Role of intercellular adhesion molecule-1 in a murine model of toluene diisocyanate-induced asthma

BACKGROUND: Adhesion molecules such as intercellular adhesion molecule-1 (ICAM-1) are thought to contribute to the airway inflammation and airway hyper-responsiveness (AHR) of allergic asthma. Some differences from allergic asthma have been noted, including airway neutrophilia, and the involvement of ICAM-1 in toluene diisocyanate (TDI) asthma is currently unclear. OBJECTIVE: We utilized mice lacking ICAM-1 expression (ICAM-1(-/-)) to investigate the role of ICAM-1 in airway inflammation and AHR in TDI-induced asthma. METHODS: Male C57BL/6J mice (ICAM-1(+/+)) and ICAM-1(-/-) mice were intranasally sensitized to TDI solution or solvent alone. Airway inflammation, AHR and cytokine secretion were assessed 24 h after challenge by TDI or solvent. The production of antigen-specific IgG and IgE by TDI sensitized and non-sensitized mice was determined. RESULTS: TDI challenge to ICAM-1(+/+) mice induced an increase in airway inflammatory cell numbers, AHR and cytokine secretion of TNF-alpha, macrophage inflammatory protein-2 (MIP-2), IL-4, IL-5 and IFN-gamma into the bronchoalveolar lavage fluid. All these pathophysiological changes were reduced in ICAM-1(-/-) mice. Serum levels of TDI-specific IgG and IgE of ICAM-1(-/-) and ICAM-1(+/+) mice were comparable. CONCLUSION: These results suggest that ICAM-1 plays an essential role in airway inflammation and AHR in TDI-induced asthma.     

DNA analysis of a patient with two different marker chromosomes using Y-specific DNA probes

A female patient with unilateral gonadal dysgenesis was a mosaic for three cell lines, 45,X/46,X, + marI/46,X, + marII, including two different marker chromosomes. DNA analysis using 17 Y-specific DNA probes revealed that each marker consists of different segments of the Y chromosome.     

Survey of recognition and utilization of guidelines for the diagnosis and management of bronchial asthma in Japan

BACKGROUND: In Japan in 1993, the Japanese Society of Allergology (JSA) developed guidelines for diagnosis and management of asthma (JGL), which were based on the concept that asthma is a chronic inflammatory disorder of the airway. METHODS: This survey study was intended to investigate the recognition and utilization of JGL among physicians who had treated asthma. The survey comprised two methods: a quantitative mail survey and a qualitative door-to-door survey conducted by trained interviewers. RESULTS: In the mail survey, a total of 1028 physicians responded; 552 members of the JSA and 476 nonmembers. Ninety-four percent of JSA members were aware of adult asthma management guidelines, while 53% of nonmembers were aware of them. Although approximately half of the physicians, both members and nonmembers, found differences between the asthma management policies in JGL and their previous policies, most of them utilized JGL once they read it. In the qualitative door-to-door survey, 80-90% of physicians evaluated JGL as good after they read it. CONCLUSIONS: JGL was recognized and utilized by most JSA members, but only half of nonmember physicians were aware of JGL, although they utilized JGL after they read it. Further action to implement JGL among nonspecialist physicians is needed to improve management of asthma.     

Independent Associations of the HLA-B27 Antigen and the Complement Haplotype SC21 in Chronic Anterior Uveitis

There is evidence of an association between major histocompatibility complex (MHC) genes and acute anterior uveitis; here the authors report the frequency of class I and class III MHC phenotypes in 32 Mexican mestizo patients with chronic anterior uveitis and compared them to those present in 100 ethnically matched healthy controls. Results showed in patients statistically significant increased frequencies of HLA-B(27) antigen (pC=0.02, OR=6.33, 95+ CI:1.63-26.47) and the complotype SC(21) (pC=0.04, OR=4.5, 95+ CI:1.40-14.67); the authors found a decreased frequency of HLA-B(35) (p=0.006, OR=0.10, 95+ CI: 0.00-0.65) as compared to normal controls. None of the individuals bearing the SC(21) complotype were positive for HLA-B(27), suggesting independent roles of the class I and class III antigens in the genetic susceptibility to chronic anterior uveitis.     

Increased expression of extracellular matrix metalloproteinase inducer (EMMPRIN) and MMP10, MMP23 in inflammatory bowel disease: Cross‐sectional study

It has been reported that EMMPRIN is involved in the regulation of immune response and the induction of MMPs production by fibroblasts. The aim of this study was to describe the intestinal gene expression and protein production of EMMPRIN, MMP23 and MMP10 in patients with ulcerative colitis (UC) and Crohn’s disease (CD) and compared them with a control group. Gene expression of EMMPRIN, MMP10 and MMP23B was measured by RT‐PCR. In order to determine EMMPRIN and MMP protein expression, colonic tissues were immunostained. The results of the study showed EMMPRIN gene expression was upregulated in rectal mucosa from active (a)UC versus aCD patients (P = .045), remission (r)CD group (P = .0009) and controls (P < .0001). We detected differences between rUC and aCD (P = .004), rCD (P < .0001) or control group (P < .0001). EMMPRIN showed a higher expression in mucosa (intraepithelial lymphocytes), submucosa and adventitia (endothelial cells) from aCD patients. MMP23 levels were increased in aUC and aCD compared to rUC and rCD and the control group (P = .0001). EMMPRIN+/MMP23+─expressing cells were localized mainly in mucosa, muscular and adventitia from active UC patients. MMP10 gene expression was increased in aUC versus CD patients and the control group (P = .0001). MMP10 gene expression is associated with inflammation in UC patients (P = .0001, r² = .585). EMMPRIN+/MMP10+─producing cells were found mainly in all intestinal layers and perivascular inflammatory infiltrates from aUC patients. In conclusion, EMMPRIN, MMP23 and MMP10 were upregulated in patients with active UC versus remission UC , CD and control groups suggesting that, they are involved in the inflammatory process.     

