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Biomedical subjects

Shinji Nakao

Publications and source records attributed to Shinji Nakao.

At least 91 records · Page 5Linked to original sources
PubMed2002

Alpha(1L)-, but not alpha(1H)-, adrenoceptor antagonist prevents allergic bronchoconstriction in guinea pigs in vivo.

alpha-Adrenoceptors have been classified into alpha(1)- and alpha(2)-adrenoceptors. Recently, the alpha(1)-adrenoceptors were divided into two subtypes: alpha(1L) with low affinity and alpha(1H) with high affinity for prazosin. Little is known concerning the role of each subtype of alpha(1)-adrenoceptor in asthma. We investigated the effects of specific antagonists of alpha(1)- and alpha(2)-, alpha(1H)-, alpha(1L)-, and alpha(2)-adrenoceptors, namely moxisylyte, prazosin, 3-[N-[2-(4-hydroxy-2-isopropyl-5-methylphenoxy) ethyl]-N-methylaminomethyl]-4-methoxy-2, 5, 6-trimethylphenol hemifumarate (JTH-601), and yohimbine, respectively, on antigen-induced airway reactions in guinea pigs. Fifteen minutes after intravenous administration of moxisylyte (0.01, 0.1 or 1 mg/kg), prazosin (0.01, 0.1, 1 or 10 mg/kg), JTH-601 (1, 3, 6 or 10 mg/kg) or yohimbine (0.1 or 1 mg/kg), passively sensitized and artificially ventilated animals received an aerosolized antigen challenge. Bronchial responsiveness to inhaled methacholine was assessed as the dose of methacholine required to produce a 200% increase in the pressure at the airway opening (PC(200)) in non-sensitized animals. JTH-601 and moxisylyte, but not prazosin or yohimbine, dose dependently inhibited antigen-induced bronchoconstriction. None of the tested drugs altered PC(200). JTH-601 significantly reduced leukotriene C(4) levels in bronchoalveolar lavage fluid obtained 5 min after antigen challenge, but prazosin did not. These results indicate that prevention of antigen-induced bronchoconstriction by blockade of alpha-adrenoceptors is due to the inhibition of mediator release via alpha(1L)-adrenoceptor antagonism.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2002

Clinical significance of a minor population of paroxysmal nocturnal hemoglobinuria-type cells in bone marrow failure syndrome.

A minor population of blood cells deficient of glycosylphosphatidylinositol (GPI)-anchored membrane proteins is often detected in patients with aplastic anemia (AA), though the clinical significance of such paroxysmal nocturnal hemoglobinuria (PNH)-type cells remains unclear. To clarify this issue, we studied 164 patients with myelodysplastic syndrome (MDS) for the presence of CD55(-)CD59(-) granulocytes and red blood cells using sensitive flow cytometry. Among the different subgroups of MDS, a significant increase (ie, at least 0.003%) of PNH-type cells was detected in 21 of 119 patients with refractory anemia (RA); this frequency (17.6%) of RA patients with increased PNH-type cells (PNH(+) patients) was much lower than what we previously reported (52.0%) for AA patients. PNH(+) RA patients had distinct clinical features compared with RA patients without increased PNH-type cells (PNH(-) patients), such as less pronounced morphologic abnormality of blood cells, more severe thrombocytopenia, lower rates of karyotypic abnormality (4.8% vs 32.8%) and of progression to acute leukemia (0% vs 6.2%), higher probability of response to cyclosporine therapy (77.8% vs 0%), and higher incidence of HLA-DR15 (90.5% vs 18.5%). These data indicate that the presence of a minor population of PNH-type cells suggests a benign type of bone marrow failure, probably caused by an immunologic mechanism. To choose an appropriate therapy, peripheral blood should be tested using sensitive flow cytometry for the presence of PNH-type cells in all patients with bone marrow failure before treatment.

Adolescent↗
PubMed2002

Identification of novel minor histocompatibility antigens responsible for graft-versus-leukemia (GVL) effect on chronic myeloid leukemia: usefulness of determining the clonotype of T cells associated with GVL effect after donor leukocyte infusion.

