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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Antibodies to single stranded (SS-) and double stranded (DS-) DNA and RNA were determined by a passive microhemagglutination assay in sera from 80 children with juvenile-onset diabetes mellitus (JDM) and 129 children with asthma. The latter group was chosen for comparison with the JDM group because of their increased susceptibility to viral infection and the nonautoimmune nature of the disease. We found that JDM patients had increased titers of antibodies to SS-DNA (61.3%), synthetic polyadenylicpolyuridylic acid (Poly A-U) (78.8%), synthetic polyinosinicpolycytidylic acid (Poly I-C) (62.5%), and DS-RNA of statolon virus (51.3%) and reovirus (27.3%), respectively, in contrast to asthmatics (15.5, 34.9, 3.9, 20.2, and 2.3%, respectively) or to healthy controls. The difference of the incidence of antibodies among the groups is statistically significant (P less than 0.001). Presence of SS-DNA antibody found in two thirds of cases of JDM further support the increased prevalence of autoimmune phenomenon in that disease. Furthermore, the increased prevalence of DS-RNA antibodies in patients with JDM, found especially in cases of recent onset, is suggestive of an active immune response against the underlying viral replications that may have led to beta cell injury in islets of pancreas.
Diabetes 1978 Nov
PMID:Antibodies to nucleic acids in juvenile-onset diabetes. 72 Jul 70

Diabetes in the non-obese diabetic (NOD) mouse is a multigenic autoimmune disease and is possibly controlled by three recessive loci, including one that is linked to the major histocompatibility complex (MHC). The first external domain of the Class II MHC I-A beta chain in these mice is unique and has been suggested as being responsible for autoimmunity. The I-A alpha chain in these mice is I-A alpha d, and they lack the expression of I-E molecules. We have investigated immune responses to various Ir gene control antigens in NOD mice to determine the influence of the NOD Ia and particularly the I-A beta chain. We find that sheep insulin is highly immunogenic while other insulins are weakly immunogenic in these mice. Hen egg lysozyme, pigeon cytochrome C and the synthetic polypeptide Poly 18, Poly EYK(EYA)5 antigen produce good antibody responses. Apart from H-2d, NOD are the only mice where Poly 18 antigen is immunogenic. In these mice Poly 18 induced good T-cell proliferative response, which was inhibited by anti-Ia antibody, and the mice were able to respond to tyrosine-containing polypeptide Poly EYA but not to the phenylalanine-containing antigen Poly EFA. We also found that synthetic peptide 48-60 of the NOD I-A beta chain is highly immunogenic in syngeneic NOD mice both for T cells and B cells. Using an I-A beta chain-specific monoclonal antibody, we are able to prevent induction of diabetes when the antibody was administrated in prediabetic, young mice. Our results suggest that the immune response to various antigens and autoimmune diabetes in NOD mice is directly influenced by the I-A beta chain.
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PMID:Role of the first external domain of I-A beta chain in immune responses and diabetes in non-obese diabetic (NOD) mice. 170

An improved rapid cell enzyme-linked immunosorbent assay (CELISA) is described which is suitable for the large scale screening of monoclonal antibodies to islet cell surface antigens. 5 x 10(4) insulin-producing rat insulinoma (RIN) cells were seeded per well in a 96-well flat-bottomed polystyrene plate coated one day before a 0.01% poly-D-lysine solution in PBS. After culture for 4 days in 200 microliters/well RPMI 1640 supplemented with 7.5% heat-inactivated fetal calf serum, the cell number per well was up to 2.1 x 10(5). These monolayer RIN cell cultures were used as a target for the detection of islet cell surface antibodies (ICSA) in the supernatants of hybridomas. The cells were used without fixation to avoid modification of sensitive surface antigens. Poly-D-lysine did not cause non-specific binding of immunoglobulins to the plastic wells as tested with irrelevant monoclonals. The specificity and sensitivity of the method is comparable to indirect immunofluorescence. All mc-ICSA primary screened by indirect immunofluorescence using viable RIN cell suspensions were positive in this CELISA. There was a correlation (r = 0.7; n = 44) between the antibody binding measured by CELISA and the indirect immunofluorescence technique. The advantage of this CELISA is that cell surface structures are well preserved in a viable cell monolayer used as target without chemical fixation. This assay procedure should be generally suitable for the initial screening of monoclonal antibodies to cell surface antigens of cells growing under culture conditions.
Diabetes Res 1991 Jan
PMID:CELISA for rapid screening of monoclonal islet cell surface antibodies using living rat insulinoma cells as target. 181 97

