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Biomedical subjects

A Nagai

Publications and source records attributed to A Nagai.

At least 127 records · Page 7Linked to original sources
PubMed1997

Role of Na(+)-K+ ATPase in cyclic GMP-mediated relaxation of canine pulmonary artery smooth muscle cells.

1. Sodium-potassium adenosine triphosphate (Na(+)-K+ ATPase) plays a role in the regulation of vascular tone, but contribution of this enzyme to intravasodilator-induced pulmonary vasodilation remains uncertain. We thus studied the interaction between guanosine 3':5'-cyclic monophosphate (cyclic GMP) and Na(+)-K+ ATPase in smooth muscle cells isolated from canine pulmonary artery. 2. To assess the contractile properties, changes in smooth muscle cell length were determined microscopically. Application of potassium chloride (KCl) shortened the cell length, an effect which was reduced by sodium nitroprusside and 8-bromo-cyclic GMP in a concentration-dependent manner. Pretreatment of cells with the cyclic GMP-dependent kinase inhibitor KT 5823 (2 microM) abolished the effects of sodium nitroprusside and 8-bromo-cyclic GMP. 3. Ouabain (0.3 microM) did not alter the KCl-induced muscle shortening, but inhibited the relevant responses to sodium nitroprusside and 8-bromo-cyclic GMP. 4. Incubation of smooth muscle cells with sodium nitroprusside concentration-dependently increased intracellular cyclic GMP levels and ouabain-sensitive 86Rb uptake, and these values were significantly correlated. In the presence of KT 5823, sodium nitroprusside increased cyclic GMP levels but did not alter ouabain-sensitive 86Rb uptake. 5. These results suggest that there is a link between accumulation of intracellular cyclic AMP and activation of sarcolemmal Na(+)-K+ ATPase in pulmonary artery smooth muscle cells and that this link may be involved in the sodium nitroprusside-induced pulmonary vasodilatation.

Animals↗
PubMed1997

Assessment of in vitro interleukin-2-producing capacity of peripheral blood lymphocytes from patients with periodontitis.

In this cross-sectional study, we assessed the in vitro interleukin-2 (IL-2) producing capacity of peripheral blood mononuclear cells (PBMC) and lymphocytes from patients with different forms of periodontitis. 45 patients (12 with localised early onset periodontitis (LEOP), 20 with generalised early onset periodontitis (GEOP), and 13 with adult periodontitis (AP), and 20 periodontally healthy subjects (HS), participated in this study. PBMC and lymphocytes were isolated from the subjects and their cells were stimulated with an anti-CD3 monoclonal antibody (anti-CD3 MoAb) and the secreted IL-2 levels in the culture were bioassayed. No significant differences could be found in IL-2 producing activity of PBMC between the patients and HS group. There was wide interindividual variation and high and low "IL-2 producers" were noted. We found a LEOP patient who was a high producer of IL-2 (> mean + 8 SD) and 2 LEOP patients and a HS who were low producers of IL-2 (< mean - 1.5 SD) with their lymphocytes. Incidentally, the HS became a LEOP patient during 2 years after this study. The low IL-2 producing activity of their PBMC and lymphocytes against anti-CD3 MoAb could not be overcome by stimulation with phorbol myristate acetate and ionomycin. Thus, we found high and low IL-2 producing capacity by PBMC and lymphocytes in certain subjects and these subjects may be useful models in assessing the role of systemic IL-2 productivity associated with their progression of periodontal disease.

Adolescent↗
PubMed1997

Effect of adenosine on adrenergic neurotransmission and modulation by endothelium in canine pulmonary artery.

To determine the effect of adenosine on adrenergic neurotransmission in pulmonary vasculature and its modulation by endothelial cells, we studied canine pulmonary arteries under isometric conditions in vitro. Adenosine decreased the contractile responses to electrical field stimulation but had no effect on those to norepinephrine. This inhibitory effect was concentration dependent, with a rank order of potency of NECA > 2-chloroadenosine > adenosine >> APNEA (an A3-adenosine-receptor agonist) > CGS-21680 (an A2a agonist) > CCPA (an A1 agonist). Adenosine reduced the electrical field stimulation-evoked 3H overflow in superfused pulmonary artery previously soaked in [3H]norepinephrine. Pretreatment with the adenosine uptake blocker dipyridamole or the adenosine deaminase inhibitor deoxycoformycin enhanced the adenosine action, and this enhancement was not observed in the endothelium-denuded tissues. Adenosine deaminase activity was found in endothelial cells. Therefore, adenosine inhibits norepinephrine release via an A2b-receptor mechanism, an effect that may be modulated by uptake and metabolism by endothelial cells.

