Biomedical subjects

T Murayama

Publications and source records attributed to T Murayama.

At least 109 records · Page 6Linked to original sources

PubMed1999

[Genetic disorders causing abnormal LDL-cholesterol levels].

Various epidemiological studies and lipid intervention trials have revealed that serum LDL-cholesterol level correlates to the incidence in ischemic heart disease, and decreasing the level can prevent cardiac events. Inherited diseases causing abnormal LDL-cholesterol levels are discussed in this article, including their animal models. Familial hypercholesterolemia, familial ligand-defective apolipoprotein B100, familial combined hyperlipidemia and cholesterol ester storage disease result in elevation of serum LDL-cholesterol. On the other hand, serum LDL-cholesterol is decreased in abetalipoproteinemia and familial hypobetalipoproteinemia. The development of genetic engineering technology has elucidated the mechanism of these genetic disorders and elaborated their animal models. Although most of them cause atherosclerotic or psychoneurological diseases, fundamental therapy remains to be established, such as gene therapy.

Abetalipoproteinemia↗

PubMed1998

Regulation of noradrenaline release by S-nitroso-cysteine: inhibition in PC12 cells in a cyclic GMP-independent manner.

Nitric oxide (NO), including NO free radicals (*NO) and peroxynitrite (OONO-), modulates the release of neurotransmitters from neuronal tissues. Although we reported that S-nitroso-cysteine stimulated noradrenaline release in brain slices, we now show that only S-nitroso-cysteine inhibits noradrenaline release from PC12 cells. S-Nitroso-cysteine inhibited, in a dose-dependent manner (up to 0.6 mM), the Ca2+ -dependent [3H]noradrenaline release induced by ionomycin, adenosine 5'-O-(3-thiotriphosphate), or high K+, from PC12 cells labeled with [3H]noradrenaline. Sodium nitroprusside, S-nitroso-N-acetylpenicillamine, and 1-hydroxy-2-oxo-3,3-bis(2-aminoethyl)-1-triazene, which specifically release NO free radicals in neutral buffer, had minimal effects on [3H]noradrenaline release, although they markedly stimulated cyclic GMP accumulation. 3-Morpholinosydonimine, which releases peroxynitrite, had no effect on either [3H]noradrenaline release or cyclic GMP accumulation. S-Nitroso-cysteine inhibited phorbol 12-myristate 13-acetate- and mastoparan (wasp venom toxin)-induced [3H]noradrenaline release. These findings suggest that 1) S-nitroso-cysteine, but not other NO donors, inhibits some common process occurring during noradrenaline release in PC12 cells, 2) neither NO radicals, peroxynitrite, nor cyclic GMP mediate the inhibitory effects of S-nitroso-cysteine in PC12 cells.

Animals↗

PubMed1998

Regulation of cyclic GMP and cyclic AMP production by S-nitroso-cysteine in rat thymocytes.

Nitrogen monoxides regulate cellular functions via cyclic GMP accumulation induced by nitric oxide (NO). However, the effects of NO on the cyclic AMP system have not been studied in detail. In this study, we investigated the effects of various NO donors on cyclic GMP and cyclic AMP accumulation in rat thymocytes. Addition of S-nitroso-cysteine stimulated cyclic GMP accumulation at concentrations up to 10 microM, but was inhibitory at higher concentrations. Other NO donors such as sodium nitroprusside stimulated cyclic GMP accumulation markedly without causing inhibition. S-Nitroso-cysteine, but not other NO donors, inhibited forskolin-stimulated cyclic AMP accumulation in intact thymocytes and thymocyte membrane preparations. The inhibitory effect of S-nitroso-cysteine on cyclic AMP accumulation in membranes was partially reversed by dithiothreitol treatment. These findings suggest that the cyclic AMP system in thymocytes is specifically modified by S-nitroso-cysteine, and not by the NO/cyclic GMP system.

Adenylyl Cyclase Inhibitors↗

PubMed1998

Exocytotic stimulation promotes association of the ADP-ribosylation factor with PC12 cell membranes.

