Development and results of the Spanish registry of patients with alpha-1-antitrypsin deficiency

The Spanish registry of alpha-1 antitrypsin deficiency was founded in 1993 and became a member of the International Registry (AIR) in 1999. We describe the updating process following its incorporation into AIR and compare the data collected in the first period (1993–1999) and the second period (1999–2005), during which time patients were included exclusively by internet.The registry included 301 patients during period 1, 69% males and 46% had a history of smoking. Their mean age was 46 years (SD = 13) and 284 (94%) had the ZZ phenotype, 49% received augmentation therapy. During period 2, 161 new cases were included, 63% of whom were males with a mean age of 44 years (SD = 16). A total of 126 (78%) had the ZZ phenotype. Only 12% received augmentation therapy. A total of 462 different patients were included in both periods. Significant differences were observed in the number of cases with the SZ phenotype and the severity of FEV₁ impairment between the two periods.Implementation of an internet-based collection of data did not result in a lower rate of reporting to the registry. However, data from a significant number of patient included in period 1 could not be actualized in the new data base.     

Common human Toll-like receptor 9 polymorphisms and haplotypes: association with atopy and functional relevance

BACKGROUND: Toll-like receptor 9 (TLR9) is a pattern-recognition receptor that detects unmethylated CpG motifs prevalent in bacterial and viral DNA. TLR9 stimulation is a key event after bacterial infection, triggering innate immunity and T-helper type 1 skewed adaptive immunity. Synthetic CpG-oligodeoxynucleotides (CpG-ODNs) represent a promising and novel class of immune adjuvants for allergy treatment, vaccination, and cancer therapy. However, common functional TLR9 gene variants could interfere with the clinical utilization of CpG-ODN in immunotherapy. Recently, a possible association of TLR9 polymorphism C-1237T with asthma has been reported. OBJECTIVE: The aim of the present study was to investigate whether TLR9 polymorphisms or haplotypes have functional relevance and are associated with atopy. METHODS: We genotyped five common TLR9 single-nucleotide polymorphisms (SNPs) in promoter, exon, and intron regions of the gene in 527 healthy blood donors, and estimated four common haplotypes. The total IgE and specific IgE levels against the most common aeroallergens were measured (n=303). IFN-alpha production by plasmacytoid dendritic cells (pDCs) was analysed after stimulation with TLR9 ligand CpG-ODN (n=220). RESULTS: No significant influence of common TLR9 polymorphisms and haplotypes on the total and specific IgE levels was found. Functional analysis of CpG-ODN-induced IFN-alpha did not indicate a significant role for common TLR9 gene polymorphisms in TLR9 function. CONCLUSION: We conclude that common genetic differences in the TLR9 gene exert no major influence on allergy susceptibility, and are unlikely to have on impact on clinical application of CpG-ODNs.     

Body composition and physical activity in end-stage renal disease.

OBJECTIVE: The study objective was to examine the relationship between visceral and somatic protein stores and physical activity in individuals with end-stage renal disease. DESIGN: This was a prospective single-center study. SETTING: The study took place at the Vanderbilt University Outpatient Dialysis Unit and General Clinical Research Center. PATIENTS: Fifty-five patients with prevalent chronic hemodialysis (CHD) were included: 33 males, 22 females, 45 African Americans, 9 Caucasians, and 1 Asian. The mean age was 47.0 +/- 1.6 years, height was 166.4 +/- 13.9 cm, and weight was 83.1 +/- 2.6 kg. METHODS: Body composition was measured by dual-energy x-ray absorptiometry. Minute-by-minute physical activity was assessed over a 7-day period with a triaxial accelerometer. Participants were interviewed by a trained registered dietitian for two 24-hour diet recalls (one from a hemodialysis day; one from a nonhemodialysis day). Laboratory values for serum concentrations of albumin, prealbumin, C-reactive protein, and creatinine were also collected. MAIN OUTCOME MEASURE: Predictors of somatic protein stores were the main outcome measure. RESULTS: Serum albumin was negatively and significantly correlated with the percentage of fat mass (P = .016) and kg of fat mass (P = .044). C-reactive protein was positively and significantly correlated with body weight (P = .006), percentage of fat mass (P = .017), kg of fat mass (P = .006), and body mass index (P = .004). Physical activity and total daily protein intake were the strongest predictors of the amount of lean body mass (P = .01 and .003, respectively). CONCLUSION: The association between somatic protein and visceral protein stores is weak in patients with CHD. Whereas increased levels of physical activity and total daily protein intake are associated with higher lean body mass in patients with CHD, higher adiposity is associated with higher C-reactive protein and lower albumin values.     

Obesity and litigation predict workers' compensation costs associated with interbody cage lumbar fusion.

