Clinical features and functional significance of the P369S/R408Q variant in pyrin, the familial Mediterranean fever protein.

OBJECTIVES: Familial Mediterranean fever (FMF) is caused by mutations in MEFV, which encodes pyrin. The nature of substitutions P369S and R408Q in exon 3 remains unclear. Exon 3 encoding pyrin's B-box domain is necessary for interactions with proline serine threonine phosphatase interacting protein 1 (PSTPIP1). The aim was to characterise the phenotype of patients with these substitutions and to determine their functional significance. METHODS: A database of genetic tests undertaken at the US National Institutes of Health was interrogated. Symptoms and signs were classified according to Tel-Hashomer criteria. Coimmunoprecipitation techniques were employed to determine the variants' effects on pyrin/PSTPIP1 interactions. RESULTS: A total of 40 symptomatic and 4 asymptomatic family members with these substitutions were identified. P369S and R408Q were found in cis, and cosegregated in all patients sequenced. Clinical details were available on 22 patients. In all, 5 patients had symptoms and signs fulfilling a clinical diagnosis of FMF, and 15 received colchicine. In patients not achieving the criteria, trials of anti-tumour necrosis factor (TNF) agents resulted in partial or no benefit; resolution of symptoms was noted in those receiving anakinra. The carrier frequency was higher in the patient cohort than in controls but was not statistically significant. Coimmunoprecipitation studies demonstrated that these pyrin variants did not affect binding to PSTPIP1. CONCLUSIONS: P369S/R408Q substitutions are associated with a highly variable phenotype, and are infrequently associated with typical FMF symptoms, however a trial of colchicine is warranted in all. Functional and modelling studies suggest that these substitutions do not significantly affect pyrin's interaction with PSTPIP1. This study highlights the need for caution in interpreting genetic tests in patients with atypical symptoms.

Factors affecting the selling price of feeder cattle sold at Arkansas livestock auctions in 2005.

Data were collected from 15 Arkansas livestock auctions to determine factors affecting selling price. Data included how calves were sold (single or groups), sex, breed or breed type, color, muscle thickness, horn status, frame score, fill, body condition, age, health, BW, and price. Data were randomly collected on 52,401 lots consisting of 105,542 calves. Selling prices for steers ($124.20 +/- 0.07), bulls ($117.93 +/- 0.12), and heifers ($112.81 +/- 0.07) were different from each other (P <0.001). Hereford x Charolais feeder calves sold for the highest price ($122.66 +/- 0.14) and Longhorns sold for the lowest price ($74.52 +/- 0.46). Yellow feeder cattle received the highest selling price ($96.47 +/- 0.12), and spotted or striped feeder cattle received the lowest price ($83.84 +/- 0.23). The selling price of singles was lower than the price for calves sold in groups of 6 or more ($117.26 +/- 0.06 vs. $122.61 +/- 0.21; P <0.001). For cattle classified as having muscle scores of 1, 2, 3, and 4, selling prices were $120.45 +/- 0.05, $111.31 +/- 0.09, $96.28 +/- 0.44, and $82.21 +/- 1.87, respectively. Polled feeder cattle sold for $118.57 +/- 0.05, and horned feeder cattle sold for $114.87 +/- 0.14 (P <0.001). Interactions (P <0.001) were detected between frame score and BW groups, and muscle score and BW groups on the selling price of cattle. A number of management and genetic factors affected the selling price of feeder cattle.

Comparing the 2000 and 2005 factors affecting the selling price of feeder cattle sold at Arkansas livestock auctions.

