Hotspot for deletions in the CGG repeat region of FMR1 in fragile X patients

The fragile X syndrome is the most frequent cause of inheritedmental retardation. The molecular mechanism of the disorderis based on the expansion of a CGG repeat in the 5' UTR of theFMR1 gene In the majority of fragile X patients. The instabilityof this CGG repeat containing region is not restricted to theCGG repeat Itself but expands to the flanking region as well.We describe four unrelated fragile X patients that are mosaicfor both a full mutation and a small deletion in the CGG repeatcontaining region. Sequence analysis of the regions surroundingthe deletions showed that both the (CGG)_n repeat and some flankingsequences were missing in all four patients. The 5' breakpointsof the deletions were found to be located between 75–53bp proximal to the CGG repeat. This suggests the presence ofa hot spot region for deletions in the CGG repeat region ofthe FMR1 gene and emphasizes the instability of this regionIn the presence of an expanded CGG repeat.     

~(131)I治疗Graves’病后发生甲低与TGA,TMA及TRAb的关系

目的 :从甲状腺自身免疫方面探讨1 3 1 I治疗甲亢的效果及甲低发生的因素。方法 :选择1 3 1 I治疗的88例Graves’病甲亢患者随访 3年 ,分为第 1组 (TGA、TMA、TRAb均阳性 )和第二组 (TGA、TMA阴性 ,TRAb阳性 )。采用x2 分析自身抗体水平与甲低发生的关系。结果 :1组甲低发生率为 31 4 % ,2组为 3 8% ,1组明显高于 2组 ,差异有显著性。结论 :TGA、TMA和TRAb水平与确定1 3 1 I剂量及甲低的发生关系密切。认为TGA、TMA水平高的患者应酌情减少1 3 1 I用量     

Immunogenicity and T cell recognition in swine of foot-and-mouth disease virus polymerase 3D

Immunization of domestic pigs with a vaccinia virus (VV) recombinant expressing foot-and-mouth disease virus (FMDV) 3D protein conferred partial protection against challenge with infectious virus. The severity reduction of the clinical symptoms developed by the challenged animals occurred in the absence of significant levels of anti-3D circulating antibodies. This observation suggested that the partial protection observed was mediated by the induction of a 3D-specific cellular immune response. To gain information on the T cell recognition of FMDV 3D protein, we conducted in vitro proliferative assays using lymphocytes from outbred pigs experimentally infected with FMDV and 90 overlapping peptides spanning the complete 3D sequence. The use of pools of two to three peptides allowed the identification of T cell epitopes that were efficiently recognized by lymphocytes from at least four of the five animals analyzed. This recognition was heterotypic because anti-peptide responses increased upon reinfection of animals with a FMDV isolate from a different serotype. The results obtained with individual peptides confirmed the antigenicity observed with peptide pools. Detection of cytokine mRNAs by RT-PCR in lymphocytes stimulated in vitro by individual 3D peptides revealed that IFN-gamma mRNA was the most consistently induced, suggesting that the activated T cells belong to the Th 1 subset. These results indicate that 3D protein contains epitopes that can be efficiently recognized by porcine T lymphocytes from different infected animals, both upon primary and secondary (heterotypic) FMDV infection. These epitopes can extend the repertoire of viral T cell epitopes to be included in subunit and synthetic FMD vaccines.     

Duplication of distal 22q

We report on three patients with duplication of distal 22q. One patient is a de novo carrier of the translocation t(21;22) (p13;q11), the other two are offspring of a translocation carrier t(10;22) (q26;q12). The clinical manifestations of these patients demonstrate the variability of the dup(22q) syndrome.     

Victimization over the life span: a comparison of lesbian, gay, bisexual, and heterosexual siblings

Lifetime victimization was examined in a primarily European American sample that comprised 557 lesbian/gay, 163 bisexual, and 525 heterosexual adults. Lesbian, gay, and bisexual (LGB) participants were recruited via LGB e-mail lists, periodicals, and organizations; these participants recruited 1 or more siblings for participation in the study (81% heterosexual, 19% LGB). In hierarchical linear modeling analyses, sexual orientation was a significant predictor of most of the victimization variables. Compared with heterosexual participants, LGB participants reported more childhood psychological and physical abuse by parents or caretakers, more childhood sexual abuse, more partner psychological and physical victimization in adulthood, and more sexual assault experiences in adulthood. Sexual orientation differences in sexual victimization were greater among men than among women.     