Detection of the earliest ventricular contraction site in patients with Wolff-Parkinson-White syndrome using two-dimensional guided M-mode tissue Doppler echocardiography

OBJECTIVE: The purpose of this study was to examine the feasibility of M-mode tissue Doppler imaging for localizing the accessory pathway in patients with Wolff-Parkinson-White (WPW) syndrome. METHODS: Two-dimensional guided tissue Doppler M-mode was recorded at the mitral and tricuspid annular levels in 13 WPW patients. Time intervals were measured from the onset of the delta wave or the R wave to the beginning of the ventricular systolic motion. The earliest contraction site was defined as the site demonstrating the shortest time interval, and compared with the earliest activated site determined by body surface mapping and the successful ablation site. RESULTS: In 6 patients with a left-sided pathway, tissue Doppler localization was identical to the ablation site. In 3 with a left-sided pathway and 3 with a right-sided pathway, localization was judged as an adjacent region of the ablation site. In 1 patient with a right lateral pathway, the pathway location was misdiagnosed. The tissue Doppler diagnosis for the left-sided pathways correlated well with the ablation site, in contrast to the right-sided pathways (p = 0.05). Prediction of the accessory pathway localization by tissue Doppler M-mode was equivalent to localization based on body surface mapping. CONCLUSIONS: In WPW syndrome, tissue Doppler M-mode can detect the earliest contraction sites and seems helpful in localizing the left-sided accessory pathways, but is of limited use for right-sided pathways.     

Effects of oral befunolol on heart rate and systolic blood pressure during submaximal exercise in man

For the purpose of determining exercise intensity required for evaluating the effect of beta-blocking agents, the multi-stage treadmill exercise was carried out up to intensity of 85% of maximal oxygen intake (VO2max) after administration of beta-blocking agents in 7 healthy men. To obtain a stable dose response in the inhibitory effect of beta-blocking agents on heart rate (HR) and systolic blood pressure (S-BP), the exercise intensity more than 65% of VO2max (75% of maximal heart rate) was needed. In order to evaluate the effect of befunolol (BFE), a submaximal treadmill exercise of 75% of the age adjusted predicted maximal heart rate was loaded in 6 healthy men at 1.5, 4, and 8 hours following a single oral administration of 10 mg, 20 mg or 40 mg of BFE and 20 mg or 40 mg of propranolol. Simultaneously, the plasma concentration of BFE was determined 1.5, 4, 6 and 8 hours after the administration of BFE at each dose. In human serum, BFE was detected together with its metabolite, revealing a significant correlation between BFE and metabolite (r = 0.94, p < 0.001). Almost a certain rate of metabolite (4--5 times) was detected against BFE. As for the biological half life, it was 1.79 +/- 0.13 hours with BFE and 3.67 +/- 1.33 hours with metabolite. The inhibitory effect of BFE on HR and S-BP during exercise exhibited a dose response with the oral dose and its plasma concentration, and was almost twice as much as that of propranolol at the same dose. Accordingly, the myocardial oxygen consumption which may be represented as rate pressure product was inhibited twice as much as propranolol. BFE is characteristic of its more rapid elimination of its effect compared to the other beta-blocking agents. The decrease in the inhibitory effect of BFE or HR during exercise was about 1.8 times quicker than that of propranolol.     

Benidipine reduces ischemia reperfusion-induced systemic oxidative stress through suppression of aldosterone production in mice

Aldosterone is implicated in the pathogenesis of several cardiovascular diseases, including ischemia reperfusion (I/R) and myocardial infarction, and also causes oxidative stress and inflammation in cardiovascular systems. Benidipine, a long-acting T- and L-type calcium channel blocker, reduces infarct size following myocardial I/R in rabbits. Benidipine also inhibits the production of aldosterone in vitro. However, the precise mechanism of this phenomenon in vivo remains unknown. We therefore evaluated whether benedipine has a beneficial role through the regulation of oxidative stress in myocardial I/R. C57BL/6J mice were subjected to 30?min of left ascending coronary I/R. Benidipine was administered orally at 3?mg?kg(-1) daily for 3 weeks without any changes in hemodynamic variables. Benidipine significantly reduced infarction size (13.4±2.5%) compared with controls (25.5±3.6%). Urinary 8-hydroxy-2' deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, increased significantly after I/R. I/R induced increases in 8-OHdG were significantly lower with benidipine. Local myocardial 8-OHdG was also elevated in I/R, but this augmentation was significantly suppressed with benidipine. The plasma aldosterone concentration (PAC) significantly increased 2 days after I/R and remained elevated at least 7 days after I/R. Treatment with benidipine significantly decreased I/R-induced elevation of the PAC. I/R-induced markers of fibrosis in hearts also reduced in benidipine. These results suggest that the administration of benidipine reduces myocardial infarct size as well as systemic oxidative stress after I/R. These phenomena are partially linked to reduced plasma aldosterone levels.