The objectives of the study were to determine how factors affecting the selling price of feeder calves changed from 2000 to 2005 and to examine the perception that discounts narrow or even disappear as calf supplies decrease and selling prices increase. Data from weekly Arkansas livestock auctions were collected from January 1 to December 31 in 2000 and 2005. Data included calf sex, breed type, color, muscle score, horn status, frame score, fill, condition, health, and BW. Mean selling prices for 2000 and 2005 were $92.91 +/- 15.05 and $118.32 +/- 15.13 (mean +/- SD; $/45.45 kg), respectively. Individual price observations were subtracted from the respective annual means and became the dependent variable. The selling prices for feeder calves sold in groups of 2 to 5 calves and in groups of >/= 6 calves were greater in 2005 than 2000 (P < 0.001). Steers received a greater premium ($6.48 +/- 0.09 vs. $6.02 +/- 0.08; mean +/- SE) and bull calves received greater discounts ($0.30 +/- 0.14 vs. $1.68 +/- 0.09) in 2005 than in 2000. Breeds types that increased in value from 2000 to 2005 were Angus x Hereford, Angus, Angus x Charolais, and Brahman (P < 0.001). Breed types that received a reduced selling price in 2005 compared with 2000 (P < 0.001) were one-fourth Brahman Cross, Charolais, Charolais x Limousin, Hereford x Limousin, Limousin, Limousin x one-fourth Brahman, Longhorn, Saler and Simmental. Yellow-white face, black-white face, black, and gray feeder calves received an increase in selling price from 2000 to 2005 (P < 0.001). Although fewer horned feeder calves were sold in 2005 (P < 0.01), they received greater discounts in 2005 than 2000 (-$2.86 +/- 0.16 and -$0.51 +/- 0.09; P < 0.001). In 2005, large-framed feeder calves did not receive the premium detected in 2000, but medium-framed feeder calves in 2005 received a greater selling price compared with 2000. Feeder calves with a muscle score of 1 received a greater premium in 2005 compared with 2000 ($2.58 +/- 0.06 and $0.02 +/- 0.09, respectively; P < 0.001). Feeder calves with a muscle score of 2 were discounted in both years, but the discount in 2005 was not as great as in 2000 (P < 0.001). Full and tanked feeder calves received greater discounts in 2005 than in 2000 (P < 0.001). Discounts for fleshy and fat feeder calves were greater in 2005 than in 2000. Most factors affecting the selling price of Arkansas feeder calves in 2000 affected the selling price in 2005. Although feeder calf supplies were smaller in 2005 than 2000, many discounts increased.

Supplemental vitamin D3 concentration and biological type of steers. II. Tenderness, quality, and residues of beef.

Vitamin D3 was orally supplemented to determine the supplemental dose that improved beef tenderness in different cattle breed types. Feedlot steers (n = 142) were arranged in a 4 x 3 factorial arrangement consisting of four levels of supplemental vitamin D3 (0, 0.5, 1, and 5 million IU/steer daily) administered for eight consecutive days antemortem using three biological types (Bos indicus, Bos Taurus-Continental, and Bos Taurus-English). Warner-Bratzler shear force (WBSF) was measured at 3, 7, 10, 14, and 21 d postmortem, and trained sensory analysis was conducted at 7 d postmortem on LM, semimembranosus, gluteus medius, and supraspinatus steaks. Concentrations of vitamin D3 and the metabolites 25-hydroxyvitamin D3, and 1,25-dihydroxyvitamin D3 were determined in the LM, liver, kidney, and plasma. Biological type of cattle did not interact (P > 0.10) with vitamin D3 supplementation for sensory or tenderness traits, suggesting that feeding vitamin D3 for 8 d before slaughter affected the different biological types of cattle similarly. Supplementing steers with 0.5, 1, or 5 million IU/(steer(d) decreased (P < 0.05) LM WBSF at 7, 10, 14, and 21 d postmortem compared with controls, and vitamin D3 treatments of 0.5, 1, and 5 million IU decreased (P < 0.05) semimembranosus WBSF at 3, 7, and 14 d postmortem. In general, vitamin D3-induced improvements in WBSF were most consistent and intense in LM steaks. Sensory panel tenderness was improved (P < 0.05) by all vitamin D3 treatments in LM steaks. Sensory traits ofjuiciness, flavor, connective tissue, and off-flavor were not (P > 0.05) affected by vitamin D3 treatments. All vitamin D3 treatments decreased micro-calpain activity and increased muscle Ca concentrations (P < 0.05). Vitamin D3 concentrations were increased (P < 0.05) by supplementation in all tissues tested (liver, kidney, LM, and plasma); however, cooking steaks to 71 degrees C decreased (P < 0.05) treatment residue effects. The vitamin D metabolite 1,25-dihydroxyvitamin D3 was increased (P < 0.05) only in plasma samples as a result of the vitamin D3 treatments. These results indicate that supplementation with vitamin D3 at 0.5 million IU/steer daily for eight consecutive days before slaughter improved tenderness in steaks from different subprimal cuts by affecting muscle Ca concentrations, micro-calpain activities, and muscle proteolysis, with only a small effect on tissue residues of vitamin D3.

Effects of growth implants on consumer perceptions of meat tenderness in beef steers.

