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Pinhas-Hamiel O Frumin K Gabis L Mazor-Aronovich K Modan-Moses D Reichman B Lerner-Geva L 《Obesity (Silver Spring, Md.)》2008,16(3):659-663
Objective: To assess the association between obesity and primary headaches in children and adolescents. Methods and Procedures: In a prospective study, the short‐questionnaire version based on existing International Headache Society diagnostic criteria was administered. Two hundred and seventy‐three children and adolescents (61% females) aged 9–17 years were assessed. One hundred and sixteen (42.5%) subjects were of normal weight, 45 (16.5%) were at risk for overweight (BMI >85th and <95th percentile for age and gender) and 112 (41%) were overweight (BMI ≥95th percentile). The outcome measures were prevalence of headaches, type of headaches, association between headaches and elevated blood pressure in overweight subjects. Results: Headache was reported in 39 (14.3%) subjects, with a similar rate in females (14.5%) and males (14%). Among 39 subjects with headaches, 20 (17.9%) were overweight, 7 (15.6%) were at risk for overweight and 12 (10.3%) were normal‐weight children. Among females, 7.7% of normal‐weight group suffered from headaches, compared with 14.8% of the at risk for overweight group and 20.3% of the overweight group (P for trend 0.04). Among males, the occurrence of headaches was similar in all three weight groups (P = 0.96). The occurrence of headaches increased from 10.6% among children aged 9–11 years to 21.8% in the 15–18 years age group (P < 0.05). In multivariate analysis, a significant independent risk for headaches was present in overweight females (odds ratio (OR) = 3.93, 95% confidence interval (CI) 1.28–12.1) and in adolescents aged 15–18 years (OR = 2.62, 95% CI 1.07–6.45). Elevated blood pressure was not independently associated with headaches. Of the 15 children with migraine, 12 were either at risk for overweight or overweight. Discussion: Overweight females had an almost fourfold excess risk of headaches when compared with normal‐weight girls. 相似文献
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A network of molecular interactions is required in the developing vertebrate hindbrain for the formation and anterior-posterior patterning of the rhombomeres. FGF signaling is required in this network to upregulate the expression of the Krox20 and Kreisler segmentation genes, but little is known of how FGF gene expression is regulated in the hindbrain. We show that the dynamic expression of FGF3 in chick hindbrain segments and boundaries is similar to that of the BMP antagonist, follistatin. Consistent with a regulatory relationship between BMP signaling and FGF3 expression, we find that an increase in BMP activity due to blocking of follistatin translation by morpholino antisense oligonucleotides or overexpression of BMP results in strong inhibition of FGF3 expression. Conversely, addition of follistatin leads to an increase in the level of FGF3 expression. Furthermore, the segmental inhibition of BMP activity by follistatin is required for the expression of Krox20, Hoxb1 and EphA4 in the hindbrain. In addition, we show that the maintenance of FGF3 gene expression requires FGF activity, suggestive of an autoregulatory loop. These results reveal an antagonistic relationship between BMP activity and FGF3 expression that is required for correct segmental gene expression in the chick hindbrain, in which follistatin enables FGF3 expression by inhibiting BMP activity. 相似文献
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Ido Wolf Shiri Shahmoon Michal Ben Ami Yael Levy-Shraga Kineret Mazor-Aronovitch Orit Pinhas-Hamiel Yonatan Yeshayahu Rina Hemi Hannah Kanety Tami Rubinek Dalit Modan-Moses 《PloS one》2014,9(9)
Objective
Klotho is an aging-modulating protein expressed mainly in the kidneys and choroid plexus, which can also be shed, released into the circulation and act as a hormone. Klotho deficient mice are smaller compared to their wild-type counterparts and their somatotropes show marked atrophy and reduced number of secretory granules. Recent data also indicated an association between klotho levels and growth hormone (GH) levels in acromegaly. We aimed to study the association between klotho levels and GH deficiency (GHD) in children with growth impairment.Design
Prospective study comprising 99 children and adolescents (aged 9.0±3.7 years, 49 male) undergoing GH stimulation tests for short stature (height-SDS = −2.1±0.6). Klotho serum levels were measured using an α-klotho ELISA kit.Results
Klotho levels were significantly lower (p<0.001) among children with organic GHD (n = 11, 727±273 pg/ml) compared to both GH sufficient participants (n = 59, 1497±754 pg/ml) and those with idiopathic GHD (n = 29, 1645±778 pg/ml). The difference between GHS children and children with idiopathic GHD was not significant. Klotho levels positively correlated with IGF-1- standard deviation scores (SDS) (R = 0.45, p<0.001), but were not associated with gender, pubertal status, age or anthropometric measurements.Conclusions
We have shown, for the first time, an association between low serum klotho levels and organic GHD. If validated by additional studies, serum klotho may serve as novel biomarker of organic GHD. 相似文献16.
