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Biomedical subjects

T Yamada

Publications and source records attributed to T Yamada.

At least 253 records · Page 14Linked to original sources
PubMed2001

Possible involvement of auxin-induced ethylene in an apoptotic cell death during temperature-sensitive lethality expressed by hybrid between Nicotiana glutinosa and N. repanda.

Interspecific hybrids of Nicotiana glutinosa L. x N. repanda Willd. express temperature-sensitive lethality induced by apoptotic cell death. Hybrid seedlings cultured at 28 degrees C began to exhibit lethal symptoms during early growth stages, and then they showed a high level of endogenous auxin compared with those of parental seedlings. Meanwhile, the level of auxin in hybrid seedlings cultured at 32 degrees C, which is a condition suppressing the lethality of this cross combination, was equal to or lower than those of parental seedlings. Administration of 2,3,5-triiodobenzoic acid (TIBA) as an auxin transport inhibitor into the hybrid seedlings suppressed lethal symptoms and had a life-extending effect. Additionally, TIBA has an effect to suppress DNA fragmentation, which is one of characteristics of apoptosis and has been detected in the hybrid seedlings expressing the lethality. Administration of aminooxyacetic acid (AOA) as an ethylene synthesis inhibitor, which could inhibit ethylene production, also showed the same effects as TIBA for the lethality. From these results, we suggested that auxin and ethylene were involved in an apoptotic cell death during the lethality, and the abnormal increase of endogenous auxin may lead to the ethylene production in hybrid seedlings during early growth stages.

Aminooxyacetic Acid↗
PubMed2001

Gramine increase associated with rapid and transient systemic resistance in barley seedlings induced by mechanical and biological stresses.

Systemic acquired resistance (SAR) is one of the intriguing issues for studying the mechanism in signal transduction system in a whole plant. We found that SAR and increase of an antifungal compound were induced rapidly and transiently in barley (Hordeum vulgare L. cv. Goseshikoku) by mechanical and biological stresses. One of the major antifungal compounds was identified as an indole alkaloid, gramine (N,N-dimethyl-3-aminomethylindole), by mass spectrum and NMR analyses. Gramine is well known as a constitutive compound of barley, but it increased significantly in the primary and secondary leaves of barley seedlings within 12 h after pruning or inoculating with the powdery mildew fungi of barley (Blumeria graminis f.sp. hordei) and wheat (B. graminis f.sp. tritici). However, in the leaf detached from unwounded seedlings or in the leaf inoculated with the barley powdery mildew fungus, gramine did not increase at all. In the water droplets contacted with barley leaves, the amount of leaked gramine increased dependently upon the time after the seedling was injured mechanically. We also found a tight correlation between gramine increase and enhancement of resistance to the barley powdery mildew fungus in barley leaves treated with an endogenous elicitor. Furthermore, such a systemic resistance was not observed in a barley cultivar Morex that lacks the biosynthetic pathway of gramine. From these results, we conclude that gramine is the excellent marker in rapid and transient systemic acquired resistance in barley.

Alkaloids↗
PubMed2001

Use of intraoperative transesophageal echocardiography to predict atrial fibrillation after coronary artery bypass grafting.

BACKGROUND: Postoperative atrial fibrillation in coronary artery bypass graft surgery occurs in 10-40% of patients. It is associated with a significant degree of morbidity and results in prolonged lengths of stay in both the intensive care unit and hospital. METHODS: The authors prospectively evaluated patients undergoing coronary artery bypass with detailed transesophageal echocardiography examinations conducted before and after cardiopulmonary bypass to study whether risk factors for atrial fibrillation could be identified. Demographic and surgical parameters were also included in the analysis. Selected variables were subjected to univariate and subsequent multivariate analyses to test for their independent or joint influence on atrial fibrillation. RESULTS: Seventy-nine patients had assessable transesophageal echocardiography examinations. Significant univariate predictors of atrial fibrillation included advanced age (P = 0.002), pre-cardiopulmonary bypass left atrial appendage area (P = 0.04), and post-cardiopulmonary bypass left upper pulmonary vein systole/diastole velocity ratio (P = 0.03). When these three factors were considered together in a multiple logistic regression analysis, left upper pulmonary vein systole/diastole velocity ratio was a significant predictor (P < 0.05), as was the joint effect of age plus pre-cardiopulmonary bypass left atrial appendage area (P = 0.005). The probability of developing atrial fibrillation for the combination of age = 75 yr, post-cardiopulmonary bypass left upper pulmonary vein systole/diastole velocity ratio = 0.5, and left atrial appendage area = 4.0 cm was 0.83 (95% confidence interval, 0.51-0.96). CONCLUSIONS: Early identification of patients at risk for postoperative atrial fibrillation may be feasible using the parameters identified in this study.

