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81.
82.
Bone-specific antibodies in sera from patients with celiac disease: characterization and implications in osteoporosis 总被引:5,自引:0,他引:5
Sugai E Cherñavsky A Pedreira S Smecuol E Vazquez H Niveloni S Mazure R Mauriro E Rabinovich GA Bai JC 《Journal of clinical immunology》2002,22(6):353-362
Osteopenia and osteoporosis are well-known complications detected in celiac disease patients with still obscure pathogenesis. In the present study we investigated the presence of circulating anti-bone autoantibodies in patients with celiac disease and explored their role in the associated bone disease. We evaluated serum samples from 33 patients at the time of diagnosis and from 20 of them after treatment. Sera from patients with inflammatory bowel disease (n = 9), nonceliac osteoporotic (n = 18), and healthy individuals (n = 10) were used as controls. The presence of IgA specific anti-bone antibodies was first investigated using indirect immunofluorescence on cryosections of fetal rat tibia (20-day pregnancy). Furthermore, samples were homogenized and total tissue extracts were subjected to Western blot analysis to confirm immunoreactivity. At diagnosis, sera from 51.5% (17/33) of celiac patients had antibodies that recognized antigenic structures in chondrocytes and the extracellular matrix along mature cartilage, bone interface, and perichondrium of fetal rat bone. Among controls, only two osteoporotic patients showed very low titles of anti-bone autoantibodies. The immunostaining was localized in areas where an active mineralization process occurred and was similar to the distribution of the native bone tissue transglutaminase. The frequency of patients with positive baseline titers of anti-bone antibodies diminished significantly after treatment (P = 0.048). Western blot assays confirmed the presence of autoantibodies in sera from patients with a positive immunofluorescence staining. Autoantibodies recognized a major protein band on tissue extracts with a molecular weight of 77–80 kDa, which could be displaced when sera were preadsorbed with human recombinant tissue transglutaminase. We provide original evidence that patients with celiac disease have IgA-type circulating autoantibodies against intra- and extracellular structures of fetal rat tibia. Our findings suggest that these antibodies recognize bone tissue transglutaminase as the autoantigen, and based on the localization of the immunoreactivity we speculate that they might have an active role in the pathophysiology of celiac disease-associated bone complications. 相似文献
83.
Chun Jiang Theodore R. Cummins Gabriel G. Haddad 《Experimental brain research. Experimentelle Hirnforschung. Expérimentation cérébrale》1994,100(3):407-420
It is well known that neuronal firing properties are determined by synaptic inputs and inherent membrane functions such as
specific ionic currents. To characterize the ionic currents of brainstem cardio-respiratory neurons, cells from the hypoglossal
(XII) nucleus and the dorsal motor nucleus of the vagus (DMX) were freshly dissociated and membrane ionic currents were studied
under whole-cell voltage and current clamp. Both of these neurons showed a TTX-sensitive Na+ current with a much larger current density in XII than DMX neurons. This Na+ current had two (fast and slow) distinct inactivation decay components. The ratio of the magnitudes of the fast to slow component
was roughly two-fold greater in DMX than in XII cells. Both DMX and XII neurons also showed a high voltage-activated Ca2+ current, but this current density was significantly greater (three-fold) in DMX than XII neurons. A relatively small amount
of low-voltage activated Ca2+ current was also observed in DMX neurons, but not in the majority of XII cells. A transient and a sustained outward current
components were observed in DMX cells, but only sustained currents were present in XII neurons. These outward currents had
a reversal potential of about − 70 mV with 3 mM external K+ and −30 mV with 25 mM K+, and substitution of K+ with cesium and tetraethylammonium suppressed more than 90% the outward currents, indicating that most outward currents were
carried by K+. The transient outward current consisted of two components with onesensitive to 4-aminopyridine and the other to intracellular
Ca2+. In XII neurons, BRL 38227 (lemakalim), an ATP-sensitive K+ (KATP) channel activator, increased the sustained K+ currents by 10% of control, and glibenclamide, a KATP channel blocker, decreased the sustained K+ currents by 20%. Evidence for the presence of an inward rectifier K+ current was also obtained from both XII and DMX neurons. These results on XII and DMX neurons indicate that (1) the methods
used to dissociate neurons provide a useful means to overcome voltage clamp technical difficulties; (2) ion channel characteristics
such as density and biophysical properties of DMX neurons are very different from those of XII neurons; and (3) several newly
discovered membrane ionic currents are present in these cells. 相似文献
84.
