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)

Twenty consecutive symptomatic patients of mitral valve prolapse (MVP) and 20 normal age, sex and symptom matched controls were studied. Ambulatory monitoring studies revealed the presence of atrial premature beats (APC) in 16 subjects in each group. Isolated ventricular premature beats (VPC) were observed in 12 patients with MVP and 15 subjects in control group (p = ns). Complex VPCs (Lown IVa, IVb) were recorded in 4 patients of MVP vs 3 controls (p = ns). There was no correlation between the occurrence of arrhythmias with the degree of MVP or the degree of mitral regurgitation. Likewise, MVP patients with prolonged QTc interval did not show higher incidence of spontaneous arrhythmias when compared to those with normal QTc interval. Nineteen patients underwent electrophysiological studies. Two patients showed evidence of abnormal sinus node function. Both these patients in addition had AV nodal abnormalities, manifested by prolonged AH interval. Programmed stimulation studies induced AV nodal tachycardia in one and non-sustained ventricular tachycardia in two (polymorphic in one and monomorphic in the other). Ambulatory monitoring in both these patients did not show any evidence of complex VPCs or VT, indicating poor correlation between inducibility and presence of spontaneous complex VPCs. Patients with MVP do not have a higher prevalence of spontaneous atrial or ventricular arrhythmias when compared to matched normal controls with similar symptomatology. The presence of mitral regurgitation, severity of MVP and associated prolonged QTc interval is not associated with higher prevalence of arrhythmias. The correlation between spontaneous and inducible arrhythmias is poor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Arrhythmias and conduction defects in patients with mitral valve prolapse: a study based on ambulatory monitoring and electrophysiologic studies. 145 58

We have previously demonstrated that the introduction of the bm12 mutation into NZB mice results in animals that spontaneously produce high titer IgG autoantibodies to dsDNA. The observation that NZB.H-2bm12 develop lupus although NZB.H-2b control mice do not, provides a unique system to study the role of Th cells in the production of antibodies to dsDNA. We have isolated, in the absence of a known stimulating autoantigen, a series of seven autoreactive T cell clones that provide help in vitro for the production of IgG anti-dsDNA antibodies by syngeneic B cells. The data on these seven cloned T cell lines was compared to two cloned T cell lines specific for keyhole limpet hemocyanin. The seven cloned T cell lines, coined clones 19D, 23G, 410F, 410H, C1, C15, and C52 all show significant help in vitro for production of IgM and IgG antibodies to ssDNA and dsDNA; antibody levels increased 7- to 30-fold compared to cultures without T cells. Clones C1, C15, and C52 were furthered studied and were shown to provide help for IgM antihistone and anti-OVA responses but provided significantly less help for IgG antibodies. In contrast, keyhole limpet hemocyanin-specific cloned T cell lines TK2 and TK5 provided help for IgM antibodies to ssDNA, dsDNA, and histone, but failed to significantly increase IgG antibodies to ssDNA, dsDNA, or histone. The cloned T cell lines were restricted to H-2bm12 and proliferated only in response to APC from NZB.H-2bm12 and B6.C-H-2bm12 but not NZB.H-2b or NZB.H-2d mice; their in vitro helper activity was inhibited by antibodies to class II. All cloned T cell lines expressed Thy-1, CD5, and TCR-alpha/beta. Three of the seven clones used TCR-V beta 4. However, the V beta expression of the four remaining autoreactive T cell clones could not be determined. All of the autoreactive cloned T cell lines produce significant IL-4 but no detectable IL-2 or IFN-gamma. We believe that HPLC-purified peptides eluted from I-Abm12 molecules from APC can potentially provide insight on the putative autoantigen.
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PMID:Generation and characterization of cloned T helper cell lines for anti-DNA responses in NZB.H-2bm12 mice. 146 Feb 94

Tumorigenesis is thought to be a multistep process in which genetic alterations accumulate to bring about the neoplastic phenotype. Colorectal tumors appear to arise as a result of the mutational activation of oncogenes coupled with the inactivation of several tumor suppressor genes. We have found frequent allelic deletions of specific portions of chromosomes 5, 17, and 18 which presumably harbor suppressor genes. The target of allelic loss events on chromosome 17 has been shown to be the p53 gene, which is frequently mutated not only in colon cancer but in several other tumor types as well. Candidate suppressor genes have also recently been identified on chromosomes 18 and 5. The DCC gene on chromosome 18q encodes a protein with significant sequence similarity to neural cell adhesion molecules and other related cell surface glycoproteins. Alterations of this gene may interfere with normal cell growth and differentiation by disrupting cell-cell or cell-substrate interactions. Two genes (MCC and APC) on chromosome 5q have also recently been identified and partially cloned. These genes are located in a region tightly linked to familial adenomatous polyposis (FAP). While MCC mutations have been found only in sporadic colon tumors, APC mutations have been identified in sporadic tumors as well as the germline of patients with FAP. Studies are currently in progress to increase our understanding of how alterations of these genes affect colorectal tumor cell growth.
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PMID:Suppressor gene alterations in the colorectal adenoma-carcinoma sequence. 146 93