Adenosine↗
PubMed1997

Invasive thymoma with CD4+CD8+ double-positive T cell lymphocytosis.

Lymphocytosis in the peripheral blood is a very rare manifestation of thymoma. A 45-year-old man presented with a giant mediastinal mass involving pleural dissemination and peripheral T cell lymphocytosis. Biopsy of the mediastinal mass revealed invasive thymoma, and two-color analysis of peripheral lymphocytes showed a marked increase in CD4+CD8+ double-positive cells. Both thymoma and lymphocytosis were improved by a combination of chemotherapy and mediastinal irradiation.

CD4 Antigens↗
PubMed1997

Leukotriene antagonist prevents exacerbation of asthma during reduction of high-dose inhaled corticosteroid. The Tokyo Joshi-Idai Asthma Research Group.

To test whether the leukotriene antagonist ONO-1078 (pranlukast) prevents asthma exacerbations during reduction of high-dose inhaled corticosteroid, we conducted a randomized, double-blind, placebo-controlled study in 79 asthma patients requiring high doses (1,500 microg/d or more) of inhaled beclomethasone dipropionate (BDI) for clinical control (duration of asthma, 11.0 +/- 3.1 yr; duration of BDI treatment, 0.5 +/- 0.3 yr; FEV1 percentage of predicted, 80.7 +/- 2.0%). After a 2-wk run-in period, the doses of BDI were halved, while the patients were assigned to receive orally ONO-1078, 450 mg twice daily, or placebo. In the placebo group FEV1 decreased by 0.33 +/- 0.20 L after 6 wk (p < 0.001). Likewise, morning and evening PEF decreased by 46 +/- 7 L/min and 18 +/- 6 L/min, respectively. By contrast these variables were sustained above baseline in the ONO-1078 group. The number of daytime and nighttime asthma symptoms and the use of beta2-agonist increased in the placebo group, whereas they remained unchanged in the ONO-1078 group. In the placebo group concentrations of serum eosinophil cationic protein and exhaled nitric oxide increased (p = 0.007 and p = 0.025, respectively), compared with no change in the ONO-1078 group. Therefore, the leukotriene antagonist ONO-1078 prevents the asthma deterioration provoked by a 6-wk reduction of the dose of inhaled BDI into half.

Administration, Inhalation↗
PubMed1997

Host defensive, immunological, and microbiological observations of an early-onset periodontitis patient with virus-associated hemophagocytic syndrome.

Virus-associated hemophagocytic syndrome (VAHS) is a disorder characterized by benign generalized histiocytic proliferation and marked hemophagocytosis associated with systemic viral infection. An immunodeficiency which includes an extremely decreased leukocyte and platelet count together with abnormalities in the CD4/CD8 ratio are the most common features of VAHS. Here we report an early-onset periodontitis (EOP) patient with VAHS from the standpoint of host-parasite interaction to understand the effect of this systemic disorder which might possibly influence susceptibility to periodontal disease. The patient is a 16-year-old Japanese male clinically diagnosed as having generalized EOP with slight gingival inflammation and moderate bone loss. This patient manifested VAHS at 3 years of age, and then had an unusual 4 recurrences (at 5, 7, 11, and 14 years old). Laboratory tests conducted include: 1) complete blood analyses: 2) peripheral neutrophil functions (chemotaxis, phagocytosis, superoxide production, and adherence); 3) peripheral lymphocyte subpopulations and functions, T-cell proliferative activity and productivity of cytokines (interleukin-2 [IL-2], interferon gamma [IFN-gamma], and tumor necrosis factor alpha [TNF-alpha]); 4) serum cytokine levels (IL-1 beta, IL-2, soluble IL-2 receptor [sIL-2R], IL-4, IL-6, IFN-gamma, and TNF-alpha; 5) serum immunoglobulin G (IgG) antibody titers against periodontopathic bacteria; 6) serological human leukocyte antigen (HLA) typing; and 7) determination of bacterial flora of the periodontal pockets. The results indicated that the patient's neutrophil chemotaxis and random migration were below the normal range. In lymphocyte examinations, T-cell proliferative activity, IL-2, and IFN-gamma productivity were elevated. Serum IFN-gamma level was also significantly higher than normal range. No specific periodontopathic bacteria were predominant in the periodontal pockets, however, the serum IgG titer against Porphyromonas gingivalis was elevated throughout the examination period. It is suggested that VAHS might be a possible risk factor for periodontal disease, and hence may serve as a model in understanding the role of host defense mechanisms in the establishment of inflammatory periodontal disease.