ADP-ribosylation factors (ARFs) are a family of small molecular, monomeric GTP-binding (G) proteins, initially identified by their ability to enhance cholera toxin (CTX) ADP-ribosyltransferase activity. ARFs have been implicated in protein transport and vesicle and endosome fusion. Although several reports show that synthetic peptides of the N-terminus of ARF inhibited Ca(2+)-dependent exocytosis in permeabilized adrenal chromaffin cells, the role of ARFs in exocytosis has not been established. In this study, we investigated the translocation of ARFs to the membrane fraction from the cytosol fraction in PC12 cells after exocytotic stimulation by measuring the immunoreactivity of ARFs (with anti-ARF anti-serum and with anti-ARF3 antibodies) and enzymatic ARF activity, which enhances the CTX effect. Both the immunoreactivity and the enzymatic activity of ARF in the membrane fraction increased about twofold, significantly, after exocytotic stimulation with ATP and KCl. The translocation of ARF and noradrenaline release was observed in the presence of extracellular CaCl2, but not in the absence of CaCl2. The ARF translocated to the membrane fraction after stimulation in intact cells seemed to be an inactive, perhaps is the GDP form, because ARF did not activate CTX in the absence of guanosine 5'-O-(thiotriphosphate) (GTP gamma S). As previously reported, ARF in the active, GTP gamma S-bound state bound to the membrane fractions. Thus ARF may have been active during translocation and inactivated later. The immunoreactivity of Gs alpha, one of the trimeric G proteins, was not changed before or after stimulation. These findings suggest that ARFs translocate to membranes from the cytosolic fraction after exocytotic stimulation in PC12 cells, and raise the possibility that ARFs regulate exocytosis.

ADP-Ribosylation Factors↗

PubMed1998

Death by a dopaminergic neurotoxin, 1-methyl-4-phenylpyridinium ion (MPP+) and protection by EGF in GH3 cells.

In this study we investigated the uptake and effect of a dopaminergic neurotoxin, 1-methyl-4-phenylpyridinium ion (MPP+) on a clonal strain, GH3 cells, established from rat anterior pituitary. Although the level was very low compared with that in PC12 cells, a clonal rat pheochromocytoma cell line, there was a detectable amount of tyrosine hydroxylase protein in GH3 cells. The levels of monoamines including dopamine in GH3 cells were also very low compared with those in PC12 cells. [3H]MPP+ was incorporated to GH3 cells in a concentration-dependent manner and the uptake was inhibited by nomifensine, an inhibitor of dopamine transporter. Addition of 200 microM MPP+ stimulated the leakage of lactate dehydrogenase (LDH) after a lag of 24 h. Pretreatment with 50 ng/ml of epidermal growth factor (EGF), but not nerve growth factor (NGF) or brain-derived neurotrophic factor (BDNF), protected against MPP+-induced cell death. These findings show that: (1) MPP+ uptake to GH3 cells was via an effective dopamine transport system and causes delayed cell death, and (2) EGF protects against MPP+-induced cell death. A possible role for GH3 cells as dopaminergic neurons is discussed.

1-Methyl-4-phenylpyridinium↗

PubMed1998

P2 receptor-mediated inhibition of adenylyl cyclase in PC12 cells.

PC12 pheochromocytoma cells have P2 receptors which are coupled to Ca2+ influx and catecholamine release. Previously we reported that ATP stimulated cyclic AMP accumulation at low concentrations up to 100 microM but showed inhibitory effects above this concentration [Yakushi, Y., Watanabe. A.. Murayama, T., Nomura, Y., 1996. Eur. J. Pharmacol. (314) 243-248]. In this study we investigated the characteristics of the inhibitory effects of ATP analogs. In the presence of 10 microM forskolin, an activator of adenylyl cyclase, ATP, adenosine 5'-O-(3-thiotriphosphate) (ATPgammaS), 2',3'-O-(4-benzoyl) benzoyl ATP, 2-methylthio ATP and adenosine 5'-O-(2-thiodiphosphate) inhibited cyclic AMP accumulation in a dose-dependent manner from 100 microM. UTP, alphabeta and betagamma-methylene ATP had no or very limited effects. The relative order of ATP analogs suggests that the ATP receptor appears to be P2Y-like. However, suramin, an antagonist of P2X and P2Y receptors, and reactive blue-2, which inhibited betagamma-methylene ATP-induced cyclic AMP accumulation, did not modify the inhibitory effect of ATPgammaS. Treatment with pertussis toxin, which completely abolished the effect of carbachol, had no effect on the action of ATP over 300 microM. The existence of a new type of ATP receptor-mediated inhibition of adenylyl cyclase is proposed in PC12 cells.

