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Biomedical subjects

K Hirata

Publications and source records attributed to K Hirata.

At least 73 records · Page 4Linked to original sources
PubMed2002

Survey of residual solvents in natural food additives by standard addition head-space GC.

Residual levels of 12 solvents in 87 natural food additives (66 samples of food colours, 19 samples of natural antioxidants and two natural preservatives) collected between 1997 and 1999 were determined by automated head-space GC using FID, with a porous-polymer (PLOT) column. Calibration curves were prepared by the method of standard addition. Confirmation was by manually injected head-space GC using mass spectrometric detection. 1,2-Dichloroethane was found in turmeric colour (natural food colour) collected in 1997 at the concentrations of 8.6 microg g(-1), but was not found in samples collected in 1998 and 1999. Hexane was found in three samples of dunaliella carotene (11, 72 and 75 microg g(-1)), and in chlorophyll at 93 microg g(-1) (both natural food colours). Acetone was found in turmeric colour, annatto colour, dunaliella carotene, kaoliang colour, cacao colour at a concentration between 8.7 and 42 microg g(-1) (all natural food colours).

Antioxidants↗
PubMed2002

Involvement of vascular endothelial growth factor in exercise induced bronchoconstriction in asthmatic patients.

BACKGROUND: There is evidence that the bronchial microcirculation has the potential to contribute to the pathophysiological mechanisms of exercise induced bronchoconstriction (EIB) in asthmatic subjects. Vascular endothelial growth factor (VEGF), which is highly expressed in asthmatic airways, increases vascular permeability. The relationship between VEGF levels in induced sputum and the severity of EIB in asthmatic subjects was studied. METHODS: The concentration of VEGF in induced sputum was examined in 23 asthmatic subjects and 11 normal controls. The asthmatic subjects performed an exercise test and the % maximal fall in forced expiratory volume in 1 second (FEV(1)) was measured. Beclomethasone dipropionate (BDP) 400 micro g twice daily was administered to the asthmatic subjects for 8 weeks and the exercise test and sputum induction were repeated. RESULTS: The concentration of VEGF in induced sputum was significantly higher in asthmatic subjects than in normal controls. There was a significant correlation between the concentration of VEGF and the % maximal fall in FEV(1) (r=0.826, p=0.0001) and between the concentration of VEGF and airway vascular permeability index (r=0.621, p=0.0037). After treatment with inhaled BDP there was a significant decrease in the concentration of VEGF in the asthmatic subjects (before treatment: 7051 (2361) pg/ml, after treatment: 4498 (2135) pg/ml, p<0.0001). The change in the concentration of VEGF was significantly correlated with the change in the % maximal fall in FEV(1) (r=0.463, p=0.031). CONCLUSIONS: Excessive production of VEGF in asthmatic airways may contribute to the pathogenesis of EIB via increased airway vascular permeability.

Administration, Inhalation↗
PubMed2002

Decreased peroxynitrite inhibitory activity in induced sputum in patients with bronchial asthma.

BACKGROUND: The production of peroxynitrite, an extremely potent oxidant, is increased in inflammatory lung disease. It is therefore important to measure antioxidant activity against peroxynitrite in epithelial lining fluid to examine the physiological effects of peroxynitrite in the airways of patients with asthma. This study was designed to determine whether peroxynitrite inhibitory activity in induced sputum is correlated with clinical characteristics and airway inflammatory indices in asthmatic patients. METHODS: Inflammatory indices were measured in induced sputum from 25 patients with asthma and 12 normal control subjects. Peroxynitrite inhibitory activity was also measured by monitoring rhodamine formation in sputum samples. RESULTS: Peroxynitrite inhibitory activity in induced sputum was significantly lower in asthmatic patients (52.4 (24.5)%) than in normal control subjects (92.1 (3.9)%, p<0.0001). Its activity was significantly correlated with forced expiratory volume in 1 second (FEV(1)) % predicted (r=0.774, p<0.0001) and bronchial hyperreactivity to methacholine (r=0.464, p=0.023). There was a significant negative correlation between peroxynitrite inhibitory activity and the degree of eosinophilic airway inflammation (% eosinophils, r=-0.758, p<0.0001; eosinophil cationic protein, r=-0.780, p<0.0001). CONCLUSIONS: Decreased peroxynitrite inhibitory activity occurs in induced sputum of asthmatic patients. Since even in patients with stable asthma the airway lining fluid lacks peroxynitrite inhibitory activity, large amounts of peroxynitrite, which are further increased during an acute asthma attack, would not be completely inactivated and asthmatic airways might have markedly increased susceptibility to peroxynitrite induced airway injury.

