Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033036 (APC)
 10,214 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In this article, the mechanisms by which infection at a distant site could lead to ReA and whether they could explain the association of ReA with HLA-B27 have been discussed. We propose that ReA synovitis is primarily due to specific synovial T-cell proliferation to fragments of the triggering bacterial found in the joint. Nonspecific T cells amplify synovitis with antibodies playing only a secondary role. First, we have shown that the triggering bacterial antigen is present in a nonviable form in ReA synovium and that this, not cross-reactive joint autoantigen, stimulates the specific synovial immune response. Second, the studies of the humoral immune response in ReA have been reviewed. Further evidence of bacterial persistence in the joint comes from work demonstrating intrasynovial bacteria-specific antibody synthesis. Continuing maturation of the antibody response also points to persisting antigen. In enteric but not genitourinary ReA, the humoral response is mainly IgA, implying chronic stimulation of the gut mucosa. Analysis of the molecules against which the humoral response is directed has shown no difference between yersinia arthritis and yersiniosis, but in CTA, the response to the 57kD and 59kD antigens differs from CT urethritis suggesting they may be arthritogenic. Finally, the antibody response may be absent in ReA patients rendering antibody titres diagnostically less useful and confirming their secondary role in the pathogenesis of synovitis. Third, studies of cellular response in ReA have been analyzed. We show there is a specific synovial MNC proliferative response to fragments of the triggering bacteria found in the joint, which is potentially of diagnostic use. The proliferation is due to CD4+ and CD8+ T cells and restricted by MHC class I and II antigens. This antigen-specific T-cell response is accompanied by an antigen-independent recruitment of nonspecific T cells, which may contribute to the amplification of synovitis. The importance of the synovial APC in determining the synovial immune response is unarguable but the exact mechanisms are unclear. Further details on the possible role of HLA-B27 in the presentation of arthritogenic peptides and on the exact identity of the antigenic epitopes recognized in ReA must await analysis of a large panel of T-cell clones. Finally, it is hoped that advances in this field will lead to specific and effective immunologic therapies or vaccines for this currently untreatable disease.
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PMID:Antigenic responses in reactive arthritis. 156 9

Van der Woude syndrome (VWS) is an orofacial clefting disorder with an autosomal dominant pattern of inheritance. In our efforts to clone the VWS gene, 900 kb of genomic sequence from the VWS candidate region at chromosome 1q32-q41 was analyzed for new DNA sequence variants. We observed that in clone CTA-321i20 a 7922 bp sequence is absent relative to the sequence present in PAC clone RP4-782d21 at positions 1669-9590, suggesting the presence of a deletion/insertion (del/ins) polymorphism. Embedded in this 7922 bp region was a TTCC short tandem repeat (STR). Genotype analysis showed that both the internal STR and the (del/ins) mutation were true polymorphisms. This is a novel example of intraallelic variation, a polymorphism within a polymorphism, and we suggest that it be termed a "Matroshka" polymorphism. Further genetic and DNA sequence analysis indicated that the ancestral state of the 1669-9590 del/ins polymorphism was the insertion allele and that the original deletion mutation probably occurred only once. A second class of novel DNA sequence variation was discovered on chromosome 5 that shared a 328 bp identical sequence with this region on chromosome 1. A single nucleotide polymorphism (SNP) was detected by SSCP using a pair of primers derived from the chromosome 1 sequence. Surprisingly, these primers also amplified the identical locus on chromosome 5, and the SNP was only located on chromosome 5. Since the probe unexpectedly detected alleles from another locus, we suggest that this type of sequence variant be termed an "ectopic" polymorphism. These two novel classes of DNA sequence polymorphisms have the potential to confound genetic and DNA sequence analysis and may also contribute to variation in disease phenotypes.
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PMID:Matroshka and ectopic polymorphisms: Two new classes of DNA sequence variation identified at the Van der Woude syndrome locus on 1q32-q41. 1166 35

Targeting the mitotic machinery using anti-mitotic drugs for elimination of cancer cells is a century-old concept, which continues to be routinely used as a first line of treatment in the clinic. However, patient response remains unpredictable and drug resistance limits effectiveness of these drugs. Cancer cells exit from drug-induced mitotic arrest (mitotic slippage) to avoid subsequent cell death which is thought to be a major mechanism contributing to this resistance. The tumor cells that acquire resistance to anti-mitotic drugs have chromosomal instability (CIN) and are often aneuploid. In this review, we outline the key mechanisms involved in dictating the cell fate during perturbed mitosis and how these processes impede the efficacy of anti-mitotic therapies. Further, we emphasize the recent work from our laboratory, which highlights the functional role of CEP55 in protecting aneuploid cells from death. We also discuss the rationale of targeting CEP55 in vivo, which could prove to be a novel and effective therapeutic strategy for sensitizing cells to microtubule inhibitors and might offer significantly improved patient outcome. Abbreviations: APC/C: Anaphase-Promoting Complex/Cyclosome; BAD: BCL2-Associated agonist of cell Death; BAK1: BCL2 Antagonist Kinase1; BAX: BCL2-Associated X; BCL2: B-cell Chronic Lymphocytic Leukaemia (CLL)/Lymphoma 2; BH: BCL2 Homology Domain; BID: BH3-Interacting domain Death agonist; BIM: BCL2-Interacting Mediator of cell death; BUB: Budding Uninhibited by Benzimidazoles; CDC: Cell Division Cycle; CDH1: Cadherin-1; CDK1: Cyclin-Dependent Kinase 1; CEP55: Centrosomal Protein (55 KDa): CIN: Chromosomal Instability; CTA: Cancer Testis Antigen; EGR1: Early Growth Response protein 1; ERK: Extracellular Signal-Regulated Kinase; ESCRT: Endosomal Sorting Complexes Required for Transport; GIN: Genomic Instability; MAD2: Mitotic Arrest Deficient 2; MCL1: Myeloid Cell Leukemia sequence 1; MPS1: Monopolar Spindle 1 Kinase; MYT1: MYelin Transcription factor 1; PLK1: Polo Like Kinase 1; PUMA: p53-Upregulated Mediator of Apoptosis; SAC: Spindle Assembly Checkpoint; TAA: Tumor-Associated Antigen.
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PMID:Mitotic slippage: an old tale with a new twist. 3060 Oct 84