Age Factors↗
PubMed2001

Low-dose erythromycin reduces delayed gastric emptying and improves gastric motility after Billroth I pylorus-preserving pancreaticoduodenectomy.

OBJECTIVE: To test the hypothesis that early and low doses of erythromycin reduce the incidence of early delayed gastric emptying (DGE) and induce phase 3 of the migratory motor complex in the stomach after Billroth I pylorus-preserving pancreaticoduodenectomy (PPPD). SUMMARY BACKGROUND DATA: Delayed gastric emptying is a leading cause of complications after PPPD, occurring in up to 50% of patients. High doses of erythromycin (200 mg) accelerate gastric emptying after pancreaticoduodenectomy and reduce the incidence of DGE, although they induce strong contractions that do not migrate to the duodenum. METHODS: Thirty-one patients were randomly assigned to either the erythromycin or control groups. The patients received erythromycin lactobionate (1 mg/kg) every 8 hours, or H2-receptor antagonists and gastrokinetic drugs from days 1 to 14 after surgery. On postoperative day 30, gastroduodenal motility was recorded in 14 patients. RESULTS: Preoperative, intraoperative, and postoperative factors were comparable in the erythromycin and control groups. The erythromycin group had a shorter duration of nasogastric drainage, earlier resumption of eating, and a 75% reduction in the incidence of DGE. Erythromycin was an independent influence on nasogastric tube removal, and preservation of the right gastric vessels was a significant covariate. Low doses of erythromycin induced phase 3 of the migratory motor complex and phase 3-like activity, with the same characteristics as spontaneous phase 3, in 86% of patients: two had quiescent stomachs and the others had spontaneous phase 3 or phase 3-like activity. CONCLUSIONS: Low doses of erythromycin reduced the incidence of DGE by 75% and induced phase 3 of the migratory motor complex after Billroth I PPPD. Low doses of erythromycin are preferable to high doses in the unfed period after PPPD.

Adult↗
PubMed2001

Role of Atp7b gene in spontaneous and N-diethylnitrosamine-induced carcinogenesis in a new congenic strain, WKAH.C-Atp7b rats.

To examine whether Long-Evans Cinnamon (LEC) rats, a mutant rat model of Wilson's disease, have a susceptibility gene(s) to hepatocarcinogenesis in addition to the causative gene, Atp7b, we established a new congenic strain, WKAH.C-Atp7b rats, in which the Atp7b gene of the LEC rats is inserted into the normal Wistar-King Aptekman Hokkaido (WKAH) background. Hepatocellular tumors developed spontaneously in both sexes of WKAH.C-Atp7b rats, their incidence being slightly lower than that in LEC rats. Incidences of spontaneous liver tumors in LEC, WKAH.C-Atp7b and WKAH rats correlated with hepatic copper and iron concentrations. Medium-term liver bioassay showed that LEC rats were more susceptible to the induction of glutathione S-transferase placental form-positive preneoplastic foci than WKAH.C-Atp7b rats, and WKAH.C-Atp7b rats were more susceptible than WKAH rats. In an N-diethylnitrosamine (DEN)-induced long-term carcinogenicity study, 1) LEC rats were similarly or rather less susceptible to hepatocellular tumors than WKAH.C-Atp7b and WKAH rats, indicating that the progression of the preneoplastic foci to liver cancer in LEC rats was worse than that in WKAH.C-Atp7b and WKAH rats, 2) the incidences of kidney tumors in LEC and WKAH.C-Atp7b rats were higher than that in WKAH rats and high copper concentrations in the kidneys were observed in LEC and WKAH.C-Atp7b rats, 3) LEC rats were resistant to lung carcinogenesis. These data indicate that the susceptibility of LEC rats to liver and kidney carcinogenesis could be explained by Atp7b gene mutation and that the susceptibility to lung carcinogenesis is controlled by gene(s) other than Atp7b.

Adenosine Triphosphatases↗
PubMed2001

Management of pregnancy with congenital antithrombin III deficiency: two case reports and a review of the literature.