Several rodent studies based on molecular biology have suggested that accumulation of genetic alterations in cancer-associated genes is required to convert a normal cell into a malignant cell. Activation of oncogenes and inactivation of tumor suppressor genes appear to be involved in carcinogenesis. In renal cell carcinomas, we have recently implied that the presence of tumor suppressor genes at chromosome 3p13-14.3 and 21.3, the regions where are also commonly deleted in adenocarcinoma of the lung; at chromosome 5q21, the region where the MCC (mutated in colorectal cancer) gene and APC (adenomatous polyposis coli) gene are located; at chromosome 6q27; and at 10q 21-23. We have also indicated that genes on 3p is probably important for development of RCCs and genes on 5q, 6q, and 10q may be associated with progression of RCCs.
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PMID:[Tumor suppressor genes associated with development of human renal cell carcinoma]. 149 60

Homozygous protein C (PC) deficiency is a rare genetic defect that usually results in fatal thrombotic complications (purpura fulminans and DIC), but it can be successfully managed with oral anticoagulants or PC replacement. The successful use of PC replacement for two individuals is described. The activity and antigen levels of PC in fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC) are also reported. The concentration of PC in FFP is 87 +/- 15 units/dl. PC is present in all PCC analyzed; however, a ten-fold difference between the various brands and/or lots is noted. The PC activity and antigen correlates well with no significant levels of APC. Upon infusion of FFP into two homozygous PC-deficient children, the PC levels obtained were less than or equal to 30 units/dl post-infusion and undetectable after 12-18 hr. With infusions of PCC, plasma levels of PC obtained were 100-145 units/dl and less than 10 units/dl after 48 hr. The percent recovery and half-lives of PC from FFP and PCC were 49.8% and 7.8 hr, and 84% and 7.4 hr, respectively. One infant was treated every 48 hr for 2 years without significant purpura fulminans or DIC complications. The levels of the other PC system components did not change during the infusion of the PC-rich material. Based on this information, a specific replacement protocol has been developed using a PC-rich concentrate. However, several problems may arise with the "less pure" PC-rich concentrates: catheter-tip thrombosis, related large vessel thrombosis and blood-transmitted diseases. With a specific PC concentrate, replacement therapy is a viable alternative for the long-term management/treatment of homozygous PC deficiency.
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PMID:Protein C survival during replacement therapy in homozygous protein C deficiency. 150 96

Current recommendations for screening large populations for colorectal neoplasia have been promulgated by a number of researchers and authorities who generally agree that ongoing screening is justifiable in high-risk groups but not yet in average-risk groups. Nonetheless, it is thought to be justifiable to provide screening for average-risk individuals upon request. Choice of tools for screening remains under discussion. Colonoscopy is generally agreed to be justifiable in those patients with the highest risk, ie, members of families with a clear inherited tendency to develop colorectal cancer or those with a personal history of colorectal neoplasia. There is currently no agreement concerning the recommended tools for those with a weaker family history (one or two affected relatives), but regular fecal occult blood testing with occasional limited endoscopic examination of the bowel is usually favored. The new immunochemical-based occult blood tests show great promise for improved sensitivity and specificity. The evidence of the association between Helicobacter pylori gastritis and gastric cancer has been strengthened by three studies that show that patients with gastric cancer are more likely to have had infection in the years (up to 20) prior to diagnosis. The relative risk for cancer when infected with H. pylori is 3.6 to 6, but many H. pylori-positive individuals do not develop gastric cancer and additional factors must be operative. Probably the most exciting development for gastroenterology in 1991 is the identification of the gene on chromosome 5, designated APC, which is responsible for familial adenomatous polyposis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The genetics, epidemiology, and early detection of gastrointestinal cancers. 151 Oct 28

The ability of normal B cells, peritoneal macrophages, and splenic APC to process and present OVA to a panel of T-T hybridomas with different specificities was investigated. In all cases, B cells were less efficient than unfractionated splenocytes in presenting OVA or its peptides. However, when the presentation of native Ag was compared to the presentation of peptides, it was obvious that there were marked differences in the ability of these two APC populations to generate different epitopes from OVA. Leupeptin inhibits the processing of selected epitopes from native OVA differently when it was presented by spleen cells or B cells, suggesting that these two APC populations differ in their protease content. The effect of in vitro culture on the ability of splenic and peritoneal APC to process OVA was also investigated. Native OVA presentation by macrophages and spleen cells was affected by in vitro culture, more for some epitopes than for other epitopes. In contrast, presentation of exogenous peptides by paraformaldehyde-fixed APC was either not affected by previous culturing for 3 days, or very much improved. Altogether, these data demonstrate that different epitopes on the same protein may be independently and differentially processed by B cells and spleen cells. Furthermore, the precise peptides that are produced may vary with the physiologic state of the APC.
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PMID:Heterogeneity in antigen processing by different types of antigen-presenting cells. Effect of cell culture on antigen processing ability. 151 61

