The effects of growth factors on Tenon''s capsule fibroblasts in serum-free culture

Recent studies from our laboratory have shown that in the mouse and rat nephron Ca2+ and Mg2+ are not reabsorbed in the medullary part of the thick ascending limb (mTAL) of Henle's loop. The aim of the present study was to investigate whether the absence of transepithelial Ca2+ and Mg2+ transport in the mouse mTAL is due to its relative low permeability to divalent cations. For this purpose, transepithelial ion net fluxes were measured by electron probe analysis in isolated perfused mouse mTAL segments, when the transepithelial potential difference (PDte.) was varied by chemical voltage clamp, during active NaCl transport inhibition by luminal furosemide. The results show that transepithelial Ca2+ and Mg2+ net fluxes in the mTAL are not driven by the transepithelial PDte. At zero voltage, a small but significant net secretion of Ca2+ into the tubular lumen was observed. With a high lumen-positive PDte generated by creating a transepithelial bath-to-lumen NaCl concentration gradient, no Ca2+ and Mg2+ reabsorption was noted; instead significant and sustained Ca2+ and Mg2+ net secretion occurred. When a lumen-positive PDte was generated in the absence of apical furosemide, but in the presence of a transepithelial bath-to-lumen NaCl concentration gradient, a huge Ca2+ net secretion and a lesser Mg2+ net secretion, not modified by ADH, were observed. Replacement of Na+ by K+ in the lumen perfusate induced, in the absence of PDte changes, important but reversible net secretions of Ca2+ and Mg2+. In conclusion, our results indicate that the passive permeability of the mouse mTAL to divalent cations is very low and not influenced by ADH. This nephron segment can secrete Ca2+ and Mg2+ into the luminal fluid under conditions which elicit large lumen-positive transepithelial potential differences. Given the impermeability of this epithelium to Ca2+ and Mg2+, the secretory processes would appear to be of cellular origin.     

Selective interactions among the multiple connexin proteins expressed in the vertebrate lens: the second extracellular domain is a determinant of compatibility between connexins

Gap junctions are collections of intercellular channels composed of structural proteins called connexins (Cx). We have examined the functional interactions of the three rodent connexins present in the lens, Cx43, Cx46, and Cx50, by expressing them in paired Xenopus oocytes. Homotypic channels containing Cx43, Cx46, or Cx50 all developed high conductance. heterotypic channels composed of Cx46 paired with either Cx43 or Cx50 were also well coupled, whereas Cx50 did not form functional channels with Cx43. We also examined the functional response of homotypic and heterotypic channels to transjunctional voltage and cytoplasmic acidification. We show that all lens connexins exhibited sensitivity to cytoplasmic acidification as well as to voltage, and that voltage-dependent closure of heterotypic channels for a given connexin was dramatically influenced by its partner connexins in the adjacent cell. Based on the observation that Cx43 can discriminate between Cx46 and Cx50, we investigated the molecular determinants that specify compatibility by constructing chimeric connexins from portions of Cx46 and Cx50 and testing them for their ability to form channels with Cx43. When the second extracellular (E2) domain in Cx46 was replaced with the E2 of Cx50, the resulting chimera could no longer form heterotypic channels with Cx43. A reciprocal chimera, where the E2 of Cx46 was inserted into Cx50, acquired the ability to functionally interact with Cx43. Together, these results demonstrate that formation of intercellular channels is a selective process dependent on the identity of the connexins expressed in adjacent cells, and that the second extracellular domain is a determinant of heterotypic compatibility between connexins.     

Tower of London performance in relation to Magnetic Resonance Imaging following closed head injury in children.