Women with antithrombin (AT) III deficiency are prone to pregnancy-associated venous thromboembolism. We report 2 cases with genetically confirmed ATIII deficiency, one with a mutation in exon 3A and the other with an exon 4 deletion, in whom the pregnancies were successfully managed with prophylactic therapies for thrombosis. A 35-year-old pregnant woman was treated with intravenous infusions of ATIII concentrate alone, and the other 22-year-old pregnant woman was mainly treated with subcutaneous injections of heparin and oral low-dose aspirin therapy. Both pregnancies resulted in vaginal deliveries of healthy neonates. The literature concerning prophylactic therapies for thrombosis in ATIII deficiency-complicated pregnancy is reviewed, and the clinical problems, including the adverse effects of the therapies, are discussed.

Adult↗
PubMed2001

TNF-alpha-mediated activation of HIV-1 LTR in monocytoid cells by mycobacteria.

Mycobacterial infection occurs commonly in patients with acquired immune deficiency syndrome. Incubation of monocytoid cell line U937 cells, which was cotransfected HIV-1 long terminal repeat sequence (LTR) chloramphenicol acetyltransferase (CAT) plasmid and Tat expression plasmid, with Mycobacterium smegmatis, Mycobacterium avium, Mycobacterium bovis BCG and Mycobacterium tuberculosis resulted in enhancement of CAT production, indicating that these mycobacteria could activate LTR in this cell line. The amount of CAT in the cells coexisting with M. smegmatis was higher than that infected with other mycobacteria. The amounts of CAT production in the cells coculturing with M. avium and M. bovis BCG were intermediate. M. tuberculosis slightly stimulated CAT production. The amount of tumor necrosis factor (TNF)-alpha produced by transfected U937 cells was correlated with the amount of CAT production. The interleukin (IL)-1beta and IL-6 levels in the supernatant from coculturing with all species were similar. The antibody to TNF-alpha inhibited CAT production induced by mycobacterial infections. The anti-IL-1beta and anti-IL-6 antibodies, however, scarcely influenced stimulation of LTR by mycobacteria. In addition, U937 cells transfected with full length LTR CAT plasmid showed increased CAT production by activation with mycobacteria, but the cells transfected with mutant LTR CAT constructs from which the nuclear factor (NF)-kappaB binding site was deleted did not show activation. These findings indicated that activation of Mycobacterium-induced LTR CAT is NF-kappaB dependent. These findings suggested that activation of HIV-1 LTR by mycobacteria was mainly mediated by NF-kappaB-induced secondary release of cytokine TNF-alpha.

Cell Line↗
PubMed2001

Expression of peroxisome proliferator-activated receptor subtypes in human atherosclerosis.

To clarify the involvement of peroxisome proliferator-activated receptors (PPARs) in atherosclerotic plaque formation, we investigated the expression patterns of mRNA and protein of PPARalpha and PPARgamma in human aorta. Atheromatous plaque, fatty streak, and diffuse intimal thickening (DIT) were separated macroscopically, and each sample was divided into halves. Half of them were used for analysis of mRNA expression with reverse transcription-polymerase chain reaction and the others were used for histologic analysis. Both PPARalpha and PPARgamma mRNA were detected in all atheromatous plaques, all fatty streaks, and in some DIT. However, expressions of PPARalpha and PPARgamma were obviously less frequently found in DIT than in atheromatous plaques, and the intensity of these expressions was stronger in the atheromatous plaques than in the DIT. Compared with PPARalpha, PPARgamma mRNA was expressed more frequently in atheromatous plaques. In atheromatous plaques, PPARgamma mRNA was expressed independently, whereas PPARalpha mRNA was coexpressed with PPARgamma. PPARgamma protein was obviously found in the nuclei of endothelial cells, macrophages, mononuclear cells, and smooth muscle cells in the aortic intima. These results suggest that expressions of PPARalpha and PPARgamma in human aortic wall are involved in atherogenesis from the early stages.

Arteriosclerosis↗
PubMed2001

Protective cytotoxic T lymphocyte responses induced by DNA immunization against immunodominant and subdominant epitopes of Listeria monocytogenes are noncompetitive.

Taking advantage of the fact that plasmid DNA encoding a single cytotoxic T lymphocyte (CTL) epitope can induce CTLs, we examined the influence of T-cell responses to dominant epitopes on those to a subdominant epitope derived from Listeria monocytogenes. Our data suggest that interaction between T cells against dominant and subdominant epitopes does not operate in the generation of the hierarchy. Furthermore, we found that a single dominant epitope is sufficient for the induction of protective immunity.

3T3 Cells↗
PubMed2001

Relative serum amyloid A (SAA) values: the influence of SAA1 genotypes and corticosteroid treatment in Japanese patients with rheumatoid arthritis.