Adenosine Triphosphate↗

PubMed1998

Potential involvement of IL-8 in the pathogenesis of human cytomegalovirus infection.

The observations that several types of viruses induced interleukin (IL)-8 production prompted us to investigate the interrelationship between IL-8 and cytomegalovirus (CMV) infection. CMV infection caused IL-8 production in a human monocytic cell line, THP-1, in dose- and time-dependent manners. Moreover, CMV induced IL-8 gene expression by concurrently activating transcription factors, NF-kappaB and AP-1. Furthermore, CMV infection of human fibroblast cell lines increased gene expression of a specific receptor for IL-8, CXCR1. IL-8 in turn enhanced CMV replication in a human embryonic fibroblast, MRC-5, in dose- and time-dependent manners. Augmented replication eventually culminated in the increased production of infectious CMV virions. Moreover, IL-8 can attenuate the antiviral activity of interferon (IFN), particularly that of alpha-type against picornaviruses such as encephalomyocarditis virus and poliovirus. The inhibitory effects were associated with reduced 2',5'-A oligoadenylate synthetase activity. These results would imply that CMV can induce IL-8, which can augment CMV replication directly and indirectly by counteracting antiviral activity of IFN.

Antiviral Agents↗

PubMed1998

Regulation of inducible NO synthase expression by endothelin in primary cultured glial cells.

Nitric oxide (NO), initially identified as an endothelium-derived relaxing factor, is a molecular mediator that has been implicated in many physiological and pathological processes. In primary cultured rat glial cells, a combination of inflammatory cytokines (tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta)) and bacterial lipopolysaccharide (LPS) stimulates production of nitrite via expression of the inducible form of nitric oxide synthase (iNOS). In these cells, simultaneous addition of endothelin (ET) markedly inhibited TNF-alpha/IL-1beta-induced and LPS-induced nitrite production and iNOS expression, although ET by itself had no effect. The inhibitory effect of ETs appears to be mediated by ET(B) receptors. Forskolin also inhibited the iNOS expression. By contrast, pretreatment with ET for 24 hours enhanced LPS-induced nitrite production and iNOS expression. This stimulatory effect of ETs was suppressed by calphostin C, a protein kinase C inhibitor, and pretreatment with phorbol ester enhanced LPS-induced iNOS expression. Our findings present the possibility that ET has dual effects on iNOS expression in glial cells.

Animals↗

PubMed1998

Proliferative reaction of myelogenous leukemia cells with cytokines G-CSF, GM-CSF, M-CSF, SCF and TPO.

In recent years, many cytokines have been defined and some of them used clinically. In hematological malignancies, cytokines, including granulocyte colony-stimulating factor (G-CSF), have been widely used for leukopenia after chemotherapy. However, in acute myelogenous leukemia (AML), some leukemic cells may be induced to proliferate by these cytokines and they must be used with care. In this study, we have investigated cell reactivity and proliferation with G-CSF, granulocyte-macrophage colony-stimulating factor (GM-CMF), macrophage colony-stimulating factor (M-CSF), stem cell factor (SCF) and thrombopoietin (TPO) in cases of AML. We have also investigated the reactivity of some myeloid leukemia cell lines to TPO. G-CSF, GM-CSF, M-CSF, SCF and TPO caused proliferation of leukemic cells in 25%, 58.3%, 8.3%, 21.1% and 0% of cases, respectively. Because of this result, the use of G-CSF in AML should be regarded as potentially hazardous. TPO did not cause proliferation of leukemic cells in any case of AML, or in cell lines except MO7E, which is a megakaryocytic cell line. This result suggests that TPO might cause proliferation of some megakaryocytic leukemia cells. We cannot conclude that TPO does not cause proliferation of other AML cells, as the number of cases was small and it has been reported elsewhere that leukemia cells may proliferate when exposed to TPO in 50% of AML cases. Reactivity of AM L cells to TPO is an important factor when deciding the indications of TPO in AML and myelodysplastic syndrome.

Cell Division↗

PubMed1998

Enhancement of expression of inducible NO synthase and inhibition of DNA synthesis in rat thymocytes by in vivo hydrocortisone treatment.

