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961.
A combination of a particular HLA-DP beta allele and an HLA-DQ heterodimer confers susceptibility to coeliac disease 总被引:5,自引:0,他引:5
Coeliac disease is an autoimmune disease of the intestinal mucosa, elicited by ingestion of wheat gluten in genetically susceptible individuals. Susceptibility to coeliac disease has been associated with the serologically defined variants DR3 and DR7 of the class II antigens encoded by the HLA-D region. Three related class II antigens, each consisting of an alpha and a beta glycoprotein chain, have been identified and are designated HLA-DR, HLA-DQ, and HLA-DP. These highly polymorphic transmembrane proteins bind peptides derived from the processing of foreign antigens and present them to T lymphocytes; they also influence the specificity of the mature T-cell repertoire. The role of HLA-DP polymorphism in susceptibility has not been as fully explored as that of the other class II antigens because of the complexity of the primed lymphocyte typing (PLT) method for determining DPw specificities. Here we use a new DNA-based method of HLA-DP typing to analyse the distribution of DP beta alleles in a group of coeliac disease patients and healthy controls. Two specific DP beta alleles (DPB4.2 and DPB3) are increased in the patient population. Comparison of the DP beta sequences suggests that the polymorphic residues at position 69 and at 56 and 57 may be critical in conferring susceptibility. Further, the contribution of the susceptible DP beta alleles appears to be independent of linkage to the previously reported DR3 and DR7 markers for coeliac disease. The distribution of DQ alpha and beta alleles in patients suggests that a specific DQ heterodimer may be responsible for the observed DR associations. Individuals with both this DQ antigen and a specific DP beta allele are at increased risk for coeliac disease. 相似文献
962.
Summary Peptidylarginine (protein-L-arginine) deiminase activities have been demonstrated in extracts of rat and mouse peritoneal macrophages, bone marrow cells, splenic adherent cells, neutrophils, and mouse monocyte/macrophage cell lines. The enzyme in these cells is indistinguishable from the skeletal muscle enzyme with respect to immunochemical properties. 相似文献
963.
M. D. Gershon M. Takaki H. Tamir T. Branchek 《Cellular and molecular life sciences : CMLS》1985,41(7):863-868
Summary An enteric neural receptor for serotonin (5-HT) has been characterized. This receptor was assayed, using3H-5-HT as a radiologand, by rapid filtration of isolated enteric membranes and by radioautography. In addition, intracellular recordings were made from ganglion cells of the myenteric plexus. High affinity, saturable, reversible, and specific binding of3H-5-HT was demonstrated both to membranes of the dissected longitudinal muscle with adherent myenteric plexus and the mucosa-submucosa. Radioautographs showed these3H-5-HT binding sites to be in myenteric ganglia and in a broad unresolved band at the mucosal-submucosal interface. Antagonists active at receptors for other neurotransmitters than 5-HT, at either of the two known types of CNS 5-HT receptor, and at 5-HT uptake sites on serotonergic neurons failed to inhibit binding of3H-5-HT. The structural requirements of analogues for binding to the enteric 5-HT receptor matched the known pharmacology of M or neural 5-HT receptors. A novel 5-HT antagonist was found. This compound, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide (5-HTP-DP), antagonized the action of 5-HT on type II/AH cells of the myenteric plexus but did not affect the release or actions of acetylcholine (nicotinic or muscarinic) or substance P. 5-HTP-DP was also an equally potent displacer of3H-5-HT from its binding sites on enteric membranes. It is concluded that the sites responsible for specific binding of3H-5-HT are enteric M or neural 5-HT receptors. These receptors differ from those now known to be present in the CNS. 相似文献
964.
T. Honda 《复旦学报(自然科学版)》2005,44(5):779-780
Naturally occurring Securinega alkaloids (1-4) (Fig. 1), with their wide range of structural and stereochemical features, continue to provide challenging synthetic targets, since these alkaloids exhibit attractive biological activities. Securinine (1), isolated from Securinega suffruticosa , was structurally determined to contain an indolizidine skeleton with an azabicyclo octane system together with an α,β-unsaturated γ-1actone ring.This alkaloid has been clinically used in Russia as a CNS stimulating drug, and has been shown to act as a stereospecific antagonist at the GABA binding site of the GABAA-receptor complex. 相似文献
965.
966.
967.
Both normetanephrine and metanephrine were found to be oxidized by both types of monoamine oxidase in mouse liver mitochondria. Both Km and Vmax values of type B MAO for both substrates were higher than those of type A MAO, which caused the shift of inhibition curves with clorgyline and deprenyl according to the increase in substrate concentration. 相似文献
968.
