Autoantibodies against bactericidal/permeability-increasing protein in patients with cystic fibrosis

Cystic fibrosis (CF), a genetic disorder, is characterized by chronic pulmonary infection/inflammation which leads to respiratory failure. The presence of anti-neutrophil cytoplasmic autoantibodies (ANCA) has previously been observed in the sera of patients with CF. In view of the known relationship of ANCA with primary vasculitis and of their putative pathogenetic role in these disorders, we studied the presence, specificity and isotype of ANCA and their clinical associations in 66 adult CF patients. None of the 66 CF samples had autoantibodies to the major ANCA antigens, proteinase 3 or myeloperoxidase. However, 60/66 (91%) CF samples contained IgG and 55/66 (83%) IgA, autoantibodies to bactericidal/permeability increasing protein (BPI), a recently characterized ANCA specificity. All the IgA anti-BPI-positive samples were also IgG anti-BPI-positive. The autoantibody specificity was confirmed by inhibition assay and immunoblotting of CF sera against a neutrophil granule preparation. Furthermore, in this cross-sectional study, anti-BPI levels were inversely correlated with the observed reductions in FEV1 and FVC (IgA anti-BPI and FEV1: r = 0.508, <it>p</it> &lt; 0.0001), and both IgG and IgA anti-BPI levels were higher in CF patients with secondary vasculitis (<it>n</it> = 6) than in those without (<it>p</it> &lt; 0.05). ANCA with specificity for BPI were present in the majority of CF sera in this study and autoimmune processes may be associated with the development of pulmonary injury in CF.      

Intermittent claudication in Quebec men from 1974-1986: the Quebec Cardiovascular Study

The incidence and risk factors of intermittent claudication (IC) and its association with coronary heart disease were evaluated in a cohort of 4570 men, aged 35 to 64 in 1973, free of cardiovascular diseases and followed for 12 years. During the follow-up, 188 developed IC, an annual incidence of 41/10,000. The risk of IC increased with age. In comparison to the rest of the cohort, men with IC were older and had a higher prevalence of smoking, elevated blood pressure, and diabetes. Cigarette smoking was the predominant factor, quadrupling the risk of IC compared to those who never smoked, while those who stopped smoking one year before the study had a risk similar to non-smokers. Quintile 5 of systolic blood pressure doubled the risk of IC. Diabetes requiring a pharmacological treatment at entry in the study was significantly more prevalent in men with than in men without IC (7.5% vs 1.5%). There was no significant relationship between IC and serum cholesterol, body weight, or number of years at school. During the follow-up, 84 of the 188 men with IC had a coronary heart disease event, angina being the most frequent manifestation. Furthermore, 11% of men with IC died and in nearly two-thirds of these, death was attributable to coronary heart disease; this was twice the rate observed in the other men. In these Quebec men, IC is a common health problem and is associated with a high rate of coronary heart disease. Since IC is related to modifiable risk factors, primary prevention of these factors appears warrant.     

The effect of cuff pressure deflation rate on accuracy in indirect measurement of blood pressure with the auscultatory method

The importance of cuff deflation rate in the auscultatory method of measuring blood pressure was investigated using a computer-based model. To determine the relationship between the cuff deflation rate and the measurement error, two cuff deflation protocols were used, one based on heart rate (mm Hg per heartbeat), the other on a constant rate (mm Hg per second). The different deflation protocols and rates were tested using a constant blood pressure of 120/80 mm Hg and heart rates ranging from 40 to 120 beats/min. It was confirmed that a cuff deflation rate that is time based will introduce larger errors at low heart rates. Using heart rate as a basis for cuff deflation rate yields a constant error that is independent of heart rate. The currently used standard of 3 mm Hg/s could result in a maximum error of 2.5 mm Hg in both systolic and diastolic pressures at a heart rate of 72 beats/min. The maximum systolic and diastolic errors increase to more than 4 mm Hg at 40 beats/min. A deflation rate of 2 mm Hg/beat, however, yields a maximum error of 2 mm Hg for both systolic and diastolic pressures, independent of heart rate. A cuff deflation rate based on heart rate is recommended to help minimize changes in measurement error when measuring blood pressure if a wide range of heart rates will be encountered.Supported by grants from IVAC, San Diego, CA, and Physio Control, Redmond, WA.     

Factors influencing capnography in the bain circuit

The Bain circuit provides continuous fresh gas flow near the airway. The potential mixing of this fresh gas with expired gas may prevent reliable analysis of expired gas. We therefore investigated the interaction of sampling site, fresh gas flow rate, expiratory flow rate, and sampling flow rate on expiratory capnography. Sampling near the fresh gas outlet yielded inaccurate results under several of these conditions. The magnitude of the error was related to the fresh gas and expiratory flow rates. A reliable sampling region near the endotracheal tube was identified.     

Microarray Analysis of Somatostatin Receptor 5-Regulated Gene Expression Profiles in Murine Pancreas

Background  We previously demonstrated that somatostatin receptor type 5 (SSTR5) gene ablation results in alterations in insulin secretion and glucose metabolism, accompanied by morphologic alterations in the islets of Langerhans. The underlying mechanism(s) by which SSTR5 exerts its cellular functions remain(s) unknown. We hypothesized that SSTR5 mediates the inhibitory effect of somatostatin (SST) on insulin secretion and islet proliferation by regulating a specific set of pancreatic genes. Methods  To identify SSTR5-regulated pancreatic genes, gene expression microarray analysis was performed on the whole pancreas of 1- and 3-month-old wild-type (WT) and SSTR5 knockout (SSTR5 ^−/−) male mice. Real-time RT-PCR and immunofluorescence were performed to validate selected differentially expressed genes. Results  A set of 143 probes were identified to be differentially expressed in the pancreas of 1-month-old SSTR5 ^−/− mice, 72 of which were downregulated and 71 upregulated. At 3 months of age, SSTR5 gene ablation resulted in downregulation of a set of 30 probes and upregulation of a set of 37 probes. Among these differentially expressed genes, there were 15 and 5 genes that were upregulated and downregulated, respectively, in mice at both 1 and 3 months of age. Three genes, PAP/INGAP, ANG, and TDE1, were selected to be validated by real-time RT-PCR and immunofluorescence. Conclusions  A specific set of genes linked to a wide range of cellular functions such as islet proliferation, apoptosis, angiogenesis, and tumorigenesis were either upregulated or downregulated in SSTR5-deficient male mice compared with their expression in wild-type mice. Therefore, these genes are potential SSTR5-regulated genes during normal pancreatic development and functional maintenance. This work was presented at the Molecular Surgeon Symposium on Personalized Genomic Medicine and Surgery, Baylor College of Medicine, Houston, TX, USA, 12 April 2008. The symposium was supported by a grant from the National Institutes of Health (R13 CA132572 to Changyi Chen).     

A new variant of the ATP13A2 gene in Chinese patients with early-onset parkinsonism

Parkinson＇s disease （PD） is the second most common neurodegenerative disorder characterized by a selective loss of nigrostriatal dopaminergic neurons. Clinical manifestations of this complex disease include resting tremor, bradykinesia, postural instability, gait difficulty and rigidity. Approximately 5%-10% of patients have genetic factors, yet etiology of PD remains unclear. Genetic deficits, environmental exposure, oxidative stress, mitochondrial dysfunction,