Voltage-gated Ca2+ channel Ca(V)1.3 subunit expressed in the hair cell epithelium of the sacculus of the trout Oncorhynchus mykiss: cloning and comparison across vertebrate classes

Full-length sequence (>6.5 kb) has been determined for the Ca(V)1.3 pore-forming subunit of the voltage-gated Ca(2+) channel from the saccular hair cells of the rainbow trout (Oncorhynchus mykiss). Primary structure was obtained from overlapping PCR and cloned fragments, amplified by primers based on teleost, avian, and mammalian sources. Trout saccular Ca(V)1.3 was localized to hair cells, as evidenced by its isolation from an epithelial layer in which the hair cell is the only intact cell type. The predicted amino acid sequence of the trout hair cell Ca(V)1.3 is approximately 70% identical to the sequences of avian and mammalian Ca(V)1.3 subunits and shows L-type characteristics. The trout hair cell Ca(V)1.3 expresses a 26-aa insert in the I-II cytoplasmic loop (exon 9a) and a 10-aa insert in the IVS2-IVS3 cytoplasmic loop (exon 30a), neither of which is appreciably represented in trout brain. The exon 9a insert also occurs in hair cell organs of chick and rat, and appears as an exon in human genomic Ca(V)1.3 sequence (but not in the Ca(V)1.3 coding sequence expressed in human brain or pancreas). The exon 30a insert, although expressed in hair cells of chick as well as trout, does not appear in comparable rat or human tissues. Further, the IIIS2 region shows a splice choice (exon 22a) that is associated with the hair cell organs of trout, chick, and rat, but is not found in human genomic sequence. The elucidation of the primary structure of the voltage-gated Ca(2+) channel Ca(V)1.3 subunit from hair cells of the teleost, representing the lowest of the vertebrate classes, suggests a generality of sensory mechanism for Ca(V)1.3 across hair cell systems. In particular, the exon 9a insert of this channel appears to be the molecular feature most consistently associated with hair cells from fish to mammal, consonant with the hypothesis that the latter region may be a signature for the hair cell.     

Age does not influence the bone response to treadmill exercise in female rats

PURPOSE: Because it is believed that bone may respond to exercise differently at different ages, we compared bone responses in immature and mature rats after 12 wk of treadmill running. METHODS: Twenty-two immature (5-wk-old) and 21 mature (17-wk-old) female Sprague Dawley rats were randomized into a running (trained, P = 10 immature, 9 mature) or a control group (controls, P = 12 immature, 12 mature) before sacrifice 12 wk later. Rats ran on a treadmill five times per week for 60-70 min at speeds up to 26 m.min. Both at baseline and after intervention, we measured total body, lumbar spine, and proximal femoral bone mineral, as well as total body soft tissue composition using dual-energy x-ray absorptiometry (DXA). After sacrificing the animals, we measured dynamic and static histomorphometry and three-point bending strength of the tibia. RESULTS: Running training was associated with greater differences in tibial subperiosteal area, cortical cross-sectional area, peak load, stiffness, and moment of inertia in immature and mature rats (P < 0.05). The trained rats had greater periosteal bone formation rates (P < 0.01) than controls, but there was no difference in tibial trabecular bone histomorphometry. Similar running-related gains were seen in DXA lumbar spine area (P = 0.04) and bone mineral content (BMC; P = 0.03) at both ages. For total body bone area and BMC, the immature trained group increased significantly compared with controls (P < 0.05), whereas the mature trained group gained less than did controls (P < 0.01). CONCLUSION: In this model, where a similar physical training program was performed by immature and mature female rats, we demonstrated that both age groups were sensitive to loading and that bone strength gains appeared to result more from changes in bone geometry than from improved material properties.     

Standardized mortality ratios and fatal pulmonary embolism rates following total knee replacement: a cohort of 936 consecutive cases

Mortality and fatal pulmonary embolism rates in 936 consecutive primary total knee replacements (TKR) were determined during a 3-month postoperative period. Postmortem examinations verified the cause of death in all but 3 patients, and follow-up was performed on all but 1 patient. All patients had elastic stockings as mechanical prophylaxis. No deaths occurred from pulmonary embolism confirmed by postmortem examinations. At worst, the fatal pulmonary embolism rate was 0.43% (4/936; confidence interval [CI]=0.14%-1.17%). The all-cause mortality rate was 0.64% (6/936; CI=0.26%-1.46%). The patient mortality was compared with the population mortality of England and Wales using standardized mortality ratios. The standardized mortality ratios for both sexes combined was 0.74 (CI=0.29-1.52). A lower mortality was observed in women (0.67) than in men (0.84) during the first 3 postoperative months compared to the general population. Fatal pulmonary embolism after TKR with the routine use of graded elastic stockings and early mobilization is rare. In this series, the death rate in patients undergoing TKR appears to be lower than that in the general population.     