X-ray studies show that influenza hemagglutinin (HA) forms an elongated structure connecting the influenza virus at one end to cell-surface receptors at the other. At neutral pH, the 20 N-terminal residues of HA2—referred to as the fusion peptide—are buried in a hydrophobic pocket, about 100 Å away from the receptor-binding site, and thus seem unlikely to affect HA binding to the receptor. To test this assumption, we mutated residues in the fusion peptide, heterologically expressed the mutated proteins in COS7 cells, and examined their ability to bind fluorescently labeled red blood cells (RBCs). Surprisingly, a significantly reduced binding was recorded for some of the mutants. Ample experimental data indicate that HA has at least two forms: the native structure at neutral pH (N) that is metastable and the fusogenic form (F), observed at low pH, which is stable. Thus, a simple interpretation of our data is that HA can bind to its receptors at the RBC surface in the N form much more effectively than in the F (or in any other stable) form and that the altered binding properties are due to destabilizing effects of the mutations on the N form. That is, some of the mutations involve reduction in the free energy barrier between the N and F forms. This, in turn, leads to reduction in the population of the N form, which is the only form capable of binding to the cell-surface receptors. To explore this possibility, we estimated the stability free energy difference between HA wild-type (wt) and mutants in the N form using an empirical surface tension coefficient. The calculated stability differences correlated well with the measured binding, supporting the above interpretation. Our results are examined taking into account the available experimental data on the affinity of different soluble and membrane-attached forms of HA to its receptors. 相似文献
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Mira Malcov Dalit Ben-Yosef Tova Glaser Ruth Shalgi 《Molecular reproduction and development》1997,48(1):119-126
Resumption of meiosis at fertilization is mediated by increased levels of calcium which activate several calcium-dependent enzymes. Calpain, a neutral calcium-activated thiol protease, is present in the cytoplasm of many cells. Its activation is associated with limited autolysis and relocalization in the cell. Calpain is thought to participate in the regulation of mitosis and resumption of meiosis in Xenopus oocytes. In this study we followed the activation and localization of calpain during maturation and fertilization in rat eggs using a polyclonal antibody raised against chicken muscle calpain. A band of 80 kDa was detected in GV oocytes and its level increased in unfertilized MII eggs. At the early stages of fertilization, we observed a transient decrease in the level of calpain which was regained at the pronuclear stage. Adding Ca2+ to lysate of MII eggs resulted in an additional band, representing the degraded fragment of the activated protein. In eggs activated by ionomycin, calpain level decreased, followed by an increase in a dynamic similar to that observed in fertilized eggs. Egg activation also led to changes in calpain localization. A homogenous distribution was observed in GV and in MII eggs, while in activated eggs it was localized predominantly overlying the metaphase plate. In the current study we demonstrate the presence of calpain in the rat egg. During maturation, calpain level increases; however, during egg activation, in response to [Ca2+]i changes, calpain undergoes autolysis, translocation, and fluctuation in its level. We therefore suggest a correlation between calpain activation and fertilization. Mol. Reprod. Dev. 48:119–126, 1997. © 1997 Wiley-Liss, Inc. 相似文献
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Strauss-Ayali D Baneth G Shor S Okano F Jaffe CL 《International journal for parasitology》2005,35(1):63-73
The dog is the major reservoir for human visceral leishmaniasis caused by Leishmania infantum. Interleukin-12 is considered to have an essential role in the development of both innate and adaptive immunity to Leishmania spp. and other intracellular pathogens. This study focused on the influence of IL-12 in experimental and natural canine visceral leishmaniasis. Responses of peripheral blood mononuclear cells to IL-12, interleukin-10 and Leishmania soluble antigen were evaluated in L. infantum experimentally infected oligosymptomatic beagles, uninfected beagles, naturally infected polysymptomatic dogs, and their matched uninfected controls. Leishmania soluble antigen induced strong peripheral blood mononuclear cells proliferation both in experimentally infected dogs (median stimulation index [SI]=15.01), and in naturally infected dogs (SI=8.86), but not by cells from the control groups. IL-12 addition further enhanced cell proliferation in naturally (SI=14.95), but not in experimentally infected animals. Peripheral blood mononuclear cells from experimentally infected dogs were able to produce significant amounts of IFN-gamma (3.39 ng/ml) upon LSA stimulation, but no such production was detected in cells from naturally infected or control animals. Interestingly, addition of IL-12 reversed the inhibitory effect of LSA on IFN-gamma production by cells from polysymptomatic naturally infected dogs and the uninfected beagles (4.84 and 7.45 ng/ml, respectively), and further increased IFN-gamma production by peripheral blood mononuclear cells from experimentally infected oligosymptomatic dogs (29.28 ng/ml). IFN-gamma mRNA expression correlated well with IFN-gamma production. Addition of IL-10 to Leishmania soluble antigen stimulated peripheral blood mononuclear cells inhibited proliferation and IFN-gamma production in experimentally infected dogs. Thus, the ability of IL-12 to augment IFN-gamma production by peripheral blood mononuclear cells from dogs with experimental or natural symptomatic canine visceral leishmaniasis makes it a good candidate for cytokine therapy in dogs that are refractory to current therapy. 相似文献
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Dalit Modan-Moses Amit Yaroslavsky Brigitte Kochavi Anat Toledano Sharon Segev Fadel Balawi Edith Mitrany Daniel Stein 《PloS one》2012,7(9)