Polymorphisms in the C-type lectin genes cluster in chromosome 19 and predisposition to severe acute respiratory syndrome coronavirus (SARS-CoV) infection

Background: Polymorphisms of CLEC4M have been associated with predisposition for infection by the severe acute respiratory syndrome coronavirus (SARS-CoV). DC-SIGNR, a C-type lectin encoded by CLEC4M, is a receptor for the virus. A variable number tandem

Characterization of TRPC2, an Essential Genetic Component of VNS Chemoreception, Provides Insights into the Evolution of Pheromonal Olfaction in Secondary-Adapted Marine Mammals

Pheromones are chemical cues released and sensed by individuals of the same species, which are of major importance in regulating reproductive and social behaviors of mammals. Generally, they are detected by the vomeronasal system (VNS). Here, we first investigated and compared an essential genetic component of vomeronasal chemoreception, that is, TRPC2 gene, of four marine mammals varying the degree of aquatic specialization and related terrestrial species in order to provide insights into the evolution of pheromonal olfaction in the mammalian transition from land to water. Our results based on sequence characterizations and evolutionary analyses, for the first time, show the evidence for the ancestral impairment of vomeronasal pheromone signal transduction pathway in fully aquatic cetaceans, supporting a reduced or absent dependence on olfaction as a result of the complete adaptation to the marine habitat, whereas the amphibious California sea lion was found to have a putatively functional TRPC2 gene, which is still under strong selective pressures, reflecting the reliance of terrestrial environment on chemical recognition among the semiadapted marine mammals. Interestingly, our study found that, unlike that of the California sea lion, TRPC2 genes of the harbor seal and the river otter, both of which are also semiaquatic, are pseudogenes. Our data suggest that other unknown selective pressures or sensory modalities might have promoted the independent absence of a functional VNS in these two species. In this respect, the evolution of pheromonal olfaction in marine mammals appears to be more complex and confusing than has been previously thought. Our study makes a useful contribution to the current understanding of the evolution of pheromone perception of mammals in response to selective pressures from an aquatic environment.

Respiratory pattern of captive Yangtze finless porpoises (Neophocaena phocaenoides asiaeorientalis)

Cetacean respiration usually happen in bouts. The most widely applied quantitative method used to analyze the structure of these bouts is the log(e)-survivorship analysis, based on the assumption that the respiratory intervals are distributed as negative exponentials. However, for the data collected from three captive Yangtze finless porpoises (Neophocaena phocaenoides asiaeorientalis), we failed to obtain a convergent result with the application of log,survivorship analysis. However, the two-Gaussian model, which was recently proposed to analyze the feeding behavior of cows, was successfully fitted to the data. According to the fitting results, the overall respiratory pattern of the captive Yangtze finless porpoises can be described as a dive with a mean duration of around 30-40 s, followed by two or three ventilations with a mean interval of approximately 9 s. The average intra-bout intervals during both active and inactive periods are constant at 7.7-9.9 s for all individuals. However, when shifting from active to inactive states, the adult male and female decrease their mean numbers of respirations per bout and average length of inter-bout respiratory intervals, while the estimates of both parameters increase for the juvenile female. It was pointed out that the two-Gaussian model might be more adequate for cetacean respiratory-bout structure analyses than the log(e)-survivorship technique.

Measurement of respiratory acoustic impedance in children by a modified forced oscillation method

An introduction to a modified forced oscillation method, square-wave excitation technique, including fundamentals and methods, as used in respiratory function examination. On the basis of experimental results and theoretical predictions, we suggest that Respiratory Acoustic Impedance (RAI) measurement by spectral analysis can significantly improve estimation of contribution to RAI from different part of respiratory tract. The outcome is of considerable interest in the study of lung disease, such as COPD and asthma in young children.

Influence of Hypericum perforatum Extract on Piglet Infected with Porcine Respiratory and Reproductive Syndrome Virus

