Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The insulin receptor exists in two isoforms differing by the absence (HIR-A) or presence (HIR-B) of 12 amino acids in the COOH-terminus of the alpha-subunit as a consequence of alternative splicing of exon 11. In this study, we developed a radioimmunoassay for the two isoforms employing antibodies raised against two peptides, one (Pep-12) corresponding to residues encoded by exon 11, and the other (Pep-13) corresponding to a COOH-terminal domain of the alpha-subunit which is common to both HIR-A and HIR-B isoforms. These peptides were iodinated and used as both ligands and standards. The assay is specific, highly reproducible, and sensitive with a detection limit of 10 fmol of receptor. One mole of purified insulin receptor, measured by Scatchard analysis, is read as one mole of receptor in the radioimmunoassay with either Pep-12 or Pep-13 as standards. The radioimmunoassay is applicable to the measurement of total content and relative abundance of the two isoforms in extracts from various tissues. We applied the radioimmunoassay to measure the relative abundance of the two isoforms in fat and muscle from normal, obese non-diabetic and non-insulin-dependent diabetic (NIDDM) subjects. Results demonstrate that expression of the low-affinity HIR-B form is significantly increased in obese and NIDDM subjects compared with control subjects. In addition, the increased expression of the HIR-B isoform was significantly correlated with both body mass index (r = 0.52; p = 0.006) and fasting glucose levels (r = 0.59; p = 0.001).
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PMID:Peptide-based radioimmunoassay for the two isoforms of the human insulin receptor. 779 85

Hemorrhage, necrosis and edema are some of the effects often observed following snake bites. This paper reports studies on the isolation and biological properties of hemorrhagic toxin from Crotalus viridis viridis (Prairie rattlesnake) venom. A hemorrhagic toxin was isolated from C. v. viridis venom by Sephadex G-50, DEAE-Sephacel and Q-Sepharose column chromatographies. The hemorrhagic toxin from C. v. viridis venom was shown to be homogenous as demonstrated by a single band on polyacrylamide gel electrophoresis and immunodiffusion. Its molecular weight was approximately 54,000 daltons, and it contained 471 amino acid residues. The toxin possessed hemorrhagic activity with a minimum hemorrhagic dose (MHD) of 0.11 micrograms and hydrolytic activity on dimethylcasein, casein, azocasein, azoalbumin, azocoll and hide powder azure. Hemorrhagic and casein hydrolytic activities were inhibited by EDTA, o-phenanthroline or dithiothreitol. The toxin contained 1 mole of zinc per mole of protein and zinc is essential for both hemorrhagic and proteolytic activities. Hemorrhagic toxin possessed hydrolytic activity on the B-chain of insulin, which cleaves His(5)-Leu(6), His(10)-Leu(11), Ala(14)-Leu(15), Tyr(16)-Leu(17) and Phe(24)-Phe(25) bonds. This toxin also hydrolyzed A alpha and B beta chains of fibrinogen. Intramuscular injections of hemorrhagic toxin caused an increase of creatine phosphokinase activity in mice serum from 50.3 mU/ml to 1133 mU/ml. A toxin isolated from C. v. viridis venom was shown to have strong hemorrhagic activity. Partial characterization is reported for this major hemorrhagic toxin in C. v. viridis venom.
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PMID:Biochemical characterization of hemorrhagic toxin from Crotalus viridis viridis (prairie rattlesnake) venom. 789 Jan 22

Rates of basal and glucose-stimulated insulin and glutathione secretion were studied in experiments with isolated rat pancreas, as were prooxidant effects on these values. The rate of oxidized and recovered glutathione release was found increased at glucose concentration increase to 16.7 mmoles in perfusion solution. Addition of prooxidants (tert-butyl hydroperoxide and Fe2+) in concentrations 10(-4) mole did not change basal insulin secretion but resulted in reduction of glucose-stimulated hormone release. Under such conditions a reduction of the rate of oxidized and recovered glutathione release by the pancreas was observed which was adequate to changed GSH/GSSG ratio in isolated Langerhans' islets. It may be supposed that lipid peroxidation results in changed thiol-disulfide ratio in Langerhans' islets B cells and in reduction of their sensitivity to secretogen effect.
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PMID:[Insulin secretion by isolated rat pancreas as affected by prooxidants; relationship to glutathione release]. 807 2

We examined the urinary excretion of magnesium and zinc in 175 diabetics [19 insulin-dependent (type I) and 156 insulin-independent (type II)] and in 160 control subjects of the same origin by determining the ratio of the concentration of each of these metals to that of creatinine (creat). Electrothermal atomic absorption spectrophotometry was used for analyzing Mg and Zn in urine. There was no significant difference in the urinary excretion of Mg between the control group [mean (SEM) = 362.6 (15.1) mmole of Mg/mole of creat] and the overall [350.2 (15.7) mmole Mg/mole creat], type I [368.4 (45.0) mmole Mg/mole creat], or type II [347.9 (16.7) mmole Mg/mole creat] diabetics regardless of the disorders associated with diabetes (cardiovascular diseases, neuropathy, retinopathy, infections, and hepatic disease). In contrast, diabetics of both types [2.67 (0.14) mmole Zn/mole creat] with or without a diabetes associated disorder excreted significantly (p = 0.031 to 0.0000) more Zn than did the control subjects [1.76 (0.09) mmole Zn/mole creat]. There was positive correlation between hemoglobin A1c and urinary loss of Mg (p = 0.013) or Zn (p = 0.0241) in patients with type II diabetes. From these data, it appears that of the two elements examined only Zn is associated with higher urinary loss in diabetic state. The discrepancy between our results and those of previous studies for Mg may be ascribed to dissimilarities in the diet habits and metabolism of Mg among diabetics of different geographical origins.
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PMID:Effect of diabetic state and related disorders on the urinary excretion of magnesium and zinc in patients. 820 39

