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Biomedical subjects

T Nakabayashi

Publications and source records attributed to T Nakabayashi.

At least 37 records · Page 2Linked to original sources

Analysis of hemoglobin and globin chain variants by a commonly used capillary isoelectric focusing method.

To analyze both hemoglobin (Hb) and globin chain variants, we modified a commonly used method, capillary isoelectric focusing (CIEF), with detection at 280 nm. The samples were hemolysates prepared from red blood cells, and globin chains obtained from the hemolysates by treatment with cold acidified acetone. When the migration time for the internal reference, carbonic anhydrase I (isoelectric point, pI 6.60), was taken as 1.0, the migration ratio for Hb A0 in normal human blood was 0.877 +/- 0.004 (mean +/- SD, n = 9), and those of the alpha- and beta-globin chains were 0.673 +/- 0.004 and 0.847 +/- 0.005 (mean +/- SD, n = 4), respectively. The ratio of peak heights between the beta- and alpha-globin chains (beta/alpha) in the normal Hbs obtained from four subjects was almost constant at 2.5 +/- 0.1 (mean +/- SD). This ratio indicates which of the globin chains includes a mutation (if one exists). When an Hb variant, Hb Hoshida (in which Gln is substituted for Glu at residue 43 in the beta-globin chain), was analyzed by this method, two main peaks were observed (migration ratios 0.836 and 0.877, corresponding to an abnormal and the normal Hb, respectively). An additional peak with an abnormal migration ratio of 0.788 was also detected in the globin chain profiles. The ratio of peak heights between normal beta- and alpha-globin chains was 1.57, indicating that a mutation exists in the beta-globin chain. We thus established a convenient system using CIEF that provides a rapid and reproducible method for the random analysis of both Hb and globin chain variants.

Electrophoresis, Capillary↗

Stressful delivery influences circulating thrombopoietin (TPO) levels in newborns: possible role for cortisol in TPO-mpl binding.

The regulation mechanism of circulating thrombopoietin (TPO) level in human newborns remains unknown. In the present study, we examined whether the TPO concentrations in cord blood were influenced by the difference in the delivery method and the presence or absence of maternal/fetal complications. Cortisol levels were simultaneously measured to assess the adrenal response of fetuses. Both the TPO level and the cortisol level were substantially greater in the neonates delivered vaginally with and without the complications than in those delivered by cesarean section without the complications. The binding assay showed that the incubation of mpl(+)/BaF3 cells with cortisol gave rise to a significant decrease in the binding sites of TPO. These results suggest that the stress to the fetuses near the time of delivery affects the cord blood TPO levels, which may be mediated in part by the action of cortisol on the TPO-mpl binding system.

Binding Sites↗

Prevention of left ventricular remodeling by percutaneous transluminal coronary angioplasty performed 24 hours after the onset of acute myocardial infarction.

It remains controversial whether percutaneous transluminal coronary angioplasty (PTCA) performed 24 hours after the onset of acute myocardial infarction (AMI) in coronary arteries with 99% stenosis is useful in preserving left ventricular function. We investigated the effectiveness of PTCA in preventing left ventricular remodeling when it was performed 24 hours after the onset of AMI in infarct-related coronary arteries (IRCAs) having 99% stenosis and thrombolysis in myocardial infarction (TIMI) grade 3 flow. The subjects were 19 patients with AMI (anterior wall, 9 patients; inferior wall, 7 patients; and non-Q, 3 patients) who, within 24 hours of the onset of AMI, underwent coronary angiography and left ventriculography during the acute and/ or chronic phases. The patients were divided into a PTCA group, comprised of patients in whom PTCA was successfully performed 24 hours after the onset of AMI (n = 10), and a non-PTCA group (n = 9). The non-PCTA group included patients who were successfully reperfused by thrombolysis and did not include patients who had spontaneous reperfusion or reperfusion after PTCA. In the non-PTCA group, the left ventricular end-diastolic volume (mean +/- SD) was significantly increased in the chronic phase (86 +/- 23 mL/m(2)) as compared with the acute phase (67 +/- 13 mL/m(2)), whereas in the PTCA group no significant difference was observed between end-diastolic volumes in the acute and chronic phases (67 +/- 26 and 68 +/- 13 mL/m(2), respectively). Left ventricular remodeling is prevented by PTCA when it is performed 24 hours after the onset of AMI in IRCAs with 99% stenosis and TIMI grade 3 flow.