To study the influence of Hypericum perforatum extract (HPE) on piglets infected with porcine respiratory and reproductive syndrome virus (PRRSV), enzyme-labeled immunosorbent assay (ELISA) and cytopathic effect (CPE) were used to determine in vitro whether HPE could induce swine pulmonary alveolar macrophages (PAMs) to secrete IFN-gamma, and whether PRRSV titers in PAMs were affected by the levels of HPE-induced IFN-gamma. HPE (200 mg kg(-1)) was administrated by oral gavage to piglets infected with the PRRSV in vivo to observe whether HPE affected the viremia, lung viral titers, and weight gain of piglets infected with PRRSV. The results showed that HPE was capable of inducing PAMs to produce IFN-gamma in a dose dependent manner and HPE pretreatment was capable of significantly reducing PRRSV viral titers in PAMs (P<0.01). Administration of HPE to the PRRSV-infected animals significantly (P<0.05) reduced viremia over time as compared with the PRRSV-infected animals. But there was not significant decrease in lung viral titers at day 21 post-infection between the HPE-treated animals and the PRRSV-infected control piglets. There were no significant differences in weight gain over time among the HPE-treatment animals, the normal control, and the HPE control animals. The PRRSV-infected animals caused significant (P<0.01) growth retardation as compared with the HPE controls and the normal piglets. It suggested that HPE might be an effective novel therapeutic approach to diminish the PRRSV-induced disease in swine.

Genetic predisposition to acute respiratory distress syndrome in patients with severe sepsis

The objective of this study was to analyze the association between candidate gene polymorphisms and susceptibility to acute respiratory distress syndrome (ARDS) in patients with severe sepsis. Patients older than 18 years admitted to the intensive care un

Optimal assessment of the ability of children with recurrent respiratory tract infections to produce anti-polysaccharide antibodies.

Specific anti-polysaccharide antibody deficiency (SPAD) is an immune disorder. Diagnostic criteria have not yet been defined clearly. One hundred and seventy-six children evaluated for recurrent respiratory tract infections were analysed retrospectively. For each subject, specific anti-pneumococcal antibodies had been measured with two enzyme-linked immunosorbent assays (ELISAs), one overall assay (OA) using the 23-valent pneumococcal polysaccharide vaccine (23-PPSV) as detecting antigen and the other purified pneumococcal polysaccharide serotypes (serotype-specific assay, SSA) (serotypes 14, 19F and 23F). Antibody levels were measured before (n = 176) and after (n = 93) immunization with the 23-PPSV. Before immunization, low titres were found for 138 of 176 patients (78%) with OA, compared to 20 of 176 patients (11%) with the SSA. We found a significant correlation between OA and SSA results. After immunization, 88% (71 of 81) of the patients considered as responders in the OA test were also responders in the SSA; 93% (71 of 76) of the patients classified as responders according to the SSA were also responders in the OA. SPAD was diagnosed in 8% (seven of 93) of patients on the basis of the absence of response in both tests. Thus, we propose to use OA as a screening test for SPAD before 23-PPSV immunization. After immunization, SSA should be used only in case of a low response in OA. Only the absence of or a very low antibody response detected by both tests should be used as a diagnostic criterion for SPAD.

Co-regulation of nuclear respiratory factor-1 by NFkappaB and CREB links LPS-induced inflammation to mitochondrial biogenesis.

The nuclear respiratory factor-1 (NRF1) gene is activated by lipopolysaccharide (LPS), which might reflect TLR4-mediated mitigation of cellular inflammatory damage via initiation of mitochondrial biogenesis. To test this hypothesis, we examined NRF1 promoter regulation by NFκB, and identified interspecies-conserved κB-responsive promoter and intronic elements in the NRF1 locus. In mice, activation of Nrf1 and its downstream target, Tfam, by Escherichia coli was contingent on NFκB, and in LPS-treated hepatocytes, NFκB served as an NRF1 enhancer element in conjunction with NFκB promoter binding. Unexpectedly, optimal NRF1 promoter activity after LPS also required binding by the energy-state-dependent transcription factor CREB. EMSA and ChIP assays confirmed p65 and CREB binding to the NRF1 promoter and p65 binding to intron 1. Functionality for both transcription factors was validated by gene-knockdown studies. LPS regulation of NRF1 led to mtDNA-encoded gene expression and expansion of mtDNA copy number. In cells expressing plasmid constructs containing the NRF-1 promoter and GFP, LPS-dependent reporter activity was abolished by cis-acting κB-element mutations, and nuclear accumulation of NFκB and CREB demonstrated dependence on mitochondrial H(2)O(2). These findings indicate that TLR4-dependent NFκB and CREB activation co-regulate the NRF1 promoter with NFκB intronic enhancement and redox-regulated nuclear translocation, leading to downstream target-gene expression, and identify NRF-1 as an early-phase component of the host antibacterial defenses.

Menthol attenuates respiratory irritation and elevates blood cotinine in cigarette smoke exposed mice.