OBJECTIVES: (1) To determine whether serum concentration of serum amyloid A (SAA) protein is influenced by the SAA1 allele in Japanese patients with rheumatoid arthritis (RA) as previously shown in a healthy control group; and (2) to analyse what factors, based on such an allelic bias, influence the relative SAA values of those patients. METHODS: SAA and C reactive protein (CRP) concentrations together with SAA1 genotypes were determined in 316 Japanese patients with RA. The relative SAA values were evaluated as an SAA/CRP ratio. RESULTS: Comparison of the three SAA1 homozygote groups showed that the SAA/CRP ratio was highest in the 1.5/1.5 group (mean 9.0, p<0.01 v the other two homozygote groups) followed by the 1.3/1.3 group (mean 7.2, NS v the 1.1/1.1 group) and the 1.1/1.1 group (mean 4.0). The SAA/CRP ratio was significantly higher in patients receiving corticosteroids regardless of the presence of allele 1.5. No clear differences in the ratio between patients with or without amyloidosis were found. CONCLUSION: The SAA1.5 allele and corticosteroid treatment had a positive influence on SAA concentrations in serum. These findings are important when evaluating SAA concentration in inflammatory diseases and when considering the cause or treatment of amyloidosis.

Adolescent↗
PubMed2001

Light induced apoptosis is accelerated in transgenic retina overexpressing human EAT/mcl-1, an anti-apoptotic bcl-2 related gene.

BACKGROUND/AIM: EAT/mcl-1 (EAT), an immediate early gene, functions in a similar way to bcl-2 in neutralising Bax mediated cytotoxicity, suggesting that EAT is a blocker of cell death. The aim of this study was to determine the effect of overexpression of the human EAT gene on light induced retinal cell apoptosis. METHODS: EAT transgenic mice incorporating the EF-1alpha promoter were utilised, and expression of human EAT was detected by RT-PCR. Light damage was induced by raising mice under constant illumination. Two groups of animals, EAT transgenic mice (n=14) and littermates (n=13), were examined by ERG testing and histopathology at regular time points up to 20 weeks of constant light stimulation. Electrophysiological and histopathological findings were evaluated by established systems of arbitrary scoring as scores 0-2 and scores 0-3, respectively. RESULTS: The mean score (SD) of ERG response was significantly lower in EAT transgenic mice (0.79 (0.89)) than in littermates (1.69 (0.48)) (p<0.01). Although the differences between the two survival curves did not reach statistical significance (p=0.1156), the estimated incidence of electrophysiological retinal damage was higher in EAT mice (0.0495/mouse/week; 95% confidence interval (CI) 0.0347-0.0500) than in littermates (0. 0199/mouse/week; 95% CI 0.0035-0.0364). The mean scores (SD) for histopathological retinal degeneration were 2.31 (0.63) in littermates and 1.43 (1.22) in EAT transgenic mice (p=0.065). However, Kaplan-Meier curves for histopathological failure in two groups of mice showed that retinal photoreceptor cells were preserved significantly against constant light in the littermate compared with transgenic mice (p=0.0241). The estimated incidence of histopathological retinal damage was 0.0042/mouse/week in the littermates (95% CI 0-0.0120) and 0.0419/mouse/week in the EAT mice (95% CI 0.0286-0.0500). CONCLUSION: Retinal photoreceptor cell apoptosis under constant light stimulation is likely to be accelerated in transgenic retina overexpressing EAT.

Animals↗
PubMed2001

Prognostic significance of cardiac (123)I metaiodobenzylguanidine imaging for mortality and morbidity in patients with chronic heart failure: a prospective study.

OBJECTIVE: To determine whether cardiac iodine-123 metaiodobenzylguanidine ((123)I MIBG) imaging is useful in predicting the prognosis of patients with chronic heart failure. DESIGN: Cardiac (123)I MIBG imaging was done on entry to the study. The cardiac MIBG washout rate was calculated from anterior chest view images obtained 20 and 200 minutes after injection of the isotope. Study patients were divided into two groups with washout rates above and below 27% (the mean value + 2 SD obtained in 20 normal subjects), and were then followed up. SETTING: Tertiary referral centre. PATIENTS: 79 patients with chronic heart failure in whom the left ventricular ejection fraction was less than 40%. RESULTS: There were 37 patients in group 1 (washout rate of >/= 27%) and 42 in group 2 (< 27%). During a follow up period of between 1 and 52 months, eight patients died suddenly and five died of worsening heart failure in group 1, while none died in group 2; 13 patients in group 1 and four in group 2 were admitted to hospital for progressive heart failure. Kaplan-Meier analysis showed that group 1 had a significantly higher mortality and morbidity (p = 0.001 and p < 0.001, respectively) than group 2. CONCLUSIONS: Cardiac (123)I MIBG washout rate seems to be a good predictor of prognosis in patients with chronic heart failure.