Aged↗

Prostaglandin E2 stimulates motilin release via a cholinergic muscarinic pathway in the dog.

Prostaglandins are well known to be widely distributed in mammalian gastrointestinal tissues and to play a role in the regulation of gastrointestinal hormones and contractions. The present study was undertaken to determine whether prostaglandins have an effect on the endogenous release of motilin in the dog. In six conscious dogs, gastrointestinal contractions were monitored by means of chronically implanted force transducers. Prostaglandin E2 (PGE2; 3, 10, 30 microgram kg-1) was given intravenously during the interdigestive phase I period with or without a muscarinic or nicotinic receptor antagonist. Blood samples were collected from 10 min before, to 30 min after, prostaglandin injection. Indomethacin (5 mg kg-1) was given intravenously to investigate the effect of endogenous prostaglandins on motilin release. PGE2 significantly stimulated motilin release but not gastric contractions. Atropine, but not hexamethonium, blocked PGE2-induced motilin release. Motilin release in response to PGE2 was significantly increased by pretreatment with hexamethonium. Indomethacin inhibited the cyclic release of motilin and gastric phase III contractions. We conclude that PGE2 appears to stimulate motilin release via cholinergic muscarinic pathways, and nicotinic receptors modulate this reaction. PGE2 may be involved in part in the regulation of the cyclic release of motilin and the occurrence of gastric phase III.

Animals↗

Percutaneous transluminal coronary angioplasty performed 24-48 hours after the onset of acute myocardial infarction improves chronic-phase left ventricular regional wall motion.

The authors investigated the capacity of percutaneous transluminal coronary angioplasty (PTCA) performed 24-48 hours after the onset of acute myocardial infarction (AMI) to improve regional left ventricular wall motion. Twenty-four patients were divided into two groups: a PTCA group who received successful PTCA (14 cases) and a non-PTCA group (10 cases) who did not receive PTCA. Left ventricular end-diastolic volume (LVEDV) increased significantly (p<0.01) from 57+/-14 mL/m2 during the acute phase to 83+/-16 mL/m2 during the chronic phase in the non-PTCA group, whereas no significant change in LVEDV was seen in the PTCA group (69+/-26 vs. 76+/-16 mL/m2). In addition, in patients with 99% stenosis/thrombolysis in myocardial infarction (TIMI) grade 3 flow, increases in regional left ventricular wall motion (delta(sd)/chord) at the infarcted site between the acute and chronic phases were significantly greater in the PTCA group than in the non-PTCA group (2.49+/-1.05 vs. 0.67+/-0.65, p<0.01). PTCA performed 24-48 hours after the onset of AMI improved wall motion at the infarcted site.

Aged↗

Prevention of coronary arterial renarrowing by continuous 3-day infusion of tissue plasminogen activator after successful percutaneous transluminal coronary angioplasty: a randomized, double-blind, placebo-controlled study.

Vascular injury resulting from percutaneous transluminal coronary angioplasty (PTCA) and subsequent thrombus formation are important factors in the pathogenesis of coronary arterial restenosis. The present study was undertaken to determine whether infusions of tissue plasminogen activator (tPA), beginning immediately after PTCA, would decrease the renarrowing of the coronary arterial lumen. Patients were randomized and divided into two groups: one group (15 patients, 16 lesions) received continuous, 3-day, intravenous infusions of tPA (0.25 mg/kg/day in 0.9% saline), beginning immediately after successful PTCA, while the other group (17 patients, 17 lesions) received saline alone. Coronary angiography was performed before, immediately after, 24 hours after, and 3 months after PTCA. Coronary stenosis (%), reference diameters, and minimum luminal diameters were measured by quantitative coronary angiography. The incidence of restenosis tended to be lower in the tPA group than in the placebo group (tPA group, 13%; placebo group, 41%; NS), although diameter stenoses before and immediately after PTCA were not significantly different in the two groups. Three months later, however, diameter stenoses were significantly smaller in the tPA group (35.6 +/- 13.3 vs 47.7 +/- 18.9%; P<0.05). Thus, intravenous tPA infusion beginning immediately after successful PTCA may inhibit renarrowing of the coronary arterial lumen.