Adult↗
PubMed2002

beta-Catenin alteration in cancer of the ampulla of Vater.

To investigate the contribution of beta-catenin to the development of carcinoma of the ampulla of Vater, genetic alterations of beta-catenin gene, CTNNB-1 were searched. Mutational analysis of exon3 in CTNNB-1, which encodes the serine/threonine residues for GSK-3beta phosphorylation sites, was performed on 21 cases of carcinoma of the ampulla of Vater, by means of polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) followed by nucleotide sequencing. We found one deleted mutation at codon 32 to approximately 65 in one case of carcinoma of the ampulla of Vater. We also analyzed subcellular localization of beta-catenin protein in all cases immunohistochemically, and confirmed its accumulation in the nucleus in four cases including in a CTNNB-1 mutated one. This is the first study to show CTNNB-1 mutation and beta-catenin expression in carcinoma of the ampulla of Vater. These results suggested that abnormal Wnt-wingless signaling and in particular beta-catenin alteration caused accumulation of beta-catenin, which might partially contribute to the development of carcinoma of the ampulla of Vater.

Aged↗
PubMed2001

Pressure-altering agents affect central aortic pressures more than is apparent from upper limb measurements in hypertensive patients: the role of arterial wave reflections.

The pressure pulse does not have the same amplitude in central and peripheral arteries, but it is amplified toward the periphery; the degree of this amplification depends principally on wave reflection. Despite the conventional clinical and epidemiological focus on peripheral pressures, the most physiologically relevant pressures for both cardiac and vascular effects are central pressures. The reflected wave contributes differently in the configuration of the peripheral and central pressure waveform. Therefore, we hypothesized that agents that alter wave reflections could have an unequal effect on central and peripheral pressures in hypertensive patients. Thus, the effect of caffeine was investigated in 10 hypertensive subjects according to a randomized, placebo-controlled, double-blind, crossover design. Central aortic pressures and wave reflection were assessed with applanation tonometry and pulse wave analysis. After caffeine, augmentation index and augmented pressure increased by 4.6%, (P<0.005) and 5.7 mm Hg (P<0.001), respectively, indicating increased effect of wave reflection from the periphery. The increase in aortic systolic pressure was greater compared with that in radial artery pressure at 30 minutes (25%) and marginally greater at 60 minutes (21%). Furthermore, the increase in aortic pulse pressure was greater at 30 and 60 minutes (34% and 40%, respectively). The intensified reflected wave after caffeine was largely responsible for the disparate effect between central and peripheral pressures by boosting the peak of the central and not of the peripheral waveform. This study shows that pressure-altering agents might affect central pressures more than is apparent from the corresponding upper limb values because of the concomitant changes in wave reflection.

Aorta↗
PubMed2001

Derivatization of fullerene dimer C120 by the Bingel reaction and a 3He NMR study of 3He@C120 monoadducts.

Cyclopropanation with diethyl bromomalonate and base (the Bingel reaction) was conducted on fullerene dimer C120 to give a mixture of "monoadducts" (45% yield) and "bisadducts" (< or =37% yield), while 18% of the C120 remained unchanged. The "monoadducts" were separated into five positional isomers, i.e., e(face), e(edge), trans-4, trans-3, and trans-2, by preparative HPLC. Assignments were made based on 1H (and 13C) NMR and confirmed by theoretical calculations of the addends' 1H NMR chemical shifts. The relative yields of these isomers were in fair agreement with those observed for the Bingel bisaddition of C60. The Bingel reaction was also carried out on the dimer C120 encapsulating 3He in one of the C60 cages. Each positional isomer of the "monoadduct" exhibited a pair of 3He NMR signals corresponding to an isomer with functionalization on the 3He-containing cage and the other isomer with functionalization on the empty cage. Using the 3He NMR spectroscopy, a pair of signals for the trans-1 isomer, which eluded detection by 1H NMR, were observed, in addition to pairs of signals for e(face), e(edge), trans-4, trans-3, and trans-2 isomers. The 3He NMR signals for isomers with functionalization on the 3He-containing cage were spread out over a 1.82-ppm range reflecting the direct effects of the addition pattern on the C60 surface. In contrast, the isomers with functionalization on the empty cage exhibited 3He NMR signals that appeared over a 0.14-ppm range, which was shown to be primarily due to changes in the diamagnetism of the functionalized cage based on theoretical calculations of 3He NMR chemical shifts for the model system in which the C60 cage encapsulating 3He was removed.