3-Iodobenzylguanidine↗
PubMed2001

Dual trafficking of Slit3 to mitochondria and cell surface demonstrates novel localization for Slit protein.

Drosophila slit is a secreted protein involved in midline patterning. Three vertebrate orthologs of the fly slit gene, Slit1, 2, and 3, have been isolated. Each displays overlapping, but distinct, patterns of expression in the developing vertebrate central nervous system, implying conservation of function. However, vertebrate Slit genes are also expressed in nonneuronal tissues where their cellular locations and functions are unknown. In this study, we characterized the cellular distribution and processing of mammalian Slit3 gene product, the least evolutionarily conserved of the vertebrate Slit genes, in kidney epithelial cells, using both cellular fractionation and immunolabeling. Slit3, but not Slit2, was predominantly localized within the mitochondria. This localization was confirmed using immunoelectron microscopy in cell lines and in mouse kidney proximal tubule cells. In confluent epithelial monolayers, Slit3 was also transported to the cell surface. However, we found no evidence of Slit3 proteolytic processing similar to that seen for Slit2. We demonstrated that Slit3 contains an NH(2)-terminal mitochondrial localization signal that can direct a reporter green fluorescent protein to the mitochondria. The equivalent region from Slit1 cannot elicit mitochondrial targeting. We conclude that Slit3 protein is targeted to and localized at two distinct sites within epithelial cells: the mitochondria, and then, in more confluent cells, the cell surface. Targeting to both locations is driven by specific NH(2)-terminal sequences. This is the first examination of Slit protein localization in nonneuronal cells, and this study implies that Slit3 has potentially unique functions not shared by other Slit proteins.

Amino Acid Sequence↗
PubMed2001

Role of T cells in development of chronic pancreatitis in male Wistar Bonn/Kobori rats: effects of tacrolimus.

We assessed T cell association with acinar cell apoptosis and a preventive effect of tacrolimus, a T cell suppressant, on the development of chronic pancreatitis in male Wistar Bonn/Kobori rats. At 15 wk, cellular infiltrates composed of F4/80-positive cells (monocytes/macrophages), CD4-positive cells, and CD8-positive cells were extensive in the interlobular connective tissue and parenchyma. In particular, CD8-positive cells invaded pancreatic lobules and formed close associations with acinar cells, some of which demonstrated features of apoptosis. At 20 wk, CD8-positive cells were still abundant in the fibrotic tissue formed with loss of acinar cells. Repeated subcutaneous injection of 0.1 mg x kg(-1) x day(-1) but not 0.025 mg x kg(-1) x day(-1) of tacrolimus for 10 wk completely prevented the occurrence of acinar cell apoptosis, infiltration of CD4- and CD8-positive cells, and development of pancreatitis at the age of 20 wk, but these maneuvers did not recover the decreased plasma corticosterone levels, which may be responsible for the development of disease. We demonstrated that T cells, possibly CD8-positive cells, are involved in inducing apoptosis of acinar cells, raising the possibility that tacrolimus might find clinical application in the treatment of autoimmune chronic pancreatitis.

Animals↗
PubMed2001

Maximal and submaximal forces of slow fibers in human soleus after bed rest.

The effects of 2 and 4 mo of bed rest, with or without exercise countermeasures, on the contractile properties of slow fibers in the human soleus muscle were examined. Mean fiber diameters were 8 and 36% smaller after 2 and 4 mo of bed rest, respectively, than the pre-bed rest level. Maximum tetanic force (P(o)), maximum activated force (F(max)) per cross-sectional area (CSA), and the common-logarithm value of free Ca(2+) concentration required for half-maximal activation (pCa(50)) also decreased after 2 and 4 mo of bed rest. In contrast, maximum unloaded shortening velocity (V(o)) was increased after 2 and 4 mo of bed rest. After 1 mo of recovery, fiber diameters, P(o), F(max) per CSA (P > 0.05), and pCa(50) were increased and V(o) decreased toward pre-bed rest levels. Effects of knee extension/flexion exercise by wearing an anti-G Penguin suit for 10 h daily, and the effects of loading or unloading of the plantar flexors with (Penguin-1) or without (Penguin-2) placing the elastic loading elements of the suit, respectively, were investigated during ~2 mo of bed rest. In the Penguin-1 group, mean fiber diameter, P(o), F(max) per CSA, V(o), and pCa(50) were similar before and after bed rest. However, the responses of fiber size and contractile properties to bed rest were not prevented in the Penguin-2 group, although the degree of the changes was less than those induced by bed rest without any countermeasure. These results indicate that long-term bed rest results in reductions of fiber size, force-generation capacity, and Ca(2+) sensitivity, and enhancement of shortening velocity in slow fibers of the soleus. The data indicate that continuous mechanical loading on muscle, such as stretching of muscle, is an effective countermeasure for the prevention of muscular adaptations to gravitational unloading.

