Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To study the expression of HLA-DQ beta chain alleles associated with type 1 diabetes, mAbs were generated from mice immunized with synthetic peptides representing allelic HLA-DQw7 and HLA-DQw8 beta chain sequences. The splenocytes from immunized mice were fused with myeloma cells, either immediately after or following additional in vitro boosting with peptide. Peptide-specific mAbs, predominantly of the IgG isotype, were isolated only from in vitro boosted splenocytes. Immunoblot analysis showed that several of the mAbs cross-reacted with DQ beta chain molecules. One mAb to a peptide representing DQw8 beta position [49-60] specifically recognised the DQw8 beta chain. Three mAbs to a peptide representing DQw8 beta position [39-52] specifically recognised an epitope consisting of Gly-Val-Tyr in position 45-47, i.e., all DQ beta alleles except DQw7 beta (position 45-47: Glu-Val-Tyr) and DQw2 beta (position 45-47; Gly-Glu-Phe). In FACS analysis these mAbs bound lymphocytes with the same specificity as found by immunoblotting analysis. Thus, by combining in vivo and in vitro immunization we have generated a number of epitope specific monoclonal IgG antibodies that distinguish closely related HLA-DQ beta chain alleles in predetermined positions.
 ...
PMID:Production of epitope specific monoclonal IgG antibodies to HLA class II molecules by combining in vivo and in vitro immunization. 137 72

The autoimmune nonobese diabetic mouse, a model of human juvenile type I diabetes mellitus, exhibits features of both B and T cell autoreactivity against insulin-producing cells. Using the neonatal cell transfer model of the disease, which we have described previously, we have shown that B cell suppression of newborn recipients by anti-mu treatment did not affect the transfer of diabetes by means of T cells. B cell-depleted, purified T cells from diabetic adults were injected into newborns treated with either IR-52, a control rat myeloma protein, or LOMM.9, a rat anti-mouse mu-chain mAb. Both groups developed diabetes over a similar time scale. Although the pancreases in both groups showed massive infiltration by T lymphocytes, B lymphocytes, presumably recruited in the host, were present in the IR-52-treated group, whereas they were absent in the LOMM.9-treated group. Anti-mu-treated diabetic animals showed substantial B cell suppression in vivo and in vitro when compared with IR-52-treated controls. These results suggest that B cell autoreactivity is a secondary phenomenon that is unimportant during the effector phase of diabetes in nonobese diabetic mice.
 ...
PMID:Adoptive T cell transfer of autoimmune nonobese diabetic mouse diabetes does not require recruitment of host B lymphocytes. 326 66

Monoclonal antibody 3A4 to islet cell surface antigen has been previously established in our laboratory, using hybridization of spleen lymphocytes from non-obese diabetic (NOD) mice transferred into immunologically incompetent recipient mice. In the present study, monoclonal islet cell surface antibody 5C12 could be newly obtained in the 10:1 ratio of NOD mice spleen cells and mouse myeloma cells (SP2/0) without any modifications. Protein A radioligand assay and indirect immunofluorescence on living cells showed that 5C12 antibody reacted to normal rat islet cells and cultured rat insulinoma cells (RIN-r), but not to cultured lymphocytes (Bri-7, IM-9) and Chang-liver cells. Analysis of 125I-labeled antibody binding revealed that unlabeled 5C12 effectively inhibited subsequent 125I-5C12 binding to RIN-r cells, whereas unlabeled 3A4 did not. The scatchard plot from these data showed the curvilinearity, and about 150,000 binding sites to antibody per RIN-r cell were counted. The treatment of RIN-r cells with papain and neuraminidase reduced the binding of 5C12 to RIN-r cells, whereas the effect of trypsin was not observed. Immunoprecipitation of 125I-labeled insulinoma cell lysates followed by SDS-PAGE and autoradiography indicated that 5C12 recognized 105K dalton cell surface protein in RIN-r cells. Immunoblotting also showed that 5C12 antibody recognized 105K dalton cell surface protein in RIN-r cells. These results demonstrated that 5C12 was an important tool for clarifying the immunoresponse against certain antigenic determinants on pancreatic B cells. Furthermore, 5C12 has not only qualitatively and quantitatively improved diagnostic methodology, but it may also provide new reagents useful to the treatment and prevention of type 1 diabetes.
 ...
PMID:[An analysis of islet cell surface antigen defined by monoclonal islet cell surface antibody 5C12]. 354 94