Stromal cells play a critical role in haematopoiesis, both in a permissive and, probably, in a directive manner. Study of the interactions between stromal cells and haematopoietic stem cells, however, is difficult to perform using whole bone marrow, in which stem cells are indistinguishable from precursor cells and maturing haematopoietic cells, and where stromal and haematopoietic cells co-exist in a heterogeneous mixture. We have purified primitive haematopoietic spleen colony-forming cells (CFU-S) using fluorescence-activated cell sorting (FACS) and produced CFU-S populations which approach 100% purity (ref. 6 and B.I.L. and E.S., in preparation). This cell population is devoid of significant stromal cells and mature haematopoietic cells. Here, we report that when purified CFU-S are seeded onto a stromal adherent layer in vitro, foci of haematopoietic cells develop within the stroma followed by production of a wave of maturing and mature progeny. However, self-renewal of CFU-S does not occur and haematopoietic activity rapidly declines, indicating that caution should be applied in the use of highly purified stem cells for human bone marrow transplantation. 相似文献
969.
Morphological transformation in vivo of human uterine cervix with papillomavirus from condylomata acuminata 总被引:3,自引:0,他引:3
J W Kreider M K Howett S A Wolfe G L Bartlett R J Zaino T Sedlacek R Mortel 《Nature》1985,317(6038):639-641
Carcinoma of the human uterine cervix has been associated with several infectious agents including papillomavirus. Papillomavirus group-specific antigen (GSA) and viral particles have been demonstrated in human condylomata acuminata (CA) and flat warts of the uterine cervix. Cell alterations consisting of nuclear enlargement, hyperchromasia, irregularity, binucleation and cytoplasmic clearing (koilocytosis) are often interpreted as mild to moderate dysplasia. Present evidence that human papillomavirus (HPV) is responsible for the development of these lesions relies on the association of GSA and virus particles in the affected tissue, fulfilling the first two of Koch's postulates. Direct proof of an aetiological relationship, however, requires induction of the CA change in normal, human uterine cervix after exposure to papillomavirus. Infecting human subjects with HPV is ethically unacceptable and no satisfactory alternative systems have been defined. Also, human cell cultures do not support growth or transformation by HPV. Here we report the first demonstration of the morphological transformation of human tissues with a human papillomavirus under controlled, experimental conditions. 'Transformation' is used here in its literal sense to refer to a heritable morphological alteration in the appearance of the cells. The use of this term does not indicate that the changes described are neoplastic, but they are identical to the dysplastic changes found in biopsies of uterine cervical CA. Our results demonstrate the direct involvement of CA virus in dysplastic change of human cervical tissue and indicate that the experimental system described may be useful in elucidating the contribution of human papillomaviruses to the pathogenesis of human cervical cancer. 相似文献
970.
N T Chang J Huang J Ghrayeb S McKinney P K Chanda T W Chang S Putney M G Sarngadharan F Wong-Staal R C Gallo 《Nature》1985,315(6015):151-154
Human T-cell lymphotropic retrovirus type III (HTLV-III), also called lymphadenopathy-associated virus (LAV), has been identified as the aetiological agent of acquired immune deficiency syndrome (AIDS). The sera of most patients with AIDS or AIDS-related complexes, and of asymptomatic individuals infected with HTLV-III, contain antibodies against antigens of HTLV-III. The characterization of these antibodies and their corresponding viral antigens is important not only for understanding immunity against HTLV-III and the pathology of AIDS, but also for the development of diagnostic methods and preventive vaccine for AIDS. Following the successful establishment of a long-term T-cell line permissive for HTLV-III replication, large quantities of virus have been produced, facilitating the purification of viral proteins and the development of mouse monoclonal antibodies against several viral antigens. More recently, the structure of HTLV-III proviral DNA has been elucidated. We now report the production, by genetic engineering methods, of a peptide encoded by a gene segment of HTLV-III. A 1.1-kilobase (kb) EcoRI DNA segment from an isolate of HTLV-III was inserted into a lpp and lac promoter-coupled expression vector, pIN-III-ompA. Escherichia coli transformants of this plasmid produced a peptide of relative molecular mass (Mr) 15,000 (15K) which was strongly immunoreactive with anti-HTLV-III antibodies present in sera from AIDS patients. Lysates of the clones expressing this 15K peptide inhibited the reactivity of the p31 virion protein with AIDS sera, suggesting that it is a fragment of the viral p31 protein. The peptide reacted with sera from all 20 AIDS patients but none of the 8 normal controls tested. These results suggest that the peptide may be useful for detecting anti-HTLV-III antibodies in blood samples. 相似文献