Journal Article↗
PubMed2001

Expression of carbamoylphosphate synthetase I and glutamine synthetase in hepatic organoids reconstructed by rat small hepatocytes and hepatic nonparenchymal cells.

The objective of this study was to investigate the expression of carbamoylphosphate synthetase I (CPS) and glutamine synthetase (GS) in small hepatocyte colonies and whether the heterogeneous expression of the enzymes could be induced during the maturation of small hepatocytes. Small hepatocytes isolated from an adult rat liver were cultured and proliferated to form colonies. The expression of CPS and GS was examined using immunocytochemistry and immunoblotting. In this culture more than 99% of morphologically hepatic cells were positive for CPS and all small hepatocytes were negative for GS at day 5. CPS-positive cells dramatically decreased with time in culture, whereas GS-positive ones appeared and their number increased in the colonies. Two to 3 weeks after plating, colonies with rising and piled-up cells appeared and the number of such colonies reached about 25% of all colonies at day 30. In most rising and piled-up cells in colonies both proteins were strongly expressed, whereas many small hepatocytes in monolayer colonies did not express either protein. When small hepatocytes in monolayer colonies were overlayed with Matrigel, the cells gradually piled up and both CPS and GS proteins were dramatically induced. The expression of CPS and GS in small hepatocytes may interact with the extracellular matrix because the rising and piled-up cells appear to be induced by the extracellular matrix produced by hepatic nonparenchymal cells.

Animals↗
PubMed2001

The spatiotemporal relationship among Schwann cells, axons and postsynaptic acetylcholine receptor regions during muscle reinnervation in aged rats.

To morphologically define the aging-related features during muscle reinnervation the spatiotemporal relationships among the major components of the neuromuscular junctions (NMJs) were investigated. A total of 64 rats, 30 adults (4 months old) and 34 aged adults (24 months old), were used. Between 1 and 12 weeks after sciatic nerve-crushing injury, cryosections of skeletal muscle were single or double labeled for S100, a marker of Schwann cells (SCs), for protein gene product 9.5, a neuronal marker, and for alpha-bungarotoxin (alpha-BT), a marker of the acetylcholine receptor site (AChR site), and then observed by confocal laser microscopy. The most obvious age changes were noted: (1) the regenerating SCs and axons were delayed in their arrival at the NMJ, (2) the dimensions of terminal SCs and AChR sites displayed a drastic and long-lasting drop (for terminal SCs, during 1-8 weeks; for AChR sites, during 1-12 weeks); (3) the degree of spatial overlap between AChR sites and terminal SCs was markedly low until 8 weeks post-crush; (4) damage and poor formation in the SCs, terminal axons and AChR sites, together with poor process extension from the terminal SC or terminal axon, were pronounced; (5) persistent aberrant changes, such as multiple innervation and terminal axon sprouting, together with poorly formed collateral innervation, nerve bundles, and NMJs, more frequently occurred in the later reinnervation period. Thus, with aging, regeneration is impaired during the period in which regenerating SC strands and axons extend into NMJs and the subsequent establishment of nerve-muscle contact is in progress. A complex set of morphological abnormalities between or among the TSCs, terminal axons, and AChR sites may be important in slowing of regeneration and reinnervation in aged motor endplates.

Aging↗
PubMed2001

Telomerase reverse transcriptase and telomeric-repeat binding factor protein 1 as regulators of telomerase activity in pancreatic cancer cells.