Adolescent↗
PubMed1997

[Significance of rectal contractions during multichannel urodynamic study].

BACKGROUND: The influence of rectal contractions on urination was examined using multichannel urodynamic study. METHODS: We reviewed a total of 246 consecutive urodynamic studies. Each study consisted of a uroflow measurement and multi-channel urodynamic study, evaluating total vesical pressure, abdominal (rectal) pressure, subtracted detrusor pressure and perianal electromyography. Rectal contractions were defined as periodic fluctuations over 5 cmH2O in abdominal pressure detected by a rectal balloon catheter. No relationship of these contractions with cough and breathing was observed. RESULTS: Of the 246 patients, 17 (6.9%) had a positive study for rectal contractions. The patients, who had positive rectal contractions, averaged 70-year-old were older than negative subjects averaged 62-year-old. In multichannel urodynamics, the flow rate was significantly decreased, and electromyographic activity was increased at the moment of each rectal contractions. CONCLUSIONS: The rectal contractions are not artifactual and may be regarded as one of causes responsible for urinary difficulty in the elderly.

Adult↗
PubMed1997

[A case of non-smoking female with peripheral small lung squamous cell carcinoma discovered after operation of spontaneous pneumothorax].

We have experienced a lung cancer patient discovered after operation of pneumothorax by chance. The patient was 44-year-old female who had been followed up for right pneumothorax in menstruation. She got pneumothorax in menstruation recurrently complained of chest pain. Chest X-p revealed right pneumothorax. We never discovered views of catamenial pneumothorax by thoracoscopy. Partial resection of hypertrophic pleura of right S1 was performed by video assist thoracoscopic surgery. Histological diagnosis was bulla formation with a tiny focus of squamous cell carcinoma in situ. In addition, right upper lobectomy and lymph node dissection were performed. Metastasis was not recognized any lymph node. No recurrence has been observed for 17 months.

Adult↗
PubMed1997

[Role of neutrophil elastase in allergen-induced airway microvascular leakage in sensitized guinea pigs].

To determine the role of neutrophil elastase in allergen-induced airway microvascular leakage, we assessed vascular permeability of guinea pig trachea by measuring the extravasation of Evans blue dye in the circulating blood. Inhalation of ovalbumin (OA) to guinea pigs sensitized with OA caused Evans blue extravasation, indicating an increased microvascular permeability. Pretreatment with ONO-5046 a specific inhibitor of neutrophil elastase, inhibited OA-induced vascular leakage in a dose-dependent manner. Tracheal instillation of human neutrophil elastase likewise increased microvascular permeability, and this effect was almost completely abolished by ONO-5046. Challenge with OA increased the number of neutrophils and neutrophil elastase activity in the bronchoalveolar lavage fluid, and these effects were inhibited by ONO-5046. These results suggest that neutrophil accumulation into the airway and the subsequent release of neutrophil elastase may play a role in the airway microvascular leakage produced by antigen challenge.

Animals↗
PubMed1997

Japanese population DNA typing data for the loci LDLR, GYPA, HBGG, D7S8, and GC.

Population studies on the five loci LDLR, GYPA, HBGG, D7S8, and GC (PM loci) were carried out in a sample of 366 unrelated Japanese individuals living in Gifu Prefecture (central region of Japan) using the AmpliType PM PCR Amplification and Typing kit (Perkin Elmer). For all loci, no significant deviations from Hardy-Weinberg equilibrium could be found in our Japanese population sample. The combined mean exclusion chance and power of discrimination for the PM loci were 0.68 and 0.993, respectively. The Japanese and Chinese population data were similar for the all loci. The Japanese and Korean population data were similar for all loci other than D7S8. Significant differences were observed between the Japanese population data and the 16 other population data compared for 3 loci or more.

