Meta-analysis of association between ALDH2 rs671 polymorphism and essential hypertension in Asian populations.

BACKGROUND: Mitochondrial aldehyde dehydrogenase-2 (ALDH2) is an enzyme that oxidizes acetaldehyde into acetic acid during alcohol metabolism. Many studies indicate that the rs671 GG genotype in the ALDH2 gene may play a critical role in increasing the risk of essential hypertension (EH) associated with alcohol consumption, which predominantly occurs in men. However, the literature is inconclusive in this regard. This meta-analysis aims to derive a more precise estimation of the relationship between the rs671 polymorphism and EH for both male and female drinkers and nondrinkers. METHODS: Ten cohort and case-control studies were included in the analysis with a total of 12,161 subjects; 7,062 patients and 5,099 healthy controls. RESULTS: Our results show that the rs671 GG genotype was associated with an increased risk of EH compared with the AG+AA genotype (OR = 1.27, 95 % CI = 1.17-1.37, p < 0.00001). When comparing male and female subjects, only among male individuals was a higher risk of EH found in the GG genotype compared with the AG+ AA genotype (OR = 1.59, 95 % CI = 1.40-1.80, p < 0.00001). By contrast, among female subjects, the risk of EH in the rs671 GG genotype did not differ from that detected in the AA + GG genotype. The proportion of patients with EH was significantly higher for the GG genotype carriers than for the AG+AA genotype carriers, both in the subset of drinkers (OR = 1.51, 95 % CI = 1.23-1.86, p < 0.0001) and in that of nondrinkers (OR = 1.22, 95 % CI = 1.01-1.47, p = 0.03). In addition, among carriers of the GG genotype, the risk of EH among the drinkers was similar to that found in the nondrinkers' subset (OR = 1.12, 95 %CI = 0.89-1.41, p = 0.34). CONCLUSION: Our meta-analysis demonstrates that the rs671 GG genotype increases the risks of EH, especially in men, and is independent of alcohol consumption.

Defective aeroallergen surveillance by airway mucosal dendritic cells as a determinant of risk for persistent airways hyper-responsiveness in experimental asthma.

A hallmark of atopic asthma is development of chronic airways hyper-responsiveness (AHR) that persists in the face of ongoing exposure to perennial aeroallergens. We investigated underlying mechanisms in sensitized rats focusing on a strain expressing the high-allergen-responder phenotype characteristic of human atopic asthmatics, and find that their high susceptibility to aeroallergen-induced persistent AHR is associated with deficiencies in the immunoregulatory and mucosal trafficking properties of inducible T-regulatory cells (iTregs). Counterintuitively, AHR susceptibility was inversely related to aeroallergen exposure level, high exposures conferring protection. We demonstrate that underlying this AHR-susceptible phenotype is reduced capacity of airway mucosal dendritic cells (AMDCs) for allergen sampling in vivo; this defect is microenvironmentally acquired, as allergen uptake by these cells in vitro is normal. Moreover, intranasal transfer of in vitro aeroallergen-loaded AMDC from naïve animals into AHR-susceptible animals during prolonged aerosol challenge markedly boosts subsequent accumulation of iTregs in the airway mucosa and rapidly resolves their chronic AHR, suggesting that compromised antigen surveillance by AMDC resulting in defective functional programming of iTreg may be causally related to AHR susceptibility.

T-cell activation genes differentially expressed at birth in CD4+ T-cells from children who develop IgE food allergy.

