HLA-DPB1 gene polymorphism and multiple sclerosis: a large case-control study in the southwest of France

The polymorphism at the HLA-DPB1 locus has been characterized in a large number of patients with multiple sclerosis (n = 112) and in healthy controls (n = 115). Both patients and controls lived in the southwest of France (in the Pyrénées Atlantiques) and had similar ethnic background. The typing procedure involved the selective amplification of the second exon of the DPB1 locus by polymerase chain reaction, followed by hybridization of the amplified DNA with 14 sequence-specific oligonucleotide probes. Individual alleles were identified by the pattern of hybridization of the different probes. The distribution of the DPB1 alleles was not significantly different in multiple sclerosis patients and controls (p = 0.11). This does not corroborate the reported association of multiple sclerosis with the primed lymphocyte typing (PLT)-defined DPw4 specificity and is not in favour of a role played by polymorphic residues of the DP molecule in susceptibility to multiple sclerosis.     

Three highly polymorphic microsatellites at the human myelin oligodendrocyte glycoprotein locus, 100 kb telomeric to HLA-F : Characterization and relation to HLA haplotypes

The MOG locus, located on chromosomal bands 6p21.3-p22 and mapped about 100 kb telomeric to HLA-F, was isolated from cosmid ICRFcl09A2434 and shown to contain three microsatellites. These CA-repeat polymorphic markers were characterized in a sample of 173 healthy unrelated individuals and 84 DNAs from the HLA Workshop reference panel, by a method combining fluorescence labeling of PCR products and use of an automated DNA sequencer. For the three markers, frequencies of heterozygotes are well predicted from allele frequencies by the Hardy—Weinberg rule, which suggests that problems of allele nonamplification are unlikely. Typing of cell lines homozygous in the HLA region allowed unambiguous definition of 81 HLA-MOG haplotypes and showed that several HLA ancestral haplotypes extended to the MOG region. The high degree of polymorphism (59%, 51%, and 81% at the three loci, respectively, and 87% at the haplotype level) makes these new markers informative for association or linkage studies with diseases such as hemochromatosis or multiple sclerosis, and for studies aimed at precisely delineating the site of crossover in chromosomes in which recombination occurred in the distal part of the HLA class I region.     

Neurectodermal differentiation of extraskeletal myxoid chondrosarcoma: a classical feature?

Extraskeletal myxoid chondrosarcoma (EMC) is a phenotypically and genotypically distinct entity with a protracted course. A documented case of an extraskeletal myxoid chondrosarcoma characterized by a t(9; 17) (q22; q11) translocation with a neuroendocrine and neural differentiation is reported.     

Recombination pattern of the TCR γ locus in human peripheral T-cell lymphomas

The recombination events of the γ and β T-cell receptor (TCR) loci were analysed in a series of 39 peripheral T-cell lymphomas (PTCLs) in association with the expression of TCR chains. In TCR αβ PTCLs, 22/23 cases showed a γ-gene rearrangement while only 18/23 showed a concomitant β-gene rearrangement. The germline configuration of the β locus was found in angioimmunoblastic lymphadenopathy and lymphoepithelioid lymphomas. Three γδ PTCLs rearranged both γ and β genes. TCR silent PTCLs showed three different patterns of γ- and β-gene rearrangements. Three cases were in germline configuration for both loci; five cases had a rearranged γ and a germline β locus; and five cases had the two loci rearranged. Regarding the variable genes in the γ-rearranged alleles, members of the VγI subgroup were the most frequently presented (39/50), followed by VγII, VγIII, and VγIV (9/50, 1/50, and 1/50, respectively). Joining segment usage was as follows: J1 or J2 (32/50), JP1 or JP2 (17/50), and JP (1/50). Taken together, these data demonstrate that the γ locus is more frequently rearranged whatever the TCR expression. The γ-locus analysis provides a better diagnostic yield than the β locus in the study of PTCL clonality.     