Adult↗
PubMed2001

Analysis of beta(2)-microglobulin kinetics in hemodialysis by a modified variable-volume one-compartment model.

It has been reported that deposition of beta(2)-microglobulin (BMG) is associated with the occurrence of dialysis-related amyloidosis (DRA) in long-term hemodialysis (HD) patients. Though reduction of the BMG burden is essential in preventing DRA, simple BMG kinetic models applicable to clinical practice have not been established. We have reported a modified variable-volume one-compartment model (1CM) for analyzing urea nitrogen (UN) kinetics, in which no specific parameters other than a modification factor are necessary. If there is a constant relation between the BMG concentration of the dialyzer arterial line and the mean BMG concentration in the body during HD, the modified 1CM may also be applied to BMG. As such, in order to verify its validity, we analyzed UN and BMG kinetics by the modified 1CM in 28 HD patients in whom polysulfone dialyzers were used, and compared the calculated and measured solute rebound. In 3 of the patients, the spent dialysate was collected in a tank, and the BMG removal mass, calculated by the modified 1CM, was compared with that recovered in the tank. The BMG rebound ratio (%), calculated by the modified 1CM, was not different from the measured one (36.3 +/- 9.9 vs. 36.5 +/- 11.5, p = 0.954), as in the case of UN (15.8 +/- 4.5 vs. 16.3 +/- 4.6, p = 0.541). The solute dilution in the blood circuit by solute disequilibrium and blood recirculations for BMG was estimated to be 74% stronger than that for UN. The normalized solute generation rate (mg/min/l) and the time-averaged solute concentration over a 1-week period (mg/l) were 0.142 +/- 0.023 and 448 +/- 68 for UN and 0.00578 +/- 0.00125 and 22.4 +/- 4.6 for BMG, respectively. The differences between these two solutes resulted in a Dilution index for BMG that was 23% lower than that for UN (2.62 +/- 0.44 vs. 3.21 +/- 0.39, p < 0.0001). The modified 1CM overestimated the BMG removal mass (mg) by about 20% compared with that recovered in the tank (195 +/- 22 vs. 162 +/- 17, p < 0.0001). One of the causes of this discrepancy was speculated to be adsorption of BMG by polysulfone dialyzers. It was concluded that, despite several problems in quantitative analysis, the modified 1CM would be a useful model for estimating the dialysis efficiency for BMG removal in clinical practice.

Adsorption↗
PubMed2001

The effect of leukotriene D(4) inhalation on the antigen-induced airway hyperresponsiveness and inflammation in 5-lipoxygenase gene-deficient mice.

BACKGROUND: The role of 5-lipoxygenase (5-LO) products in the asthmatic bronchoconstriction is evident. However, the role of 5-LO products in airway hyperresponsiveness (AHR) and airway inflammation is still under discussion. The aim of the present study is to investigate the role of leukotriene D(4) (LTD(4)) in AHR and allergic airway eosinophilia in mice. METHODS: The effect of LTD(4) inhalation on antigen-induced AHR and airway eosinophilia was investigated in 5-LO gene-deficient mice. RESULTS: After three inhalations of LTD(4), airway responsiveness to acetylcholine was not altered in normal or allergic wild-type and 5-LO knockout (KO) mice. In contrast, the number of eosinophils in 5-LO KO allergic mice increased to the level of wild-type allergic mice after the inhalation of LTD(4). These observations were confirmed by a histopathological study of the lungs. No change in the cytokine levels in bronchoalveolar lavage fluid and serum immunoglobulin levels was shown after LTD(4) inhalation. CONCLUSION: These findings suggest that LTD(4) plays a role in eosinophilic airway inflammation but not in AHR in mice.

Administration, Inhalation↗