BACKGROUND: Presymptomatic immaturity in neonatal T-cell function is a consistent antecedent of allergic disease, including reduced responsiveness to polyclonal activation. METHODS: To elucidate the underlying mechanisms, we examined for differences in T-cell gene expression in longitudinal samples collected at birth and at 1 year of age in children with (n = 30) and without IgE-mediated food allergy (n = 30). We employed a low-level soluble anti-CD3 stimulus to activate the T-cell receptor (TCR) and surveyed gene expression by DNA microarray in purified CD4(+) T-cells. Allergen-specific responses were assessed in parallel functional studies. RESULTS: At birth, the allergic group showed a reduced number of genes up regulated in response to anti-CD3 treatment on the microarray and a reduced lympho proliferative capacity, suggesting clear differences in T-cell signalling pathways. Polymerase chain reaction (PCR) validation of candidate genes confirmed significantly lower expression of a number of genes in the allergic group including RELB, NFKB2, LIF and FAS. By 12 months of age, there were marked changes in the anti-CD3 response in all infants, culminating in upregulation of cytokine genes (IL-5, IL-13, IL-17 and IL-22). Neonatal differences were no longer apparent. Instead, the allergic group, all symptomatic by this age, showed differential expression of T-cell lineage pathways including GATA-3, MAL and FcER1 in unstimulated T-cells. Allergen stimulation induced significantly higher cytokines production (IL-5, IL-13 and IFNγ) in the allergic group. CONCLUSION: Although transient, suboptimal neonatal T-cell activation pathways that signal through the NF-κB complex may affect the developmental transition of T-cell phenotypes in the periphery shortly after birth and may increase the risk of food allergy.

Four-part proximal humeral fractures: diagnosis with the 'sunset' sign on anteroposterior radiograph.

INTRODUCTION: Four-part proximal humeral fractures require surgical intervention. However, they can be difficult to diagnose in radiological images. We aim to define a new, easily recognisable, radiological sign as a predictor of four-part fracture of the proximal humerus in a plain anteroposterior radiograph of the shoulder. PATIENTS AND METHODS: We describe our 'sunset' sign as 'articular surface of humeral head pointing away from the glenoid and tilted upwards, in the presence of a displaced greater tuberosity fracture'. We postulate that a patient with proximal humerus fracture showing this sign has four-part fracture until proven otherwise. Between 2002 and 2006, 80 consecutive patients had surgical treatment of their proximal humeral fractures in our unit. Pre-operative radiographs and operative notes of 79 patients were evaluated independently by three blinded observers. The presence of 'sunset' sign was recorded. Findings were then correlated with the operative diagnoses to confirm whether they were four-part fractures or not. With 95% confidence interval, we calculated the sensitivity, specificity, positive and negative predictive values for our diagnostic sign. RESULTS: Of 79 patients, 30 displayed 'sunset' sign in their pre-operative radiograph. Of these, 28 had confirmed four-part fractures operatively. The positive predictive value of 'sunset' sign was 93%. The specificity and sensitivity were 95% and 78%, respectively. The sensitivity was affected by eight patients with four-part fractures with displaced articular head fragment which had dropped either medially or posteriorly. CONCLUSIONS: These results suggest that, in patients with proximal humeral fractures, the presence of 'sunset' sign in the anteroposterior radiograph is a reliable indicator of four-part fracture.

Study of 2-H-heptafluoropropane and its thermal decomposition using UV photoelectron spectroscopy and ab initio molecular orbital calculations.

The thermal decomposition of 2-H-heptafluoropropane, CF(3)CHFCF(3), at low pressure, heavily diluted in argon, has been studied over the temperature range 600-2000 degrees C using photoelectron spectroscopy. Comparison of the results obtained has been made with results of recent electronic structure calculations of possible decomposition pathways and results of a shock tube study. The most favored reaction thermodynamically, to produce CF(3)CF=CF(2) + HF, is found to be the main decomposition reaction at lower temperatures, 600-900 degrees C. At higher temperatures, 900-1200 degrees C, the decomposition reaction to give C(2)F(4) + CF(3)H was found to become important. No evidence for CF(3)CHFCF(3) --> CF(3)CHF + CF(3), a reaction expected to be important from a shock tube study, performed at much higher pressures, or for CF(3)CHFCF(3) --> CF(3)CF + CF(3)H was obtained, although for the latter reaction it is likely that CF(3)CF converts into C(2)F(4) under the conditions used before photoionization, in the ionization region of the photoelectron spectrometer. At higher temperatures C(3)F(6) decomposes to C(2)F(4) + CF(2), and C(2)F(4) decomposes to CF(2). Ab initio calculations have been performed of the adiabatic and vertical ionization energies of possible primary pyrolysis products to assist assignment of the photoelectron spectra recorded for heated flowing gas samples. A comparison is made between the threshold photoelectron spectrum and the photoelectron spectrum of CF(3)CF=CF(2).

