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91.
92.
Ofek Freund Baker Elsana Nadav Agam Matan M. Jean Amit Safran Tomer Poleg Nir Roguin Libe Gradstein Erez Tsumi Ohad S. Birk 《American journal of medical genetics. Part A》2023,191(11):2768-2774
Thirteen affected individuals of six generations of a single kindred presented with epiphora evident from infancy. Physical exam and Schirmer test revealed variable expression of tear deficiency, congenital punctal atresia, and dry mouth with multiple caries, without concomitant abnormalities of the ears or digits, commensurate with a diagnosis of aplasia of the lacrimal and salivary glands (ALSG). Reconstruction of the upper lacrimal drainage system was performed in some of the affected individuals. Genetic analysis, testing six affected individuals and three non-affected family members, identified a single novel heterozygous splice-site variant, c.429 + 1, G > T in fibroblast growth factor 10 (FGF10) (NM_004465.1), segregating throughout the family as expected for dominant heredity. RT-PCR assays of HEK-293 cells transfected with wild type or mutant FGF10 demonstrated that the variant causes skipping of Exon 2. Notably, individuals sharing the same variant exhibited phenotypic variability, with unilateral or bilateral epiphora, as well as variable expression of dry mouth and caries. Moreover, one of the variant carriers had no ALSG-related clinical findings, demonstrating incomplete penetrance. While coding mutations in FGF10 are known to cause malformations in the nasolacrimal system, this is the second FGF10 splice-site variant and the first donor-site variant reported to cause ALSG. Thus, our study of a unique large kindred with multiple affected individuals heterozygous for the same FGF10 variant highlights intronic splice-site mutations and phenotypic variability/partial penetrance in ALSG. 相似文献
93.
In the context of neo-liberal retrenchments humanitarian NGOs have become alternative healthcare providers that partially fill the vacuum left by the welfare state's withdrawal from the provision of services to migrants and other marginalized populations. In many cases they thus help to build legitimacy for the state's retreat from social responsibilities. Human rights organizations play an important role in advocating for migrants' rights, but in many cases they represent a legalistic and individualized conceptualization of the right to health that limits their claims for social justice. This paper analyzes the interactions and tensions between the discourses of medical humanitarianism, human rights and political advocacy using the example of an "Open Clinic" run by an Israeli human rights organization as a case-study: In 2007 dramatically increasing patient numbers provoked an intense internal debate concerning the proposal to temporarily close the "Open Clinic" in order to press the government to take action. Based on protocols from internal meetings and parliamentary hearings and in-depth interviews, we have analyzed divergent contextualizations of the Clinic's closure. These reflect conflicting notions regarding the Clinic's variegated spectrum of roles--humanitarian, political, legitimizing, symbolic, empowering and organizational--and underlying conceptualizations of migrants' "deservingness". Our case-study thus helps to illuminate NGOs' role in the realm of migrant healthcare and points out options for a possible fruitful relationship between the divergent paradigms of medical humanitarianism, human rights and political advocacy. 相似文献
94.
Acute Xenograft Rejection Mediated by Antibodies Produced Independently of TH 1/TH 2 Cytokine Profiles
Nadav Dujovny Anncy Varghese Jikun Shen Dengping Yin Shaoquan Ji LianLi Ma Alison Finnegan Anita S. Chong 《American journal of transplantation》2002,2(6):526-534
There is substantial support for the hypothesis that T(H)1 cytokine responses are critical for the normal elaboration of allograft rejection. Recent studies by Wang et al. (1) underscore the importance of T(H)2 responses in xenograft rejection and revealed that T(H)1 cytokines, IL-12 and interferon-gamma (IFN-gamma), can negatively regulate the development of humoral responses necessary for xenograft rejection. Their exceptional studies prompted us to test whether the ability of allografts to elicit cellular rejection and xenografts to induce humoral rejection also result from the differential ability to induce T(H)1 and T(H)2 responses. We compared the kinetics of antibody and cytokine (IFN-gamma and IL-4) production in C57BL/6 mice following allograft transplantation with BALB/c hearts and in C57BL/6 and BALB/c mice following transplantation with Lewis rat hearts. We also compared the ability of BALB/c mice, deficient in the ability to produce IL-4 or IFN-gamma, to reject xenografts and produce xenoantibodies. We observed that T(H)1/T(H)2 cytokine production minimally affected the kinetics of graft rejection but regulated the magnitude of IgG subclass production. Anti-graft IgM played a critical role in initiating acute antibody-mediated xenograft rejection, and the production antigraft IgM was unaffected by IL-4 or IFN-gamma deficiency. In contrast to the report by Wang et al. (1), we conclude that antibody-mediated xenograft rejection in the concordant Lewis rat heart-to-C57BL/6 mouse xenotransplantation model is dependent on anti-IgM production but independent of T(H) cytokine profiles. 相似文献
95.