Islet transplants for large numbers of patients with diabetes will require xenografts. Microencapsulation is an appealing method for islet xenografting. However, graft function has been limited by a cellular reaction, particularly intense in spontaneously diabetic, NOD mice. The purpose of this study was to elucidate the mechanism of this reaction. Poly-1-lysine-alginate microcapsules containing 4000-12,000 dog or 1800-2000 rat islets were xenografted intraperitoneally into streptozotocin (SZN)-diabetic C57BL/6J and NOD mice, with or without recipient treatment with GK 1.5 (anti-CD4 monoclonal antibody) (20-30 microliters i.p. every 5 days, begun on day -7. Grafts were considered technically successful if random blood glucose (BG) was normalized (less than 150 mg/dl) within 36 hr. Graft failure was defined as BG greater than 250 mg/dl. Dog and rat islets in microcapsules normalized BG in both SZN and NOD mice within 24 hr routinely. Empty microcapsules and GK 1.5 treatments alone did not affect BG. NODs destroyed both microencapsulated dog and rat islets more rapidly than did SZN-diabetic mice (P less than .01). Graft biopsies showed an intense cellular reaction, composed of lymphocytes, macrophages and giant cells, and no viable islets. GK 1.5 treatment significantly prolonged both dog-to-NOD and rat-to-NOD grafts (P less than 0.01). Biopsies of long-term functioning grafts (on days 65-85) demonstrated viable islets and no cellular reaction around microcapsules; 1/4 rat and 1/8 dog islet xenografts continued to function indefinitely in NOD recipients, even after cessation of GK 1.5 therapy. Prediabetic NODs receiving encapsulated dog or rat islets mounted a moderate cellular reaction to grafts. Empty microcapsules excited no cellular reaction in diabetic or prediabetic NODs. We conclude that the NOD reaction to microencapsulated xenogeneic islets is helper T cell-dependent, and that the target of this reaction is not the microcapsule itself, but the donor cells within.
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PMID:The role of CD4+ helper T cells in the destruction of microencapsulated islet xenografts in nod mice. 196 98

We measured the amounts of epidermal growth factor receptor (EGFR) in plasma membranes from human placentas at term delivery in three groups: appropriate for gestational age (AGA), intrauterine growth-retarded (IUGR), and diabetes mellitus-complicated (DM) pregnancies. At the same time, EGFR mRNA levels were examined in three groups by dot and Northern blot analyses. Binding studies were performed using 125I-labeled human EGF as a ligand, and two classes (high and low) of binding sites were found in all specimens. Although dissociation constants (Kd) were not significantly different among three groups, the number of binding sites was significantly decreased in IUGR and DM placentas compared to that in the AGA group. Total cellular RNA was isolated from a part of the placentas used for binding studies using the guanidinium CsCl method, denatured, and dot blotted onto nitrocellulose filter. Poly(A)+ RNA was selected from the total RNA, electrophoresed in 1% agarose gel, and transferred onto nitrocellulose filters. Then, hybridization with 32P-labeled pE7 (a cDNA of EGFR), autoradiography, and densitometry were performed. The amounts of mRNA hybridized with pE7 were reduced in IUGR and DM placentas compared to that in the AGA group. The molecular sizes of EGFR mRNA were 10 and 5.6 kilobases in all three groups. These results suggest possible physiological actions of EGF on adequate feto-placental growth and development in human pregnancy.
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PMID:Decrease in epidermal growth factor receptor and its messenger ribonucleic acid levels in intrauterine growth-retarded and diabetes mellitus-complicated pregnancies. 202 55