Glucocorticoids (GC) are known to inhibit the mitogen-induced proliferation of T cells. Some of the effects of GC have been ascribed to the inhibition of nitrogen monoxide (NO) production, since NO is involved in the effecter function of phagocytic cells. Although the effects of GC in vitro on thymocytes are known, the effect of in vivo GC treatment on proliferation and NO synthesis in thymocytes has not been clarified. In this study, we investigated the effects of the administration of hydrocortisone succinate (HC), a potent anti-inflammatory GC, in Sprague-Dawley rats by s.c. injection (100 mg/kg). A substantial reduction of concanavalin A (Con A)-stimulated [3H]thymidine incorporation was observed in the thymocytes from HC-treated rats. This effect was accompanied by an increase in the Con A-stimulated expression of the inducible type of nitric oxide synthase (iNOS) and nitrite accumulation. The constitutive type of NOS (cNOS) in thymocytes did not change during the course of in vivo HC treatment. Addition of NO donors, which stimulated cyclic GMP accumulation, to rat thymocytes in vitro inhibited Con A-stimulated DNA synthesis. Addition of dibutyryl cyclic GMP, a membrane permeable analog, also inhibited DNA synthesis. Co-culture with N(G)monomethyl-L-arginine, an inhibitor of NOS, recovered Con A-stimulated [3H]thymidine incorporation in the thymocytes from HC-treated rats. These findings suggest that NO and cyclic GMP inhibited DNA synthesis in rat thymocytes and that HC treatment in vivo inhibited DNA synthesis via the expression of the iNOS protein, and the accumulation of NO and cyclic GMP. Although it is known that GC regulate iNOS expression negatively in several types of cells in vitro, GC treatment in vivo regulates iNOS protein expression positively in rat thymocytes.

Animals↗

PubMed1998

Stimulation by polyols of the two ryanodine receptor isoforms of frog skeletal muscle.

While the stimulating effect of concentrated salts on ryanodine receptor (RyR) is widely accepted in Ca(2+)-induced Ca2+ release (CICR) and [3H]ryanodine binding, the effect of non-ionic solutes on RyR is controversial. We investigated the effects of polyols on [3H]ryanodine binding to alpha- and beta-RyR purified from bullfrog skeletal muscle, and on CICR from sarcoplasmic reticulum (SR) in a skinned frog skeletal muscle fibre. Addition of polyols (glucose, sucrose, sorbitol, glycerol and ethylene glycol) in submolar to molar concentrations to an isotonic salt medium increased dose-dependently Ca(2+)-activated [3H]ryanodine binding to alpha- and beta-RyR of a similar magnitude. The increase is due to the rise in both apparent affinity (1/KD) and maximal numbers of binding sites (Bmax) for ryanodine. In addition to this stimulating effect, glucose sensitized both isoforms to Ca2+ in the Ca(2+)-activated reaction, which is distinct in mechanism(s) from caffeine. These stimulating effects of polyols were not observed unless some NaCl was present, which might explain the discrepancy among reported results. Consistent with these findings, polyols reversibly enhanced the rate of CICR from SR in skinned fibres with an increase in the Ca2+ sensitivity. The enhanced CICR was still sensitive to well-known modulators for CICR (Ca2+, Mg2+, adenine nucleotides and procaine), as with [3H]ryanodine binding. The results of this study reveal that polyols stimulate alpha- and beta-RyR in frog skeletal muscle, bringing about increased CICR activity. The finding that the specific activity of polyols in stimulation of [3H]ryanodine binding was approximately proportional to their molecular weights leads us to discuss the possible modification of protein surface-water molecule interaction as an underlying mechanism.

Animals↗

PubMed1998

Serum eosinophil cationic protein as a marker of eosinophilic inflammation in asthma.