The presence of islet cell cytoplasmic antibodies (ICA) and islet cell surface antibodies (ICSA) at the time of diagnosis of type 1 (insulin-dependent) diabetes mellitus has been taken as evidence that autoimmune mechanisms are involved in the pathogenesis of the disease. The demonstration that ICSA in the presence of complement are preferentially lytic for beta-cells may be important in defining the role of these autoantibodies in the pathogenesis of type 1 diabetes. Because of the polyclonality of the immune response, the ICA and ICSA molecules of diabetic patient vary enormously in their binding parameters. For this reason we have generated monoclonal antibodies (MC-Ab) to islet cell antigens. In this study we investigate the effect of the two MC-Ab K28 A1 and K28 D6 resulted from the same fusion of the P3-X63-Ag8 murine myeloma cell line with the spleen cells of a Balb/c mouse immunized with rat islet cells on the hormone release of isolated rat islet in co-culture with the antibody-secreting hybridomas. The MC-Ab K28 D6 binds to both islet cell cytoplasmic and surface antigens, the K28 A1 is only reactive with cytoplasmic antigens. Surprisingly, in contrast to the monoclonal antibody K28 A1, K28 D6 enhanced the glucagon content and diminished the insulin secretion of the islets. Either the K28 D6 is directed to an epitope occurring on the beta- as well as alpha-cells or the antibody-mediated inhibition of the glucagon release results in a significantly reduced insulin secretion.
 ...
PMID:Inhibition of glucagon release of isolated islets of Langerhans by monoclonal antibodies. 388 11

Nuclear factor-kappaB (NF-kappaB) is responsible for the expression by regulating many genes for immune response, cell adhesion, differentiation, proliferation, angiogenesis and apoptosis. The function of NF-kappaB is inhibited by binding to NF-kappaB inhibitor (IkappaB), and imbalance of NF-kappaB and IkappaB has been associated with development of many diseases, including tumours. In this review, we focus on polymorphisms of the NFKB and NFKBI genes in relation to development of common inflammatory diseases including ulcerative colitis (UC), Crohn's disease (CD), rheumatoid arthritis, systemic lupus erythematosus, psoriatic arthritis, giant cell arthritis, type 1 diabetes, multiple sclerosis, celiac disease, and Parkinson's disease, as well as susceptibility of several cancers, such as oral squamous cell carcinoma, colorectal cancer (CRC), hepatocellular carcinoma, breast cancer and myeloma.
 ...
PMID:NFKB and NFKBI polymorphisms in relation to susceptibility of tumour and other diseases. 1770 19

Vitamin D deficiency, diagnosed when the serum 25-hydroxyvitamin D (25-OHD(3)) concentration is less than 20 ng/mL, has joined vitamin A deficiency as two of the most common nutrition-responsive medical conditions worldwide. There have been more scientific articles published about vitamin D in the 21st century than about any other vitamin, reflecting the massive expansion of the field of vitamin D research. Adequate vitamin D status has been linked to decreased risks of developing specific cancers, including cancers of the esophagus, stomach, colon, rectum, gallbladder, pancreas, lung, breast, uterus, ovary, prostate, urinary bladder, kidney, skin, thyroid, and hematopoietic system (e.g., Hodgkin's lymphoma, non-Hodgkin's lymphoma, multiple myeloma); bacterial infections; rheumatoid arthritis; Crohn's disease; periodontal disease; multiple sclerosis; asthma; type 2 diabetes; cardiovascular disease; stroke; peripheral artery disease; hypertension; chronic kidney disease; muscle weakness; cognitive impairment; Alzheimer's disease; clinical depression; and premature death. On the other hand, inadequate vitamin D status during human pregnancy may be associated with increased risk for the development of type 1 diabetes in the offspring. However, this point of view may be excessively optimistic. There also is evidence that despite the current heavy reliance on serum 25-OHD(3) concentration for the diagnosis of an individual's vitamin D status, local tissue vitamin D intoxication may be present in individuals with much lower serum 25-OHD(3) concentrations than are currently appreciated. Only rarely are the symptoms of local tissue vitamin D intoxication associated with vitamin D status or intake. An individual's serum 25-OHD(3) concentration may appear to be "low" for reasons totally independent of sunlight exposure or vitamin D intake. Serum 25-OHD(3) concentration is only poorly responsive to increases in vitamin D intake, and the prolonged routine consumption of thousands of international units of vitamin D may interfere with the regulation of phosphate homeostasis by fibroblast growth factor-23 (FGF23) and the Klotho gene product, with consequences that are detrimental to human health. In light of these counterbalancing observations, curbing excessive enthusiasm for universally increasing vitamin D intake recommendations may be in order.
 ...
PMID:Vitamin D: health panacea or false prophet? 2358 82