Mycoplasma pneumoniae-associated nephritis in children

 Mycoplasma pneumoniae infection is a rare cause of acute nephritis. Six children (2 girls) aged 5–10 years, admitted for nephritis, had serological tests showing recent Mycoplasma pneumoniae infection. The diagnosis of Mycoplasma pneumoniae infection was based on the presence of serum IgM, detected either by immunofluorescence (IF) (n=1) or enzyme-linked immunosorbent assay (n=5). Four children had a renal biospy, with analysis of parenchymal Mycoplasma pneumoniae components by indirect IF and polymerase chain reaction. Extrarenal symptoms were: respiratory (n=3), ear, nose, and throat (n=2), gastrointestinal (n=3), hepatic (n=1), neurological (n=1), articular (n=1), and hematological (n=3). The patients presented with acute nephritis (1 had a nephrotic syndrome) or with acute renal failure and proteinuria. Pathological findings included type 1 membranoproliferative glomerulonephritis (MPGN, n=1), proliferative endocapillary glomerulonephritis (n=2), and minimal change disease (n=1). The patient with type 1 MPGN progressed rapidly towards end-stage renal failure because of a congenital solitary kidney. Among the patients with endocapillary glomerulonephritis, 1 relapsed 6 months later and remained proteinuric, while the other recovered, as did the child with minimal change disease. The search for Mycoplasma pneumoniae antigens and nucleic acids in renal tissue was negative. However, the absence of the microorganism in the kidney is a common feature of post-streptococcal glomerulonephritis. We conclude that Mycoplasma pneumoniae is a rare yet potential cause of acute glomerulonephritis. Received: 13 September 1996 / Revised: 16 June 1998 / Accepted: 18 June 1998     

Contralateral spondylolysis and fracture of the lumbar pedicle in an elite female gymnast: a case report

STUDY DESIGN: The case of an elite female gymnast whose pathology started in her 12th year and whose evolution has been exceptional is reported. OBJECTIVE: To present a fracture of the right lumbar pedicle showing complete spontaneous consolidation despite gymnastic practice 15 hours a week. SUMMARY OF BACKGROUND DATA: Lumbar pain, which has an incidence of approximately 75% among young athletes, often results from diseases of the posterior arch of vertebrae in gymnasts, including spondylolysis. The association between unilateral spondylolysis and fracture of the contralateral lumbar pedicle in young athletes is poorly described. METHODS: An elite young female gymnast underwent clinical examination and lumbar radiographs (as systematically required by the French Federation for high-level gymnasts) from 1994 to 1997 to join a sports program in gymnastics. RESULTS: Clinical examination and lumbar radiographs systematically required of an asymptomatic female gymnast allowed the condensation of the right pedicle to be observed before lysis of the left isthmus of L5 in 1994, unilateral lysis of the left isthmus of L5 in 1995, a right pedicular fracture of L5 in 1996, and healing of the pedicular fracture in 1997. CONCLUSION: Inconsistency between radiographs and clinical observations can be noted, and spontaneous consolidation of pedicular fractures can occur despite the practice of the gymnastics 15 hours a week.     

Induction of activin B by inflammatory stimuli up-regulates expression of the iron-regulatory peptide hepcidin through Smad1/5/8 signaling

Anemia is very common in patients suffering from infections or chronic inflammation and can add substantially to the morbidity of the underlying disease. It is mediated by excessive production of the iron-regulatory peptide hepcidin, but the signaling pathway responsible for hepcidin up-regulation in the inflammatory context is still not understood completely. In the present study, we show that activin B has an unexpected but crucial role in the induction of hepcidin by inflammation. There is a dramatic induction of Inhbb mRNA, encoding the activin β(B)-subunit, in the livers of mice challenged with lipopolysaccharide, slightly preceding an increase in Smad1/5/8 phosphorylation and Hamp mRNA. Activin B also induces Smad1/5/8 phosphorylation in human hepatoma-derived cells and, synergistically with IL-6 and STAT-3 signaling, up-regulates hepcidin expression markedly, an observation confirmed in mouse primary hepatocytes. Pretreatment with a bone morphogenic protein type I receptor inhibitor showed that the effect of activin B on hepcidin expression is entirely attributable to its effect on bone morphogenetic protein signaling, most likely via activin receptor-like kinase 3. Activin B is therefore a novel and specific target for the treatment of anemia of inflammation.     

Research agenda for mass gatherings: a call to action

Public health research is essential for the development of effective policies and planning to address health security and risks associated with mass gatherings (MGs). Crucial research topics related to MGs and their effects on global health security are discussed in this review. The research agenda for MGs consists of a framework of five major public health research directions that address issues related to reducing the risk of public health emergencies during MGs; restricting the occurrence of non-communicable and communicable diseases; minimisation of the effect of public health events associated with MGs; optimisation of the medical services and treatment of diseases during MGs; and development and application of modern public health measures. Implementation of the proposed research topics would be expected to provide benefits over the medium to long term in planning for MGs.