In an attempt to identify novel mHas that induce GVL effect on chronic myeloid leukemia (CML), we analyzed peripheral blood T cells of 4 CML patients who relapsed after allogeneic stem cell transplantation and received donor leukocyte infusion (DLI), for the presence of antigen-specific T-cell proliferation. When peripheral blood lymphocyte collected from patients every 2-4 weeks after DLI were subjected to complementarity determining region (CDR) 3 size distribution analysis of T-cell receptor beta chain, clonal proliferation of a limited number of CD4+ T cells was detected in all patients 2-4 months after DLI in association with the occurrence of GVL effect. To identify an epitope of the T-cell clone that probably mediates GVL effect, we determined nucleotide sequence of CDR3 of the T cells and screened the database for the presence of T cells with a CDR3 sequence similar to that of the GVL-mediating T cells. In one of 4 patients who showed clonal proliferation of a BV16+ T cell, a CDR3 motif QDR was shared by a T-cell clone that recognized an 85-99 peptide of myelin basic protein presented by HLA-DRB1*1501. When the I domain of CD49b, a candidate peptides that could bind to this CDR3 motif in the context of DRB1*1501, was studied, codon 256 in the I domain of the recipient was ATT (Ile) while that of the donor was GTT (Val). The BV16+ T cells showed proliferative response to DRB1*1501 L-cell transfectant pulsed with the recipient type CD49b. Thus, identification of a clonotype of T cells that mediate GVL effect in patients receiving DLI and a search for T-cell clones with a similar clonotype to the GVL-mediating T cells followed by screening of polymorphic peptides that could stimulate the T cells appears to be useful in identifying novel mHas serving a target antigens of GVL effect.

Base Sequence↗
PubMed2002

Accelerated telomere length shortening in granulocytes: a diagnostic marker for myeloproliferative diseases.

OBJECTIVE: The telomere in mature myeloid cells derived from abnormal progenitor cells of myeloproliferative diseases (MPDs) may shorten more rapidly than that in T lymphocytes, which are considered to be derived from normal clones. To test this hypothesis, we measured telomere lengths in granulocytes and T lymphocytes from patients with MPDs and compared them with those from normal individuals. MATERIALS AND METHODS: Granulocytes and T lymphocytes were separated from the peripheral blood of 65 patients with MPDs (25 chronic myelogenous leukemia [CML], 16 polycythemia vera, 19 essential thrombocythemia, 5 chronic idiopathic myelofibrosis) and 35 normal individuals. Genomic DNA from each cell fraction was subjected to Southern blot hybridization to determine the mean telomere length. RESULTS: Telomere lengths in granulocytes from patients with MPDs were significantly shorter than those from normal individuals (vs CML, p = 0.002; vs other MPDs, p < 0.0001). However, there was no statistical difference in telomere length in T lymphocytes between MPD patients and normal individuals (vs CML, p = 0.35; vs other MPDs, p = 0.85). DeltaTRF (terminal restriction fragment) in patients with MPDs, which is defined as the difference in telomere length between granulocytes and T lymphocytes, was significantly longer than that in normal individuals. CONCLUSIONS: The results support the disease theory that MPDs result from extensive proliferation of myeloid progenitor cells, leading to accelerated telomere length shortening in mature granulocytes. An increase in DeltaTRF over the standard value (>1.74 kb) may be useful for discriminating leukocytosis due to MPDs from reactive leukocytosis.

Adult↗
PubMed2002

Effect of candesartan, a type 1 angiotensin II receptor antagonist, on bronchial hyper-responsiveness to methacholine in patients with bronchial asthma.

AIMS: Angiotensin II is a putative mediator in bronchial asthma. There have been very few studies investigating the involvement of angiotensin II receptors in bronchial hyper-responsiveness in asthmatic patients. We examined the effect of candesartan cilexetil, a specific angiotensin II type 1 (AT1) receptor antagonist, on bronchial responsiveness to inhaled methacholine in patients with asthma. METHODS: Bronchial responsiveness to methacholine, assessed as the concentration of methacholine producing a 20% fall in FEV1 (PC20-FEV1), was measured on three occasions 2 weeks apart in 11 stable asthmatic patients. Candesartan cilexetil (8 mg once a day) or a placebo was orally administered for 1 week before the methacholine provocation test in a double-blind, randomized, crossover manner. RESULTS: Although there were no significant differences between treatment periods in FEV1 values at baseline, the geometric mean (95% CI) PC20-FEV1 values increased significantly (P = 0.041) from 0.691 (0.379, 1.259) mg ml-1 with placebo to 0.837 (0.506, 1.384) mg ml-1 with candesartan. Candesartan decreased the mean (95% CI) arterial blood pressure (placebo: 95.6 (89.0, 102.2) mmHg, candesartan: 86.4 (79.8, 93.1) mmHg, P = 0.015). There was no correlation between the change in blood pressure and the change in PC20-FEV1. CONCLUSIONS: We conclude that AT1 receptors are involved in bronchial hyper-responsiveness in asthmatic patients.

