HCV) was established by an enzyme-linked immunosorbent assay based on genotype-specific recombinant peptides of the NS4 region (genotyping ELISA). The concentration of HCV RNA was measured by a branched DNA assay (bDNA assay). Seventy-eight patients received the same regimen of IFN alpha 2a. Of the 74 patients assessed who completed the program, 38 (51.4%) were responders; i.e., their serum aminotransferase levels remained normal for 6 months or longer after stopping IFN, while 36 (48.6%) were nonresponders. The results of the HCV genotype determined by the genotyping ELISA and by the polymerase chain reaction (PCR) assay based on genotype-specific primers were similar. The serum concentrations of HCV RNA as measured by the bDNA assay and by the competitive PCR assay correlated closely and significantly (r = 0.82, P < 0.001). Multiple logistic regression analysis showed that the serum concentration of HCV RNA determined by the bDNA assay, the HCV genotype determined by the genotyping ELISA, and the histology activity index (HAI) of the liver were independently associated with IFN efficacy. By using these three variables in combination, a predictive rate of 82.4% was obtained. A lower level of HCV RNA, genotype 2 and a lower HAI score for liver histology were predictive of a favorable response to IFN. Thus, the genotyping ELSIA and the bDNA assay appear to be useful for clinical management of patients receiving IFN therapy.

Adult↗

Clinical significance of the trimethadione tolerance test in chronic hepatitis: a useful indicator of hepatic drug metabolizing capacity.

Trimethadione (TMO) was chosen as an indicator of quantitative hepatic microsomal function, and its pharmacokinetics were studied in 52 patients with chronic hepatitis. Findings in these patients were compared with those for 26 healthy subjects and 13 patients with renal failure. Patients with chronic hepatitis, but not those with renal failure, showed significant reduction in clearance (CL) and prolongation of half-life (t1/2), and the extent of abnormalities was found to reflect the severity of histologic changes in liver tissue. The serum dimethadione (DMO)/TMO ratio 4 h after the administration of TMO altered in parallel with the CL and t1/2 of TMO, and abnormalities in this simple ratio were also related to the histologic severity of changes in the liver tissue. A low DMO/TMO ratio (< 0.4) was associated with advanced histologic changes (chronic active hepatitis with bridging or chronic active hepatitis with cirrhosis), whereas a high DMO/TMO ratio (> 0.4) was associated with mild histologic changes (chronic persistent hepatitis or chronic active hepatitis) (sensitivity, 0.81; specificity, 0.86). These results indicate that the DMO/TMO ratio, which can be obtained from a single blood sampling, reflects the histologic severity of changes in tissue liver, and that the TMO tolerance test is a useful indicator of quantitative liver function.

Chronic Disease↗

New design of N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) lung imaging in the patient with lung cancer.

N-isopropyl-p-[123I]iodoamphetamine (123I-IMP) was injected intravenously into primary non small cell lung carcinoma patients (n = 17). The average pixel count ratios of the cancerous area to the whole lung was measured in the initial and delayed images. In the initial image, this ratio was less than 1.0 for the entire group of patients, and was thought to reflect decreased blood flow in the cancerous tissues. The rate of counts within a ROI in the delayed image to counts in the same ROI in the initial image was also calculated and called the remain rate. The remain rate (delayed count/initial count) was significantly higher in the cancerous area than in the whole lung (0.65 +/- 0.30, median 0.62, 0.38 +/- 0.05, median 0.38, p < 0.01). This observation was thought to be due to a relative decrease in the blood flow and the accumulation of IMP, which forms pools within the alveolar spaces of the cancerous areas. The image prepared with the remain rate revealed a hot image in the cancerous regions, even when this was not apparent in the delayed image. The remain rate image may therefore be useful in the identification of cancerous areas in lung tissue if it is used in comparison with the initial image.

Adult↗

Simple fluorescent enzyme immunoassay for detection and quantification of hepatitis C viremia.

The viral load of hepatitis C virus, as reflected by hepatitis C virus viremia, has been shown to have important clinical implications. In this study the hepatitis C virus core protein level in serum was evaluated for the detection and quantification of hepatitis C virus viremia. Hepatitis C virus core protein in serum was detected using a simple and sensitive fluorescent enzyme immunoassay. Hepatitis C virus core protein was quantitated in 100 healthy subjects, 258 patients with hepatitis C virus infection and 108 patients with non-hepatitis-C-virus-related chronic liver diseases. HCV-RNA was determined using the branched DNA (bDNA) assay and reverse-transcription polymerase chain reaction. The detection limit of this fluorescent enzyme immunoassay was found between 10(4) - 10(5) copies/ml HCV-RNA equivalent. There was a good correlation between the core protein and bDNA assay results (p <0.01). Hepatitis C virus core protein was detected in 81% of patients with hepatitis C virus infection (acute hepatitis 4/5, chronic hepatitis 85/104, cirrhosis 64/73 and hepatocellular carcinoma 56/76) but in none of the healthy subjects and patients with non-hepatitis C virus chronic liver diseases. The amount of hepatitis C virus core protein in patients with hepatitis-C-virus-related hepatocellular carcinoma was lower compared to chronic hepatitis and cirrhosis (p <0.05). All 26 patients treated with interferon-alpha showed parallel changes between HCV-RNA and core protein levels. This fluorescent enzyme immunoassay is simple and quick (assay time <3 h) with sensitivity at least matching the bDNA assay. Similar levels of hepatitis C virus core protein were detected in patients with chronic hepatitis and cirrhosis, but patients with hepatocellular carcinoma tended to have a lower level of hepatitis C virus core protein.