Study of pentafluoroethane and its thermal decomposition using UV photoelectron spectroscopy and ab initio molecular orbital calculations.

The UV photoelectron spectrum of CF(3)CHF(2) has been recorded and assigned using EOM-CCSD calculations. For the first band, the adiabatic ionization energy (AIE) and vertical ionization energy (VIE) have been measured as (12.71 +/- 0.05) and (13.76 +/- 0.02) eV, respectively. The measured AIE is higher than the recommended value from state-of-the-art ab initio calculations of (12.26 +/- 0.02) eV because of a large geometry change on ionization, mainly arising from a significant increase in the C-C bond length, which results in poor Franck-Condon factors in the adiabatic region. The experimental VIE also shows poor agreement with the computed value of 14.05 +/- 0.06 eV because, in the higher energy region of the first photoelectron band, dissociation of CF(3)CHF(2)(+) to CHF(2)(+) + CF(3) occurs. This has a calculated thermodynamic onset of (12.89 +/- 0.20) eV. Recommendations are made for the heats of formation, DeltaH(f,298)(slashed circle), of CF(3)CHF(2) and CF(3)CHF(2)(+), based on the results of the ab initio calculations. Pyrolysis of flowing CF(3)CHF(2) diluted in argon shows evidence of production of C(2)F(4) and HF at lower temperatures and CF(2) and CF(3)H at higher temperatures. The relative temperature dependence of the observed photoelectron bands associated with these molecules is interpreted in terms of two decomposition reactions of CF(3)CHF(2) as well as the reaction C(2)F(4) --> 2CF(2).

Open repair of massive rotator cuff tears in patients aged sixty-five years or over: is it worthwhile?

The purpose of the study was to evaluate the functional outcome and identify possible preoperative prognostic factors in patients aged 65 years or over undergoing open repair for a massive (>5 cm) full-thickness rotator cuff tear. Patients were assessed after a mean of 48 months by an independent observer by use of the Constant score and the Oxford Shoulder Questionnaire. The outcome was excellent or good in 44% and poor in 23%. The patient satisfaction rate was 84%. Pain relief was obtained in 93%. We found three preoperative variables to be significantly associated with a poor outcome: female sex, duration of symptoms greater than 34 months before surgery, and American Society of Anesthesiologists grade. The results of our study suggest that appropriately selected patients who are aged 65 years or over with a massive full-thickness rotator cuff tear can be expected to have a good functional outcome and pain relief after repair.

Risk compensation in children's activities: A pilot study.

BACKGROUND: The intent of protective equipment (PE) in sports and leisure activities is to reduce injuries. However, some postulate that any safety measure prompts riskier behaviour, a phenomenon known as 'risk homeostasis' or 'risk compensation.' This study explores one approach to examining this in children. The rationale for this pilot study was to establish if children between six and 16 years old could answer questions about risk-taking sensibly and which questions, if any, could be eliminated; to establish the reliability of response; and to determine the numbers needed for a definitive study. METHODS: Sixty-three children with nonsevere injuries, ages six to 16 years, were interviewed while waiting to be seen at the Montreal Children's Hospital emergency department. An interviewer administered a questionnaire comprising three sections. The first part only applied to those who were injured in an activity for which some form of PE was available (n=19). The second part examined customary risk-taking behaviour using the thrill and adventure seeking scales of a standardized questionnaire (Zuckerman) (n=63). The third section posed hypothetical questions about likely risk-taking when using PE to those who had engaged in such activities (n=58). RESULTS: The approach and questionnaire proved feasible with this age group. The responses suggest that children wearing PE were more likely to report increased risk-taking than those who did not wear PE. For most of the hypothetical questions, the majority also reported changes toward riskier behaviour when using PE. However, those wearing PE scored lower on the thrill and adventure seeking scale, suggesting that they are, by nature, less venturesome. CONCLUSION: The results indicate that risk compensation may modify the effectiveness of PE for children engaged in sports and leisure activities. Conversely, the findings also suggest that those wearing PE may be a cautious subgroup.

