Mayan alleles of the HLA-DRB1 major histocompatibility complex might contribute to the genetic susceptibility to systemic lupus erythematosus in Mexican patients from Tapachula,Chiapas

Clinical Rheumatology - Systemic lupus erythematosus (SLE) is the prototypic autoimmune disease that disrupts numerous immunity mechanisms with the potential to exert damage to any organ or tissue....     

Characterization of von Willebrand factor in primary pulmonary hypertension

Summary The aim of this study was to determine the value of von Willebrand factor (vWF), a well-characterized endothelial cell protein secretion, as a marker for prognosis in patients with primary pulmonary hypertension (PPH). Venous and arterial blood samples were obtained from 18 clinically diagnosed PPH patients and 12 case controls matched for age and sex. Plasma vWF antigen was determined by enzymelinked immunosorbent assay (ELISA). The patients' multimeric vWF pattern was analyzed by sodium dodecylsulfate (SDS)-agarose-acrylamide electrophoresis, Western blot, and densitometric analysis. vWF sialic acid content was determined by a lectin-based ELISA. The PPH patients showed a higher content of vWF antigen in venous (P = 0.0026) and arterial (P = 0.0094) blood samples than controls. The mean vWF sialic acid content of the PPH patients corresponded to 37.7% of the mean value for the control group. On the basis of the hemodynamic response to vasodilator trial, the PPH patients were grouped as responders or nonresponders. The latter group showed a significantly higher plasma vWF antigen antecubital vein/radial artery ratio, an increased number of unusually large vWF multimers, and a diminished content of vWF sialic acid in comparison with the first group. We believe that our results establish the nature of vWF alterations that are related to endothelial cell damage in patients with primary pulmonary hypertension and that this could be of value when establishing the prognosis in this group of patients.     

Role of DISC1 Interacting Proteins in Schizophrenia Risk from Genome‐Wide Analysis of Missense SNPs

A balanced translocation affecting DISC1 cosegregates with several psychiatric disorders, including schizophrenia, in a Scottish family. DISC1 is a hub protein of a network of protein–protein interactions involved in multiple developmental pathways within the brain. Gene set‐based analysis has been proposed as an alternative to individual analysis of single nucleotide polymorphisms (SNPs) to get information from genome‐wide association studies. In this work, we tested for an overrepresentation of the DISC1 interacting proteins within the top results of our ranked list of genes based on our previous genome‐wide association study of missense SNPs in schizophrenia. Our data set consisted of 5100 common missense SNPs genotyped in 476 schizophrenic patients and 447 control subjects from Galicia, NW Spain. We used a modification of the Gene Set Enrichment Analysis adapted for SNPs, as implemented in the GenGen software. The analysis detected an overrepresentation of the DISC1 interacting proteins (permuted P‐value = 0.0158), indicative of the role of this gene set in schizophrenia risk. We identified seven leading‐edge genes, MACF1, UTRN, DST, DISC1, KIF3A, SYNE1, and AKAP9, responsible for the overrepresentation. These genes are involved in neuronal cytoskeleton organization and intracellular transport through the microtubule cytoskeleton, suggesting that these processes may be impaired in schizophrenia.     

Thalamic atrophy in patients with pure hereditary spastic paraplegia type 4

Journal of Neurology - SPG4 is an autosomal dominant pure form of hereditary spastic paraplegia (HSP) caused by mutations in the SPAST gene. HSP is considered an upper motor neuron disorder...     

Incontinence after lateral internal sphincterotomy

PURPOSE: This study was designed to evaluate the anatomic and functional consequences of lateral internal sphincterotomy in patients who developed anal incontinence and in matched controls. METHODS: The study includes 13 patients with anal incontinence after lateral internal sphincterotomy and 13 controls who underwent the same operation and were continent and satisfied with the results of the procedure. Patients underwent clinical evaluation, anorectal manometry, pudendal nerve terminal motor latency testing, and endoanal ultrasonography. RESULTS: Sphincterotomies were longer in incontinent patients (75vs. 57 percent), but the resting pressure and length of the high-pressure zone were not different between groups. Surprisingly, maximum voluntary contraction was higher in incontinent patients than in continent controls (136vs. 100 mmHg). Rectal sensation and pudendal nerve terminal motor latency were similar in both groups. The defect in the internal sphincter was wider in incontinent patients than in continent controls (17.3vs. 14.4 mm), but these differences were not statistically significant. The thickness of the internal sphincter measured by endoanal ultrasound was identical in both groups, but the external sphincter was thinner in incontinent patients both at the site of the sphincterotomy (6.8vs. 8.1 mm) and in the posterior midline (7.1vs. 8.6 mm). CONCLUSIONS: Anal incontinence after lateral internal sphincterotomy is directly related to the length of the sphincterotomy. Whether secondary to preoperative sphincter abnormality or the result of lateral internal sphincterotomy, the external sphincter is thinner in incontinent patients than in continent controls.Read at the meeting of The American Society of Colon and Rectal Surgeons, Montreal, Quebec, Canada, May 7 to 12, 1995.