Hepatitis C infection is associated with autoimmune disorders, such as the production of autoantibodies. Anti-LKM1 and anti-LC1, immunomarkers of type 2 autoimmune hepatitis, have been previously associated with a HCV infection. Anti-Soluble-Liver-Antigen autoantibodies (SLA) are specifically associated with type 1 and type 2 autoimmune hepatitis and more closely related to patients who relapse after steroid therapy. The recent molecular cloning of the soluble liver antigen provides the opportunity to develop more specific tests for the detection of antibodies against it. The aim of this work is to characterize anti-soluble-liver autoantibodies in sera from patients chronically infected by HCV. A recombinant cDNA from activated Jurkat cells coding for the full length tRNP(Ser)Sec/SLA antigen was obtained. ELISA, Western Blot and immunoprecipitation tests were developed and used to search for linear and conformational epitopes recognized by anti-SLA antibodies in sera from patients chronically infected by HCV. Anti-soluble liver antigen antibodies were found in sera from 10.4% of HCV-infected patients. The prevalence was significantly increased to 27% when anti-LKM1 was also present. Most anti-SLA reactivity was directed against conformational epitopes on the antigen. The means titers by ELISA were lower than those obtained in type 2 AIH. The result of autoantibody isotyping showed a subclass restriction to IgG1 and also IgG4. This study shows the presence of anti-SLA antibodies in approximately 10% of HCV infected patients. The prevalence of SLA autoantibodies in HCV infected patients increases when LKM1 autoantibodies are also present. The relationship between the prevalence of this characteristic autoimmune hepatitis autoantibody and the implication of an autoimmune phenomenon in the liver injury of patients chronically infected by HCV needs further investigation. 相似文献
85.
Gene-for-gene interactions of five cloned avirulence genes from Xanthomonas campestris pv. malvacearum with specific resistance genes in cotton 总被引:13,自引:3,他引:10
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Gabriel DW Burges A Lazo GR 《Proceedings of the National Academy of Sciences of the United States of America》1986,83(17):6415-6419
A total DNA clone bank of a strain of Xanthomonas campestris pv. malvacearum (Xcm) was constructed in the cosmid vector pSa747 and transfected into Escherichia coli. The Xcm strain carries at least nine identifiable avirulence (A) genes. Clones in E. coli were mated individually into a recombination-proficient Xcm isolate carrying no known A genes. Screening was for incompatibility on congenic cotton host lines that differ by single specific resistance (R) genes. Ten different cosmid clones conferring race-specific avirulence were recovered. In most cases, the same A gene clone was recovered independently several times. Using the congenic host lines and the merodiploid transconjugant pathogen strains, five of the A genes were shown to specifically interact, gene-for-gene, with individual R genes in the congenic cotton lines. Some A/R gene interactions appeared qualitatively different from others, suggesting that the physiological mechanism(s) of gene-for-gene specified incompatibility may be unique to the interactive gene pair. All A genes appeared to be chromosomally determined, three were found linked on a single 32-kilobase clone, and the rest were spaced more than 31 kilobases apart. Colinearity of the cosmid inserts with the Xcm recipient (carrying no known A genes) chromosome was demonstrated in two of the three tested. This and other evidence suggests that at least some A genes in bacteria may have the equivalent of virulence (a) alleles. The genetics of race specificity in this phytopathogenic bacterium appeared in all respects to be identical to that found in phytopathogenic fungi. 相似文献
86.
Summary Copovithane is an uncharged, water-soluble, synthetic polymer with an average molecular weight of 5800 daltons. It demonstrates antitumor activity in vivo against a variety of tumors in animal models but is inactive in vitro. This agent has been found to have immunorestorative activity in man. In concert with its phase I clinical trial, copovithane concentrations were analyzed by HPLC in plasma, urine, and autopsy and in tumor biopsy specimens obtained from patients. Copovithane was cleared from plasma biphasically with a mean t1/2 of 11.1±4 min and a t1/2 of 246±78 min at the dose of 1 g/m2, while the plasma half-lives increased to 57.7±12 and 718±149 for the alpha and beta phases, respectively, at the 10 g/m2 dose, demonstrating clear, dose-dependent pharmacokinetics. There were no significant differences between dose 1 and dose 4 pharmacokinetics. The apparent volume of distribution (Vd) was 14.5±1. at the 1 g/m2 dose and increased to 73 1. at the 33 g/m2 dose. The calculated mean clearance rate for copovithane in plasma was between 2.4 and 5.4 mg/kg x min and did not appear to be dose-dependent. The urinary excretion of copovithane was approximately 5% of the administered dose over 120 h at the 1 g/m2 dose and decreased to 1% at the 33 g/m2 dose. In seven tumor biopsy samples, concentrations of drug in tumor varied from 1- to 1000-fold higher than that found in concurrent plasma samples. In three autopsy samples, the highest concentrations were found in kidney, intestine, and liver, in decreasing order. These studies show that copovithane exhibits dose-dependent changes in pharmacokinetics at doses between 1 and 33 g/m2. However, copovithane does penetrate well to tumor tissues, achieving high tumor/plasma ratios. In addition, copovithane concentrations were highest in kidney tissue, which may be a site for potential organ toxicity. 相似文献
87.