A solid-phase blocking ELISA for detection of antibodies to Nipah virus

A monoclonal antibody (MAb) based solid-phase blocking ELISA was developed for detection of antibodies to Nipah virus. The ELISA was designed to detect remaining antigens on the plate with anti-Nipah MAb conjugate after the reaction with sample serum, and enabled simple procedure, detection of neutralizing antibody to Nipah virus, and application of samples from different animal species. Forty of 200 swine reference sera examined were positive by the ELISA, of which thirty seven were found positive by serum neutralization test. Sera from a total of 131 fruit bats captured in Malaysia were also tested and all found negative by the both tests. It is considered that the solid-phase blocking ELISA can be used as a screening test for Nipah virus infection followed by the serum neutralization test as confirmatory test.     

Tumor necrosis factor-mediated inhibition of interleukin-18 in the brain: a clinical and experimental study in head-injured patients and in a murine model of closed head injury.

Tumor necrosis factor (TNF) and interleukin-(IL)-18 are important mediators of neuroinflammation after closed head injury (CHI). Both mediators have been previously found to be significantly elevated in the intracranial compartment after brain injury, both in patients as well as in experimental model systems. However, the interrelation and regulation of these crucial cytokines within the injured brain has not yet been investigated. The present study was designed to assess a potential regulation of intracranial IL-18 levels by TNF based on a clinical study in head-injured patients and an experimental model in mice. In the first part, we investigated the interrelationship between the daily TNF and IL-18 cerebrospinal fluid levels in 10 patients with severe CHI for up to 14 days after trauma. In the second part of the study, the potential TNF-dependent regulation of intracerebral IL-18 levels was further characterized in an experimental set-up in mice: (1) in a standardized model of CHI in TNF/lymphotoxin-alpha gene-deficient mice and wild-type (WT) littermates, and (2) by intracerebro-ventricular injection of mouse recombinant TNF in WT C57BL/6 mice. The results demonstrate an inverse correlation of intrathecal TNF and IL-18 levels in head-injured patients and a TNF-dependent inhibition of IL-18 after intracerebral injection in mice. These findings imply a potential new anti-inflammatory mechanism of TNF by attenuation of IL-18, thus confirming the proposed "dual" function of this cytokine in the pathophysiology of traumatic brain injury.     

Opposing effects of D1 and D2 receptor activation on odor discrimination learning

Dopaminergic modulation of cortical activity has been implicated in the formation of reward associations. There is abundant evidence for dopaminergic effects on olfactory processing. Using an olfactory discrimination task, the authors show that D1 and D2 dopamine receptors can regulate rats' olfactory discrimination capacities and that the effects of receptor activation functionally oppose one another. Injection of either the D1 agonist SKF 38393 (10 mg/kg) or the D2 antagonist spiperone (0.62 mg/kg) facilitated the discrimination of similar odorants but had no effect on the discrimination of dissimilar odorants, whereas both the D, antagonist SCH 23390 (0.025 mg/kg) and the D2 agonist quinpirole (0.2 mg/kg) significantly impaired rats' ability to discriminate similar and dissimilar odorants.     

Differential expression of FIZZ1 and Ym1 in alternatively versus classically activated macrophages

Alternatively activated macrophages (aaMphi) display molecular and biological characteristics that differ from those of classically activated macrophages (caMphi). Recently, we described an experimental model of murine trypanosomosis in which the early stage of infection of mice with a Trypanosoma brucei brucei variant is characterized by the development of caMphi, whereas in the late and chronic stages of infection, aaMphi develop. In the present study, we used suppression subtractive hybridization (SSH) to identify genes that are expressed differentially in aaMphi versus caMphi elicited during infection with this T. b. brucei variant. We show that FIZZ1 and Ym1 are induced strongly in in vivo- and in vitro-elicited aaMphi as compared with caMphi. Furthermore, we demonstrate that the in vivo induction of FIZZ1 and Ym1 in macrophages depends on IL-4 and that in vitro, IFN-gamma antagonizes the effect of IL-4 on the expression of FIZZ1 and Ym1. Collectively, these results open perspectives for new insights into the functional properties of aaMphi and establish FIZZ1 and Ym1 as markers for aaMphi.