Diabetes susceptibility in non-obese diabetic (NOD) mice may entail faulty activation of immunoregulatory cells resulting from cytokine deficiencies. Depletion of T cells prevents disease onset in these mice. Since we had previously shown that IL-2 treatment in vivo restored the ability of NOD/Lt mice to produce self-restricted suppressor T cells (Ts) in a syngeneic mixed lymphocyte reaction (SMLR), we investigated the possibility that diabetes could be circumvented by treatment with immunostimulatory agents that increase cytokine production. By 20 weeks of age, 75% of vehicle-treated NOD/Lt female controls had become glycosuric, while glycosuria developed in only 17% of NOD/Lt females injected with human recombinant interleukin-2 (rIL-2, 250 U twice weekly) beginning at 6 weeks of age. Treatment of mice with Poly [I:C] alone [50 micrograms twice weekly, an inducer of Interferon (IFN) alpha/beta] or in conjunction with rIL-2 was even more effective, completely preventing glycosuria for 20 weeks. However, therapeutic effects required continuous administration of the immunostimulants since pancreatic insulin content declined and severity of insulitis increased following cessation of treatment. IL-2 treatment increased transcription of interleukin-1 (IL-1) mRNA in peritoneal macrophages and increased lipopolysaccharide (LPS)-stimulated IL-1 secretion in comparison to controls. In the presence of stimulators from IL-2-treated mice, T lymphocytes isolated from both controls and IL-2-treated NOD/Lt mice proliferated in a SMLR and acquired Ts function. Peritoneal macrophages from Poly [I:C]-treated mice exhibited increased IFN alpha gene transcription and LPS-stimulated IL-1 secretion. T cells isolated from Poly [I:C]-treated mice were capable of suppressing NOD-Lt T cell responses to alloantigens in a mixed lymphocyte culture without prior activation in a SMLR. Thus, Poly [I:C] treatment may recruit a different population of regulatory cells than those elicited by treatment with IL-2. However, the mechanisms by which autoreactive T-cell clones may be regulated by these two treatments in NOD/Lt mice may be synergistic. These results indicate that in addition to T-cell depletion protocols, diabetes in NOD mice can be prevented by treatment with immunostimulatory agents.
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PMID:Immunostimulation circumvents diabetes in NOD/Lt mice. 253 2

The influence of insulin on the downregulation of its receptor was studied in AR42J cultured pancreatic acinar cells, a cell line that has been demonstrated to be metabolically responsive to insulin. Downregulation induced by insulin was time and dose dependent. After a 20-h incubation with 1 microM insulin, Scatchard analysis revealed approximately 80% loss of insulin receptors. Studies of receptor half-life indicated that treatment with insulin accelerated the degradation of both the alpha- and beta-subunits of the insulin receptor by 30-60%. In addition, biosynthetic-labeling studies indicated that insulin inhibited the biosynthesis of the insulin-receptor precursor by greater than 30%. This decreased biosynthesis of the precursor was associated with decreased production of mature receptor subunits. Poly(A)+ RNA was extracted from control cells and cells treated for 24 h with 100 nM insulin. Slot blots and Northern transfers revealed that insulin induced an approximately 50% decrease in insulin-receptor mRNA levels. Therefore, these studies indicate that insulin may diminish the concentration of its receptors in target cells by at least two mechanisms: acceleration of receptor degradation and inhibition of receptor biosynthesis at the level of mRNA.
Diabetes 1989 Feb
PMID:Mechanisms of insulin-induced insulin-receptor downregulation. Decrease of receptor biosynthesis and mRNA levels. 264 41

Utilizing a monoclonal antibody (Poly C9-MA) to a neoantigen of the C9 portion of the membrane attack complex of complement (MAC), immunoelectron (IEM) and immunofluorescent (IF) microscopy were performed on kidney tissue from normal humans and patients with insulin-dependent diabetes mellitus (IDDM) and type II membrano-proliferative glomerulonephritis (MPGN II). Comparative studies were conducted using polyclonal antibodies to human C3, C5, IgG, IgA, and IgM. In normal human tissue, there was a close correlation between increasing chronologic age and the quantity of MAC deposited in the mesangial stalk, along the interstitial aspect of and within tubular basement membranes (TBMs) and in arteriolar walls. IF of kidney tissues from 12 patients with IDDM with varying degrees of mesangial expansion and glomerulosclerosis demonstrated a direct relationship between the degree of tissue damage and the amount of MAC deposited in the mesangium. IEM of three normal and four diabetic specimens revealed reaction product of Poly C9-MA on linear and circular membranous structures within the mesangium, TBMs, and vessel walls, and within the glomerular basement membranes (GBMs) in diabetic subjects. Evidence is presented that these structures, which have been previously described by routine electron microscopy, represent cellular debris in these loci on which Poly C9-MA has been deposited. In MPGN II, Poly C9-MA and C3 were distributed within subepithelial deposits, along either side of the dense deposits (DDs) within the GBMs and TBMs, and around circular masses of DDs within the mesangium.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Ultrastructural localization of the membrane attack complex of complement in human renal tissues. 354 35