Mazar J Rogachev B Shaked G Ziv NY Czeiger D Chaimovitz C Zlotnik M Mukmenev I Byk G Douvdevani A 《Anesthesiology》2005,102(6):1174-1181
BACKGROUND: Ketamine is an anesthetic drug. Subanesthetic doses of ketamine have been shown to reduce interleukin-6 concentrations after surgery and to reduce mortality and the production of tumor necrosis factor alpha and interleukin 6 in septic animals. Similarly, adenosine was shown to reduce tumor necrosis factor alpha and mortality of septic animals. The aim of this study was to determine whether adenosine mediates the antiinflammatory effects of ketamine. METHODS: Sepsis was induced in mice by lipopolysaccharide or Escherichia coli inoculation. Leukocyte recruitment and cytokine concentrations were used as inflammation markers. Adenosine concentrations were assayed by high-performance liquid chromatography, and the involvement of adenosine in the effects of ketamine was demonstrated by adenosine receptor agonists and antagonists. RESULTS: Ketamine markedly reduced mortality from sepsis, leukocyte recruitment, and tumor necrosis factor-alpha and interleukin-6 concentrations. Ketamine administration in mice and rats was associated with a surge at 20-35 min of adenosine in serum (up to 5 microm) and peritoneal fluid. The adenosine A2A receptor agonist CGS-21680 mimicked the effect of ketamine in peritonitis, whereas the A2A receptor antagonists DMPX and ZM 241385 blocked its antiinflammatory effects. In contrast, A1 and A3 receptor antagonists had no effect. ZM 241385 reversed the beneficial effect of ketamine on survival from bacterial sepsis. CONCLUSIONS: The current data suggest that the sepsis-protective antiinflammatory effects of ketamine are mediated by the release of adenosine acting through the A2A receptor. 相似文献
96.
BACKGROUND: Many studies use questionnaires to determine smoking status and age of smoking onset. This study aimed to determine the reliability of self-reported smoking history and age of smoking initiation. METHOD: The proportion of inconsistent answers and correlation coefficients of reported age of initial smoking were measured by an answer-reanswer analysis of questionnaires in an ongoing, two-step, population-based survey of health behavior. Interviews were conducted on the day of recruitment to and the day of discharge from mandatory military service in Israel among a sample of 25,437 young men and women recruited between 1986 and 2000. RESULTS: Of 7276 participants reporting current or past smoking upon recruitment, 559 (7.7%) reported never having smoked upon discharge, thus demonstrating prima facie inconsistency. Variables significantly associated with reliable reporting in a multivariate logistic regression model were female gender (P = 0.04) and more than 4 years of military service (P < 0.01). 6010 subjects who reported a positive smoking history at both recruitment and discharge were available for analysis of reliability of reported age at smoking onset. Intraclass correlation coefficients for recruitment/discharge consistency in reported age at first cigarette were 0.73 (95% CI: 0.71-0.74) and 0.76 (95% CI: 0.74-0.78) for men and women, respectively. Eastern origin, lower subject education level, and lower paternal education level were also associated with lower reliability. CONCLUSIONS: Our results showed a relatively high level of answer-reanswer reliability, with some variance attributable to personal characteristics. These results suggest that self-reported age at onset of tobacco use is practical and reliable in normative, young adult populations. However, time elapsed between questionnaires and demographic and lifestyle characteristics may affect reliability rates, and thus should be carefully regarded in future studies. 相似文献
97.
Sidi G Davidovitch N Balicer RD Anis E Grotto I Schwartz E 《Emerging infectious diseases》2005,11(11):1784-1786
We evaluated the epidemiology of relapsing fever from 1971 to 2003 in Israel. In civilians, incidence declined from 0.35 to 0.11 cases per 100,000 persons annually; in military personnel it averaged 6.4 cases per 100,000 persons annually. These data imply that the pathogen and vector continue to exist in Israel. 相似文献
98.
Nodal protein processing and fibroblast growth factor 4 synergize to maintain a trophoblast stem cell microenvironment 总被引:1,自引:0,他引:1
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Guzman-Ayala M Ben-Haim N Beck S Constam DB 《Proceedings of the National Academy of Sciences of the United States of America》2004,101(44):15656-15660
Before implantation in the uterus, mammalian embryos set aside trophoblast stem cells that are maintained in the extraembryonic ectoderm (ExE) during gastrulation to generate the fetal portion of the placenta. Their proliferation depends on diffusible signals from neighboring cells in the epiblast, including fibroblast growth factor 4 (Fgf4). Here, we show that Fgf4 expression is induced by the transforming growth factor beta-related protein Nodal. Together with Fgf4, Nodal also acts directly on neighboring ExE to sustain a microenvironment that inhibits precocious differentiation of trophoblast stem cells. Because the ExE itself produces the proteases Furin and PACE4 to activate Nodal, it represents the first example, to our knowledge, of a stem cell compartment that actively maintains its own microenvironment. 相似文献
99.
100.
A widespread distribution of immunoreactive dynorphin (ir-Dyn) in rat brain and spinal cord was demonstrated by means of a highly specific radioimmunoassay. The highest concentrations of ir-Dyn (greater than 399 pg/mg protein) were found in hypothalamic nuclei, i.e. the premamillary, anterior hypothalamic and dorsomedial nuclei and median eminence. Relatively high concentrations of ir-Dyn (between 320 and 399 pg/mg protein) were found in other hypothalamic nuclei such as the medial and lateral preoptic, perifornical, suprachiasmatic, ventromedial nuclei and in the medulla oblongata in the area postrema and in the nucleus of the solitary tract (commissural part). Moderate levels of ir-Dyn (between 140 and 320 pg/mg protein) were found in most diencephalic areas other than the hypothalamic nuclei and further nuclei in the medulla oblongata, in the mesencephalon, pons and spinal cord. Low to moderate levels of ir-Dyn were found in the telencephalon, with lowest levels (less than 140 pg/mg protein) found in the cerebral cortex, olfactory bulb, dorsal septal nucleus, medial amygdaloid nucleus, caudate-putamen, superior collicle, cerebellum and certain areas of the reticular formation. 相似文献