Telomerase adds hexameric repeats of 5'-TTAGGG-3' termed telomeres to ends of chromosomal DNA. This enzyme has been implicated in cellular immortalization and cellular senescence. Recently, a number of relevant genes have been cloned, including these encoding three major components of human telomerase: human telomerase RNA component (hTR), human telomerase reverse transcriptase (hTERT), and telomerase-associated protein-1 (TEP1). Also important are genes encoding human telomeric-repeat binding factor protein (TRF) 1 and 2. To clarify mechanisms regulating telomerase activity, we studied telomerase activity, the telomeric restriction fragment (TRF) length and gene expression of these telomerase components and the telomeric-repeat binding factor proteins in sequential observation following X-irradiation of cultured pancreatic cancer cells. We previously reported that PANC-1 cells are better able to tolerate thermal stress, antineoplastic drugs, and exposure to tumour necrosis factor than MIAPaCa-2 cells. MIAPaCa-2 and PANC-1 cells were exposed to X-irradiation, their telomerase activity was increased at 2 days and then decreased gradually. Of the three telomerase components, only hTERT mRNA expression showed parallel changes. TRF length was stable just before and after X-irradiation. Among binding factor proteins, TRF1 mRNA showed reciprocal changes possibly directed toward maintaining a stable telomere length. In this study, our results demonstrate that not only hTERT but also TRF1 are important regulator of telomerase activity.

Cell Count↗
PubMed2001

Prediction of sensitivity of esophageal tumors to adjuvant chemotherapy by cDNA microarray analysis of gene-expression profiles.

We applied cDNA microarray analyses of 9216 genes to establish a genetic method for predicting the outcome of adjuvant chemotherapy to esophageal cancers. We analyzed expression profiles of 20 esophageal cancer tissues from patients who were treated with the same adjuvant chemotherapy after removal of tumor by operation, and we attempted to find genes associated with the duration of survival after surgery. By comparing expression profiles of those cancer tissues, we identified by statistical analysis 52 genes that were likely to be correlated with prognosis and possibly with sensitivity/resistance to the anticancer drugs. We also developed a drug response score based on the differential expression of these genes, and we found a significant correlation between the drug response score and individual patients' prognoses. Our results indicated that this scoring system, based on microarray analysis of selected genes, is likely to have great potential for predicting the prognosis of individual cancer patients with the adjuvant chemotherapy.

Aged↗
PubMed2001

Miller Fisher syndrome and Haemophilus influenzae infection.

OBJECTIVE: To examine the association between Miller Fisher syndrome (MFS) and antecedent Haemophilus influenzae infection. BACKGROUND: Little is known about agents in prior respiratory tract infection of MFS, whereas antecedent upper respiratory symptoms are frequent. H. influenzae is a major pathogen that can cause human respiratory tract infection. METHODS: The authors used ELISA to detect serum antibody against the bacterium in 70 consecutive patients with MFS and 110 with Guillain-Barré syndrome (GBS). RESULTS: Serum anti-H. influenzae IgG and IgM antibody activities were significantly higher in the MFS group than in age- and sex-matched patients with other neurologic diseases (n = 62) and normal control subjects (n = 82). The GBS group showed no significant increase in any class of antibody activities compared with control groups. Serologic evidence of recent infection was found in five (7%) of the patients with MFS and two (2%) of 110 patients with GBS, all of whom had a history of antecedent respiratory tract infection. They frequently showed ophthalmoplegia, but other neurologic features were not remarkable. Serum anti-GQ1b IgG antibody that had cross-reactivity with GT1a ganglioside was detected in six of these seven patients. Thin-layer chromatography with immunostaining showed that serum IgG from H. influenzae-seropositive patients with high anti-GQ1b and anti-GT1a IgG antibody titers bound to the lipopolysaccharide fraction extracted from the type b H. influenzae serostrain. These bands were also stained by anti-GT1a monoclonal antibody (GMR11), indicating that the lipopolysaccharide bears the GT1a epitope. CONCLUSIONS: These findings point to H. influenzae being an agent associated with MFS. Epitopic overlap between H. influenzae and human nerve tissue may be involved in the development of MFS much as GBS is associated with Campylobacter jejuni enteritis.

Adolescent↗
PubMed2001

Acute effects of passive smoking on the coronary circulation in healthy young adults.