Delayed fracture of the ceramic femoral head after trauma.

There are various ways in which a total hip arthroplasty may fail catastrophically. Failure of the ceramic femoral head component is well known and described. It may fail because of trauma, but delayed fracture after trauma has not been described previously. This case report describes this phenomenon and postulates a possible mechanism for this failure.

TGFbeta and PTHrP control chondrocyte proliferation by activating cyclin D1 expression.

Exact coordination of growth plate chondrocyte proliferation is necessary for normal endochondral bone development and growth. Here we show that PTHrP and TGFbeta control chondrocyte cell cycle progression and proliferation by stimulating signaling pathways that activate transcription from the cyclin D1 promoter. The TGFbeta pathway activates the transcription factor ATF-2, whereas PTHrP uses the related transcription factor CREB, to stimulate cyclin D1 promoter activity via the CRE promoter element. Inhibition of cyclin D1 expression with antisense oligonucleotides causes a delay in progression of chondrocytes through the G1 phase of the cell cycle, reduced E2F activity, and decreased proliferation. Growth plates from cyclin D1-deficient mice display a smaller zone of proliferating chondrocytes, confirming the requirement for cyclin D1 in chondrocyte proliferation in vivo. These data identify the cyclin D1 gene as an essential component of chondrocyte proliferation as well as a fundamental target gene of TGFbeta and PTHrP during skeletal growth.

A maize cytokinin gene encoding an O-glucosyltransferase specific to cis-zeatin.

Zeatin is a naturally occurring cytokinin. Biosynthesis and metabolism studies of zeatin have been directed mostly at the trans isomer, although cis-zeatin and its riboside occur as major components in some plant species. It is not known whether parallel regulatory pathways exist for the two isomers. Based on the sequence of the gene ZOG1 encoding a trans-zeatin O-glucosyltransferase from Phaseolus (EC ), a cis-zeatin-specific O-glucosyltransferase was isolated from maize. This gene, cisZOG1, contains an ORF of 1,401 nucleotides encoding a protein of 51.1 kDa with 41% identity to the Phaseolus ZOG1 protein. Unexpectedly, the maize enzyme recognizes as substrates cis-zeatin and UDP-glucose but not cis-ribosylzeatin, trans-zeatin, or trans-ribosylzeatin. This finding indicates the existence of cis-specific regulatory elements in plants and suggests that cis-zeatin and derivatives may be more important in cytokinin homeostasis than currently recognized.

A gene encoding the cytokinin enzyme zeatin O-xylosyltransferase of Phaseolus vulgaris.

Zeatin is the most active and ubiquitous form of the naturally occurring cytokinins. Glycosyl conjugates of zeatin are found in many plant tissues and are considered important for storage and protection against degradative enzymes. Two enzymes catalyzing the formation of O-glycosyl derivatives of zeatin have been characterized, O-glucosyltransferase and O-xylosyltransferase, occurring in seeds of lima bean (Phaseolus lunatus) and bean (Phaseolus vulgaris), respectively. Recently, the ZOG1 gene (zeatin O-glucosyltansferase) was isolated from P. lunatis (). Based on the ZOG1 sequence, the ZOX1 gene (zeatin O-xylosyltransferase) was cloned from P. vulgaris. ZOX1 contains an open reading frame of 1362 bp that codes for a 454-amino acid peptide of 51 kD. The recombinant protein has properties identical to the native enzyme: it catalyzes O-xylosylzeatin formation with UDP-Xyl as a glycosyl donor but does not recognize UDP-Glucose as a substrate. The ZOX1 and ZOG1 genes exhibit 93% identity at the nucleotide level and 90% similarity at the amino acid level. Neither gene contains introns. These zeatin-specific genes and their promoters will be useful for studies of the regulation of active versus storage forms of cytokinins. Comparison of sequences encoding similar enzymes with distinct substrate specificity may lead to identification of epitopes specific to cytokinin and glycosyl donor molecules.

