Treatment of uterine prolapse stage 2 or higher: a randomized multicenter trial comparing sacrospinous fixation with vaginal hysterectomy (SAVE U trial)

Background  

Pelvic organ prolapse is a common health problem, affecting up to 40% of parous women over 50 years old, with significant negative influence on quality of life. Vaginal hysterectomy is currently the leading treatment method for patients with symptomatic uterine prolapse. Several studies have shown that sacrospinous fixation in case of uterine prolapse is a safe and effective alternative to vaginal hysterectomy. However, no large randomized trials with long-term follow-up have been performed to compare efficacy and quality of life between both techniques.     

Mutational analysis of the histamine H1-receptor binding pocket of histaprodifens

Histaprodifens constitute a new class of histamine H(1)-receptor agonists. These ligands can be regarded as hybrid molecules, consisting of a histamine moiety linked at the two-position of the imidazole ring by a propyl chain to two phenyl rings, one of the characteristic features of several H(1)-receptor antagonists. To delineate the binding site of various histaprodifen-like ligands, we generated mutant histamine H(1) receptors, in which various amino acids, involved in the binding of either histamine or H(1)-receptor antagonists, were replaced by alanine. Wild-type and mutant H(1) receptors were transiently expressed in African green monkey kidney cells (COS-7) and evaluated for their interaction with histamine and various histaprodifens by [(3)H]mepyramine radioligand-binding studies and by nuclear factor kappaB (NF-kappaB) reporter-gene assays. Our data show that, within the histamine H(1)-receptor binding pocket, histaprodifens interact with both agonist and antagonist binding sites, resulting in high affinity histamine H(1)-receptor agonists.     

进展期胃癌淋巴结转移与临床病理特征的关系

目的：探讨进展期胃癌淋巴结转移与临床病理特征的关系，为临床上进行合理的淋巴结清扫提供依据。方法：对55例进展期胃癌资料进行回顾性分析，术后常规解剖原发灶及各组淋巴结，并标记和计数，分析肿瘤部位、肿瘤大小、浸润深度、分化程度及Lauren分型与淋巴结转移率的关系。结果：进展期胃癌淋巴结转移率为74．5％；U、M、L区及全胃癌淋巴结转移率为85．7％、87．5％、67．6％和83．3％，各区和全胃癌淋巴结转移率差异无统计学意义（P〉0．05）；浆膜受侵的胃癌淋巴结转移率为82．5％，明显高于浆膜未受侵者（53．3％）（P〈0．05）；弥漫型胃癌淋巴结转移率为83．3％，明显高于肠型（64．0％）（P〈0．05）；直径〉5cm癌灶淋巴结转移率为90．0％，明显高于直径≤5cm的胃癌患者（65．7％）（P〈0．05）；浸润深度、Lauren分型和肿瘤大小是影响淋巴结转移率的主要因素，其中浸润深度为独立影响因素。结论：术中淋巴结清扫范围应结合肿瘤部位、肿瘤大小、浸润深度、分化程度及Lauren分型做出判断，并考虑患者的全身情况，合理选择淋巴结清扫范围。     

一阶导数光谱法测定复方红甲凝胶中乳糖酸红霉素的含量

建立测定复方红甲凝胶中乳糖酸红霉素的含量测定方法。方法：以一阶导数光谱的谷一零位值法测定乳糖酸红霉素的含量,测定波长λ谷=490±lnm。结果：回收率100.6％,RSD为3.1％,线性范围40～120μg／ml。结论：方法简便,结果准确,重现性好,适合于该制剂的含量测定。     

Altered metabolism of familial Alzheimer's disease-linked amyloid precursor protein variants in yeast artificial chromosome transgenic mice

Missense mutations in the beta-amyloid precursor protein gene (APP) co- segregate with a small subset of autosomal dominant familial Alzheimer's disease (FAD) cases wherein deposition of the 39-43 amino acid beta-amyloid (A beta) peptide and neurodegeneration are principal neuropathological hallmarks. To accurately examine the effect of missense mutations on APP metabolism and A beta production in vivo, we have introduced yeast artificial chromosomes (YACs) containing the entire approximately 400 kbp human APP gene encoding APP harboring either the asparagine for lysine and leucine for methionine FAD substitution at codons 670 and 671 (APP(K670N/M671L)), the isoleucine for valine FAD substitution at codon 717 (APP(V7171)) or a combination of both substitutions into transgenic mice. We demonstrate that, relative to YAC transgenic mice expressing wild-type APP, high levels of A beta peptides are detected in the brains of YAC transgenic mice expressing human APP(K670N/M671L) that is associated with a concomitant diminution in the levels of apha-secretase-generated soluble APP derivatives. Moreover, the levels of longer A beta peptides (species terminating at amino acids 42/43) are elevated in YAC transgenic mice expressing human APP(V7171). These mice should prove valuable for detailed analysis of the in vivo effects of the APP FAD mutations in a variety of tissues and throughout aging and for testing therapeutic agents that specifically alter APP metabolism and A beta production.      

Cloning and characterization of DXS6673E, a candidate gene for X-linked mental retardation in Xq13.1

In several families with non-specific X-linked mental retardation (XLMR) linkage analyses have assigned the underlying gene defect to the pericentromeric region of the X chromosome, but none of these genes have been isolated so far. Here, we report on the cloning and characterization of a novel gene, DXS6673E, that maps to Xq13.1, is subject to X-inactivation and is disrupted in the 5' untranslated region by a balanced X;13 translocation in a mentally retarded female. The DXS6673E gene is highly conserved among vertebrates and its expression is most abundant in brain. It encodes a hydrophilic protein of 1358 amino acids (aa) that does not show sequence homology to other known proteins. A segment of this protein consisting of neutral and hydrophobic aa with a proline residue in every second position may represent a transmembrane domain. Almost complete sequence identity was found between the 3' end of the DXS6673E gene and two expressed sequence tags (ESTs) and between the 5' end of the DXS6673E gene and a third EST. Moreover, weaker sequence similarity was observed between coding regions and two other ESTs.      

Non-specific X-linked semidominant mental retardation by mutations in a Rab GDP-dissociation inhibitor

Non-specific X-linked mental retardation (MRX) is a very common disorder which affects approximately 1 in 600 males. Despite this high frequency, little is known about the molecular defects underlying this disorder, mainly because of the clinical and genetic heterogeneity which is evident from linkage studies. Recently, a collaborative study using the candidate gene approach demonstrated the presence of mutations in GDIalpha, a Rab GDP-dissociation inhibitor encoded by a gene localized in Xq28, associated with non-specific mental retardation. GDIalpha is mainly a brain-specific protein that plays a critical role in the recycling of Rab GTPases involved in membrane vesicular transport. The study presented here was designed to assess the prevalence of mutations in the GDIalpha in mentally retarded patients and to discuss the clinical phenotypes observed in affected individuals. Mutation screening of the whole coding region of the GDIalpha gene, using a combination of denaturing gradient gel electrophoresis and direct sequencing, was carried out in 164 patients found negative for expansions across the FRAXA GCC repeat. In addition to the nonsense mutation recently reported in MRX48, we have identified a novel missense mutation in exon 11 of the GDIalpha gene in one familial form of non-specific mental retardation. In this family (family R), all affected males show moderate to severe mental retardation, and the X-linked semidominant inheritance is strongly suggested by the severe phenotypes in males with respect to mildly affected females or unaffected obligatory carriers. This study showed that the prevalence of GDIalpha mutations in non-specific mental retardation could be estimated to be 0.5-1%, and molecular diagnosis and genetic counselling in some cases of non-specific mental handicap can now be provided.