Addition of menthol to cigarettes may be associated with increased initiation of smoking. The potential mechanisms underlying this association are not known. Menthol, likely due to its effects on cold-sensing peripheral sensory neurons, is known to inhibit the sensation of irritation elicited by respiratory irritants. However, it remains unclear whether menthol modulates cigarette smoke irritancy and nicotine absorption during initial exposures to cigarettes, thereby facilitating smoking initiation. Using plethysmography in a C57Bl/6J mouse model, we examined the effects of L-menthol, the menthol isomer added to cigarettes, on the respiratory sensory irritation response to primary smoke irritants (acrolein and cyclohexanone) and smoke of Kentucky reference 2R4 cigarettes. We also studied L-menthol's effect on blood levels of the nicotine metabolite, cotinine, immediately after exposure to cigarette smoke. L-menthol suppressed the irritation response to acrolein with an apparent IC₅₀ of 4 ppm. Suppression was observed even at acrolein levels well above those necessary to produce a maximal response. Cigarette smoke, at exposure levels of 10 mg/m³ or higher, caused an immediate and marked sensory irritation response in mice. This response was significantly suppressed by L-menthol even at smoke concentrations as high as 300 mg/m³. Counterirritation by L-menthol was abolished by treatment with a selective inhibitor of Transient Receptor Potential Melastatin 8 (TRPM8), the neuronal cold/menthol receptor. Inclusion of menthol in the cigarette smoke resulted in roughly a 1.5-fold increase in plasma cotinine levels over those observed in mice exposed to smoke without added menthol. These findings document that, L-menthol, through TRPM8, is a strong suppressor of respiratory irritation responses, even during highly noxious exposures to cigarette smoke or smoke irritants, and increases blood cotinine. Therefore, L-menthol, as a cigarette additive, may promote smoking initiation and nicotine addiction.

Maternal Effects of Respiratory Syncytial Virus Infection during Pregnancy.

Given the illness and deaths caused by respiratory syncytial virus (RSV) infection during the first year of life, preventing infant RSV infections through maternal vaccination is intriguing. However, little is known about the extent and maternal effects of RSV infection during pregnancy. We describe 3 cases of maternal RSV infection diagnosed at a US center during winter 2014. Case-patient 1 (26 years old, week 33 of gestation) received a diagnosis of RSV infection and required mechanical ventilation. Case-patient 2 (27 years old, week 34 of gestation) received a diagnosis of infection with influenza A(H1N1) virus and RSV and required mechanical ventilation. Case-patient 3 (21 years old, week 32 of gestation) received a diagnosis of group A streptococcus pharyngitis and RSV infection and was monitored as an outpatient. Clarifying the effects of maternal RSV infection could yield valuable insights into potential maternal and fetal benefits of an effective RSV vaccination program.

Diminishment of respiratory sinus arrhythmia foreshadows doxorubicin-induced cardiomyopathy.

BACKGROUND: The development of a microcomputer-based device permits quick, simple, and noninvasive quantification of the respiratory sinus arrhythmia (RSA) during quiet breathing. METHODS AND RESULTS: We prospectively and serially measured the radionuclide left ventricular ejection fraction and the RSA amplitude in 34 cancer patients receiving up to nine monthly bolus treatments with doxorubicin hydrochloride (60 mg/m2). Of the eight patients who ultimately developed symptomatic doxorubicin-induced congestive heart failure, seven (87.5%) demonstrated a significant decline in RSA amplitude; five of 26 subjects without clinical symptoms of cardiotoxicity (19.2%) showed a similar RSA amplitude decline. On average, significant RSA amplitude decline occurred 3 months before the last planned doxorubicin dose in patients destined to develop clinical congestive heart failure. CONCLUSION: Overall, RSA amplitude abnormality proved to be a more specific predictor of clinically significant congestive heart failure than did serial resting radionuclide ejection fractions.

The art of auscultation: evaluating a patient's respiratory pathology

This article considers national policy drivers promoting the development of advanced assessment skills and practical procedures for the safe and effective use of the stethoscope in the clinical area. The evidence base underpinning effective use of the stethoscope in clinical practice is explored, including the preparation of the patient and the environment, applying infection control policies, and placing an emphasis on privacy and dignity. This is followed by a practical guide to auscultation technique of the respiratory system for nurses developing advanced practice skills.

Respiratory auscultation: how to use a stethoscope

This article outlines the correct procedure for respiratory assessments using a stethoscope, how to use a stethoscope and how to interpret your findings.

Early growth and adult respiratory function in men and women followed from the fetal period to adulthood

While some studies suggest that poor fetal growth rate, as indicated by lower birth weight, is associated with poor respiratory function in childhood, findings among adults remain inconsistent. A study was undertaken to determine the association between early growth and adult respiratory function.