DNA, Viral↗

The role of microtubules in growth cone turning at substrate boundaries.

To understand the role of microtubules in growth cone turning, we observed fluorescently labeled microtubules in neurons as they encountered a substrate boundary. Neurons growing on a laminin-rich substrate avoided growing onto collagen type IV. Turning growth cones assumed heterogeneous morphologies and behaviors that depended primarily in their extent of adhesion to the substrate. We grouped these behaviors into three categories-sidestepping, motility, and growth-mediated reorientation. In sidestepping and motility-mediated reorientation, the growth cone and parts of the axon were not well attached to the substrate so the acquisition of an adherent lamella caused the entire growth cone to move away from the border and consequently reoriented the axon. In these cases, since the motility of the growth cone dominates its reorientation, the microtubules were passive, and reorientation occurred without significant axon growth. In growth-mediated reorientation, the growth cone and axon were attached to the substrate. In this case, microtubules reoriented within the growth cone to stabilize a lamella. Bundling of the reoriented microtubules was followed by growth cone collapse to form new axon, and further, polarized lamellipodial extension. These observations indicate that when the growth cone remains adherent to the substrate during turning, the reorientation and bundling of microtubules is an important, early step in growth cone turning.

Animals↗

The role of microtubule dynamics in growth cone motility and axonal growth.

The growth cone contains dynamic and relatively stable microtubule populations, whose function in motility and axonal growth is uncharacterized. We have used vinblastine at low doses to inhibit microtubule dynamics without appreciable depolymerization to probe the role of these dynamics in growth cone behavior. At doses of vinblastine that interfere only with dynamics, the forward and persistent movement of the growth cone is inhibited and the growth cone wanders without appreciable forward translocation; it quickly resumes forward growth after the vinblastine is washed out. Direct visualization of fluorescently tagged microtubules in these neurons shows that in the absence of dynamic microtubules, the remaining mass of polymer does not invade the peripheral lamella and does not undergo the usual cycle of bundling and splaying and the growth cone stops forward movement. These experiments argue for a role for dynamic microtubules in allowing microtubule rearrangements in the growth cone. These rearrangements seem to be necessary for microtubule bundling, the subsequent coalescence of the cortex around the bundle to form new axon, and forward translocation of the growth cone.

Animals↗

Function of RNH-1/14-3-3 beta gene in cellular differentiation and proliferation.

It has recently been reported that the members of 14-3-3 protein family participate in cell cycle control and associate with Raf, Bcr, Bcr-Abl, and polyomavirus middle tumor antigen (MT) as modulators of signal transduction. During cDNA cloning for the 17-kDa neuronal differentiation factor (K2 factor) secreted from rat hepatoma Kagura-2 (K2) cells from a K2 cDNA library using rat prepronerve growth factor (prepro NGF) cDNA as a probe, we obtained RNH-1 (rat NGF homologue) clone, which was identified as 14-3-3 beta cDNA, but not K2 factor, although no significant homology is present between 14-3-3 beta and prepro NGF cDNAs. RNH-1/14-3-3 beta gene was markedly expressed as a 2.9-kb mRNA in K2 cells and in newborn rat brain tissue. In PC12 cells the expression of this gene was down-regulated during the neuronal differentiation primed by NGF. The enforced expression of RNH-1/14-3-3 beta in PC12 and K2 cells conferred on them a higher sensitivity to NGF for neuronal differentiation and an intense growth ability in low serum medium, respectively. These results provide additional evidence that RNH-1/14-3-3 beta protein participates in cellular differentiation, proliferation and transformation through the signal transduction pathways of various growth factors.

14-3-3 Proteins↗

Modulation of adrenergic coronary vasoconstriction via ATP-sensitive potassium channel.