Jernimo P. Martins Lucia C. Silva Matheus S. Nunes Gabriel Rübensam Jarbas R. Oliveira Rodrigo B. M. Silva Maria M. Campos 《Nutrients》2021,13(4)
Dry extracts from the Eurasian plants, Ajuga turkestanica, Eurycoma longifolia, and Urtica dioica have been used as anabolic supplements, despite the limited scientific data on these effects. To assess their actions on early sarcopenia signs, male and female castrated mice were supplemented with lyophilized extracts of the three plants, isolated or in association (named TLU), and submitted to resistance exercise. Ovariectomy (OVX) led to body weight increase and non-high-density cholesterol (HDL) cholesterol elevation, which had been restored by exercise plus U. dioica extract, or by exercise and TLU, respectively. Orchiectomy (ORX) caused skeletal muscle weight loss, accompanied by increased adiposity, being the latter parameter reduced by exercise plus E. longifolia or U. dioica extracts. General physical activity was improved by exercise plus herbal extracts in either OVX or ORX animals. Exercise combined with TLU improved resistance to fatigue in OVX animals, though A. turkestanica enhanced the grip strength in ORX mice. E. longifolia or TLU also reduced the ladder climbing time in ORX mice. Resistance exercise plus herbal extracts partly altered gastrocnemius fiber size frequencies in OVX or ORX mice. We provide novel data that tested ergogenic extracts, when combined with resistance exercise, improved early sarcopenia alterations in castrated male and female mice. 相似文献
88.
Gerlinger Gabriel Mangiapane Nino Sander Julia 《Bundesgesundheitsblatt, Gesundheitsforschung, Gesundheitsschutz》2021,64(10):1213-1219
Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Versicherte haben seit 2019 einen gesetzlichen Anspruch auf Verordnung von digitalen Gesundheitsanwendungen (DiGA). Die... 相似文献
89.
Tony Wawina-Bokalanga Bert Vanmechelen Valentine Lhermitte Joan Martí-Carreras Valentijn Vergote Fara Raymond Koundouno Joseph Akoi-Bor Ruth Thom Tom Tipton Kimberley Steeds Kita Balla Moussa Ablam Amento Lies Laenen Sophie Duraffour Martin Gabriel Paula Ruibal Yper Hall Mandy Kader-Kond Stephan Günther Guy Baele Cesar Muoz-Fontela Johan Van Weyenbergh Miles W. Carroll Piet Maes 《Emerging infectious diseases》2021,27(1):76
We investigated the genetic profiles of killer cell immunoglobulin-like receptors (KIRs) in Ebola virus–infected patients. We studied the relationship between KIR–human leukocyte antigen (HLA) combinations and the clinical outcomes of patients with Ebola virus disease (EVD). We genotyped KIRs and HLA class I alleles using DNA from uninfected controls, EVD survivors, and persons who died of EVD. The activating 2DS4–003 and inhibitory 2DL5 genes were significantly more common among persons who died of EVD; 2DL2 was more common among survivors. We used logistic regression analysis and Bayesian modeling to identify 2DL2, 2DL5, 2DS4–003, HLA-B-Bw4-Thr, and HLA-B-Bw4-Ile as probably having a significant relationship with disease outcome. Our findings highlight the importance of innate immune response against Ebola virus and show the association between KIRs and the clinical outcome of EVD. 相似文献
90.
Ben Khadhra Hajer Rose-Robert Françoise Herpe Yves Edouard Sevestre Henri Choukroun Gabriel Catherine Luc Amant Carole Saint Fabien 《International urology and nephrology》2021,53(1):59-67
International Urology and Nephrology - Biomarkers for the diagnosis and monitoring treatment response of kidney cancer are urgently needed. Neutrophil gelatinase-associated lipocalin (NGAL) is a... 相似文献