Isolation of a cytokinin gene, ZOG1, encoding zeatin O-glucosyltransferase from Phaseolus lunatus.

Zeatin is the most active and ubiquitous of the naturally occurring cytokinins. The O-glucoside of zeatin, found in all plants examined, is considered to be important in cytokinin transport, storage, and protection against cytokinin oxidases. The enzyme UDPglucose:zeatin O-glucosyltransferase (EC 2.4.1.203) was previously isolated from Phaseolus lunatus seeds. Immunoscreening of an expression library with monospecific antibody resulted in the isolation of a cDNA encoding the enzyme. The recombinant protein efficiently converts labeled zeatin to O-glucosylzeatin and has properties similar to the native enzyme. The cDNA of 1.5 kb contains an ORF encoding a 51. 4-kDa polypeptide of 459 amino acids. The sequence is unique based on a BLAST search of data bases. The genomic sequence, isolated with PCR using specific primers based on the cDNA sequence, does not contain introns. The cloning of this gene provides the tools for further study of the regulation of cytokinin metabolism and analysis of the precise role of O-glucosylzeatin in plant development.

Expression of the yeast FRE genes in transgenic tobacco.

Two yeast genes, FRE1 and FRE2 (encoding Fe(III) reductases) were placed under the control of the cauliflower mosaic virus 35S promoter and introduced into tobacco (Nicotiana tabacum L.) via Agrobacterium tumefaciens-mediated transformation. Homozygous lines containing FRE1, FRE2, or FRE1 plus FRE2 were generated. Northern-blot analyses revealed mRNA of two different sizes in FRE1 lines, whereas all FRE2 lines had mRNA only of the expected length. Fe(III) reduction, chlorophyll contents, and Fe levels were determined in transgenic and control plants under Fe-sufficient and Fe-deficient conditions. In a normal growth environment, the highest root Fe(III) reduction, 4-fold higher than in controls, occurred in the double transformant (FRE1 + FRE2). Elevated Fe(III) reduction was also observed in all FRE2 and some FRE1 lines. The increased Fe(III) reduction occurred along the entire length of the roots and on shoot sections. FRE2 and double transformants were more tolerant to Fe deficiency in hydroponic culture, as shown by higher chlorophyll and Fe concentrations in younger leaves, whereas FRE1 transformants did not differ from the controls. Overall, the beneficial effects of FRE2 were consistent, suggesting that FRE2 may be used to improve Fe efficiency in crop plants.

Protein processing and auxin response in transgenic tobacco harboring a putative cDNA of zeatin O-xylosyltransferase from Phaseolus vulgaris.

Zeatin is rapidly metabolized to O-xylosylzeatin in Phaseolus vulgaris seeds. The zeatin O-xylosyltransferase mediating this conversion, a 50 kDa protein, occurs mainly in the endosperm, both in the cytoplasm and the nuclei. A monoclonal antibody specific to the enzyme was used to isolate cDNAs from an expression library derived from P. vulgaris seeds. Two highly homologous, full-length cDNAs were isolated. The ORFs encode proteins of 69 and 67 kDa, respectively, with 90% homology at the amino acid level. cDNA-encoded protein obtained from in vitro transcription/translation was processed to protein of 50 kDa by bean endosperm extract. Transgenic tobacco plants harboring the larger ORF under the control of the CaMV35S promoter were more sensitive to the auxin NAA than control plants. The symptoms included leaf chlorosis, restriction of root elongation, and eventual cessation of growth. The antigenic preprotein was processed, and labeled zeatin was converted to O-xylosylzeatin in transgenic plants grown on NAA-containing medium. Analyses of independently transformed families indicated that the presence of the transgene coincided with the increased auxin sensitivity and protein processing correlated with the manifestation of auxin-induced damage. These results suggest that posttranslational processing regulates enzyme activity, and offer the possibility that cytokinin-auxin balance may be affected by stimulation of cytokinin metabolic enzyme activity by auxin.

