A role for cysteinyl leukotrienes in airway remodeling in a mouse asthma model.

Airway inflammation and remodeling in chronic asthma are characterized by airway eosinophilia, hyperplasia of goblet cells and smooth muscle, and subepithelial fibrosis. We examined the role of leukotrienes in a mouse model of allergen-induced chronic lung inflammation and fibrosis. BALB/c mice, after intraperitoneal ovalbumin (OVA) sensitization on Days 0 and 14, received intranasal OVA periodically Days 14-75. The OVA-treated mice developed an extensive eosinophil and mononuclear cell inflammatory response, goblet cell hyperplasia, and mucus occlusion of the airways. A striking feature of this inflammatory response was the widespread deposition of collagen beneath the airway epithelial cell layer and also in the lung interstitium in the sites of leukocytic infiltration that was not observed in the saline-treated controls. The cysteinyl leukotriene(1) (CysLT(1)) receptor antagonist montelukast significantly reduced the airway eosinophil infiltration, mucus plugging, smooth muscle hyperplasia, and subepithelial fibrosis in the OVA-sensitized/challenged mice. The presence of Charcot-Leyden-like crystals in airway macrophages and the increased interleukin (IL)-4 and IL-13 mRNA expression in lung tissue and protein in BAL fluid seen in OVA-treated mice were also inhibited by CysLT(1) receptor blockade. These data suggest an important role for cysteinyl leukotrienes in the pathogenesis of chronic allergic airway inflammation with fibrosis.     

Measurements of components of resistance to breathing

Total respiratory resistance (Rrs), pulmonary resistance (RL), and airway resistance (Raw) of 12 male patients with chronic obstructive lung disease were measured by the partial occlusion method, intraesophageal balloon technique, and body plethysmography, respectively. Chest wall resistance (Rew) and lung tissue resistance (Rti) were computed. Percentages of Rew/Rrs, RL/Rrs, Raw/Rrs, Rti/Rrs, Raw/RL, and Rti/RL were calculated. The magnitude of the components of resistance to breathing of this study and the data appearing in the literature are compared. Wide variation between the data reported by various authors was observed. The possible causes of these variations are discussed.     

Neonatal screening for glucose-6-phosphate dehydrogenase deficiency in Taiwan

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathic disease in Taiwan. The mass neonatal screening of G6PD deficiency by fluorometric spot test in Taiwan was started with a pilot program in 1984. The nationwide screening was started on July 1, 1987, and a follow-up system comprising of eighteen referral hospitals, including outlying islands, was organized for confirmatory test, medical care and genetic counseling. From July 1987 to December 1997, 2,971,192 heel blood samples collected on filter paper from 1,143 delivery units were screened by four neonatal screening centers. 46,570 cases were confirmed as G6PD deficiency is estimated to be around 2.1% (male 3.1%, female 0.9%) in Taiwan. The coverage rate of neonatal screening was 99% in 1997. To assess the reliability of the confirmatory test, an external quality assurance (QA) program for G6PD assay was developed. Periodically, 3 or 5 lyophilized quality control materials with different activities of G6PD were sent to each referral hospital by speed post delivery in dry ice. From January 1988 to June 1998, 85 QA services were performed. Two hundred and seven (13.5%) abnormal QA results were found, which were attributed to clerk (11.6%), procedural (16.4%), and instrumental errors (47.3%). In aid to confirm G6PD deficiency, a method to detect the G6PD mutation by using the dried blood samples was developed. The frequencies of the mutant alleles in Taiwan were determined to be 46.8% (1376G > T), 16.2% (1388G > A), 7.9% (95A > G), 6.5% (493A > G), 5.6% (392G >T), 4.6% (1024C > T), 0.5% (487G > A) and 0.5% (519C > G), respectively.     

The influence of age and gender on HLA-DR in Chinese child-onset type 1 diabetes mellitus patients

To further clarify the association of HLA DR alleles with type 1 diabetes mellitus and the influence of age-onset and gender on type 1 diabetes, we investigated HLA-DR in 76 child onset Chinese (36 males) type 1 diabetes patients and 154 normal controls by using PCR-SSP (sequence specific primer). The mean age of onset of diabetes patients was 8.43 +/- 3.96 year-old. Our results revealed that the frequencies of DR3, DR4 and DR9 in diabetes patients were significantly higher than those in control group (all P < 0.01). The susceptible alleles were DR3, DR4, DR9, with relative risks of 8.25, 2.57 and 2.67, respectively. The protective alleles to type 1 diabetes were DR 2, DR8, DR11 and DR12 with relative risk of 0.24, 0.15, 0.16 and 0.39, respectively. There were no significant differences between the frequencies of HLA DR 3, DR4, DR9, DR3/4, DR3/9 and DR4/9 in male and female diabetic children. We divided the diabetes patients into three groups according to their age of onset (1-5 years old, 6-10 years old and 11-17 years old). There was a trend that the frequencies of DR9 decreased with the increase of age at onset, but there was no significant difference of DR3, DR4, DR9, DR3/4, DR3/9 and DR4/9 frequencies between diabetes children with age onset 0-10 years and 11-17 years. As to the influence of gender on the HLA genotypes, the frequency of DR3/4 decreased with the increase of age at onset for male patients and the frequency of DR3/4 increased with the increase of age at onset for female patients.     

Providing and monitoring quality service for smoking cessation in tuberculosis care.