Administration, Inhalation↗
PubMed2002

Aplastic anaemia with 13q-: a benign subset of bone marrow failure responsive to immunosuppressive therapy.

In an attempt to determine the pathological significance of a long arm deletion of chromosome 13 (13q-) in bone marrow failure syndrome, we reviewed the clinical records of nine patients who were initially diagnosed with aplastic anaemia due to bone marrow hypoplasia without dysplasia. Six patients responded to immunosuppressive therapy and the other three improved with steroids. None of the patients developed acute leukaemia (follow up: 54-129 months) and the estimated 5-year survival was 78%. These findings indicate that pancytopenia with 13q- represents bone marrow failure of a benign nature, similar to aplastic anaemia without karyotypic abnormalities, rather than preleukaemia.

Adult↗
PubMed2002

Effect of ozagrel hydrochloride, a thromboxane synthetase inhibitor, on alcoholic beverage-induced bronchoconstriction in asthmatic patients.

Acetaldehyde is thought to be a main factor of alcohol-induced asthma. The thromboxane (TX) synthetase inhibitor, ozagrel hydrochloride, inhibits acetaldehyde-induced bronchoconstriction in asthmatic patients. The present study evaluated the involvement of TXA(2) on alcoholic beverage-induced bronchoconstriction. Four patients with alcohol-induced asthma received ozagrel (400 mg for 4 days) or placebo using a single-blind, randomized, cross-over design. On two separate study days, each subject drank the same brand and volume of alcoholic beverage (beer or Japanese sake) and bronchoconstriction was assessed as the change in peak expiratory flow (PEF). The effect of ozagrel on the aerosolized challenge of acetaldehyde was investigated in the same subjects. Although aerosolized acetaldehyde-induced bronchoconstriction was significantly prevented by ozagrel, there were no differences in the time course of the decrease in PEF or the maximum fall in PEF after alcohol intake between placebo and ozagrel. We conclude that TXA(2) is not involved in alcoholic beverage-induced bronchoconstriction.

Acetaldehyde↗
PubMed2002

A phase I study of carboplatin and docetaxel for advanced non-small cell lung cancer using the continual reassessment method.

PURPOSE: This phase I study was designed to determine the maximum tolerated dose of carboplatin combined with a fixed dose of docetaxel (60 mg/m(2)) and the safety and efficacy of this combination chemotherapy in unresectable non-small cell lung cancer. METHODS: Patients received a 60 min intravenous infusion of docetaxel followed by a 90 min infusion of carboplatin with dose escalation using the continual reassessment method. The starting dose of carboplatin was targeted to an area under the plasma concentration curve of 3 using Calvert's equation and dose escalation was based on course 1 toxicities. RESULTS: From January 1999 to February 2000, 16 patients entered this trial. The major dose-limiting toxicity was neutropenia. Thrombocytopenia was rare and major non-hematological toxicities included fever that was not associated with neutropenia and grade 2 nausea and vomiting. Objective responses were seen in five patients (response rate 31.3%). CONCLUSIONS: Based on this phase I clinical trial, the maximum tolerated dose of carboplatin combined with 60 mg/m(2) of docetaxel was a target area under the plasma concentration curve (tAUC) of 6 and the recommended tAUC for further trials is 5.5. This combination appeared to be effective for non-small cell lung cancer. A phase II clinical trial is recommended using 60 mg/m(2) of docetaxel and carboplatin with a tAUC of 5.5.

Aged↗
PubMed2002

Marked difference in pathophysiology between tissue factor- and lipopolysaccharide-induced disseminated intravascular coagulation models in rats.