A temperature-dependent morphological mutant of tobacco.

A recessive temperature dependent shooty mutant (tds) of Nicotiana tabacum L. (W38) is described. The mutant phenotype is expressed at low temperature (21 degrees C). Mutant characteristics include thick, narrow leaves with abnormal mesophyll cells, short internodes, and near absence of apical dominance. Most plants remain vegetative and the occasional flower has petaloid stamens. High temperature (30 degrees C) reverses the mutant phenotype, with formation of normal leaves and restoration of apical dominance. However, many flowers still have petaloid stamens. Reciprocal grafting and auxincytokinin interaction experiments do not suggest shifts in auxin-cytokinin balance. Overall, this mutant bears some resemblance to transgenic tobacco overexpressing homeodomain genes from maize and Arabidopsis.

Measurement of myocardial wall thickening from PET/SPECT images: comparison of two methods.

PURPOSE: We compared two methods for measuring myocardial wall thickening from nuclear medicine perfusion scans. The first method uses the percent change in peak activity, and the second method models a profile measured across the myocardium. METHOD: Mathematical simulations of the myocardium were used. In addition, images with PET or SPECT resolution were created from real MR images. Known amounts of noise were then added. RESULTS: The percent peak thickening (% PT) is nonlinear with true percent thickening, especially for PET resolutions [7 mm full width at half-maximum (FWHM)]. For the peak method, low levels of noise (10%) introduced an error of 8%PT for PET and of 16%PT for SPECT. Additional smoothing reduced these errors. For the fitted model, at 10% noise, the error in thickening was large: 2.3 mm for PET and 7.8 mm for SPECT. CONCLUSION: The fitted model works well only with good resolution and low noise (e.g., 7 mm FWHM and 10%). The peak method is also sensitive to noise, especially for poorer resolutions. Additional smoothing gives more reliable results for the peak method but not the fitted method. The peak method is therefore the more generally reliable, but even this method may only allow classification of myocardial thickening into broad categories.

RFLP analysis of preferential transmission in interspecific hybrids of Phaseolus vulgaris and P. coccineus.

The inheritance of RFLP markers in interspecific hybrids of Phaseolus vulgaris and P. coccineus was analyzed. Of 280 cDNA probes used, 70%-85% revealed polymorphism between species while intraspecific RFLP ranged from 8% to 37%. Segregation of 63 clearly scorable markers was examined in 177 P. vulgaris x P. coccineus F2's maintained as callus. Preferential transmission of the P. vulgaris alleles was observed for 24 of the 28 loci exhibiting non-Mendelian ratios. Although the segregation ratios at 17 loci fit gametic selection, also other factors such as nuclear-cytoplasmic or embryo-endosperm interactions may be involved. In the reciprocal F2, a relatively high frequency of maternal alleles was recovered for several loci, while the paternal allele was favored at others. The cDNA clone detecting the most extreme segregation, with no P. coccineus type detected among 165 P. vulgaris x P. coccineus F2 progeny, showed high homology to histone H2A genes. The markers were mapped to nine linkage groups. Aggregation of markers with preferential maternal transmission was observed, which could be due to selection of individual chromosomes, although false linkage detection cannot be excluded. The results obtained with RFLPs may explain the skewed distribution of phenotypic traits following interspecific hybridization.

Long-term results of anterior cruciate reconstruction with the patellar tendon.

Thirty patients who had an anterior cruciate reconstruction with a patellar tendon autograph were reviewed at an average of 7.5 years (range 5-11 years) after operation. In all, 27 patients maintained their good/excellent results based on the Lysholm and Gillquist scoring system compared with the review at 2 years; two patients remained fair and one reconstruction failed at an early stage. There was no apparent deterioration of knee function at 7.5 years when compared with those at 2 years. None of the patients had symptoms related to the patellofemoral joint.