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.     

The prognostic significance of deletion of the long arm of chromosome 20 in myeloid disorders

OBJECTIVE: The effect of cigarette smoking on gallbladder (GB) emptying and refilling after a fatty meal was examined in 10 healthy volunteers (four women and six men, mean age 27.6 yr). METHODS: On three different days, the subjects underwent in randomized order: a control test without smoking (C), or they smoked two cigarettes during the early (0-20 min; S0-20), or late (20-40 min; S20-40) phase of the meal-induced GB emptying. GB volumes were measured ultrasonographically before the meal and at 10, 20, 30, 40, 60, 90, 120, 150, and 180 min postprandially. Two-way ANOVA was applied for statistical assessment of the results. RESULTS: The fasted GB volumes amounted to 15.7 +/- 1.8 cm3 (C), 15.0 +/- 1.7 cm3 (S0-20), and 18.4 +/- 2.3 cm3 (S20-40), F2;18 = 1.524, NS. Maximum GB emptying was observed until 60 min after the meal, with a nadir of the GB volume amounting to 7.3 +/- 1.3 cm3 (C), 6.6 +/- 1.2 cm3 (S0-20), and 7.1 +/- 1.1 cm3 (S20-40). No significant difference was found between the stimuli tested when absolute GB volumes were considered: F2;180 = 2.725, NS. Analysis of the GB emptying-refilling curves normalized for the fasted GB volume revealed that a significant inhibitory effect was produced by smoking two cigarettes during the late phase of GB emptying on the subsequent GB refilling: F2;162 = 11.066, p < 0.001 for the whole curve, and F2;72 = 7.126, p < 0.005 for the refilling phase. A significant contrast was found next between S20-40 and the control day (p < 0.001 whole curve; p < 0.005 refilling phase only), as well as between S20-40 and S0-20 (p < 0.001 whole curve; p < 0.025 refilling phase only). CONCLUSION: We conclude that smoking two cigarettes does not disturb the fatty meal-induced GB contraction in healthy humans. Subsequent GB refilling is delayed if smoking takes place during the late phase of the postprandial GB contraction.     

Design considerations for high performance avalanche photodiodemultiplication layers

We have studied the effect of the thickness of the multiplication region on the noise performance characteristics of avalanche photodiodes (APD's). Our simulation results are based on a full band Monte Carlo model with anisotropic threshold energies for impact ionization. Simulation results suggest that the well known McIntyre expression for the excess noise factor is not directly applicable for devices with a very thin multiplication region. Since the number of ionization events is drastically reduced when the multiplication layer is very thin, the “ionization coefficient” is not a good physical parameter to characterize the process. Instead “effective quantum yield,” which is a measure of the total electron-hole pair generation in the device, is a more appropriate parameter to consider. We also show that for the device structure considered here, modeling the excess noise factor using a “discrete Bernoulli trial” model as opposed to the conventional “continuum theory” produces closer agreement to experimental measurements. Our results reinforce the understanding that impact ionization is a strong function of carrier energy and the use of simplified field-dependent models to characterize this high energy process fails to accurately model this phenomenon     

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.     

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.     

Discrete Modeling and Suggested Measurement of Heat Transfer in Gas-Solids Flows

This article presents a two-dimensional transient model for gas-solids flow and heat transfer through pipes using the coupled Computational Fluid Dynamics and Discrete Element Method approach. Numerical simulations have been conducted to examine the modification of fluid thermal structure due to the presence of particles in a pneumatic transport pipeline. Modeled results have demonstrated the key role of transversal motion of rebounding particles in the pipe cross section in altering fluid temperature. Further implementation of this modeling technique in air-drying processes is discussed and possible experimental methods for the measurement of in situ particle and fluid motion and temperature profile are cited.     

Breakdown probabilities for thin heterostructure avalanche photodiodes

The recurrence theory for the breakdown probability in avalanche photodiodes (APDs) is generalized to heterostructure APDs that may have multiple multiplication layers. The generalization addresses layer-boundary effects such as the initial energy of injected carriers as well as the layer-dependent profile of the dead space in the multiplication region. Reducing the width of the multiplication layer serves to both downshift and sharpen the breakdown probability curve as a function of the applied reverse-bias voltage. In structures where the injected carriers have an initial energy that is comparable to the ionization threshold energy, the transition from linear mode to Geiger-mode is more abrupt than in structures in which such initial energy is negligible. The theory is applied to two recently fabricated Al/sub 0.6/Ga/sub 0.4/As-GaAs heterostructure APDs and to other homostructure thin GaAs APDs and the predictions of the breakdown-voltage thresholds are verified.