Prevalence of bronchial asthma among bank employees of Vellore using questionnaire-based data

Asthma and related allergic disorders are reported to be rare in poor and developing countries and their prevalence is expected to rise with urbanisation. Investigation was carried to see the prevalence of asthma and asthma-related symptoms by using a simple questionnaire-based data collection. One hundred and twenty bank employees were studied in the age group 25-55 years in 4 centres of Vellore town. A one-page questionnaire in English regarding asthma and allergic symptoms was used to assess the prevalence and the details of medical care utilisation by those who were asthmatics. The prevalence of self-reported bronchial asthma was 8.3% and that of asthma-related symptoms 15.8%. A significant number of subjects with symptoms suggestive of asthma self-reported themselves as non-asthmatic. There was a significant association between those who had symptoms of asthma and a positive family history of asthma. Most of the asthmatic subjects using allopathic medicines reported a poor quality of life, despite treatment. The prevalence of asthma in Vellore town is more than that reported in other studies carried out at different centres in India. The prevalence may actually be higher since a significant number of subjects with symptoms suggestive of asthma reported themselves as non-asthmatic subjects. As expected, positive family history was forthcoming in subjects with asthma symptoms. Most asthmatic subjects have not experienced a significant improvement in their quality of life, which could indicate sub-optimal management. These findings can form the basis for further studies to investigate factors that lead to these variations.     

A novel tau mutation (N296N) in familial dementia with swollen achromatic neurons and corticobasal inclusion bodies

Familial dementia with swollen achromatic neurons and corticobasal inclusion bodies is a neurodegenerative disease that resembles corticobasal degeneration. It is characterized by the presence of abundant neuronal and glial tau protein deposits. Here we describe a novel silent mutation in exon 10 of tau (N296N) in this familial dementia. By exon trapping, the mutation produced an increase in the splicing in of exon 10, indicating that it probably causes disease through an overproduction of four-repeat tau.     

Role of cysteinyl leukotrienes in airway inflammation and responsiveness following RSV infection in BALB/c mice

Cysteinyl leukotrienes (CysLTs) contribute to the development of airway obstruction and inflammation in asthma; however little information is available on the role of these molecules in the pathophysiology of respiratory syncytial virus (RSV) bronchiolitis. This study was designed to evaluate the effects of RSV infection on CysLTs production in a well-established mouse infection model. Furthermore, we assessed the effect of anti-inflammatory agents (a leukotriene receptor antagonist, MK-571, and dexamethasone) on the functional and immune changes induced by RSV infection. Six to 8-wk-old BALB/c mice were infected with human RSV (strain A2). Measurements of airway function were performed using whole body plethysmography. Lung inflammation was assessed by cell counts, measurement of cytokines and CysLTs in bronchoalveolar lavage fluid (BALF) in the absence and presence of treatment with MK-571 or dexamethasone. RSV infection produced a marked increase in CysLTs in the BALF and lung tissue, recruitment of neutrophils and lymphocytes into the airways, increased IFN-gamma levels and airway hyperresponsiveness (AHR). Treatment with MK-571 decreased RSV-induced AHR without affecting the cellular and inflammatory responses to RSV. Dexamethasone decreased AHR and markedly reduced the recruitment of inflammatory cells and production of IFN-gamma. Our findings suggest CysLTs play an important role in the pathogenesis of RSV-induced airway dysfunction. Treatment with MK-571 decreases RSV-induced AHR but does not appear to alter the lung inflammatory responses to RSV. In contrast, dexamethasone decreases RSV-induced AHR but interferes with recruitment of inflammatory cells, resulting in decreased Th1 cytokines (a potentially Th2-prone environment) in this model. These studies support recent reports on the beneficial effects of CysLT receptor antagonist in human trials and provide a model for investigating the role of CysLTs in RSV bronchiolitis.