Novel association suggests multiple independent QTLs within chromosome 5q21-33 region control variation in total humans IgE levels

Asthma is a common, heterogeneous, complex disease accompanied by raised total and specific immunoglobulin-E (IgE) antibody levels. Despite numerous previous reports of linkage and association of asthma, atopy and serum IgE levels to genes within the 5q21-33 region, definitive, replicable results are still not available. We used the classical twin design to (i) estimate the relative contributions of genes and environment to variation in total IgE levels, (ii) assess genetic linkage, and (iii) examine allelic association of 11 microsatellite markers spanning the 5q21-33 region to total IgE. Variation in total IgE level was shown to be highly heritable (65%). Although evidence for linkage of the 11 microsatellites to IgE was not observed, the omnibus test of association, not confounded by population substructure, showed positive association of D5S393 and D5S673 to IgE. Genes in the vicinity of D5S673 include hepatitis A virus receptor (HAVCR-1) and IL-12B. Recently, the mouse orthologue of HAVCR-1, the T-cell membrane family of proteins, have been shown to be in strong association with expression of airway hyperactivity in a mouse model of human asthma and atopy. IL-12B subserves many proinflammatory functions and also induces B cells proliferation.     

Comparison of hormonal changes of estrous cycle with cytology of cervical mucosa and hematological parameters in dairy heifers

Cervical mucosa cytology and hematological parameters in heifers were determined during different phases of the estrous cycle. Ten healthy Holstein heifers were synchronized by two injections of PGF_2α at 14 days interval. Blood and cervical mucosa samples were collected at days of 0, 2, 10 and 19 of estrous cycle. Differential cell counts were performed, and the progesterone level was measured by radioimmunoassay. Progesterone levels in diestrus and the percentages of neutrophils in metestrus were shown to be higher than in other phases of the estrous cycle (P<0.05). In contrast, the percentages of epithelial cells in metestrus were lower than other phases (P<0.05). A difference was also seen (P<0.05) in blood progesterone levels between four estrous cycle phases. However, there was no significant difference in RBCs, hemoglobin, hematocrit, WBCs, neutrophils, lymphocytes, monocytes, and eosinophils between four estrous cycle phases. Hormonal changes in different phases of estrous cycle affect neutrophil presence in cervical mucosa. It is important to consider cervical cytology and hormonal assay together for evaluation of dairy cow reproductive tract function.     

Obesity is Associated with Genetic Variants That Alter Dopamine Availability

Human and animal studies have implicated dopamine in appetite regulation, and family studies have shown that BMI has a strong genetic component. Dopamine availability is controlled largely by three enzymes: COMT, MAOA and MAOB, and by the dopamine transporter SLC6A3, and each gene has a well-characterized functional variant. Here we look at these four functional polymorphisms together, to investigate how heritable variation in dopamine levels influences the risk of obesity in a cohort of 1150, including 240 defined as obese (BMI ≥ 30). The COMT and SLC6A3 polymorphisms showed no association with either weight, BMI or obesity risk. We found, however, that both MAOA and MAOB show an excess of the low-activity genotypes in obese individuals ( MAOA: χ²= 15.45, p = 0.004; MAOB: χ²= 8.05, p = 0.018). Additionally, the MAOA genotype was significantly associated with both weight (p = 0.0005) and BMI (p = 0.001). When considered together, the 'at risk genotype' - low activity genotypes at both the MAOA and MAOB loci - shows a relative risk for obesity of 5.01. These results have not been replicated and, given the experience of complex trait genetics, warrant caution in interpretation. In implicating both the MAOA and MOAB variants, however, this study provides the first indication that dopamine availability (as opposed to other effects of MAOA) is involved in human obesity. It is therefore a priority to assess the associations in replication datasets.     

Prevalence of coagulase-positive staphylococci in the skin of dogs; antibacterial resistance and plasmid profile of the isolates

This study was designed to understand the prevalence of coagulase-positive staphylococci in the skin of dogs and the role of dogs as reservoirs of pathogenic and antimicrobial-resistant staphylococci. Swab samples were taken from the surface of the skin at muzzle sites of 100 clinically normal dogs. Antibiotic susceptibility of coagulase-positive staphylococci isolates was assessed by antibiotic disc diffusion method using filter paper discs and plasmid DNAs were extracted from the isolates. Staphylococci were isolated from 79 of the 100 dogs sampled and of these 51 were coagulase positive. All coagulase-positive staphylococci isolates were resistant to penicillin G, amoxicillin, cefazolin, streptomycin, erythromycin, ampicillin, tetracycline, gentamicin, trimethoprim-sulfamethoxazole, and enrofloxacine at 100%, 100%, 72%, 48%, 44%, 44%, 12%, 4%, 8%, and 4% respectively. Characterization of plasmid DNAs by agarose gel electrophoresis showed that 22 out of the 51 coagulase-positive staphylococci isolates harbored a single plasmid. The results of the present study indicate that pathogenic and resistant staphylococci are located in the skin of the dogs and may transfer to human and other hosts. It is important to establish reliable antibiotic sensitivity data regarding these bacteria to select suitable antibacterial treatment.     

Canalicular stenosis secondary to weekly versus every-3-weeks docetaxel in patients with metastatic breast cancer

PURPOSE: To compare the frequency of canalicular stenosis as a side effect of weekly versus every-3-weeks docetaxel in patients with metastatic breast cancer. DESIGN: Retrospective nonrandomized comparative trial. PATIENTS AND METHODS: Eighteen patients enrolled in a phase II study of weekly docetaxel plus trastuzumab and 18 patients enrolled in a phase II study of every-3-weeks docetaxel plus doxorubicin were evaluated. Each patient underwent a comprehensive ophthalmologic examination, probing and irrigation of the nasolacrimal duct, and, in some instances, a nuclear lacrimal scan. MAIN OUTCOME MEASURES: If epiphora (excessive tearing) was reported by the patient, its time of onset was documented. In patients with epiphora, presence or absence of canalicular stenosis was evaluated on the basis of the findings on probing and irrigation. The duration of treatment with docetaxel, the dose frequency, and the cumulative dose of docetaxel were recorded in each case. RESULTS: Fourteen patients (77%) receiving weekly docetaxel plus trastuzumab had epiphora. Nine of these patients had significant anatomic narrowing of the canaliculi. Bicanalicular silicone intubation or dacryocystorhinostomy was recommended in all nine patients. Eight patients underwent surgery and experienced complete or near complete resolution of epiphora. Although two patients (11%) receiving every-3-weeks docetaxel plus doxorubicin reported transient symptoms of epiphora, neither patient was found to have narrowing of the canaliculi, and the epiphora was not severe enough to justify surgical intervention. The mean duration of docetaxel therapy for the patients in this study was 19 weeks. The mean cumulative dose of docetaxel was higher in patients with canalicular stenosis than in patients without this side effect. CONCLUSIONS: Canalicular stenosis was more common in patients receiving weekly docetaxel than in those receiving every-3-weeks docetaxel for metastatic breast cancer. Bicanalicular silicone intubation early in the course of weekly docetaxel therapy should be considered, because this intervention can prevent complete closure of the canaliculi. Once complete or near complete stenosis of the canaliculi occurs, placement of a permanent Pyrex glass tube may become necessary to overcome the blockage of tear outflow.