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21.
β-Thalassemia (β-thal) is a hereditary anemia caused by mutations in the β-globin gene encoding the β-globin chain of hemoglobin A. In its homozygous form, the disease is characterized by a hemolytic hypochromic anemia, hepatosplenomegaly, skeletal deformation, mongoloid facies, and cardiac enlargement. The heterozygous form is usually asymptomatic but is sometimes associated with moderate anemia and splenomegaly. More than 100 β-thal mutations have been detected in the β-globin gene (Kazazian, 1990). Here we report two new β-thal mutations and observation of another rare allele, which was found previously in a single individual. © 1995 Wiley-Liss, Inc. 相似文献
22.
Escherichia coli Nissle 1917 distinctively modulates T-cell cycling and expansion via toll-like receptor 2 signaling 总被引:2,自引:0,他引:2
Sturm A Rilling K Baumgart DC Gargas K Abou-Ghazalé T Raupach B Eckert J Schumann RR Enders C Sonnenborn U Wiedenmann B Dignass AU 《Infection and immunity》2005,73(3):1452-1465
Although the probiotic Escherichia coli strain Nissle 1917 has been proven to be efficacious for the treatment of inflammatory bowel diseases, the underlying mechanisms of action still remain elusive. The aim of the present study was to analyze the effects of E. coli Nissle 1917 on cell cycling and apoptosis of peripheral blood and lamina propria T cells (PBT and LPT, respectively). Anti-CD3-stimulated PBT and LPT were treated with E. coli Nissle 1917-conditioned medium (E. coli Nissle 1917-CM) or heat-inactivated E. coli Nissle 1917. Cyclin B1, DNA content, and caspase 3 expression were measured by flow cytometry to assess cell cycle kinetics and apoptosis. Protein levels of several cell cycle and apoptosis modulators were determined by immunoblotting, and cytokine profiles were determined by cytometric bead array. E. coli Nissle 1917-CM inhibits cell cycling and expansion of peripheral blood but not mucosal T cells. Bacterial lipoproteins mimicked the effect of E. coli Nissle 1917-CM; in contrast, heat-inactivated E. coli Nissle 1917, lipopolysaccharide, or CpG DNA did not alter PBT cell cycling. E. coli Nissle 1917-CM decreased cyclin D2, B1, and retinoblastoma protein expression, contributing to the reduction of T-cell proliferation. E. coli Nissle 1917 significantly inhibited the expression of interleukin-2 (IL-2), tumor necrosis factor alpha, and gamma interferon but increased IL-10 production in PBT. Using Toll-like receptor 2 (TLR-2) knockout mice, we further demonstrate that the inhibition of PBT proliferation by E. coli Nissle 1917-CM is TLR-2 dependent. The differential reaction of circulating and tissue-bound T cells towards E. coli Nissle 1917 may explain the beneficial effect of E. coli Nissle 1917 in intestinal inflammation. E. coli Nissle 1917 may downregulate the expansion of newly recruited T cells into the mucosa and limit intestinal inflammation, while already activated tissue-bound T cells may eliminate deleterious antigens in order to maintain immunological homeostasis. 相似文献
23.
Chapelot D Marmonier C Aubert R Gausseres N Louis-Sylvestre J 《Physiology & behavior》2004,80(5):721-731
A physiological distinction between eating occasions may help account for contradictory findings on the role of eating frequency in energy homeostasis. We assessed this issue using a midafternoon eating occasion known in France as the goûter that often consists of snack foods. Among the 24 male subjects, 8 habitually consumed four meals per day, i.e., were usual goûter eaters (GE) and 16 habitually took 3 meals per day, i.e., usual non-goûter non-snack eaters (NGNSE). All subjects were time blinded from lunchtime and had to request subsequent meals. Blood was continuously withdrawn and collected with a change of tube every 10 min until dinner request. During the session, 8 of the non-goûter eaters (NGE) were offered a snack 210 min after lunch and were designated as non-goûter snack eaters (NGSE) if they ate. Results showed that the goûter was preceded by high hunger scores and a linear decline in plasma glucose (−9.0±3.0%, P<.05) and insulin concentrations (−22.9±6.0%, P<.05). These profiles were not observed before the snack. The dinner of GE was requested later and was smaller compared to NGNSE, whereas the snack altered neither time of request nor energy intake (EI) at dinner. Among blood variables, leptin at the onset of eating was the only factor that was predictive of both intermeal interval and EI. The glucose and insulin profiles indicate that snacks should not be considered as meals in studies on the role of eating frequency in energy homeostasis. 相似文献
24.
25.
Montes-Rodríguez CJ Alavez S Elder JH Haro R Morán J Prospéro-García O 《Neuroscience letters》2004,360(3):133-136
The human immunodeficiency virus (HIV) induces neuronal death, presumably by apoptosis. This effect may be triggered by the glycoprotein 120 (HIVgp120) released by HIV when infecting a cell, and mediated by tumor necrosis factor alpha (TNF), a pro-inflammatory cytokine. Both molecules, HIVgp120 and TNF, increase sleep when administered acutely in the brain. On the other hand, sleep deprivation increases the levels of several growth factors. In this context, we challenged rats with HIVgp120 or TNF simultaneously with sleep deprivation. Our results indicate that both HIVgp120 and TNF increase neuronal death in the rat cerebral cortex, but not hippocampus, and that this effect is completely prevented by total deprivation of sleep. These results suggest that acute total deprivation of sleep protects against the HIVgp120 and TNF deleterious effects. 相似文献
26.
