Parents' Views about Special Provision for their Child with Severe or Profound and Multiple Learning Difficulties

This paper reports on the findings of a research study, conducted via a postal questionnaire, which aimed to elicit the wishes, needs and satisfaction with special educational provision of parents of children with severe or profound and multiple learning difficulties. Parents' views regarding services received, type of housing and employment preferred for their child, present and future concerns are also reported. The results indicated that the majority of parents in the sample are generally satisfied with their child's current special school placement and do not want a change of placement. However, one in five parents did indicate a desire for a change of placement, with the preferred option being a special class in an ordinary school. A priority for their child's learning is communication skills. A desire for a high level of involvement in their child's education was indicated but, on the whole, parents did not achieve as high a level as they would wish. Parents were generally satisfied with services received but a significant proportion expressed a desire for additional services. In terms of the future, the majority of parents expect that their child is unlikely to live or work independently or semi-independently as an adult. The paper concludes by discussing ways of enhancing parents' involvement in the decision-making process regarding special provision for their child.     

人类精浆免疫抑制因子的研究——Ⅰ.分离和免疫活性测定

本文介绍了人类精浆免疫抑制因子分离及免疫活性测定的全过程。通过低温高速离心,SephadexG-100凝胶过滤,DEAE离子交换层析等步骤从人精浆中分离出两种免疫抑制因子——DF_1和DF_2。DF_2达到聚丙烯酰胺凝胶电泳纯,呈单一蛋白带,DF_1呈二条蛋白带。二者对PHA诱导的人外周血淋巴细胞转化和人外周血NK细胞活性均有抑制作用。100μg/ml培养液的DF_1和DF_2对PHA诱导的淋转抑制率分别为41.7%和68.2%;对NK细胞活性的抑制率分别为30.4%和81.5%。在PHA诱导的淋转中同时加入DF_1和DF_2,抑制率为80.7%。比较不同浓度的DF_1,DF_2对PHA诱导的淋转抑制作用结果表明:100μg/ml具有相对高的抑制活性。不同浓度的DF_2对NK活性抑制作用也表现出类似结果。     

Control of lymphocyte migration into brain: selective interactions of lymphocyte subpopulations with brain endothelium.

The protein antigens conalbumin (CA) and ovalbumin (OVA) are known to require uptake into antigen-presenting cells (APC) for their presentation to major histocompatibility complex (MHC) class II-restricted T cells. In both cases proteolytic cleavage is thought to be a necessary step for the generation of the respective antigenic peptides. A specific inhibitor of the endosomal protease cathepsin B, Cbz-Phe-Ala-CHN2, blocks the presentation of both CA and OVA, whereas this inhibitor has no effect on the presentation of a processing-independent OVA peptide. Furthermore, the presentation of insulin, an antigen that needs processing but no proteolytic cleavage, is enhanced when cathepsin B is inhibited during antigen pulsing. When the APC were treated with an inhibitor of acid proteases, the CA response was not affected, while the presentation of OVA was diminished under these conditions. To estimate the relevance of these findings for the generation of the antigenic CA peptide, extracellular digestions of CA by cathepsin B were carried out. The fragment(s) present in these digests was recognized by T cells without further processing. Furthermore, the time-course of intra- and extracellular CA processing with respect to the capacity to stimulate T cells was similar. Taken together these data suggest that degradation by cathepsin B may be sufficient in vivo to generate the antigenic CA fragment. On the other hand, the blocking of cathepsin B does not appear to have an adverse effect on the general mechanisms of antigen presentation.     

Anti-phospholipid antibodies in syphilis and a thrombotic subset of SLE: distinct profiles of epitope specificity.

In a study of connective tissue and infectious disease sera, we have demonstrated IgM and IgG anti-cardiolipin activity, in a solid phase radioimmunoassay, in systemic lupus erythematosus (SLE), rheumatoid arthritis, syphilis and in acute malaria caused by four different species of Plasmodium. The highest values were noted in SLE (IgM anti-cardiolipin P less than 0.005, IgG anti-cardiolipin P less than 0.01), but there was no correlation with anti-dsDNA, rheumatoid factor or VDRL titres in any disease group. Anti-cardiolipin binding was significantly associated with the lupus anticoagulant, thrombocytopenia, spontaneous abortions and thromboses in the SLE patients. Ten SLE sera from this thrombotic subset and 10 syphilitic sera with similar anti-cardiolipin activity, were tested against four phospholipid antigens and showed significantly different anti-phosphatidyl ethanolamine/anti-phosphatidyl serine binding ratios (P less than 0.001). These differences in phospholipid epitope specificity could explain the specificity of the VDRL antigen in syphilis serology, and we discuss a putative role for anti-phosphatidyl serine in the thrombotic diathesis of SLE.     