BACKGROUND CONTEXT: Results of lumbar fusion surgery have been mixed and procedures are costly. Interbody cage lumbar fusion (ICLF) has been advanced to improve arthrodesis and clinical outcomes; however, little attention has been given to ICLF costs or potential predictors of these expenses. PURPOSE: To depict medical and compensation costs associated with ICLF in a Utah cohort of patients receiving workers' compensation as well as to investigate predictors of costs. STUDY DESIGN/SETTING: A retrospective-cohort research design was used involving completion of presurgical and postsurgical medical record reviews and accrual of medical and compensation costs. Presurgical variables included in a regression model were presurgical spinal pathophysiology rating, obesity, and litigation status. PATIENT SAMPLE: Forty-three consecutive patients who were compensated by the Workers' Compensation Fund of Utah and underwent ICLF. OUTCOME MEASURES: Total accrued compensation and medical costs. METHODS: A retrospective review of presurgical variables and total accrued compensation and medical costs was conducted. RESULTS: Multiple regression analysis indicated that nonpathophysiological factors predicted compensation costs (lawyer involvement [beta=0.40]; obesity [beta=0.34]). Specifically, compensation for those with versus without lawyers was $41,657 versus $24,837, and for those who were obese versus nonobese was $46,152 versus $28,168. Arthrodesis was correlated with medical costs (r=-0.47, p=.002), with incurred costs for patients achieving solid fusion versus pseudarthrosis equaling $38,881 versus $71,655, respectively. CONCLUSIONS: Considerable costs were associated with ICLF, particularly for those who were obese, involved in litigation, or failed to achieve solid fusion. With regard to compensation costs, the findings support the importance of assessing nonpathophysiological factors in spinal fusion patients.     

Stronger association of drug-induced progressive multifocal leukoencephalopathy (PML) with biological immunomodulating agents

Aim  

The aim of the present study was to collect and compare cases of drug-induced PML in order to contribute to the debate about the role of the underlying diseases and/or drug immunosuppression in PML occurrence.     

Experimental vaccination of young chickens with a live, non-pathogenic strain of Escherichia coli

A non-pathogenic, piliated strain of Escherichia coli (BT-7; Frommer et al., 1990), isolated from a meat-type chicken flock, was studied as a candidate for a live vaccine to protect chickens from E. coli infection. Active immunization provided substantial protection of chicks vaccinated at 14 or 21 days of age, resulting in better resistance to challenge than in those vaccinated at 1 or 7 days. Chicks vaccinated at 21 days of age and challenged 1 week later with pathogenic E. coli strains 01-.K1, 02:K1 or 078:K80, exhibited good protection for at least 2 weeks against all strains. Three vaccination routes were found to give the highest resistance to challenge with pathogenic E. coli strain 078:K80. Intramuscular (i.m.) at 7 and 21 days of age, i.m. at 21 days of age and spray at 7, followed by per os at 21 days of age. Vaccination per os once at 7 or twice at 7 and 21 days resulted in good protection. Chicks exhibiting high antibody titres by ELISA were well-protected against challenge.     

The Bactrocera tryoni homologue of the Drosophila melanogaster sex-determination gene doublesex

A homologue of the bifunctional sex-determining gene, doublesex (dsx), has been identified in the tephritid fruit fly, Bactrocera tryoni, and has been found to be expressed in a sex-specific manner in adult flies. The male- and female-specific cDNAs are identical at their 5′ ends but differ at their 3′ ends and appear to be the products of alternate splicing. The level of identity of the sex-specific DSX proteins of B. tryoni with the D. melanogaster DSX proteins, across the region corresponding to the DNA binding domain and the oligomerization domains, is greater than 85%. Four sequence motifs which are ten to thirteen bases identical to the TRA/TRA-2 binding sites (thirteen-nucleotide repeat sequences) are present in the female-specific exon of the B. tryoni dsx gene.     

Seed and vascular expression of a high-affinity transporter for cationic amino acids in Arabidopsis.

In most plants amino acids represent the major transport form for organic nitrogen. A sensitive selection system in yeast mutants has allowed identification of a previously unidentified amino acid transporter in Arabidopsis. AAT1 encodes a hydrophobic membrane protein with 14 membrane-spanning regions and shares homologies with the ecotropic murine leukemia virus receptor, a bifunctional protein serving also as a cationic amino acid transporter in mammals. When expressed in yeast, AAT1 mediates high-affinity transport of basic amino acids, but to a lower extent also recognizes acidic and neutral amino acids. AAT1-mediated histidine transport is sensitive to protonophores and occurs against a concentration gradient, indicating that AAT1 may function as a proton symporter. AAT1 is specifically expressed in major veins of leaves and roots and in various floral tissues--i.e., and developing seeds.     

Stimulation of nerve growth factor and substance P expression in the iris–trigeminal axis of diabetic rats—involvement of oxidative stress and effects of aldose reductase inhibition

In rats with streptozotocin-induced diabetes, we measured increased (by 61%; P<0.05) mRNA for nerve growth factor (NGF) in the iris together with increased (by 82%; P<0.05) mRNA for preprotachykinin (the substance P precursor) in the trigeminal ganglion, suggesting that increased NGF was driving increased substance P gene expression. In other diabetic rats, these changes were prevented by treatment with either an antioxidant (butylated hydroxytoluene; 1% by diet) or an aldose reductase inhibitor (ARI) (sorbinil; 25 mg/kg/day p.o.) and the sorbinil treatment was associated with significant inhibition of polyol pathway intermediates in both lens and sciatic nerve. This suggests that polyol pathway activity in the lens may translate to oxidative stress-driving stimulation of NGF gene expression in the iris. The change is selective for NGF, because expression of the analogous neurotrophin, neurotrophin-3 (NT-3), was unaltered in the same irises. These changes suggest that oxidative stress and/or inflammation can drive up NGF expression in diabetes—a mechanism that might participate in iritis.