Anabolic steroid implants are routinely used to increase growth performance and profitability; however, there are concerns that the use of implants, particularly those containing trenbolone acetate, may have detrimental effects on carcass quality and beef tenderness. Thus, the objectives of the current study were to determine the effects of various commonly used implant regimens on shear force values, sensory properties, and consumer satisfaction of beef top loin steaks from cattle of Bos indicus influence. Cattle were supplied by producers that agreed to provide sire and dam information in exchange for carcass and sensory data. Steers (n = 2,748) were assigned randomly to one of three implant treatments (12/sire; four steers from each sire were placed into each treatment group): 1) unimplanted controls (n = 1,368); 2) Synovex-S followed by another Synovex-S (n = 660); or 3) Synovex-S followed by Revalor-S (n = 720). Steaks sampled after 3, 7, and 14 d of aging indicated that unimplanted cattle had lower (P < 0.05) Warner-Bratzler Shear force values than those from implanted animals. No differences (P > 0.05) in shear force values were found between the two treatments or the control groups for steaks sampled following a 21-d aging period. Steaks from implanted animals sampled after 3, 7, and 14 d aging were rated lower (P < 0.05) for initial and sustained trained sensory panel tenderness scores. Consumers failed to detect any differences in steak samples related to implant treatment after 7 and 14 d of aging. Consumer education level and family income did not affect overall acceptability (P > 0.10 and 0.18, respectively) or tenderness acceptability (P > 0.11 and 0.68, respectively); however, consumers with postgraduate degrees recorded lower (P < 0.05) overall quality, beef flavor, juiciness, and tenderness scores than consumers in all other education classifications. Additionally, family income had no effect on overall quality (P > 0.21), beef flavor (P > 0.28), juiciness (P > 0.58), or tenderness (P > 0.45) scores. Results indicate that using a moderate implant program in Bos indicus-influenced cattle has no detrimental effects on beef tenderness and consumer acceptability.

Effects of the transportation of beef cattle from the feedyard to the packing plant on prevalence levels of Escherichia coli O157 and Salmonella spp.

Two hundred steers and heifers from a large feedyard (65,000-head capacity) were used to determine the prevalence levels of enterohemorrhagic Escherichia coli O157 (EHEC O157) and Salmonella spp. prior to and after shipping to a commercial packing facility. Two samples, a ventral midline hide swab and a fecal sample, were aseptically collected from each animal 2 weeks prior to the date of transportation and at the packing plant immediately after exsanguination. Samples were collected from all trailers (n = 46) before animals were loaded for transport to the packing facility. The average prevalence levels of EHEC O157 on hides (18%) and in feces (9.5%) at the feedyard decreased (P > 0.05) at the packing plant to 4.5 and 5.5%, respectively. The average prevalence levels of Salmonella spp. on hides (6%) and in feces (18%) at the feedyard increased to 89 and 46%, respectively, upon arrival at the packing plant. Average prevalence levels for EHEC O157 and Salmonella spp. on the trailers were 5.43 and 59%, respectively. The results of this study demonstrate that transportation may be a potential stressor for cattle, as evidenced by the increased shedding of Salmonella spp.

CEACAM is not necessary for Neisseria gonorrhoeae to adhere to and invade female genital epithelial cells.

Neisseria gonorrhoeae has a repertoire of up to 11 opacity-associated (Opa) proteins that are adhesins. Most Opa proteins adhere to CEACAM antigens and when CEACAM molecules are present on the surface of transfected epithelial cells their binding by Opa is thought to induce invasion of these cells by gonococci. In this study, we investigated whether several malignant epithelial cell lines, normal cervical and fallopian tube epithelial cell cultures, as well as normal fallopian tube tissue express several of the CEACAM molecules, and whether gonococci use these molecules for adherence and invasion of these female genital epithelial cells. A primary cervical cell culture and metastatic cervical cell line ME180 both expressed CEACAM as shown by whole cell ELISA and flow cytometry, and increased the surface expression of total CEACAM during incubation with Opa+ gonococci. Opa+ gonococci both adhered to and invaded these cells; CEACAM-specific monoclonal antibody (MAb) partially abolished this interaction. Two primary fallopian epithelial tube cell cultures, a primary cervical cell culture and two malignant cell lines, HEC-1-B and HeLa, did not express CEACAM nor was CEACAM mRNA present. No evidence of either intracellular or secreted extracellular CEACAM was found with HEC-1-B and HeLa cells. Opa+ gonococci both adhered to and invaded CEACAM non-expressing cells; however, Opa+ gonococcal association with these non-expressing cell lines could not be inhibited with CEACAM-specific MAb. These data show that CEACAM is not always expressed on female genital epithelial cells and is not essential for gonococcal adherence and invasion. However, when CEACAM is expressed, Opa+ gonococci exploit it for the adherence to and invasion of these cells.

Enhancement of mast cell survival: a novel function of some secretory phospholipase A(2) isotypes.

