Passive transfer of resistance to frambesial infection in hamsters.

The immune mechanism by which hamsters acquire resistance to infection with Treponema pertenue, the causative agent of frambesia, or yaws, has not been elucidated. Serum or cells (spleen or lymph node) obtained from hamsters resistant to frambesial infection were transferred to normal syngenic recipients, who are subsequently infected with T. pertenue. The following parameters were used to measure the ability of immune serum of cells to confer resistance on recipient hamsters to frambesial infection: inhibition of the development of cutaneous lesions, decreased weight, and number of treponemes in the inguinal lymph nodes. This investigation demonstrated that immune serum conferred protection on recipient hamsters infected with T. pertenue. Discontinuation of the administration of immune serum (18 days after frambesial infection) did not result in the development of cutaneous lesions. Since the inguinal lymph nodes contained a sizeable number of treponemes (2.6 X 10(5)), immune serum failed to prevent frambesial infection. Recipients of immune spleen or lymph node cells initially developed frambesial lesions 9 days after infection. The frambesial lesions began to resolve 12 to 14 days after infection and by day 21 had completely regressed. These results illustrated that humoral factors and cells are involved in resistance of the hamster to frambesial infection.     

Immune complex glomerulonephritis in mice infected with Escherichia coli.

C57Bl/6 mice were injected intraperitoneally with 10(8) to 2 x 10(8) living K 38 Escherichia coli (E. coli) and serological changes and kidney involvement were studied. E. coli were found in the blood 45 min to 24 hr after injection. In serum, large amounts of deoxyribonucleic acid (DNA) were present 24 hr after E. coli injection, and thereafter disappeared. Seven days after infection, antibodies directed against E. coli, anti-DNA antibodies and C1q-binding substances were found in serum and the kinetics of the variations of these parameters were studied until day 35. Kidney lesions were evaluated immunochemically and by optical and electron microscopy. In the glomeruli, heavy granular deposits of IgG and IgM were constantly found in mesangium and along capillary walls. In most kidneys slight granular deposits of IgG and IgM were also found in the tubules. Histological studies revealed in the glomeruli mild endocapillary cell proliferation, focal thickening of glomerular basement membrane and dense deposits in mesangial and subendothelial areas and inside the glomerular basement membrane; in the tubules dense deposits were focally observed inside the tubular basement membrane.     

Autoantibodies directed against the amino-terminal domain I of human calpastatin (ACAST-DI Ab) in connective tissue diseases. High levels of ACAST-DI Ab are associated with vasculitis in lupus

To identify new autoantibody populations in patients with rheumatic diseases, a cDNA expression library was immunoscreened with a rheumatoid arthritis (RA) patient's serum which contains autoantibodies binding to uncharacterized polypeptides by Western-blotting. One clone encoding the amino-terminal region (Nt) [domain L and half of domain I] of human calpastatin was selected. Different fragments of the selected cDNA were prepared and the corresponding recombinant polypeptides were produced by in vitro translation and analysed by Western blotting. Most RA sera bound to recombinant amino-terminal region and domain I but not to domain L. This prompted us to use a recombinant polypeptide corresponding to the domain I of calpastatin as the antigen in a solid-phase ELISA to test sera from patients with various systemic rheumatic diseases and healthy controls.Anti-calpastatin domain I antibodies (ACAST-DI Ab), were detected by ELISA in RA, systemic lupus erythematosus (SLE), Sj?gren's syndrome and control sera at respective frequencies of 10, 9, 0 and 1%. These Ab did not have prognostic value in early RA; high levels were significantly associated with vasculitis in SLE. Antibodies reacting with the calpastatin amino-terminal region are produced during systemic rheumatic diseases and are predominantly directed against domain I. High levels of these Ab may constitute a marker of vasculitis in SLE.     