We examined humoral and/or locally produced vasoactive factors involved in modulating sympathetic coronary vasoconstriction via the ATP-sensitive K (KATP) channel in 42 anesthetized dogs. Glibenclamide (30 micrograms.kg-1.min-1 ic or 0.6 mg.kg-1.min-1 left atrial injection) augmented coronary vascular resistance (CVR) at baseline and during cardiac sympathetic nerve stimulation (2-20 Hz), with a greater increase seen in the subepicardial region than in the subendocardial region both during beta-adrenergic receptor blockade and alpha- and beta-receptor blockade [P < 0.05 and P < 0.05 (n = 6 and 18 dogs), analysis of variance]. In contrast, pinacidil (10 micrograms.kg-1.min-1; n = 8 dogs) suppressed CVR. Glibenclamide enhanced CVR response to locally administered norepinephrine of 0.001-0.1 microgram.kg-1.min-1 (P < 0.05, analysis of covariance; n = 5 dogs) but did not enhance norepinephrine or neuropeptide Y overflow (n = 18 dogs). CVR was not modified by calcitonin gene-related peptide (CGRP) antagonist [CGRP-(8-37)], 8-phenyltheophylline, or N omega-nitro-L-arginine (n = 11 dogs). Thus sympathetic coronary vasoconstriction is modified by coronary vascular KATP channels with a transmural difference. However, CGRP, adenosine, and endothelial nitric oxide production are not involved in the modulation.

Adenosine↗

Flow cytometric nuclear DNA content analysis of renal tumors in children: prognostic significance of nuclear DNA ploidy.

We studied, by flow cytometry, the DNA contents of paraffin-embedded tumor specimens from 90 infants and children with kidney tumors, and analyzed the relationship of DNA ploidy with histological types and prognosis. Data of adequate quality were obtained from 90 cases: 65 tumors with favorable histology, 5 congenital mesoblastic nephromas and 20 tumors with unfavorable histology. The 90 cases had nuclear DNA histogram patterns that were classified as DNA diploid in 64 tumors, aneuploid in 19 and tetraploid in 7. There were no significant correlations between DNA ploidy and histological types or clinical stages. Survival rates for patients with diploidy were 80 and 70% at 2 and 5 years, respectively, and those of patients with aneuploidy were 72 and 61% at 2 and 5 years, respectively. On the other hand, patients with a DNA tetraploid pattern had significantly worse survival rates of 43 and 29% at 2 and 5 years, respectively. Among patients with aneuploidy or tetraploidy, the S-phase fractions in those who died (mean +/- SD: 10.3 +/- 4.1 and 22.1 +/- 11.6%, respectively) appear to be greater than those in their surviving counterparts (8.8 +/- 4.0 and 12.1 +/- 2.8%). Hence, although the differences between diploid and aneuploid DNA patterns were not correlated with differential prognosis in children with kidney tumors, a tetraploid pattern clearly indicates a poor prognosis, especially in combination with histological types and clinical stages.

Adolescent↗

Inflammatory bronchial polyps associated with asthma: resolution with inhaled corticosteroid.

In a 50 year old man who complained of cough and sputum, a small endobronchial tumour was found in the left main bronchus and was biopsied via bronchoscopy. The histological diagnosis was inflammatory polyp with marked infiltration of eosinophils. Six years later, the patient developed asthma. At the same time, another polyp was found in the posterior basal bronchus of the right lower lobe. The appearance of the first polyp was unchanged endoscopically and histologically. Inhalation of beclomethasone dipropionate, 200 micrograms b.i.d., was started and symptoms of asthma soon subsided. In addition, the two polyps regressed and eventually disappeared after one year of treatment. Inhaled corticosteroids, being noninvasive and relatively safe, appear to be a possible therapeutic option in inflammatory bronchial polyps, especially in cases where the patient has asthma as an underlying condition, or the polyps are small and their management is not urgent.

Administration, Inhalation↗

Aspergillus culture filtrates and sputum sols from patients with pulmonary aspergillosis cause damage to human respiratory ciliated epithelium in vitro.

Aspergillus species frequently colonize lower respiratory tracts and lungs with localized underlying conditions (healed tuberculous cavity, cystic fibrosis, bronchiectasis, etc.) even in subjects without systemic predisposing factors. We investigated the in vitro effects of culture filtrates of Aspergillus species and sputum sols from patients with pulmonary aspergillosis on ciliary beat frequency (CBF) and epithelial integrity of human respiratory ciliated epithelium. Culture filtrates of 25 clinically isolated fungi (16 Aspergillus fumigatus, three Aspergillus niger, one Aspergillus flavus, three Candida albicans, and two Cryptococcus neoformans) were obtained by culturing the fungi in Medium-199 at 37 degrees C for 7 days, and five sputum sols were obtained from patients with pulmonary aspergillosis infected by A. fumigatus. During 6 h experiments using a photometric technique, 14 out of 16 A. fumigatus culture filtrates caused progressive and significant reduction in CBF associated with marked epithelial disruption, whilst the culture filtrates of A. niger and A. flavus caused minor epithelial damage without slowing of CBF, and Medium-199 alone (Control) showed neither epithelial damage nor slowing of CBF. All of the sputum sols also caused significant slowing of CBF as well as epithelial disruption. Culture filtrates of C. albicans and Cr. neoformans had no effects on human respiratory epithelium. We conclude that Aspergillus species, especially A. fumigatus release a factor (or factors) which causes damage to respiratory epithelium and slows CBF, and that these factors may contribute to the colonization of the lower respiratory tracts by the Aspergillus species and may possibly contribute to the further proliferation and spread of the lesions in pulmonary aspergillosis.

Adult↗