The purpose of the study was to test whether APC: alpha 1AT complex is a useful clinical marker of the activation of coagulation. The rationale for this is that activated protein C may appear in circulation at an early stage of blood coagulation, when subcoagulant amounts of thrombin are formed. Given the relatively higher half-life of APC: alpha 1AT as compared to that of thrombin:AT-III (TAT) complexes, we hypothesized that APC:alpha 1AT could represent an amplification of the thrombin generated in the first events of coagulation. Using sandwich ELISA's we measured APC: alpha 1AT and TAT complexes as well as complexes of AT-III with its target proteases in normal subjects and in several clinical groups of patients prone to thrombotic episodes, including pregnancy, preeclampsia, hemodialysis, gynecological tumors, diabetes and oral contraceptives. APC: alpha 1AT complex was significantly increased in all clinical groups as compared to normal subjects and showed relatively higher increases than did TAT and ATM complexes in the majority of the groups studied. There was a significant and positive correlation between APC: alpha 1AT and TAT complex levels in the majority of the groups, as well as between TAT and ATM and between APC: alpha 1AT and ATM complex levels. We conclude that APC: alpha 1AT complex can be used as a sensitive marker of prethrombotic states.
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PMID:Activated protein C: alpha 1-antitrypsin (APC: alpha 1 AT) complex as a marker for in vitro diagnosis of prethrombotic states. 152 6

Current theories of the aetiology of RA point to a central role for the trimolecular complex comprising the MHC class II molecule on the surface of the APC, the antigenic peptide and the TCR on the disease-inducing T cell. Thus the arthritogenic T cell is an important target for new therapy. However, it cannot be directly identified because the causative antigen is unknown, so indirect techniques such as TCV and TCR peptide vaccination are required. In TCV, T cells thought to mediate the disease, in an activated and attenuated form, are injected into the patient, who then develops a specific immune response against these pathogenic T cells. TCV has been shown to be effective in protecting against and treating a variety of animal models of autoimmune disease, including AA, EAE and IDDM in NOD mice. The vaccines initially comprised clones and lines of T cells shown to be capable of transferring the disease, but later unseparated LN cells were also shown to be effective, paralleling more closely the human situation. Interestingly, it has become clear that TCV does not create its own regulatory network but amplifies a natural immunoregulatory network which forms as the disease develops. The major stimulating moiety on the vaccinating T cell is its receptor (anti-idiotypic response), although there is also an anti-ergotypic (anti-activated T cell) response. For this reason the technique of TCR peptide vaccination was developed, which utilizes only a short peptide from the TCR of the disease-causing cells to stimulate an immune response against them. This is effective in the prevention and treatment of EAE, where there is a preferential usage of TCR-V beta 8 by encephalitogenic T cells. The application of both these techniques to human autoimmune disease is in its infancy. Studies of TCV in MS and RA have not shown clear-cut clinical benefit, although immunological changes have been observed; comparison of methodology with the animal work and assessment of results are complex and further studies are in progress. Studies of TCR peptide vaccination in MS and RA are handicapped by the lack of a consensus on TCR usage in these conditions, but a limited study is underway in MS.
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PMID:Management of early inflammatory arthritis. Intervention with immunomodulatory agents: T cell vaccination. 152 47

T lymphocytes usually recognize endogenously encoded Ag in the context of MHC class I molecules, whereas exogenous Ag is usually presented by MHC class II molecules. In vitro studies in model systems suggest that presentation of endogenous Ag by class II molecules is inhibited by the association of class II with its invariant chain (Ii). In the present study we test this hypothesis in an in vivo system in which endogenously encoded tumor peptides are presented by tumor cell MHC class II molecules. In this system, transfection of syngeneic MHC class II genes (Aak and Abk) into a highly malignant, Ii negative, mouse tumor (SaI sarcoma) produces an immunogenic tumor (SaI/Ak) that is rejected by the autologous host. The class II+ transfectants also effectively immunize autologous A/J mice against a subsequent challenge of wild-type class II- tumor cells. We have hypothesized that the SaI/Ak transfectants induce protective immunity because they function as APC for endogenously synthesized tumor peptides, and thereby stimulate tumor-specific Th cells, by-passing the need for professional APC. To test the role of Ii as an inhibitor of presentation of endogenous peptides, SaI/Ak tumor cells were supertransfected with Ii gene (SaI/Ak/Ii cells), and the tumorigenicity of the resulting cells determined. Nine SaI/Ak/Ii clones were tested, and their malignancy compared with that of SaI/Ak and SaI cells. Seven of the nine class II+/Ii+ tumor cells are more malignant than class II+/Ii- tumor cells in autologous A/J mice. Expression of Ii therefore restores the malignant phenotype, presumably by preventing presentation of endogenously synthesized tumor peptides. Ii therefore regulates Ag presentation and can be a critical parameter for in vivo tumor immunity.
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PMID:Invariant chain alters the malignant phenotype of MHC class II+ tumor cells. 152 84


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