Delineation of an estimated 6.7 MB candidate interval for an anophthalmia gene at 3q26.33-q28 and description of the syndrome associated with visible chromosome deletions of this region

Anophthalmia or microphthalmia occur in approximately one in 10 children who have severe visual impairment. These eye malformations are often of unknown aetiology, but can be inherited in autosomal dominant, recessive or X-linked forms, and can also occur in association with specific chromosome abnormalities. Four children are described in the medical literature with microphthalmia or anophthalmia in association with chromosome rearrangements involving distal 3q, suggesting the presence of a micro/anophthalmia gene in this region. We have identified two further patients with micro/anophthalmia and chromosome rearrangements involving 3q26-->3q27 and identified a 6.7 MB common deleted region. Patient 1 had multiple abnormalities including bilateral anophthalmia, abnormalities of the first and second cranial nerves and partial absence of the corpus callosum. His karyotype was 46,XY,del(3)(q26.33q28). Patient 2 had right anophthalmia and left extreme microphthalmia. Her karyotype was 46,XX,del(3)(q26.33q28)t(3;7)(q28;q21.1). Both patients had intrauterine growth retardation (IUGR) and strikingly similar dysmorphic facies consisting of bossed forehead, downward-slanting palpebral fissures, grooved bridge of the nose, prominent low-set ears, small down-turned mouth and small mandible. We identified BAC clones mapping to distal 3q from the ENSEMBL and NCBI Entrez databases. These BAC clones were used as fluorescence in situ hybridisation (FISH) probes to identify the minimum deleted region common to both patients. This interval, between clones RPC11-134F2 and RPC11-132N15, was estimated to be 6.7 MB. We conclude that there is an anophthalmia locus within this interval. Candidate genes mapping to this region include Chordin and DVL3, a homologue of the Drosophila Dishevelled gene.     

Chemokine transport across human vascular endothelial cells.

Leukocyte migration across vascular endothelium is mediated by chemokines that are either synthesized by the endothelium or transferred across the endothelium from the tissue. The mechanism of transfer of two chemokines, CXCL10 (interferon gamma-inducible protein [IP]-10) and CCL2 (macrophage chemotactic protein [MCP]-1), was compared across dermal and lung microvessel endothelium and saphenous vein endothelium. The rate of transfer depended on both the type of endothelium and the chemokine. The permeability coefficient (Pe) for CCL2 movement across saphenous vein was twice the value for dermal endothelium and four times that for lung endothelium. In contrast, the Pe value for CXCL10 was lower for saphenous vein endothelium than the other endothelia. The differences in transfer rate between endothelia was not related to variation in paracellular permeability using a paracellular tracer, inulin, and immunoelectron microscopy showed that CXCL10 was transferred from the basal membrane in a vesicular compartment, before distribution to the apical membrane. Although all three endothelia expressed high levels of the receptor for CXCL10 (CXCR3), the transfer was not readily saturable and did not appear to be receptor dependent. After 30 min, the chemokine started to be reinternalized from the apical membrane in clathrin-coated vesicles. The data suggest a model for chemokine transcytosis, with a separate pathway for clearance of the apical surface.     

Genomic instability in scleroderma

Scleroderma is an enigmatic rheumatic disorder of uncertain etio-pathogenesis. Cancer has an approximately two-fold higher incidence in scleroderma patients than in the general population. There are preliminary data of acquired genetic damage in scleroderma but the significance of these observations are uncertain. To determine somatic mutation frequency at the glycophorin-A (GPA) locus in patients with limited and diffuse cutaneous scleroderma. The GPA assay measures the total somatic mutation frequency (Vf), composed of gene inactivating mutations (NO) and mutations arising from mitotic recombination (NN) in individuals heterozygous for the GPA MN blood group. Mutation frequency was determined using a validated GPA flow cytometric assay using fluorescent labeled monoclonal antibodies specific for the GPA blood groups M and N. This assay detects and enumerates progeny of red blood cell (rbc) precursor cells which have acquired genetic damage resulting in a loss of expression of one of the GPA alleles. It was found that patients with scleroderma (n = 23) had significantly elevated Vf as compared with young healthy controls (p < 0.001) and elderly controls (p = 0.03). Patients with diffuse scleroderma had higher mean Vf as compared with limited scleroderma (p = 0.055). In comparison with controls, patients with scleroderma exhibit a higher proportion of mitotic recombinant mutations than inactivating mutations (p < 0.002). There was no correlation between Vf and disease duration, age at onset or autoantibody status. We have documented evidence of acquired genetic damage at the GPA locus in scleroderma. Evidence of acquired genetic damage in this disorder may be importance in explaining both the etio-pathogenesis of scleroderma and the association of scleroderma with cancer.