Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P30536 (PBS)
 9,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of the administration of the recently discovered immunosuppressant 15-Deoxyspergualin (DSP) on the development of insulin-dependent diabetes mellitus (IDDM) in diabetes-prone BB rats were studied. The data show that 2 mg/kg body weight DSP, administered six times a week from the 30th day up to the 105th day of age, significantly reduced the incidence of diabetes in diabetes-prone BB rats as compared with the PBS-injected controls. The drug was also able to reduce the signs of pancreatic insulitis and the percentages of W3/25+ and OX6+ splenocytes. Interruption of the treatment resulted in a later onset of diabetes in a high percentage of animals within 41 days. These findings suggest that 15-DSP may temporarily reverse the pathogenic mechanisms leading to beta cell destruction and autoimmune diabetes in a well-known experimental model of human insulin-dependent diabetes mellitus.
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PMID:The effects of deoxyspergualin on the development of diabetes in diabetes-prone BB rats. 151 35

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.
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PMID:CELISA for rapid screening of monoclonal islet cell surface antibodies using living rat insulinoma cells as target. 181 97

Dinitrophenyl (DNP) derivatives of various molecular weights were tested for their ability to elicit ocular anaphylaxis after topical application to the eye of immunized animals. Adult male Sprague-Dawley rats were immunized by intraperitoneal injection of DNP-Ascaris suum extracts and alum and were then skin-tested with DNP-bovine serum albumin on day 13 post-immunization to assess their sensitivity to the DNP hapten. On day 14, animals were challenged topically with DNP derivatives in one eye; PBS was applied to the contralateral, control eye. Animals were evaluated clinically, and ocular tissues were processed for histologic evaluation. The compounds used for topical ocular challenge included the DNP derivative of egg albumin (MW 43,500 D), soybean trypsin inhibitor (MW 20,080 D), insulin (MW 5733 D), B-chain insulin (MW 3496 D), and lysine (MW 478 D). Only di-DNP-lysine elicited clinical signs of redness, edema, and tearing and histologic evidence of mast cell degranulation. None of the other compounds, tested in solutions of either equal numbers of milligram per milliliter or equimolar concentrations, elicited ocular anaphylaxis after topical application. A compound of low molecular weight, less than 3496, is needed to elicit ocular anaphylaxis when applied topically.
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PMID:Penetrating the conjunctival barrier. The role of molecular weight. 230 28

Oral administration of porcine insulin has been shown to be effective in preventing the spontaneous occurrence of diabetes in the Non-Obese Diabetic (NOD) mouse model. In the present study, we demonstrate that feeding 6-week-old female mice with 20 units of human insulin every 2-3 days for 30 days induces an active mechanism of suppression through the generation of regulatory T cells. Adult irradiated NOD males i.v. injected with 5 x 10(6) T cells from the spleens of diabetic female donors and the same number of T cells from the spleens of insulin-fed animals had less successful diabetes transfer than controls (4/15 vs. 8/16, P < 0.001). Protection from clinical diabetes was associated with a reduction in severe insulitis (16.4 +/- 3.6% vs. 52.3 +/- 12.8%, P = 0.023). However, more than 85% of the islets were inflamed. Feeding animals for 15 days reduced the magnitude of this protection since the number of successful transfers after 1 month was comparable (12/17 vs. 14/17) despite a significant delay in diabetes onset (P < 0.001). No difference in the contribution of T cell subsets was noted by cytofluorometry in the spleens of treated animals. When T cell subsets from insulin-fed animals were co-injected with diabetogenic T cells, only purified CD4+ T cells were able to transfer protection since only 3/12 mice became diabetic after 36 days in comparison to 3/6 in the group co-injected with CD4+ T cells from PBS-fed animals, or 5/6 in the group injected with CD8+ T cells.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oral administration of human insulin to NOD mice generates CD4+ T cells that suppress adoptive transfer of diabetes. 784 Aug 57

Acting in vivo, adrenalin and noradrenalin cause a statistically significant and permanent decrease in the motility of mouse spermatozoa remaining in the vas deferens. Intratesticular injection of vasopressin, oxytocin, insulin, and glucagon results in a decrease in spermatozoa motility in vas deferens, removal the spermatozoa to PBS in vitro, and an increase in percentage of motile spermatozoa on incubation medium. Thyroxine, calcytonin, and TRH did not affect motility of mouse spermatozoa in vivo.
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PMID:Effects of selected hormones on the motility of spermatozoa in the mouse vas deferens. 785 64