CONTEXT: Recent studies have shown that passive smoking is a risk factor for ischemic heart disease and may be associated with vascular endothelial dysfunction. The acute effects of passive smoking on coronary circulation in nonsmokers are not known. OBJECTIVE: To determine the acute effects of passive smoking on coronary circulation using coronary flow velocity reserve (CFVR), assessed by noninvasive transthoracic Doppler echocardiography. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study conducted from September 2000 to November 2000 among 30 Japanese men (mean age, 27 years; 15 healthy nonsmokers and 15 asymptomatic active smokers) without history of hypertension, diabetes mellitus, or hyperlipidemia. MAIN OUTCOME MEASURES: Coronary flow velocity reserve, calculated as the ratio of hyperemic to basal coronary flow velocity induced by intravenous infusion of adenosine triphosphate and measured in each participant before and after a 30-minute exposure to environmental tobacco smoke. RESULTS: Heart rate and blood pressure responses to adenosine triphosphate infusion were not affected by passive smoking exposure in either group. Passive smoking exposure had no effect on basal coronary flow velocity in either group. Mean (SD) CFVR in nonsmokers was significantly higher than that in active smokers before passive smoking exposure (4.4 [0.91] vs 3.6 [0.88], respectively; P =.02), while CFVR after passive smoking exposure did not differ between groups (P =.83). Passive smoking exposure significantly reduced mean (SD) CFVR in nonsmokers (4.4 [0.91] vs 3.4 [0.73], respectively; P<.001). CONCLUSIONS: Passive smoking substantially reduced CFVR in healthy nonsmokers. This finding provides direct evidence that passive smoking may cause endothelial dysfunction of the coronary circulation in nonsmokers.

Adenosine Triphosphate↗
PubMed2001

Synchrotron-betatron coupling due to monochromatization.

The effects of large dispersion at the interaction point are discussed within the linear approximation of the beam-beam force. The synchrotron and betatron motions affect each other. Synchrotron and betatron tune shifts as well as bunch-length and energy-spread modifications appear, among many effects. Depending on the parameters, degradations of the luminosity can occur due to the hourglass effect. More serious is an enlargement of the collision energy spread, which may reduce the event rate and invalidate the monochromatization scheme.

Journal Article↗
PubMed2001

IV. Clinical aspects of delayed hypersensitivity in lungs: pathophysiology of hypersensitivity disorders in clinics.

Hypersensitivity pneumonitis (HP) is an immunologically mediated lung disease of inhaled antigens. HP is not a uniform disease but rather a clinical complex syndrome characterized by varying intensities of responsiveness to different organic antigens. The main aetiological agents include thermophilic bacteria, fungi, animal proteins, and chemical compounds. A combination of host and environmental factors should be considered as a requisite to developing this disease. Although the antigens differ widely, the clinical syndromes that results are very similar. HP occurs mainly in non-smokers, and clinically it may be in acute, subacute, or chronic forms. The diagnosis of HP requires a constellation of clinic, radiographic, physiologic, pathologic, and immunologic criteria. HP is characterized by a diffuse and predominantly mononuclear cell inflammation, a partly granulomatous, immune disorder of alveolar regions that often involves the small airway. A strong evidence supports that delayed cell-mediated hypersensitivity mechanisms play a role in pathogenesis of HP. Studies performed on lung cells have demonstrated that cells bearing suppressor/cytotoxic phenotype characterize the lymphocytic alveolitis in patients with hypersensitivity pneumonitis. And also recently evidence has been provided indicating that a prominent role of T-helper 1 cell-mediated hypersensitivity with an imbalance in T-lymphocyte subsets, although the deposit of immune complex may participate in an acute form of the disease as well as in the early phase of the chronic form.

Alveolitis, Extrinsic Allergic↗
PubMed2001

Fine specificity of anti-GQ1b IgG and clinical features.

Anti-GQ1b IgG frequently is present in sera of patients with Miller Fisher syndrome (MFS), Guillain-Barré syndrome (GBS) with ophthalmoplegia, Bickerstaff's brainstem encephalitis (BBE), and acute ophthalmoparesis (AO) in the acute phase. Why various clinical signs develop under these conditions, however, has yet to be clarified. We investigated the fine specificity of anti-GQ1b IgG and its clinical correlation in sera from 82 patients: 56 with MFS, 11 with GBS, 13 with BBE, and 2 with AO. Anti-GQ1b IgG antibodies were absorbed by GT1a in 80 (98%) of the 82 sera, by GD1b in 11 (13%), and by the other b-series gangliosides GD3, GD2, or GT1b in 24 (29%). The most frequent pattern of fine specificity was the cross-reaction with GT1a alone, seen in 56 (68%) samples. Of the 11 patients with anti-GQ1b IgG, cross-reacting with GD1b, 6 (55%) had impaired deep sense, and the association was significant (p=0.02). This is the first study to show that the fine specificity of anti-GQ1b IgG is heterogeneous and that the difference is correlated with the presence of a particular clinical sign.

Antibody Specificity↗