Aged↗

Higher avidity binding of apolipoprotein (E-AII) complex than of apolipoprotein E monomer to beta-amyloid.

Apolipoprotein E (apoE) is believed to be closely involved in the pathogenesis of Alzheimer's disease (AD) because of its ability to bind to beta-amyloid (Abeta), the primary component of senile plaques. The presence of cystein residues in apoE2 and apoE3 allows these isoforms to form disulfide-linked complexes, such as apo(E-AII) complex and apo(AII-E-AII) complex. A 50-kDa complex [which corresponded to apo(E-AII)-Abeta, because it reacted with any of the three antibodies, anti-apoE, anti-apoAII, or anti-Abeta] was detected by immunoblot analysis in native cerebrospinal fluid (CSF) obtained from nondementia patients with the apoE phenotype E3/E3. However, a band considered to represent apoE-Abeta was not observed. The dissociation constant (Kd) values obtained for the specific binding of recombinant apoE2, apoE3, and apoE4 to Abeta(1-42) were 48.1 +/- 2.2 nM, 63.7 +/- 2.1 nM, and 75.9 +/- 1.8 nM, respectively. In contrast, the binding affinity of the partially purified apo(E3-AII) complex to Abeta(1-42) was very high, the Kd being 5.5 +/- 0.5 nM. No basic difference was observed between lipidated and nonlipidated apoE in terms of the characteristics of the binding of apoE isoforms to Abeta(1-42); however, lipidation reduced the binding capacity of each isoform in a dose-dependent manner. These findings seem consistent with the generally accepted idea that apoE4 is a risk factor for AD, insofar as only apoE4 is unable to form a complex with apoAII owing to its lack of a cystein residue. In addition, it is possible that apoE3 monomer (and possibly apoE2 monomer), like apoE4 but unlike apo(E-AII) complex, can act as a risk factor in the pathogenesis of AD.

Amyloid beta-Peptides↗

Vitamin A toxicity secondary to excessive intake of yellow-green vegetables, liver and laver.

We report a case of sudden onset of vitamin A poisoning. A 20-year-old Japanese woman had been eating pumpkin and only a very limited amount of other foods on a daily basis for 2 years. She was overly concerned about weight reduction. Aurantiasis cutis and abnormal liver function tests were noted by her family doctor in 1995 when she was 18 years old. At that time, she stopped eating pumpkin. However, she secretly continued an excessive intake of other beta-carotene-rich vegetables, liver and laver for about 2 years. Two and one-half years after being seen by her family physician, she experienced sudden onset of low-grade fever, limb edema, cheilitis, dry skin, and headache. These symptoms worsened daily. A liver needle biopsy was performed, and it showed a normal portal tract along with fat-laden Ito cells in the space of Disse. A final diagnosis of vitamin A poisoning and hepatic injury secondary to an eating disorder was made. Her symptoms and serum beta-carotene levels returned to normal with successful adjustment of her diet.

Adult↗

Laterality of delta waves during all-night sleep.

In order to clarify the functional asymmetry of the brain function during sleep, period-amplitude analysis of delta electroencephalogram activity was performed on polysomnograms in 12 right-handed healthy males. Electroencephalograms were recorded from disc electrodes placed at C3, C4, O1 and O2 (10-20 electrode system), using A1 +A2 for reference. Although there were no significant differences in delta counts between O1 and O2, delta counts of C3 were significantly larger than those of C4. These results suggest that there exists distinct laterality in the number of delta waves in the central region, reflecting the functional asymmetry of the brain during sleep.

Adult↗

Apolipoprotein E in cerebrospinal fluid: relation to phenotype and plasma apolipoprotein E concentrations.