OBJECTIVE: Tissue factor and lipopolysaccharide frequently have been used to induce disseminated intravascular coagulation in experimental animal models. Although the pathophysiology of disseminated intravascular coagulation may differ according to the agents used to induce it, these previous models have not distinguished between the use of different disseminated intravascular coagulation-inducing agents. In this study, we attempted to evaluate the characteristic features of these agents in two types of disseminated intravascular coagulation models, with special reference to selected hemostatic parameters and pathologic findings in the kidney. DESIGN: Prospective, comparative, experimental study. SETTING: Laboratory at a university hospital. SUBJECTS: Twenty-seven male Wistar rats, age 6-7 wks, weighing 160-170 g. INTERVENTIONS: Three groups of animals were studied: a control group (n = 8) receiving physiologic saline, a tissue factor-treated group (n = 11) receiving tissue factor 3.75 units/kg, and a lipopolysaccharide-treated group (n = 8) receiving lipopolysaccharide 30 mg/kg; each group sustained infusion for 4 hrs via the tail vein. MEASUREMENTS AND MAIN RESULTS: The degree of hemostatic activation in both types of experimental disseminated intravascular coagulation was identical, based on the results of thrombin-antithrombin III complex levels. Markedly elevated D-dimer concentrations were observed without organ dysfunction or fibrin deposition in the kidney on administration of tissue factor, whereas markedly elevated plasminogen activator inhibitor activity, decreased antithrombin III activity, severe organ failure, and marked fibrin deposition in the kidney were observed for lipopolysaccharide administration. CONCLUSION: Because pathophysiology differed remarkably between the tissue factor- and lipopolysaccharide-induced disseminated intravascular coagulation models in rats, we recommend that they be assessed carefully as distinct entities to determine implications of their experimental and clinical use.

Animals↗
PubMed2002

Effect of intranasal administration of CV-11974, a type 1 angiotensin II receptor antagonist, on airway hyperresponsiveness and airway inflammation induced by antigen inhalation in guinea pigs.

BACKGROUND: Angiotensin II is a putative mediator in asthma, but the effect of topical administration of type 1 angiotensin II (AT1) receptor antagonists on allergic airway reactions is not known. OBJECTIVE: To investigate the effect of intranasal administration of CV-11974, an AT1 receptor antagonist, and of PD123319, a type 2 angiotensin II (AT2) receptor antagonist, on antigen-induced airway reactions in guinea pigs. METHODS: Thirty minutes after intranasal topical administration of CV-11974 (0.1 or 1.0 mg/ml) or PD123319 (10 mg/ml) into the airways, the animals were given an antigen challenge. Airway hyperresponsiveness and bronchoalveolar lavage fluid were analyzed 24 h after the antigen challenge. RESULTS: Although these compounds did not inhibit antigen-induced early-phase bronchoconstriction or late-phase airway eosinophilia, intranasal administration of CV-11974 (but not PD123319) inhibited antigen-induced airway hyperresponsiveness in a dose-dependent manner 24 h after the antigen challenge. CONCLUSION: Intranasal administration of an AT1 receptor antagonist reduces antigen-induced airway hyperresponsiveness.

Administration, Inhalation↗
PubMed2002

Reasons for the delays in the definitive diagnosis of lung cancer for more than one year from the recognition of abnormal chest shadows.

OBJECTIVE: Primary lung cancer generally has a poor prognosis if not diagnosed at an early stage. But some lung cancers grow very slowly. In particular, adenocarcinoma is sometimes observed for years with no change of tumor size. In this study, we examined the reasons for the delays in reaching a definitive diagnosis of lung cancer. METHODS: We retrospectively reviewed primary lung cancer cases between January 1995 and December 1999 and examined those whose definitive diagnoses were delayed for more than a year. RESULTS: A total of 222 primary lung cancers were diagnosed. Of those, 19 patients (group A, 8.6%) were diagnosed after more than a year, and the other 203 (group B, 91.4%) were diagnosed within one year. The proportion of women in group A was significantly higher than that in group B (p<0.05). The mean age of group A was significantly younger than that of group B (p<0.05). The Brinkman Index of group A was significantly lower than that of group B (p<0.05). The histologic types were significantly different between the two groups (p<0.05). In group A, 18 patients (94.7%) had adenocarcinomas. Five primary reasons for the delays in group A were identified: 1) Four patients were tentatively diagnosed as inflammation or benign tumor on CT and were consequently not followed-up. 2) The chest CT shadows in 6 patients were suspected lung cancers but transbronchial lung biopsy findings did not show malignancy. 3) Four patients were tentatively diagnosed as inflammation or benign tumor on CT, but the tumors showed only very slow growth or no change at all. 4) The chest CT shadows of 2 patients were suspected lung cancer, but the patients refused to undergo video-assisted thoracic surgery (VATS) or closer examination. 5) Three patients did not consult medical facilities for a second examination. CONCLUSIONS: Many of the adenocarcinomas reviewed in our study grew slowly or remained unchanged for years. Doctors are mainly responsible for the delays in the definitive diagnosis and should aggressively perform VATS or closer examinations without hesitation.