This study tested the hypothesis that certain secretory phospholipase A(2) (sPLA(2)) isotypes act in a cytokine-like fashion through cell surface receptors to influence mast cell survival. Initial experiments revealed that sPLA(2) activity and sPLA(2) receptor expression are increased, and mast cells lost their capacity to maintain membrane asymmetry upon cytokine depletion. Groups IB and III, but not group IIA PLA(2), prevented the loss of membrane asymmetry. Similarly, group IB prevented nucleosomal DNA fragmentation in mast cells. Providing putative products of sPLA(2) hydrolysis to cytokine-depleted mast cells did not influence survival. Furthermore, catalytic inactivation of sPLA(2) did not alter its capacity to prevent apoptosis. Inhibition of protein synthesis using cycloheximide or actinomycin reversed the antiapoptotic effect of sPLA(2). Additionally, both wild-type and catalytically inactive group IB PLA(2) induced IL-3 synthesis in mast cells. However, adding IL-3-neutralizing Ab did not change Annexin V(FITC) binding and only partially inhibited thymidine incorporation in sPLA(2)-supplemented mast cells. In contrast, IL-3-neutralizing Ab inhibited both Annexin V(FITC) binding and thymidine incorporation in mast cells maintained with IL-3. sPLA(2) enhanced phosphoinositide 3'-kinase activity, and a specific inhibitor of phosphoinositide 3'-kinase reversed the antiapoptotic effects of sPLA(2). Likewise, sPLA(2) increased the degradation of I-kappaBalpha, and specific inhibitors of nuclear factor kappa activation (NF-kappaB) reversed the antiapoptotic effects of sPLA(2). Together, these experiments reveal that certain isotypes of sPLA(2) enhance the survival of mast cells in a cytokine-like fashion by activating antiapoptotic signaling pathways independent of IL-3 and probably via sPLA(2) receptors rather than sPLA(2) catalytic products.

Poly(sodium 4-styrene sulfonate): an effective candidate topical antimicrobial for the prevention of sexually transmitted diseases.

Presently marketed vaginal barrier agents are cytotoxic and damage the vaginal epithelium and natural vaginal flora with frequent use. Novel noncytotoxic agents are needed to protect women from sexually transmitted diseases. One candidate compound is a high-molecular-mass form of soluble poly(sodium 4-styrene sulfonate) (T-PSS). The antimicrobial activity of T-PSS was evaluated in primary culture systems and in a genital herpes murine model. Results obtained indicate that T-PSS is highly effective against herpes simplex viruses, Neisseria gonorrhoeae, and Chlamydia trachomatis in vitro. A 5% T-PSS gel protected 15 of 16 mice from vaginal herpes, compared with 2 of 16 mice treated with a placebo gel. Moreover, T-PSS exhibited little or no cytotoxicity and has an excellent selectivity index. T-PSS is an excellent candidate topical antimicrobial that blocks adherence of herpes simplex virus at low concentrations, inactivates virus at higher concentrations, and exhibits a broad spectrum of antimicrobial activity.

Migration, remittances, and inequality: estimating the net effects of migration on income distribution.

"This paper examines the net effects of migration and remittances on income distribution. Potential home earnings of migrants are imputed, as are the earnings of non-migrants in migrant households, in order to construct no-migration counterfactuals to compare with the observed income distribution including remittances. The earnings functions used to impute migrant home earnings are estimated from observations on non-migrants in a selection-corrected estimation framework which incorporates migration choice and labor-force participation decisions. For a sample of households in Bluefields, Nicaragua, migration and remittances increase income inequality when compared with the no-migration counterfactual."

The "nest"--neurological environment for safe therapeutics.

How to manage neurologically impaired patients is a challenge we all face. Lions Gate Hospital in North Vancouver, B.C. successfully developed a padded environment for confused, restless, and agitated patients. The following article describes how patients are managed without restraints in a safe environment.

The flexible fiberoptic bronchoscope: diagnostic tool or medical toy?

We began using the fiberoptic bronchoscope March 1, 1971, and after more than 2,800 examinations are convinced it is a highly useful diagnostic tool. We pass the open-end straight bonchoscope into the upper trachea under local anesthesia. Then, the fiberoptic bronchoscope is passed through this conduit. The advantages of the technique are discussed. The greatest advantage of fiberoptic bronchoscopy is the extended visibility it provides of peripheral lesions in the tracheobronchial tree. In this series, which includes more than 700 patients with primary bonchogenic carcinoma, the tumor was visible in one-third of the patients when only the straight bronchoscope was used while in two-thirds it was visible with the flexible bronchoscope. There were no deaths, and complications were rare and of little consequence. Thoracic surgeons are urged to use this instrument.