Two-second long square wave tones at frequencies of 125 and 1000 Hz and 75 db sound pressure were presented to six newborn infants. Mean heart rates were computed for the 10 sec prior to and the 10 sec following stimulus onset, i.e. the prestimulus and stimulus heart rate values respectively. LIV was shown to operate strongly only in the case of the 125 Hz stimulus. Even for this stimulus, LIV depended upon the state of the infant, showing an appropriate negative correlation between prestimulus and stimulus values in regular sleep and quiet wakefulness but a slightly positive correlation in irregular sleep. In randomly selected control periods, the first 5 sec served as prestimulus values and the second 5 sec as stimulus values. Regression coefficients for these control periods did not differ significantly from those during which the stimulus was actually present. In view of the special conditions required for its demonstration, the generality of Wilder's “law” seems to be seriously questioned. 相似文献
27.
A human-mouse chimera of the alpha3alpha4alpha5(IV) collagen protomer rescues the renal phenotype in Col4a3-/- Alport mice
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Heidet L Borza DB Jouin M Sich M Mattei MG Sado Y Hudson BG Hastie N Antignac C Gubler MC 《The American journal of pathology》2003,163(4):1633-1644
Collagen IV is a major structural component of basement membranes. In the glomerular basement membrane (GBM) of the kidney, the alpha3, alpha4, and alpha5(IV) collagen chains form a distinct network that is essential for the long-term stability of the glomerular filtration barrier, and is absent in most patients affected with Alport syndrome, a progressive inherited nephropathy associated with mutation in COL4A3, COL4A4, or COL4A5 genes. To investigate, in vivo, the regulation of the expression, assembly, and function of the alpha3alpha4alpha5(IV) protomer, we have generated a yeast artificial chromosome transgenic line of mice carrying the human COL4A3-COL4A4 locus. Transgenic mice expressed the human alpha3 and alpha4(IV) chains in a tissue-specific manner. In the kidney, when expressed onto a Col4a3(-/-) background, the human alpha3(IV) chain restored the expression of and co-assembled with the mouse alpha4 and alpha5(IV) chains specifically at sites where the human alpha3(IV) was expressed, demonstrating that the expression of all three chains is required for network assembly. The co-assembly of the human and mouse chains into a hybrid network in the GBM restores a functional GBM and rescues the Alport phenotype, providing further evidence that defective assembly of the alpha3-alpha4-alpha5(IV) protomer, caused by mutations in any of the three chains, is the pathogenic mechanism responsible for the disease. This line of mice, humanized for the alpha3(IV) collagen chain, will also provide a valuable model for studying the pathogenesis of Goodpasture syndrome, an autoimmune disease caused by antibodies against this chain. 相似文献
28.
Tartour Eric; de la Salle Henri; de la Salle Corinne; Teillaud Christophe; Camoin Luc; Galinha Annie; Latour Sylvain; Hanau Daniel; Fridman Wolf H.; Sautes Catherine 《International immunology》1993,5(8):859-868
Low affinity FcR are a heterogeneous group of glycoproteinswhich exist in transmembrane (TM) as well as in soluble forms.Two membrane isoforms of the murine type II FcR, FcRilb1 andFc;Rilb2, have been described. They result from the translationof alternatively spliced premRNA, FcRilb2 lacking sequencesof the first intracytoplasmic domain (IC1). Soluble forms ofFcR (sFcR) have previously been shown to result from proteolysisof membrane receptors. We report here the identification, inmacrophages, of a mRNA derived from the FCRll gene by splicingexons encoding the TM and IC1 domains, i.e. corresponding toa TM-deleted FcRllb2 mRNA. A soluble protein possibly encodedby this mRNA was identified in macrophage supernatants. In accordancewith FcR nomenclature, we propose to name this new FcRll IsoformFcRllb3. It is the most abundant 8FcR present in serum, as comparedwith 8FcR resulting from cleavage of membrane FcR. 相似文献
29.
Souriau J Gimenes M Blouin C Benbrik I Benbrik E Churakowskyi A Churakowskyi B 《American journal of medical genetics. Part A》2005,135(3):278-281
Kabuki syndrome (KS) is associated with multiple organ system involvement. Characteristic features include long palpebral fissures with everted lower lids, prominent ears, skeletal abnormalities, mental retardation, and short stature. An increased incidence of infection has been reported in KS, and a few patients have been noted to have immune defects. However, the frequency and severity of the immune deficiency has not been clearly defined. Immunologic evaluation of 19 consecutive individuals with KS was performed at The Children's Hospital of Philadelphia. Decreased IgA levels were noted in 15/19 individuals (79%), 2 of whom had undetectable levels. Eight patients (42%) also had low total IgG levels. Specific IgG subclass abnormalities were found in 6 of 13 patients evaluated. IgM levels were less frequently decreased. One patient failed to generate anti-tetanus antibodies despite immunization. This study suggests that hypogammaglobulinemia is a frequent finding in children with KS. The pattern of antibody abnormalities seen in children with KS resembles common variable immune deficiency (CVID). Due to this increased susceptibility to infection, children with KS should have immunologic evaluations at the time of diagnosis in order to reduce preventable morbidity and mortality. 相似文献
30.
The dosimetric characteristics for a new brachytherapy seed source (I-Plant model 3600) were measured using LiF thermoluminescent dosimeters and appropriate phantom materials in conformance with the methodology and guidance provided by the AAPM Task Group 43. The I-Plant model 3600 is the successor to the I-Plant model 3500. The major difference between these sources is that the model 3600 contains a leaded-glass core to provide radio-opacity (while the model 3500 contains a silver core), which does not produce spectral contamination upon neutron activation. The dose rate constant lambda for the model 3600 was determined to be 1.00 Gy h(-1) U(-1) (with a 6% overall relative standard deviation), compared to 1.01 cGy h(-1) U(-1) reported for the model 3500 in previous studies. The remaining dosimetric characteristics also are similar for both sources. 相似文献