Asian People↗
PubMed1997

Role of the sarcolemmal sodium pump in nitroprusside-induced vasodilation of the pulmonary artery.

To elucidate the mechanism of nitrovasodilator-induced pulmonary vasodilation, we examined the role of sodium pump and K+ channels in the relaxant responses of canine pulmonary arterial rings to sodium nitroprusside (SNP) under isometric conditions in vitro. Pretreatment with the sodium pump inhibitor ouabain attenuated the SNP-induced vasodilation of KCI-contracted tissues, so that the maximal relaxation decreased from 90 +/- 7 to 62 +/- 6% (P < 0.01), and the negative logarithm of SNP concentration required to produce a half-maximal effect (pD2) decreased from 5.9 +/- 0.4 to 5.1 +/- 0.4 (P < 0.01). This effect was not altered by mechanical removal of the endothelium. In contrast, pretreatment with K+ channel blockers including iberiotoxin, apamin and glibenclamide did not change the relaxant responses to SNP. Incubation of endothelium-denuded rings with SNP increased ouabain-sensitive 86Rb uptake in a dose-dependent manner, an effect that was inhibited by KT 5823, a cGMP-dependent protein kinase inhibitor. These results suggest that activation of sarcolemmal sodium pump may be involved in the nitrovasodilator-induced cGMP-mediated pulmonary vasodilation, whereas K+ channels may play a less important role in this action.

Animals↗
PubMed1997

Inhaled cromoglycate reduces airway neurogenic inflammation via tachykinin antagonism.

To determine whether sodium cromoglycate (SCG) inhibits airway neurogenic inflammation and, if so, to elucidate the mechanism of its action, we studied plasma extravasation evoked by hypertonic saline in the rat trachea by measuring the amount of extravasated Evans blue dye. Inhalation of hypertonic saline (5-15% NaCl) produced microvascular leakage, an effect that was reduced by pretreatment with SCG in a dose-dependent manner. Inhaled SCG (10 mg/ml) for 2 min did not affect the basal vascular permeability, but significantly inhibited the 10% NaCl-induced plasma extravasation by 34%. SCG likewise inhibited the responses of microvascular leakage to substance P aerosols, whereas it was without effect on those to platelet activating factor aerosols. These results suggest that SCG inhibits airway neurogenic inflammation presumably via functional antagonism of tachykinins, and that this novel effect may be involved in the therapeutic efficacy of SCG in the treatment of airway inflammatory diseases including asthma.

Administration, Inhalation↗
PubMed1996

Crystallization and preliminary crystallographic analysis of cabbage histidinol dehydrogenase.

Recombinant Brassica oleracea histidinol dehydrogenase (HDH) has been crystallized in various space groups using the method of vapour diffusion. The presence or absence of inhibitors and substrates as well as the use of different precipitants has enabled the growth of five different crystal forms. Extensive searches with the first crystal form (A) failed to produce any useful heavy-atom derivatives, mainly because of the instability of the crystals. This provoked the search for further crystal forms in the hope of finding more suitable crystals. At least two of these crystal forms are of interest for further study.

Journal Article↗
PubMed1996

113Cd nuclear magnetic resonance studies of cabbage histidinol dehydrogenase.

Histidinol dehydrogenase (HDH), a dimeric protein, catalyzes two sequential oxidation reactions to yield L-histidine from L-histidinol via L-histidinal. HDH contains 1 mol of Zn(II) per mol of subunit, and removal of this metal abolishes the enzymatic activity. On substitution of Zn(II) with 113Cd(II), the enzyme ([113Cd]HDH) showed similar catalytic activity. The 113Cd NMR spectra of [113Cd]HDH were measured under various conditions. The 113Cd NMR spectrum of [113Cd]HDH showed a resonance at 110 ppm, which indicates that the metal ion is bound to the protein by a combination of nitrogen and oxygen ligands. 113Cd NMR spectra of [113Cd]HDH were measured as complexes with two substrates (L-histidinol and DL-histidinal) and four inhibitors (imidazole, histamine, L-histidine, and DL-4-(4-imidazolyl)-3-amino-2-butanone) in the absence and presence of NAD+. Significant shifts of [113Cd]-HDH resonance in the presence of the ligand indicate that the metal ion is located in the catalytic site of HDH and that substrates and inhibitors interact with the metal ion. The role of the metal ion in the HDH reaction is discussed.