Identification of 6 new mutations in the iduronate sulfatase gene. Mutation in brief no. 233. Online

Mucopolysaccharidosis type II (Hunter syndrome) is an X-linked lysosomal storage disorder caused by a deficiency of the enzyme iduronate-2-sulfatase. We sequenced genomic DNA and RT-PCR products in the iduronate sulfatase (IDS) gene in 6 unrelated patients with Hunter syndrome to assess genotype/phenotype relationships and offer carrier testing where required. Six novel mutations were identified: four missense mutations, one four-base pair deletion (596-599delAACA) and a cryptic splice site mutation. Three of the missense mutations were significant amino acid substitutions (S143F, S491F, E341K) of which the latter two involve amino acids conserved amongst sulfatase enzymes. The patients identified with these mutations all had a severe clinical phenotype. One missense mutation with a minimal amino acid substitution (H342Y), in a non-conserved region of the gene, was associated with a mild clinical phenotype. We identified a novel cryptic splice site (IVS5+934G>A) with some normal (wild type) mRNA processing. We predict that the normal mRNA product confered some residual functional enzyme, resulting in a mild phenotype associated with the absence of overt central nervous system disease.     

Genotype and phenotype correlation in 103 individuals with 2q37 deletion syndrome reveals incomplete penetrance and supports HDAC4 as the primary genetic contributor

The 2q37 deletion syndrome, also described in the literature as brachydactyly‐mental retardation syndrome (MIM 600430), is caused by deletion or haploinsufficiency of the HDAC4 gene, which encodes the histone deacetylase 4 protein. Although the most commonly described hallmark features of the 2q37 deletion syndrome include brachydactyly type E, developmental delay, obesity, autistic features, and craniofacial or skeletal dysmorphism, a literature review of 101 published cases plus two newly reported individuals indicates that there is a high degree of variability in the presence of some of the features that are considered the most characteristic of the syndrome: overweight and obesity (34%), cognitive‐behavioral issues (79%), dysmorphic craniofacial features (86%), and type E brachydactyly (48%). These features overlap with other neurodevelopmental conditions, including Smith‐Magenis syndrome (SMS), and may be incompletely penetrant or demonstrate variable expressivity, depending on the specific chromosomal anomaly. With the advent of fluorescence in situ hybridization (FISH), array‐based comparative genomic hybridization, and next‐generation DNA sequencing, more detailed molecular diagnoses are possible than in years past, enabling refined characterization of the genotype–phenotype correlation for subjects with 2q37 deletions. In addition, investigations into molecular and gene expression networks are expanding in neurodevelopmental conditions, and we surveyed HDAC4 downstream gene expression by quantitative real‐time polymerase chain reaction, further implicating HDAC4 in its role in the regulation of RAI1. Correlation of clinical data defining the impact on downstream gene expression and the potential clinical associations across neurodevelopment will improve our understanding of these complex conditions and potentially lead to common therapeutic approaches.     

Méthodologie de programmation des investissements biomédicaux

Sur l'initiative de la Direction et de l'ingénieur biomédical, une première évaluation des pratiques de programmation a été conduite au sein du centre hospitalo-universitaire de Nîmes avec l'ensemble des acteurs concernés. L'autoévaluation se poursuit avec l'inclusion de cinq CHU de référence. Les pratiques observées permettent l'élaboration d'un questionnaire. Le questionnaire est structuré selon les phases traditionnelles du processus de programmation : état de connaissance du patrimoine ; recueil des besoins ; analyse ; décision ; réalisation du programme. Par phases, plusieurs questions fermées explorent les variables. Trente établissements sont inclus. Les résultats de l'enquête et les données initialement collectées dressent un panorama des pratiques de programmation des investissements biomédicaux en établissements de soins publics. Le résultat obtenu semble être la première étape de l'élaboration d'un référentiel professionnel. L'ensemble a permis d'étayer une refonte concrète de nos pratiques de programmation.With the initiative of the top management and the biomedical engineer, the first-assessment of the biomedical pratical programmation of the Nîmes University Hospital Center (CHU), has been led by representatives of different departments of the center. The auditing has been done with five members of the Nîmes University Hospital Center (CHU). The practices that observed have helped to create a survey. This survey is structured according to the usual steps of a programmation: statement of properties, collection of needs, analysis, decision, and realisation of the programmation. By groups, several closed questions process the variables. Thirty establishments are taken into account. The results of the study and data initially collected show an array of the practises used for the programming of the biomedical investments into public healthcare establishments. The obtained result seems to be the first stage of the elaboration of a professional reference. The whole has enabled to support a change in the uses of the Nîmes University Hospital Centre (CHU).     