To investigate the relationship of severity of pediatric closed head injury (CHI), the contribution of frontal lobe lesions, and age at testing (6–10 yr olds vs 11–15 yr olds) to cognitive deficit, 134 head-injured patients were given the Tower of London (TOL) task and underwent magnetic resonance imaging. 89 normal controls were given the TOL for comparison. Severity of CHI and age at testing were strongly related to cognitive performance on the TOL, including the frequency of breaking the rules. Volume of frontal lobe lesion (but not extrafrontal lesion) contributed to the prediction of perfomance on the TOL even after severity of injury was taken into account. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Reliability and validity of the Gastrointestinal Symptom Rating Scale in patients with gastroesophageal reflux disease

American visceral leishmaniasis is a main public health matter in Brazil. Since dogs have been incriminated as the main urban reservoir of AVL agent Leishmania chagasi, a cohort study aimed at understanding the dynamics of the canine infection was carried out in Jequié--an endemic community in the Northeast of Brazil. The inhabited urban and periurban areas of Jequié were divided into 140 clusters of 0.25 km2. All 1681 dogs domiciled in 34 randomly selected clusters were screened for Leishmania antibodies in an enzyme-linked immunosorbent assay. After the seropositive dogs were painlessly eliminated, a cohort of 1286 seronegative dogs was followed up for 18 months, yielding a total of 1739.7 dog-years. The overall incidence of Leishmania infection, as assessed by the detection of Leishmania antibodies in blood samples collected every six months, was 6.55 cases/100 dog-years (95% confidence interval; CI 6.04-7.26). Two subsets of clusters, with 0.70 and 1.35 relative risks of infection, were identified. The annual emigration rate was 2.26 cases/100 dog-years (95% CI 1.86-2.66). The implications of these findings for the control of American visceral leishmaniasis are discussed.     

Linkage analysis of candidate genes in autoimmune thyroid disease: 1. Selected immunoregulatory genes. International Consortium for the Genetics of Autoimmune Thyroid Disease

Graves' and Hashimoto's diseases are autoimmune thyroid diseases in which the genetic contribution is complex. For this reason, identification of necessary susceptibility genes has been difficult. However, a number of immunoregulatory genes have been implicated by association studies, including: CTLA-4, a recently described protein involved in antigen presentation, located on chromosome 2q33; the T-cell receptor V alpha and V beta gene complexes, located on 14q11 and 7q35, respectively; and the Ig gene complex (IgH), located on 15q11. We used polymorphic microsatellite markers located within these genes, or gene complexes, to test for linkage (rather than association), to each of these candidates. Using markers within the loci allowed us to assume a fixed recombination fraction of 0.01 in the tested model. Three hundred eight subjects from 48 multiplex families were studied, with 142 affected subjects. Using this set of families, we have previously shown evidence of linkage with a major susceptibility locus for Graves' disease (GD-1) on 14q24.3-31, with a maximum lod (logarithm + odds) score of 2.1, at a penetrance of 80% and with a dominant mode of inheritance. In the present study, we obtained consistently negative lod scores for each of the candidate genes, assuming either dominant or recessive modes of inheritance. These data, therefore, showed evidence against linkage with all the candidate genes. Unlike association studies, linkage analyses detect major genetic influences on disease susceptibility exerted by the linked loci. The lack of linkage for the immunoregulatory genes that were studied indicated, therefore, that they were not major contributors to disease etiology.     

Comparative influence of steroid hormones and immunosuppressive agents on autoimmune expression in lacrimal glands of a female mouse model of Sj?gren's syndrome

PURPOSE: Previous research has demonstrated that testosterone therapy causes a profound suppression of autoimmune disease in lacrimal glands of female mouse models of Sj?gren's syndrome. The aim of the present study was to determine whether other anabolic androgens, nonandrogenic steroids, or immunosuppressive agents might duplicate this hormonal effect. For comparative purposes, we also evaluated the influence of these various pharmacologic compounds on the tear volume, the magnitude of lymphocyte infiltration in the submandibular gland, and the extent of mucosal and peripheral lymphadenopathy. METHODS: Female MRL/MpJ-lpr/lpr mice were administered vehicle, steroids, or immunosuppressive compounds for 21 days after the onset of disease. Lacrimal glands and tears, as well as submandibular glands, spleens, and superior cervical and mesenteric lymph nodes were collected immediately before or after treatment and then processed for analysis. RESULTS: Our results showed that: (1) the immunosuppressive impact of testosterone on lymphocyte infiltration in lacrimal tissue was reproduced by the administration of 19-nortestosterone or cyclophosphamide, but not by therapy with 17 beta-estradiol, danazol, the experimental steroid Org 4094, cyclosporine A or dexamethasone; (2) treatment with testosterone, 19-nortestosterone, cyclophosphamide, or dexamethasone significantly reduced the extent of inflammation in salivary glands; (3) exposure to cyclophosphamide markedly diminished the size of lymphatic and splenic tissues, whereas glucocorticoid treatment only decreased the weight of superior cervical lymph nodes; and (4) administration of 17 beta-estradiol, Org 4094, or dexamethasone led to a significant decrease in tear volume. CONCLUSIONS: Overall, these results demonstrate that androgen or cyclophosphamide therapy may successfully ameliorate autoimmune expression in lacrimal and salivary glands of a female mouse model of Sj?gren's syndrome.     

