Differences in t cell receptor restriction fragment length polymorphisms in patients with rheumatoid arthritis

Objective. The purpose of this study was to determine whether a T cell receptor (TCR) polymorphism, either by itself or in combination with particular HLA polymorphism, leads to susceptibility to rheumatoid arthritis (RA). Methods. Eight restriction fragment length polymorphisms (RFLPs) detected with TCR gene segments were investigated in 46 individuals with RA and were compared with data from normal control subjects. Results. A statistically significant difference in the genotype frequencies of a Taq I RFLP detected with the TCRα constant region (C_α) gene was noted. In addition, when the DR4+ subpopulations were examined, the allelic frequency of a 2-kb Bam HI fragment detected with a V_β8 gene was increased in the samples from RA patients (P < 0.0086). Conclusion. The results of this study suggest that germline differences in the TCR repertoire may be associated with RA, and that there is a contributory effect of DR4+ haplotypes with certain TCR haplotypes in susceptibility to RA.     

Investigation of outbreak cases infected with the SARS-CoV-2 B.1.640 variant in a fully vaccinated elderly population,Normandy, France,November to December 2021

Three confirmed infections with the SARS-CoV-2 B.1.640 variant under monitoring were reported in Normandy, north-western France in late November 2021. Investigations led to the identification of two events linked to the same cluster. A total of 75 confirmed and probable B.1.640 cases were reported. All had completed the primary vaccination series. Sixty-two cases were older than 65 years. Fifty-six cases had symptoms and four were hospitalised. This investigation provides preliminary results concerning a variant with limited information currently available.     

Reduced incidence and severity of collagen-induced arthritis in interleukin-12-deficient mice

Collagen-induced arthritis (CIA) is an animal model for rheumatoid arthritis. The disease is elicited by immunization of genetically susceptible DBA/1 mice with type II collagen, resulting in a debilitating arthritis characterized by inflammation and involvement of multiple joints. We investigated the role of endogenous interleukin (IL)-12 in the pathogenesis of this disease by undertaking an analysis of IL-12-deficient mice on the DBA/1 genetic background after immunization with type II collagen. Both the incidence and severity of disease were significantly reduced in mice unable to produce biologically active IL-12. Concomitant decreases were observed in serum levels of pathogenic, collagen-specific IgG2a antibodies and collagen-induced secretion of interferon-γ by immune splenocytes in vitro, consistent with an impaired T helper-1 response. There were, however, a few animals which developed severe disease in a single paw in spite of this highly diminished Th1 response. Taken together, these results demonstrate an important role for IL-12 in the pathogenesis of CIA, although it is not absolutely required for disease development.     

Homogenization of regional river dynamics by dams and global biodiversity implications

Global biodiversity in river and riparian ecosystems is generated and maintained by geographic variation in stream processes and fluvial disturbance regimes, which largely reflect regional differences in climate and geology. Extensive construction of dams by humans has greatly dampened the seasonal and interannual streamflow variability of rivers, thereby altering natural dynamics in ecologically important flows on continental to global scales. The cumulative effects of modification to regional-scale environmental templates caused by dams is largely unexplored but of critical conservation importance. Here, we use 186 long-term streamflow records on intermediate-sized rivers across the continental United States to show that dams have homogenized the flow regimes on third- through seventh-order rivers in 16 historically distinctive hydrologic regions over the course of the 20th century. This regional homogenization occurs chiefly through modification of the magnitude and timing of ecologically critical high and low flows. For 317 undammed reference rivers, no evidence for homogenization was found, despite documented changes in regional precipitation over this period. With an estimated average density of one dam every 48 km of third- through seventh-order river channel in the United States, dams arguably have a continental scale effect of homogenizing regionally distinct environmental templates, thereby creating conditions that favor the spread of cosmopolitan, nonindigenous species at the expense of locally adapted native biota. Quantitative analyses such as ours provide the basis for conservation and management actions aimed at restoring and maintaining native biodiversity and ecosystem function and resilience for regionally distinct ecosystems at continental to global scales.     

A broad spectrum of clinical presentations in congenital disorders of glycosylation I: a series of 26 cases

INTRODUCTION—Congenital disorders of glycosylation (CDG), or carbohydrate deficient glycoprotein syndromes, form a new group of multisystem disorders characterised by defective glycoprotein biosynthesis, ascribed to various biochemical mechanisms.
METHODS—We report the clinical, biological, and molecular analysis of 26 CDG I patients, including 20 CDG Ia, two CDG Ib, one CDG Ic, and three CDG Ix, detected by western blotting and isoelectric focusing of serum transferrin.
RESULTS—Based on the clinical features, CDG Ia could be split into two subtypes: a neurological form with psychomotor retardation, strabismus, cerebellar hypoplasia, and retinitis pigmentosa (n=11), and a multivisceral form with neurological and extraneurological manifestations including liver, cardiac, renal, or gastrointestinal involvement (n=9). Interestingly, dysmorphic features, inverted nipples, cerebellar hypoplasia, and abnormal subcutaneous fat distribution were not consistently observed in CDG Ia. By contrast, the two CDG Ib patients had severe liver disease, enteropathy, and hyperinsulinaemic hypoglycaemia but no neurological involvement. Finally, the CDG Ic patient and one of the CDG Ix patients had psychomotor retardation and seizures. The other CDG Ix patients had severe proximal tubulopathy, bilateral cataract, and white matter abnormalities (one patient), or multiorgan failure and multiple birth defects (one patient).
CONCLUSIONS—Owing to the remarkable clinical variability of CDG, this novel disease probably remains largely underdiagnosed. The successful treatment of CDG Ib patients with oral mannose emphasises the paramount importance of early diagnosis of PMI deficiency.


Keywords: CDG; phosphomannomutase; phosphomannose isomerase; dolichyl-phosphate glucose:mannose 9 N-acetylglycosamine 2 glucosyltransferase