Poly(A)-containing RNA in various fractions of RNA from rat skeletal muscle has been detected and quantitated by hybridization to [3H]poly(U). Comparison has been made between the RNA in skeletal muscle from normal adult rats, from rats 2 days after induction of diabetes with streptozotocin, and from diabetic rats killed 60 min after injection of insulin. The poly(A)-containing RNA constituted a similar proportion of the total RNA in skeletal muscle from each of the three types of rats. In diabetes there was a decrease in the proportion of skeletal muscle ribosomes sedimenting as polyribosomes, but this was reversed after rats had been injected with insulin. However these changes were not associated with any alterations in the relative amounts of poly(A)-containing RNA in ribosomes isolated from rat skeletal muscle. Diabetes did not significantly alter the size distribution of the poly(A)-containing RNA or its poly(A) segment. If it is assumed that poly(A)-containing RNA is mRNA, these results imply that insulin stimulates protein synthesis in the skeletal muscle of diabetic rats by affecting the translation of pre-existing mRNA. Sucrose density gradient analysis showed that there was less poly(A)-containing RNA in the polyribosome region from diabetic rats than there was in that from normal rats. The balance of the poly(A)-containing RNA in the ribosomes from diabetic rats (presumed to be the untranslated mRNA) was found associated with rapidly sedimenting aggregated ribosomes, but its native form has not yet been determined.
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PMID:The effect of diabetes and insulin on the polyadenylic acid-containing RNA of rat skeletal muscle. 615 6

A monoclonal antibody to a neoantigen of the C9 portion of the membrane attack complex (MAC) of human complement has been developed and characterized. The distribution of this neoantigen was assessed by indirect immunofluorescence microscopy in nephritic and nonnephritic renal diseases. The antibody (Poly C9-MA) reacted on enzyme-linked immunosorbent assay (ELISA) with a determinant in complement-activated serum that was undetectable in normal human serum (NHS). Zymosan particles incubated in NHS had positive immunofluorescent staining with Poly C9-MA; however, binding of Poly C9-MA was not observed with zymosan particles incubated in sera deficient in individual complement components C3, C5, C6, C7, C8, or C9. Reconstitution of C9-deficient sera with purified C9 restored the fluorescence with Poly C9-MA. Poly C9-MA reacted positively by ELISA in a dose-dependent manner with purified MC5b-9 solubilized from membranes of antibody-coated sheep erythrocytes treated with NHS but not with intermediate complement complexes. Poly C9-MA also reacted in a dose-dependent manner on ELISA and in a radioimmunoassay with polymerized C9 (37 degrees C, 64 h) (poly C9) but not with monomeric C9. Increasing amounts of either unlabeled poly C9 or purified MC5b-9 inhibited the 125I-poly C9 RIA in an identical manner. These studies demonstrate that Poly C9-MA recognizes a neoantigen of C9 common to both the MAC and to poly C9. By immunofluorescence, Poly C9-MA reacted minimally with normal kidney tissue in juxtaglomerular loci, the mesangial stalk, and vessel walls. Poly C9-MA stained kidney tissue from patients with glomerulonephritis in a pattern similar to that seen with polyclonal anti-human C3. In tissue from patients with nonnephritic renal disease--diabetes, hypertension, and obstructive uropathy--Poly C9-MA was strongly reactive in the mesangial stalk and juxtaglomerular regions, tubular basement membranes, and vascular walls. Poly C9-MA binding was especially prominent in areas of advanced tissue injury. Poly C9-MA frequently stained loci where C3 was either minimally present or absent. These studies provide strong evidence for complement activation not only in nephritic but also in nonnephritic renal diseases.
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PMID:Neoantigen of the polymerized ninth component of complement. Characterization of a monoclonal antibody and immunohistochemical localization in renal disease. 634 93


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