Catch me if you can: are catechol- and indoleamine genes pleiotropic QTLs for common mental disorders?

The aim of this study was to determine the effect of a short-term ethinyl estradiol/levonorgestrel medication on blood flow in the uterine arteries in postmenopausal women in a prospective placebo-controlled double-blind study. Twenty-one healthy postmenopausal woman at least 2 years after menopause received 60 micrograms ethinyl estradiol (EE) for 14 days followed by 40 micrograms EE plus 125 micrograms levonorgestrel (LNG) for 12 days (total treatment period 26 days). Sonographically, uterine volume, endometrial thickness, and blood flow in the uterine arteries [as reflected by pulsatility (PI) and resistance indices (RI)] were measured. Uterine size increased from 44 to 80 mL (day 14, p < 0.001) and 87 mL (day 26, p = NS). Endometrium grew from 3 to 8 mm (day 14, p < 0.001) and 11 mm (day 26, p = NS). Uterine arterial PI fell from 2.76 to 1.37 (day 14, p < 0.001) and 1.34 (day 26, p = NS), whereas RI fell from 0.9 to 0.68 (day 14 and day 26, p < 0.001). In conclusion, short-term treatment with LNG does not antagonize the vascular effect of EE on the uterine arteries as reflected by PI and RI. This result might have clinical significance in the selection of the progestin used in hormonal replacement therapy.     

Process-based cost modeling of photonics manufacture: the cost competitiveness of monolithic integration of a 1550-nm DFB laser and an electroabsorptive modulator on an InP platform

The monolithic integration of components holds promise to increase network functionality and reduce packaging expense. Integration also drives down yield due to manufacturing complexity and the compounding of failures across devices. Consensus is lacking on the economically preferred extent of integration. Previous studies on the cost feasibility of integration have used high-level estimation methods. This study instead focuses on accurate-to-industry detail, basing a process-based cost model of device manufacture on data collected from 20 firms across the optoelectronics supply chain. The model presented allows for the definition of process organization, including testing, as well as processing conditions, operational characteristics, and level of automation at each step. This study focuses on the cost implications of integration of a 1550-nm DFB laser with an electroabsorptive modulator on an InP platform. Results show the monolithically integrated design to be more cost competitive over discrete component options regardless of production scale. Dominant cost drivers are packaging, testing, and assembly. Leveraging the technical detail underlying model projections, component alignment, bonding, and metal-organic chemical vapor deposition (MOCVD) are identified as processes where technical improvements are most critical to lowering costs. Such results should encourage exploration of the cost advantages of further integration and focus cost-driven technology development.     

Electrostatic polymer processing of isotactic poly(4-methyl-1-pentene) fibrous membrane

Isotactic poly(4-methyl-1-pentene) (P4M1P) is a widely used polymer in industrial applications and specifically, in medical products. Producing micro- or nanofibers would expand the usefulness of P4M1P to a broad range of medical applications. The choice and quality of solvent for the solution used for electrospinning can have a dramatic effect on the spinnability of fibers and on their morphological appearance. In this study, four solvent systems: cyclohexane, cyclohexane/acetone mixture, cyclohexane/dimethyl formamide (DMF) mixture and cyclohexane/acetone/DMF mixture have been investigated. As demonstrated by FE-SEM, electrospun fibers with different morphologies including round, twisted with a roughened texture, curled and twisted-ribbon shapes were formed. The fiber shape and morphology depended strongly on the type and amount of non-solvent used.