Linkage of the MHC to familial multiple sclerosis suggests genetic heterogeneity. The Multiple Sclerosis Genetics Group

Multiple sclerosis (MS) is a demyelinating autoimmune disease of the central nervous system. While its etiology is not well understood, genetic factors are clearly involved. Until recently, most genetic studies in MS have been association studies using the case-control design testing specific candidate genes and studying only sporadic cases. The only consistently replicated finding has been an association with the HLA-DR2 allele within the major histocompatibility complex (MHC) on chromosome 6. Using the genetic linkage design, however, evidence for and against linkage of the MHC to MS has been found, fostering suggestions that sporadic and familial MS have different etiologies. Most recently, two of four genomic screens demonstrated linkage to the MHC, although specific allelic associations were not tested. Here, a dataset of 98 multiplex families was studied to test for an association to the HLA-DR2 allele in familial MS and to determine if genetic linkage to the MHC was due solely to such an association. Three highly polymorphic markers (HLA-DR, D6S273 and TNFbeta) in the MHC demonstrated strong genetic linkage (parametric lod scores of 4.60, 2.20 and 1.24, respectively) and a specific association with the HLA-DR2 allele was confirmed (TDT; P < 0.001). Stratifying the results by HLA-DR2 status showed that the linkage results were limited to families segregating HLA-DR2 alleles. These results demonstrate that genetic linkage to the MHC can be explained by the HLA-DR2 allelic association. They also indicate that sporadic and familial MS share a common genetic susceptibility. In addition, preliminary calculations suggest that the MHC explains between 17 and 62% of the genetic etiology of MS. This heterogeneity is also supported by the minority of families showing no linkage or association with loci within the MHC.      

Neurotoxic, hemorrhagic and proteolytic activities of Duvernoy's gland secretion from Venezuelan opisthoglyphous colubrid snakes in mice

Many colubrid snakes produce toxic oral secretions. We studied venom (Duvernoy's gland secretion) collected from Venezuelan opisthoglyphous (rear-fanged) colubrid snakes. Different proteins were present in Thamnodynastes stigilis Duvernoy's gland secretion and were characterized by 20% SDS-PAGE protein electrophoresis. The venom displayed proteolytic (gelatinase) activity that was partially purified on a chromatography ionic exchange mono Q2 column. We demonstrated hemorrhagic activity of Thamnodynastes stigilis Duvernoy's gland secretion on chicken embryos and mouse skin and peritoneum. Mice inoculated with Thamnodynastes stigilis Duvernoy's gland secretion presented signs of neurotoxicity. Thamnodynastes stigilis Duvernoy's gland secretion had proteolytic, hemorrhagic, and neurotoxic activities, not previously described in this species and identifies the presence of a new venomous colubrid in Venezuela.     

The inferior alveolar artery in its bony course

Based on the dissection of 30 hemi-mandibles, the authors report a study of the inferior alveolar artery in its intraosseous course. On morphologic considerations they propose a classification of the collaterals into two groups: the principal collaterals destined for the teeth and the bony alveolar tissue and the secondary collaterals destined for the sheath and the nerve as well as the bony tissue around the canal. Loss of the teeth and absorption of the alveolar bone modify the caliber of the inferior alveolar arterial axis, the distribution of its collaterals and possibly its mode of termination. These facts suggest a consideration of the vascularization of the mandible in terms of four sectors. They arrive at practical conclusions that may be drawn from this study in stomatology.     

Interobserver variation in the interpretation of abdominal radiographs

A total of 140 sets of abdominal radiographs were reviewed independently by four qualified diagnostic radiologists. The degree of interobserver agreement was determined by calculating kappa values for 19 commonly used radiographic signs and diagnoses. There was fair to excellent interobserver agreement for 11 signs and diagnoses and poor agreement for the remaining eight. The signs and diagnoses for which agreement is poor cannot be considered reliable and include particularly large bowel obstruction and nonspecific gas pattern.     

Effect of intersection spacing on MR image contrast and study time

The effects of section separation on image contrast and calculated T1 relaxation times were investigated in healthy volunteers and a phantom using an early commercial version magnetic resonance imaging system. The effects are explained qualitatively on the basis of side lobes of excitation occurring outside the selected section resulting in reduction of the time permitted for T1 relaxation. The options for dealing with imperfect section selection, including separation of the sections (i.e., leaving gaps) and nonsequential excitation, are illustrated and the trade-offs involved in each explained.     

Oligosaccharide sulfate inhibitors of selectin-sugar interactions in inflammatory processes]

Leucocyte migration into lymphatic tissues or inflammatory sites depends upon the expression of adhesion molecules. Among these molecules, the selectins expressed on endothelial cells (E- and P-selectins) and leucocytes (L-selectin) recognize carbohydrate ligands such as sialyl Lewis A or sialyl Lewis X oligosaccharides due to the same positioning of NeuAc, Gal and Fuc residues in both isomeric structures. We have shown that the sialic acid residue could be replaced by a sulfate group such as in the sulfated Lewis A pentasaccharide, one of the most potent monovalent ligand for human E-selectin, which was shown to be very active in the prevention of ischemia reperfusion lung injury. In the same way, we have prepared through chemoenzymatic syntheses, two disulfated Lewis X pentasaccharides, the sulfated analogs of carbohydrate ligands found on GLYCAM 1, the natural receptor of L-selectin. Finally, based on the double recognition of L-selectin with Lewis type and glycosaminoglycan structures, we tentatively introduced a possible link between the selectin- and the integrin-mediated lymphocyte adhesion systems.     

Perforation of the inferior vena cava with aortic and vertebral penetration by a suprarenal Greenfield filter

Various complications have been reported after insertion of the Greenfield filter. This report describes an unusual complication after suprarenal placement of this filter: spreading of the filter struts, with perforation of the inferior vena cava, and penetration of the aorta and a vertebral body, followed by fracture of one of the struts.