BACKGROUND: The serum level of eosinophil cationic protein (ECP) has been used as a clinical marker in asthma, on the assumption that it reflects ongoing eosinophilic inflammation of the airways. However, only a few studies have investigated this issue, using bronchial secretions but not tissue specimens. OBJECTIVE: To evaluate cross-sectionally the correlation between serum ECP level or blood eosinophil count, and the degree of eosinophilia in bronchoalveolar lavage fluid (BALF) and bronchial biopsy tissue, and disease activity, in asthmatic patients. METHODS: Thirty-three adults with symptomatic asthma and six healthy controls were studied. The blood eosinophil count, ECP levels in serum and BALF, percentage of eosinophils in BALF, number of eosinophils in bronchial tissue, pulmonary function, and methacholine bronchial responsiveness of these subjects were clarified. An asthma severity score and inhaled beta2-agonist requirement (puffs/day) were also assessed for the asthmatic patients. RESULTS: The asthmatic patients, compared with the controls, had more obstructive (as tested by %FEV1, FEV1/FVC, and FEF25-75%) and more responsive airways, and showed a significant increase in the number of eosinophils in the blood, BALF, and tissue, and in the serum ECP levels. The ECP levels in BALF were below the detection limit for most of the subjects in both groups examined. In the asthmatic patients, serum ECP level demonstrated correlations with the number or percentage of eosinophils in BALF and tissue, whereas the blood eosinophil count correlated only with the percentage of eosinophils in BALF. Serum ECP level correlated with all indices of disease activity examined; %FEV1, FEV1/FVC, FEF25-75% bronchial responsiveness, severity score and beta2-agonist usage, whereas the blood eosinophil count correlated only with %FEV1 and bronchial responsiveness. CONCLUSION: The data suggest that serum ECP level reflects the intensity of eosinophilic airway inflammation, as well as the disease activity, and may be useful as an inflammatory marker in asthma.

Adult↗

PubMed1998

Unexpected hepatotoxicities in patients with non-Hodgkin's lymphoma treated with irinotecan (CPT-11) and etoposide.

BACKGROUND: Irinotecan (CPT-11) is a topoisomerase I inhibitor that has been confirmed to be active against a broad spectrum of neoplasms including non-Hodgkin's lymphoma (NHL). Because the combination of topoisomerase I and II inhibitors seemed to be an attractive therapeutic strategy owing to their complementary functions, we conducted a combination phase I study of CPT-11 and etoposide, a topoisomerase II inhibitor, in relapsed or refractory non-Hodgkin's lymphoma (NHL). METHODS: The starting doses of CPT-11 and etoposide were 30 mg/m2/day (days 1-3 and 8-10) and 40 mg/m2 (days 1-3), respectively. RESULTS: All three patients who received the starting dose developed dose-limiting toxicities including one case of grade 4 neutropenia lasting for > 7 days, one of grade 3 serum transaminase elevation and one of grade 3 hyperbilirubinemia. All three patients presented hepatotoxicity > or = grade 2. The starting dose level was judged to be the maximum tolerated dose (MTD) and further dose escalation of this combination was halted. The patient who developed grade 3 hyperbilirubinemia presented a second peak of plasma SN-38, an active metabolite of CPT-11, on the concentration-time curve for day 3, suggesting the possibility of the enterohepatic circulation of SN-38 and of a drug-to-drug interaction. No durable objective response was observed in the three patients treated at the starting dose. CONCLUSIONS: We conclude that etoposide is not recommended for combination with CPT-11 in NHL patients because of unexpected frequent hepatotoxicities.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1998

Alternate occurrence of allergic disease and an unusual form of interstitial cystitis.

BACKGROUND: It has been postulated that interstitial cystitis can be induced by an allergy. This is partly based on the observation that many patients with interstitial cystitis also have allergic diseases. In this study, an allergic evaluation was conducted on patients with interstitial cystitis complicated by bronchial asthma, a typical allergic disease. METHODS: Clinical histories were obtained and biopsy specimens from the vesical walls of the study patients were examined histologically. Cutaneous tests and IgE radioallergosorbent tests (RAST) were performed. Further, intravesical provocation tests were carried out using IgE RAST-positive antigens, and histamine release assays were performed on the vesical biopsy specimens using anti-IgE antibodies. RESULTS: Five of 6 patients alternately exhibited symptoms of allergic disease and bladder symptoms. The eosinophil and mast cell counts in the vesical biopsy specimens of these 5 patients were increased. Furthermore, an intravesical provocation test performed using the IgE RAST-positive antigen was positive in 4 patients. The mean vesical biopsy specimen histamine release was 17.7% for patients with interstitial cystitis with bronchial asthma which was significantly higher than that for interstitial cystitis patients without bronchial asthma (8.9%) or the control group (4.5%). The prognosis of patients with interstitial cystitis with allergic complications was relatively good. CONCLUSION: Patients with bronchial asthma exhibited hypersensitivity both generally and locally in the bladder. The alternation phenomenon was observed between the hypersensitive organs.

Adult↗

PubMed1998

Modification of results of drug susceptibility tests by coexistence of Mycobacterium avium complex with Mycobacterium tuberculosis in a sputum sample: case report and experimental considerations.