BACKGROUND: Apolipoprotein (apo) E may be related to the development of Alzheimer disease, but data on apoE in cerebrospinal fluid (CSF) are limited. The aim of the present study was to measure apoE in CSF and relate its concentrations to apoE phenotype and CSF lipids. METHODS: We adapted an assay for CSF apoE sensitivity using an ELISA. It allowed us to measure CSF apoE with sufficient reproducibility and precision. RESULTS: The within- and between-run CVs were <7%, and the detection limit was 0.025 mg/L. No cross-reaction was found for other apolipoproteins. No significant differences related to sex or apoE phenotype were observed in the CSF apoE concentration. The mean CSF apoE concentration was significantly higher in the 0-5 year group (n = 6; 18.47 +/- 1.14 mg/L, mean +/- SD) than in the >5 year group (n = 34; 8.82 +/- 3.31 mg/L). The mean concentrations of total cholesterol (TC) and phospholipid (PL) in CSF were 2.68 +/- 2.16 and 6.50 +/- 2.84 mg/L (n = 52), respectively. Although no significant differences in TC or PL in the CSF were found with respect to sex or age, the concentrations in subjects with the apoE phenotype E4/E3 were significantly lower than in those with E3/E3 and E3/E2. The concentrations of apoE, TC, and PL in CSF did not correlate with those in plasma. The time-related fluctuations in CSF apoE were independent of those in total protein and IgG. CSF apoE was significantly correlated with TC and PL concentrations in the CSF, but not with the number of cells in the CSF. CONCLUSIONS: These findings support the idea that apoE and lipids are unable to cross the blood-brain barrier and that their concentrations in CSF may reflect production in central nervous tissue.

Adolescent↗

Pharmacokinetics of etoposide after intrathoracic instillation to lung cancer patients with pleural effusion.

OBJECTIVE: To examine etoposide (VP16) levels in serum and pleural effusion after intravenous infusion or intrathoracic instillation to lung cancer patients. METHODS: Four patients were administered VP16 by intrathoracic instillation and three patients were administered it intravenously. Serum, urine, and pleural effusion were collected and VP16 levels in the biological fluids were determined by HPLC. Pharmacokinetic parameters were calculated. RESULTS: VP16 distributed rapidly into pleural effusion after intravenous infusion. In two of three patients, VP16 levels in pleural effusion were maintained at constant levels more than 24 hours in spite of the decline in serum VP16 levels. After intrathoracic instillation, VP16 in pleural effusion reached high levels and eliminated slowly. Serum levels of VP16 were relatively low compared with those in pleural effusion. CONCLUSION: It was demonstrated that intrathoracic instillation of VP16 might be useful for managing malignant pleural effusion and reducing systemic side-effects by cutting down the dose.

Adenocarcinoma↗

[Clinical evaluation of PCR method for detection of cytomegalovirus DNA].

Polymerase chain reaction (PCR) to detect Cytomegalovirus (CMV)-DNA from the clinical specimens is useful to diagnose CMV infection. Eighty-one specimens of 31 patients including peripheral blood, bronchioalveolar lavage fluid, biopsy tissues, feces, urine, sputum and etc. and normal peripheral blood from 59 volunteers were used in this study. After DNA extraction each samples was amplified by the seminested PCR using primers recognizing sequences in the Immediate-early gene of CMV. This PCR method specifically detected more than 10 virus copies even in the presence of the genomic DNA. CMV-DNA was detected in only one of 59 normal peripheral bloods (1.7%). Six of 31 patients were clinically diagnosed as CMV infection by anti-CMV therapy. These 6 patients were positive in the peripheral blood by PCR for CMV, and 5 of them were positive in other samples. However, 3, 5 and 1 of 25 patients, who were clinically diagnosed as not having CMV infection, were also positive in peripheral blood, in the other samples and in both, respectively. The PCR method was able to examine any clinical samples. To examine both the peripheral blood and the samples from infected organs is helpful for the diagnosis of CMV infection.

Adolescent↗

Fas (CD95)-transduced signal preferentially stimulates lupus peripheral T lymphocytes.