Based on evidence for a direct central mechanism of insulin action in mitigating damage due to cerebral ischaemia, we have recently shown that centrally administered insulin, and to a lesser extent, insulin-like growth factor-1 (IGF-1), reduce ischaemic damage in fed rats. Because a portion of the neuroprotective effect of insulin may be due to peripheral hypoglycaemia, we undertook the present series of experiments to determine whether insulin or IGF-1 are neuroprotective in fasted rats, which already have low blood glucose values. Continuous minipump delivery of insulin (1 IU rat-1 day-1 n = 13), or IGF-1 (50 micrograms rat-1 day-1 n = 10) was compared to control rats treated with phosphate buffered saline (PBS 25 microliters rat-1 day-1 n = 10). Quantitative neuropathology was done one week after 10 min and 15 sec of transient forebrain ischaemia induced by bilateral carotid artery clamping at a mean arterial BP (MABP) of 50 mmHg. In all areas examined i.e. neocortex, striatum, and hippocampus, the three groups showed similar degrees of necrosis (p > 0.05), although there were insignificant trends for a beneficial effect of insulin in reducing selective neuronal necrosis in hippocampus. The results, in combination with previous studies, indicate that insulin is more effective in attenuating brain damage in fed rats.
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PMID:Centrally administered insulin and IGF-1 in transient forebrain ischaemia in fasted rats. 791 95

We have evaluated the effects of a treatment with soluble interleukin-1 receptor (sIL-1R) in the accelerated model of autoimmune diabetes induced by cyclophosphamide (CY) in the non-obese diabetic (NOD) mouse. Prior to the CY challenge (350 mgkg body weight), female euglycemic NOD mice were randomly divided into three groups (A-C). Groups B and C were treated daily from 1 day before to 13 days after the CY challenge with sIL-1R at doses of 0.2 and 2 mg/kg body weight. Group A was treated with PBS. By 2 weeks after CY administration, an acute form of autoimmune diabetes with glycosuria, hyperglycemia and severe insulitis occurred in the majority (13/20, 65%) of the control mice (group A). In contrast, repeated injections with sIL-1R protected NOD mice from insulin-dependent diabetes mellitus (IDDM) development in a dose-dependent fashion; the incidence of IDDM was 53.3% (8/15) in the mice treated with 0.2 mg/kg and only 6.7% (1/15) in those treated with 2 mg/kg. However, none of the doses of the sIL-1R reduced the extent of insulitis in NOD mice. Importantly, the anti-diabetogenic property of sIL-1R may not involve major T cell function impairment; accordingly, in parallel experiments, splenic lymphoid cells from NOD mice not challenged with CY, but treated with 2 mg/kg sIL-1R for 5 consecutive days showed a normal distribution of mononuclear cell subsets and maintained their capacity to secrete interferon-gamma and IL-2 and to proliferate in response to polyclonal mitogenic stimulation with concanavalin A.
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PMID:Protection from experimental autoimmune diabetes in the non-obese diabetic mouse with soluble interleukin-1 receptor. 805 41

The protein products of the jun and fos oncogenes require a functional protein-protein interaction domain, called the "leucine zipper domain", to exert their transcriptional regulatory activity. A scintillation proximity assay was developed in which the biotinylated leucine zipper domain of the Jun protein (275-315) was immobilized on streptavidin-coated microfluorospheres and in which the leucine zipper domain of the Fos protein (160-200) was used as free, labeled ligand. The Fos leucine zipper peptide specifically bound to the Jun leucine zipper peptide, and for the first time, a dissociation constant (Kd = 110 +/- 12 nM in PBS/0.1% Tween) could be determined. Optimal heterodimer formation was reached at neutral pH. Both acidic and alkaline pH decreased the association of the peptides which was, furthermore, completely abolished by 500 mM NaCl, confirming that charged residues are critical for heterodimerization. A commercially obtained recombinant Jun protein competed as efficiently as the Jun leucine zipper peptide for binding to the Fos peptide, confirming the feasibility of using the two leucine zipper peptides to study the interactions between the two transcription factors. We also injected leucine zipper peptides individually into Xenopus oocytes to study whether they would interfere with the activity of the Fos/Jun heterodimer in vivo. Both peptides blocked selectively insulin-mediated oocyte maturation with an IC50 in the range of 15 ng per oocyte. In conclusion, the scintillation proximity assay described here may be used to investigate protein-protein interactions mediated by leucine zipper structures and to identify compounds that inhibit leucine zipper association.
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PMID:An efficient screening assay for the rapid and precise determination of affinities between leucine zipper domains. 821 36