We report on a patient whose sputum contained both Mycobacterium tuberculosis and Mycobacterium avium complex (MAC). The MAC failed to be detected by the PCR-based AMPLICOR test. The unrecognized coexistence of MAC in the sample modified the results of drug susceptibility tests. Experiments revealed that the presence of both M. tuberculosis and MAC was not detected by the AMPLICOR test under certain conditions.

Humans↗

PubMed1998

Effects of Aspergillus fumigatus culture filtrate on antifungal activity of human phagocytes in vitro.

BACKGROUND: Aspergillus fumigatus can colonise the airways and the lungs with localised underlying conditions and occasionally invade the surrounding lung tissues even in subjects without systemic predisposing factors, presumably by escaping the local host defences. The aim of this study was to investigate the effects of A fumigatus culture filtrate (ACF) on the activities of human phagocytes--inhibition of germination of A fumigatus spores by alveolar macrophages (AMs) and hyphal damage by polymorphonuclear leucocytes (PMNs)--which are the critical host defences against A fumigatus. METHODS: Spores were incubated with AMs at a ratio of 1:1 in a medium containing different concentrations of ACF for 10 hours at 37 degrees C. Spore germination was visualised with light microscopy and the inhibition rate was calculated. The percentage of hyphal damage caused by PMNs pretreated with various concentrations of ACF was measured by a colorimetric tetrazolium metabolic assay. RESULTS: The inhibition rate of spore germination by AMs cultured with medium alone (control) was 90 (0.8)% whereas that by AMs cultured with the medium containing 10% ACF was significantly (p < 0.05) reduced to 41.7 (4.6)%. ACF suppressed the inhibition of spore germination in a dose dependent manner without altering the phagocytosing activity against the spores. The percentage of hyphal damage caused by PMNs pretreated with medium-199 (control) was 78.1 (2.3)% compared with 65.3 (2.8)% when PMNs were pretreated with 50% ACF (p < 0.05). CONCLUSIONS: A fumigatus releases biologically active substance(s) which suppress the inhibition of spore germination by AMs and also suppress PMN mediated hyphal damage, and thus may contribute to the pathogenicity of this fungus.

Adult↗

PubMed1998

Cell growth inhibition and DNA incorporation of mitomycin C in cell culture.

The present study was performed to clarify the effects of a 4-min exposure of mitomycin C (MMC) on cell growth, the cell cycle and MMC dose incorporated into DNA, using Chang's cultured human conjunctival cells. A low dose of MMC ranging from 0.00025 to 0.004% showed dose-dependent cytotoxicity when cell growth was active. Fifty percent cell viability was found when cells were treated with 0.001% MMC. A flow cytometer showed that 0.001% MMC inhibited the DNA synthetic phase. After 0.04% MMC was exposed to 3 x 10(6) cells and immediately rinsed, DNA was isolated to measure the dose of MMC detected from DNA. The total amount of DNA was 7 micrograms from which 3 micrograms of MMC was detected by high performance liquid chromatography. The above results revealed that the lowest concentration of MMC which caused 50% cell viability and cell cycle inhibition was 0.001% and that MMC was rapidly incorporated into DNA.

Cell Cycle↗

PubMed1998

Eosinophilic inflammation in cough variant asthma.

Eosinophils are considered to play a central pathogenetic role in asthma. We previously reported that sputum eosinophilia was observed in patients with cough variant asthma (CVA), as well as in "classic" asthma with wheezing. This study was undertaken to further investigate the involvement of eosinophils in CVA. The serum eosinophil cationic protein (ECP) level, the percentage of eosinophils in bronchoalveolar lavage (BAL) fluid, and the number of eosinophils in bronchial biopsy specimen were examined in 14 patients with CVA, 21 with classic asthma, and in seven healthy controls. For the two asthmatic groups, the clinical severity was classified with scores of 1-3. Pulmonary function and bronchial responsiveness were not significantly different between the patients with classic asthma and those with CVA. BAL, tissue eosinophil and serum ECP were all significantly increased in both classic asthma and CVA when compared with the controls but were not different between classic asthma and CVA. In both groups of asthmatics, the clinical severity significantly correlated with serum ECP and tissue eosinophils. In conclusion, eosinophilic inflammation is involved in cough variant asthma as well as in classic asthma. Anti-inflammatory treatment may be essential in patients with CVA, as in those with classic asthma.

Adult↗