Adenocarcinoma↗
PubMed2002

Atorvastatin reduces plasma levels of factor VII activity and factor VII antigen in patients with hyperlipidemia.

Atorvastatin is a powerful new synthetic 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor currently in clinical use. Its effects on plasma levels of factor VII were examined in 30 hyperlipidemic patients. After 12 weeks of atorvastatin treatment, factor VII activity (FVIIc) and factor VII antigen (FVIIag) levels had decreased by 13% (p < 0.0001) and 12% (p < 0.0001), respectively. The decreased concentrations of serum triglycerides correlated with decreases in FVIIc levels (r = 0.54, p = 0.0023) and FVIIag levels (r = 0.59, p = 0.0006) at 12 weeks of treatment with atorvastatin. No significant changes were seen in activated factor VII (FVIIa) levels. Plasma concentrations of fibrinogen were slightly, but not significantly, increased at 12 weeks. No significant changes were seen in plasminogen activator inhibitor-1 levels. The effects of atorvastatin on FVII may contribute to a decreased thrombotic potential, resulting in fewer thromboembolic events, including a reduction in coronary heart disease.

Aged↗
PubMed2002

[A case of infective endocarditis accompanied with pulmonary complications in a drug addict].

A 21-year-old man who had a history of intravenous drug addiction was admitted with complaints of high fever and a productive cough. Chest CT on admission showed multiple consolidations, and pneumonia was initially diagnosed and treated. Because echocardiography after admission showed vegetation, with no bacteriological findings, attached to the tricuspid valve, right-sided infective endocarditis was diagnosed. After antibiotic therapy was changed, his fever was reduced and the inflammatory findings were eliminated. In the western world, most cases of right-side infective endocarditis are caused by drug addicts, but in Japan, this disease is very rare. Right-side infective endocarditis in drug addicts causes a high rate of pulmonary complications, in particular, septic pulmonary embolism. Many drug addicts suffering from pulmonary complications may consult doctors, but if the latter are not well-informed about this disease, it may not be possible to give an accurate diagnosis or proper treatment.

Adult↗
PubMed2002

Induction of vasoactive substances differs in LPS-induced and TF-induced DIC models in rats.

We have investigated the role of two vasoactive substances, nitric oxide (NO)and endothelin (ET), in the pathophysiology of disseminated intravascular coagulation (DIC), using two types of DIC models. Experimental DIC was induced by sustained infusion of 0.1, 1, 10, or 50 mg/kg lipopolysaccharide (LPS), or 3.75 U/kg thromboplastin (TF), for 4 h via the rat tail vein. Plasma levels of both NOX (metabolites of NO) and ET were significantly increased following infusion of 0.1 mg/kg or greater of LPS in the LPS-induced DIC rat model. In contrast, although a marked increase in the plasma levels of NOX was observed, only a slight increase in plasma ET levels was seen in the TF-induced DIC rat model. No significant differences in the plasma levels of platelets or thrombin-ATIII complex were observed among the TF-induced and LPS (50 mg/dl)-induced DIC models. However, plasma NOX levels rose significantly higher in the TF-induced model, relative to the LPS-induced model (p <0.01). Conversely, plasma ET levels were significantly greater after LPS-induction, compared to TF-induction, of DIC (p <0.01). Vasoconstriction, as well as depressed fibrinolytic activity, may be additional factors leading to severe organ dysfunction in the LPS-induced DIC rat model. Moreover, vasodilatation, as well as enhanced fibrinolytic activity, may help to prevent rats from severe organ dysfunction in the TF-induced DIC model. Our results suggest that modulator of vasoactive substances should be examined in the treatment of DIC.

Animals↗