静电法制备小微囊包裹成年猪胰岛的实验研究

目的　探索用静电法制备小微囊包裹成年猪胰岛细胞。方法　用自制的静电微囊发生装置、制备海藻酸钠 -多聚赖氨酸 -海藻酸钠 (APA)微囊 (微囊直径 <35 0 μm) ,包裹成年猪胰岛 ,体外检测APA小微囊猪胰岛生物活性及微囊膜的通透性 .结果　静电法制备的APA微囊直径 30 0～ 35 0 μm ,大小相对均一 .小微囊包裹成年猪胰岛后 ,每个微囊内可见 1～ 2个胰岛团 ,表面光滑 .囊内胰岛组织学结构完整 ,体外培养微囊化胰岛素分泌良好 ,葡萄糖刺激释放明显 ,显示了良好的细胞活力及微囊膜通透性 .结论　用我们自制的静电微囊发生装置能制备APA微囊包裹成年猪胰岛细胞 ,微囊直径 30 0～ 35 0 μm ,表面光滑 ,囊内猪胰岛生物活性良好     

Papillary fibroelastoma: a cardiac tumor rarely reported in children

Papillary fibroelastoma is a seldom reported tumour. It usually occurs in adults and develops on the aortic and mitral valves. It is not different of giant Lambl excrescences and differential diagnostic can be difficult with the myxoma. Its systematic surgical ablation is justified by the important risk of embolic complications. It has rarely been reported in children. We report a case peculiar by fortuitous diagnostic, tricuspid site, large size and occurrence in a 3-year old child.     

Dominant carpotarsal osteochondromatosis.

Dominant carpotarsal osteochondromatosis is a particular disorder of the wrist and tibiotalar joints with abnormal bone proliferation and osteochondromas. Two patients, a mother and son, are described here; a similar condition has previously been described in seven affected members of a family. The upper and the lower limbs are affected in the same patient and the lesion can be bilateral. Autosomal dominant inheritance is a further criterion allowing the diagnosis of dysplasia epiphysealis hemimelica.     

Activation induces apoptosis in Herpesvirus saimiri-transformed T cells independent of CD95 (Fas,APO-1)

Signaling via the T cell receptor (TCR)/CD3 complex of pre-activated T cells induces apoptosis. Such an activation-induced cell death (AICD) is thought to play an important role in the regulation of cellular immune responses. In this study we analyzed pathways of AICD by using human T cells transformed by Herpesvirus saimiri. These growth-transformed T cells show the phenotype of activated mature T cells and continue to express a functionally intact TCR. We show that human H. saimiri-transformed T cell clones readily undergo cell death upon signaling via the TCR/CD3 complex or via phorbol 12-myristate 13-acetate (PMA) + ionomycin. The AICD in H. saimiri-transformed T cells was detectable a few hours after activation and it was not affected by the presence of interleukin (IL)-2 or by anti-CD4 cross-linking. However, AICD required tyrosine phosphorylation, since it could be blocked by herbimycin A. Cyclosporin A (CsA) did not block the development of AICD, but other consequences of activation in H. saimiri-transformed T cells like the production of interferon-γ. Surprisingly, the development of AICD was not reduced by neutralizing antibodies to tumor necrosis factor (TNF)-α or blocking antibodies directed to CD95 (Fas, APO-1), although H. saimiri-transformed T cells were sensitive to CD95 ligation. To confirm that this form of AICD is really independent of CD95, we have established an H. saimiri-transformed T cell line from a patient with a homozygous deletion in the CD95 gene. This CD95-deficient T cell line was as sensitive to AICD as other CD95-expressing H. saimiri-transformed T cells. In conclusion, we describe here a type of AICD in H. saimiri-transformed T cells that is independent of CD95 and TNF-α, not sensitive to CsA, but requires tyrosine phosphorylation. This system should be useful for the investigation of CD95-independent forms of AICD.