Fas (CD95) is a cell surface receptor whose biological function in circulating peripheral T cells is not well understood. To address the question of abnormal T cell sensitivity to Fas stimulation in systemic lupus erythematosus (SLE), we studied Fas-transduced stimulation and apoptosis in peripheral blood T cells from patients with SLE and normal control. Immobilized anti-Fas monoclonal antibodies (mAb) (imCH-11; IgM type) significantly stimulated SLE T cell proliferation compared to T cells from normal donors and patients with rheumatoid arthritis (p < 0.003 and p < 0.005, respectively). The soluble form of CH-11 and other immobilized anti-Fas mAb (UB-2, ZB-4; IgG type) failed to stimulate lupus T cells while immobilized human Fas ligand did. Furthermore, imCH-11 induced IL-2 and IL-6 mRNA expression. However, imCH-11 activation failed to induce expression of the T cell activation surface molecules CD25 and CD69. Addition of exogenous ceramide, a second messenger for Fas-mediated apoptosis signaling, also induced T cell proliferation in SLE and normal controls. Moreover, fumonisin B1, a specific ceramide synthase inhibitor, and caspase inhibitors markedly suppressed imCH-11 induced T cell proliferation, suggesting that the ceramide pathway may be involved in Fas-transduced stimulation signals in SLE T cells. These results show that SLE T cells have an alteration in the Fas signal transduction pathway leading to cell proliferation. This defect may be important in Fas-mediated peripheral immune homeostasis.

Adult↗

Bcl-2 family expression in salivary glands from patients with primary Sjögren's syndrome: involvement of Bax in salivary gland destruction.

To investigate the molecular mechanism of glandular parenchyma destruction in Sjögren's syndrome (SS), Bcl-2, Bax, Bcl-X, and Bak expression were studied. SS (n = 18) and control salivary glands (n = 6) were examined by immunohistochemistry. Apoptosis was assessed by in situ DNA nick end labeling. Infiltrating mononuclear cells in the SS salivary gland showed elevated Bcl-2. These mononuclear cells expressed increased Bax but did not undergo apoptosis. Both SS and control salivary gland ductal epithelial cells expressed Bcl-2, Bax, and Bcl-X. SS, but not normal, salivary gland acinar cells expressed Bax and underwent apoptosis. These results suggest that elevated Bax expression in SS salivary gland acinar cells may play an important role in the apoptotic pathway. In contrast, Bcl-2 expression in SS infiltrating mononuclear cells and ductal cells may contribute to their survival.

Apoptosis↗

Latent cerebral artery stenoses on magnetic resonance angiography in a patient diagnosed as probable Alzheimer disease.

A 65-year-old woman with hypertension developed slowly progressive memory disturbance and disorientation. She was diagnosed as having Alzheimer-type dementia according to clinical criteria. Later her cognitive deterioration was noted to fluctuate in parallel to her blood pressure. Magnetic resonance angiography and single photon emission computed tomography showed bilateral middle cerebral artery stenoses and middle cerebral artery watershed dominant hypoperfusion. It is postulated that the patient's cognitive disturbance may have originated from vascular lesions.

Aged↗

A rapid assay of granisetron in biological fluids from cancer patients.

A convenient high-performance liquid chromatography (HPLC) was developed for the rapid assay of granisetron (GRN) in biological fluids, such as serum, urine, and pleural effusion, from cancer patients. Extrelut-1 was used for the solid-phase extraction. HPLC was carried out using a LiChroCART cartridge column packed with Lichrospher 100 CN and a mobile phase consisting of 0.1 M acetate buffer (pH 3.5) and acetonitrile (7:3). A fluorescence detector of 290 nm for excitation and 365 nm for emission was used. The standard curve was linear over the range of 2 to 100 ng/ml of GRN. Assay precision, expressed as a coefficient of variation (C.V.), was in the range of 0.9-5.4% in the within-day assay and 2.5-6.9% in the between-day assay, respectively. GRN was well separated on the HPLC chromatogram from drugs such as etoposide, metclopramide, ondansetron, and domperidone which are often used together with GRN. It was suggested that the present method is useful for the rapid monitoring of GRN in the serum, urine, and pleural effusion of patients undergoing cancer chemotherapy.

Antiemetics↗