Insulin-dependent diabetics have a greatly increased risk of developing premature coronary artery disease which is not entirely explained by known risk factors. A possible explanation may be enhanced oxidative modification of low density lipoprotein (LDL). The aim of this study was to determine firstly, whether or not LDL from moderately well controlled type 1 diabetics is more readily oxidisable than LDL from healthy non-diabetics and, secondly, to assess whether potential predictors of LDL oxidisability differ between type 1 diabetics and controls. Twenty type 1 diabetic men were carefully matched with healthy non-diabetic men on the basis of age and body mass index and each pair attended the department on the same morning for blood sampling. LDL oxidisability was assessed using both copper in PBS, 15 and 30 mM glucose, and with AAPH. There was no difference between type 1 diabetics and controls in the susceptibility of the LDL to either copper-dependent or non-transition metal-dependent oxidation. Furthermore, there was no difference between the groups for LDL vitamin E content, LDL fatty acid composition in cholesteryl esters, triglycerides or phospholipids, or LDL copper reductive capacity, but LDL glycation was elevated in the IDDM subjects. Given the absence of increased LDL oxidisability in these subjects, the recommendation of vitamin E supplementation in type 1 diabetics should be considered a secondary priority to achieving adequate glucose control.
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PMID:Absence of increased susceptibility of LDL to oxidation in type 1 diabetics. 886 59

As oral administration of insulin reduces the incidence of diabetes in NOD mice, and to achieve a better approximation of oral insulin trials being developed for human studies which will use human insulin, we attempted to determine the preventive efficacy of oral administration of human insulin rather than resorting to the animal insulins used in previous studies. As the strength of prevention obtained by oral insulin has not been adequately demonstrated, we determined whether the protection persisted after the oral treatment was discontinued and whether it was resistant to a diabetogenic injection of cyclophosphamide (CY). We also determined whether the effect of insulin could be increased by oral administration of lipopolysaccharide from Escherichia coli (LPS) or another immunostimulant (glycoprotein extracts from Klebsiella pneumoniae, GEKP) which may be more feasible for human application. Female NOD mice were fed once a week (from 35 to 300 days of age) with insulin, LPS, GEKP, insulin plus LPS, insulin plus GEKP, or PBS. A decreased incidence of diabetes were observed in animals fed human insulin (p < 0.01 incidence of diabetes at 300 days of age: 31% in mice fed with insulin and 65% in those fed PBS). Prevention by insulin was not enhanced by oral LPS or GEKP. Yet unexpectedly, mice fed with LPS alone or GEKP alone displayed decreases in diabetes incidence (p < 0.01). The severity of insulitis was reduced in animals fed insulin, LPS, GEKP or combinations of insulin and either immunostimulant (p < 0.02). Although the oral treatments were stopped at 300 days of age, the incidence of diabetes at 360 days remained lower in mice previously fed insulin, LPS, GEKP or combinations of insulin and either immunostimulant (p < 0.01). In mice previously fed PBS, CY injection (60 days after withdrawal of the oral treatment) led to a final incidence of diabetes of 90% (sum of the incidence during the initial 360 days and the further CY-induced incidence). Previous feedings with insulin, LPS, GEKP or combinations of insulin and either immunostimulant did not protect against CY-induced diabetes since incidences reached the final control incidence. T splenocytes from animals fed insulin, LPS, or GEKP, similarly reduced the capacity of T cells from diabetic mice to transfer the disease (p < 0.01). It is concluded that oral treatment with human insulin to be used in human trials reduces the incidence of diabetes in NOD mice. Equivalent preventive efficacy was obtained through feedings with LPS or GEKP (even though no cumulative efficiency was observed with insulin). The latter results suggest that it would be advisable to evaluate the efficiency of oral bacterial antigens for the prevention of human Type 1 diabetes. The protection afforded by oral treatments with insulin or bacterial antigens may be attributed to cellular suppression, persists for some time after treatments are stopped, but is not resistant to major immune stimulation such as injection of CY.
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PMID:Prevention of diabetes in the nonobese diabetic mouse by oral immunological treatments. Comparative efficiency of human insulin and two bacterial antigens, lipopolysacharide from Escherichia coli and glycoprotein extract from Klebsiella pneumoniae. 889 96


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