All tobacco smokers should be identified and provided with a smoking cessation intervention (SCI) during tuberculosis (TB) treatment. To ensure that this occurs, the intervention process should be recorded and monitored. Monitoring is the best guarantee that care is standardised and offered equitably to all patients. It allows for evaluation of processes and outcomes so that population needs can be identified and appropriate techniques added or updated. In this article we propose steps for brief intervention as a part of the monitoring process, using model forms and suggested procedures for filling them in. The suggested forms are a modified TB treatment card that includes information about tobacco use, an SCI patient card to be added to the patient's TB treatment folder, SCI registers and SCI quarterly report forms and a tobacco use questionnaire for evaluation of services.     

A histochemical study on the development of hydroxysteroid dehydrogenases in tadpole ovaries.

Indifferent gonads and ovaries of Rana catesbeiana tadpoles at various developmental stages were investigated histochemically for the development of activities of Δ⁵-3β- and 17β-hydroxysteroid dehydrogenases (HSDs). It was found that activities of the two enzymes occurred simultaneously; that of 17β-HSD was usually weaker by visualization. They began to appear weakly in the indifferent gonad. The activities became stronger as the ovaries differentiated until the enzymes heavily occupied the cytoplasm of small auxocytes. While the auxocytes were growing in size, the activities of the two HSDs were decreasing and eventually became confined to a few patches in large auxocytes of metamorphosing tadpoles. Enzyme activities also occurred in follicle cells. They developed to a considerable extent in newly metamorphosed froglets. The present study presents histochemical evidence for developmental changes in the distribution of these two enzymes. The results also indicate capability of steroid hormone metabolism in the tadpole ovary during the course of sex differentiation. The localization of ooplasmic and follicular activities of the HSDs and the pattern of their development in differentiating ovaries are reported for the first time in amphibians.     

Renin-angiotensin system component expression in the HL-1 atrial cell line and in a pig model of atrial fibrillation

OBJECTIVES: Local atrial tissue angiotensin II (AngII) level is elevated in atrial fibrillation (AF), but the mechanism is unknown. We hypothesized that atrial myocytes express all components of the renin-angiotensin system (RAS) and investigated whether rapid depolarization alone is sufficient to increase paracrine AngII production by up-regulating RAS component expression. METHODS: In the HL-1 atrial cell line, rapid depolarization was induced by rapid field electrical stimulation (RES) at 1.0 V/cm and 600/min (10 Hz) in atrial HL-1 cells. In a pig model of AF, AF was induced by atrial pacing at 600/min in 10 adult pigs and 10 sham-operated pigs for comparison. RESULTS: In atrial myocytes, RES induced a sustained elevation of intracellular calcium, and up-regulation of angiotensin-converting enzyme (ACE), chymase and angiotensinogen, resulting in increased AngII production. RES-induced AngII production was attenuated by enalapril [ACE inhibitor (ACEI)] and chymostatin (chymase inhibitor). Conditioned medium from RES-stimulated atrial myocytes increased [3H]leucine uptake and atrial natriuretic peptide expression in atrial myocytes, and [3H]proline uptake and collagen type 1 alpha 1 expression in atrial fibroblasts. Both were attenuated by co-incubation with the AngII type 1 receptor blocker (ARB) losartan. In the porcine model, significant structural changes and a similar pattern of changes of RAS components were noted in AF pigs. CONCLUSIONS: Atrial cells expressed all components of RAS and rapid depolarization alone was sufficient to up-regulate RAS components, increase paracrine AngII production and induce atrial structural changes, which are attenuated by ACEI, ARB and chymase inhibitor.     

Association of the human minK gene 38G allele with atrial fibrillation: evidence of possible genetic control on the pathogenesis of atrial fibrillation

Background Human minK protein is the β-subunit of I_Ks potassium channel and plays an important role in cardiac cellular electrophysiology. We investigated the association between human atrial fibrillation and the polymorphism of minK gene (38G or 38S) with a case-control study. Methods We included 108 patients with atrial fibrillation and 108 control subjects. The case patients and control subjects were matched regarding age, sex, presence of valvular heart disease, and presence of left ventricular dysfunction. The genotype of minK was determined with polymerase chain reaction and restriction fragment analysis. Results The results showed an association between the minK 38G allele and atrial fibrillation. The odds ratios for atrial fibrillation in patients with 1 and 2 minK 38G alleles were 2.16 (95% CI 0.81-5.74) and 3.58 (95% CI 1.38-9.27), respectively, when compared with patients without minK 38G allele. In a logistic regression model, the odds ratio for atrial fibrillation was 1.80 (95% CI 1.20-2.71, P < .0046) for patients with 1 more minK 38G allele. Conclusion We report the association between the minK 38G allele and clinical atrial fibrillation. Our findings suggest possible genetic control on the pathogenesis of atrial fibrillation. (Am Heart J 2002;144:485-90.)     

The value of transesophageal echocardiography in the diagnosis of cardiac metastasis

To assess the diagnostic value of transesophageal two-dimensional echocardiography (TEE) as compared with transthoracic echocardiography (TTE), TTE and TEE were performed in eight consecutive patients (age range from 20 to 76 years, six male and two female) with clinical evidence of malignant tumors arising from the liver (n = 1), lung (n = 3), larynx (n = 1), osteogenic sarcoma (n = 1), lymphoma (n = 1), and yolk sac tumor in the anterior mediastinum (n = 1). In one case, the gastroscope could not be inserted because of tumor compression of the esophagus. Transesophageal echocardiography provided superior imaging in the detection of intracavitary metastatic lesions. In the case of right ventricular outflow tract tumor and greater vessel involvement, TTE may provide more imaging than TEE due to a blind area in this region by the transesophageal approach. In conclusion, TEE is complementary to TTE in the diagnosis of metastatic cardiac tumor.