Alcohol Oxidoreductases↗
PubMed1996

Analysis of the STR loci HUMF13A01, HUMFXIIIB, HUMLIPOL, HUMTH01, HUMTPOX and HUMVWFA31 in a Japanese population.

Population studies on six short tandem repeat loci, HUMF13A01, HUMFXIIIB, HUMLIPOL, HUMTH01, HUMTPOX and HUMVWFA31 were carried out in a sample of unrelated Japanese individuals (n = 337-545) living in Gifu Prefecture (central region of Japan). Five alleles could be identified for HUMFXIIIB, six for HUMF13A01, HUMLIPOL, HUMTH01 and HUMTPOX, and eight for HUMVWFA31. For all/six loci no deviations from the Hardy-Weinberg equilibrium hypothesis were detected. The mean exclusion chance ranged from 0.22 to 0.60, the power of discrimination from 0.63 to 0.93, and the expected heterozygosity from 0.43 to 0.80. Allele frequency distributions for the loci in the Japanese sample were not similar to those in samples from other racial or ethnic groups except for the Chinese (for HUMTPOX). The results demonstrate that HUMTH01, HUMTPOX and HUMVWFA31 are more useful for forensic investigations in the Japanese population that the other three loci.

Alleles↗
PubMed1996

Nicotine prolongs neutrophil survival by suppressing apoptosis.

Neutrophil accumulation in the lung is implicated in the pathogenesis of pulmonary emphysema and chronic bronchitis associated with cigarette smoking. To determine whether nicotine contributes to this accumulation through the prolongation of neutrophil survival, we examined the survival rates of isolated neutrophils cultured with or without nicotine. We found that nicotine prolonged neutrophil survival in a dose-dependent fashion, with a maximum effect at 10(-6) mol/L. The survival rate at 72 hours was 35.6% +/- 1.2% in medium with 10(-6) mol/L nicotine, compared with 15.5% +/- 0.5% in control medium (mean +/- SEM; p < 0.01), as determined by trypan blue dye exclusion. This prolongation was brought about by suppression of apoptosis, as evidenced by both transmission electron and fluorescence microscopy, and was associated with the preservation of neutrophil functions such as chemotaxis and O2- generation. The prolongation of survival caused by nicotine was abrogated by the addition of Pro-Lys-Arg-NH2, a competitive inhibitor of the specific binding of nicotine to noncholinergic receptors on neutrophils. However, the prolongation of survival caused by nicotine was not suppressed in the presence of K-252b, an inhibitor of protein kinase C. These findings suggest that nicotine prolongs neutrophil survival through noncholinergic nicotine receptors and new protein synthesis, without activation of protein kinase C.

Analysis of Variance↗
PubMed1996

Function of beta 1 integrins on human decidual cells during implantation.

In the present study, the effects of antibodies against specific beta 1 integrin heterodimers on mouse embryo attachment and spreading were tested to identify the role of the beta 1 integrins in early implantation. We developed assays for the attachment of mouse embryos and for trophoblastic spreading on cultured human decidual cells. Blastocysts became attached to the cultured decidual cells in the presence of a purified mouse monoclonal IgG1 antibody (negative control) after the embryos hatched from the zona pellucida. The majority of hatched blastocysts attached within 24 h of culture. Blastocysts that were attached to decidual cells exhibited extensive outgrowth after 48 h. The addition of antibodies directed against the beta 1 and alpha integrin subunits to the cultured decidual cells did not affect the rates of hatching or attachment of the blastocysts. However, the outgrowth of embryos on the decidual cells was inhibited by the addition of a monoclonal antibody against the beta 1 subunit in a dose-dependent manner, implying that blastocyst attachment and outgrowth are mediated by different mechanisms. Although the area of trophoblast outgrowth in the presence of a mouse monoclonal lgG1 antibody was increased during 96 h of culture, anti-beta 1 antibody blocked the outgrowth of trophoblasts in a dose-dependent manner. Both the incidence and extent of trophoblastic outgrowth were also significantly reduced in the presence of antibodies against the alpha 1, alpha 2, alpha 5, and alpha 6 subunits. These observations suggest that beta 1 integrins on decidual cells may be involved in blastocyst development and differentiation following attachment.

Adult↗