Cells isolated from congenital melanocytic nevi and cultured in vitro have growth characteristics that resemble their premalignant stage in situ. A serum-free, chemically defined medium has been developed that allows continuous growth of established nevus cultures for up to several months. Like primary melanoma cells, nevus cells in high-calcium-containing W489 medium require insulin for growth. In contrast to melanoma cells, nevus cells in serum-free medium require the presence of alpha-melanocyte-stimulating hormone, which enhanced intracellular levels of cyclic adenosine monophosphate. In contrast to the requirements of normal human melanocytes from newborn foreskin, congenital nevus cells grow with less dependency on basic fibroblast growth factor (bFGF). Nevus cultures contain bFGF-like activity, and they express bFGF mRNA. Nevic cells of compound nevi also express bFGF mRNA in situ but only in the junctional areas. These results indicate that bFGF plays an important growth regulatory role for nevus cells in vitro and in vivo.
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PMID:Growth regulation of cultured human nevus cells. 844 Sep 4

A simple laser-induced fluorescence (LIF) imaging detector and an ultrasensitive LIF imaging detector are described for capillary isoelectric focusing (CIEF). An argon ion laser beam of 496.5 nm is used as excitation source. In the simple LIF imaging detector, the excitation beam is directed into a capillary column by an optic fiber array. In the ultrasensitive LIF imaging detector, the laser beam is first expanded, then is focused into the 4.5 cm long capillary column by a cylindrical lens. Fluorescence emission is detected by a charge-coupled device (CCD) camera. The feasibility and performance of the LIF imaging detector system for CIEF are first verified with a naturally fluorescent protein, b-phycoerythrin. Then, the ultrasensitive LIF imaging system is used as a detector for CIEF of proteins labeled with fluorescein isothiocyanate (FITC). Three FITC-labeled proteins (i) alpha-D-galatosylated FITC-albumin, (ii) insulin-FITC, and (iii) casein-FITC, are used as model samples. Fluorescence images of the model samples are measured during the CIEF process. The focusing of the protein samples is complete in about 1.5 min. The ultrasensitive detector's detection limits for the FITC-labeled proteins are at the level of 10(-10) M, and the mass detection limits are about 4.5 x 10(-17) mole, even though only 10% of the fluorescence emission is collected. Therefore, the method is capable of separating and detecting 10(-11) M or amole (10(-18) mole) level protein samples with a band-pass filter more specific to the fluorescence light.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Fluorescence imaging detection for capillary isoelectric focusing. 852 17

Current data on patients treated with human growth hormone (GH) were analyzed for the following safety topics. New leukemia. Thirteen of 46 new cases of leukemia were in non-Japanese patients without risk factors for leukemia (compared with at least 13 new cases expected). A possible increased occurrence of leukemia with GH treatment appears to be limited to patients with risk factors. Nonleukemic extracranial neoplasms. The number of cases reported (10) does not differ significantly from the number expected. Acute pancreatitis. In five of the seven cases reported risk factors (renal failure, valproic acid use, insulin-dependent diabetes mellitus) were present. The available data do not indicate a clear cause-and-effect relation between GH therapy and pancreatitis. Prepubertal gynecomastia. Of 15 possible cases, two were pubertal, eight resolved or improved with continued GH therapy, and two resolved with the cessation of GH therapy. An effect of GH treatment on prepubertal gynecomastia remains unknown. Scoliosis. Scoliosis is reported in fewer than 1 percent of the patients in the National Cooperative Growth Study (general-population prevalence, 1.5% to 3%). Curvature progression can occur during growth acceleration, and a causal association with GH treatment is not substantiated. Pigmented nevi. Nevi growth may be increased with GH treatment. Biopsies have detected no neoplasia or premalignant nevi transformations.
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PMID:Safety of human growth hormone therapy: current topics. 1124 Oct 65

Growth of normal melanocytes, nevus cells and primary melanoma cells is enhanced by insulin/insulin-like growth factor-I (IGF-I) in vitro. It has been shown that a melanoma cell line possesses the IGF-I receptor which plays a role in activation of the chemotactic response. Little is known about the in vivo expression of the IGF-I receptor and its role in melanocytic lesions. In an immunohistochemical study, we investigated the expression of IGF-I receptor in frozen sections of congenital pigmented nevi from 10 patients (ages 8 months to 4 yrs) using the monoclonal antibody alpha IR3, which specifically recognizes the extracellular alpha subunit of the IGF-I receptor. The proliferative activity of the nevus cells was examined by staining with Ki67 monoclonal antibody (reactive with all actively cycling cells). IGF-I receptor was found to be widely expressed by the cell surface of the nevus cells. Membrane staining was occasionally stronger in the superficial portion of the congenital pigmented nevi. In contrast, Ki67-positive cells were only sparsely scattered throughout the nevi with some tendency to localization to the superficial portion. This study indicates that in vivo the IGF-I receptor is widely expressed by congenital pigmented nevus cells. As opposed to keratinocytes, in which IGF-I receptor expression defines the proliferation pool of the normal and disordered epidermis, the IGF-I receptor is expressed by all nevus cells, irrespective of their proliferative status. Further studies are needed to assess whether the IGF-I receptor expression can serve as a marker for increased risk for development of malignancy in various types of benign melanocytic lesions.
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PMID:In vivo expression of the insulin-like growth factor-I (IGF-I) receptor in congenital pigmented nevi. 872 Sep 82

Signaling by phosphorylated species of phosphatidylinositol (PI) appears to regulate diverse responses in eukaryotic cells. A differential display screen for fat- and muscle-specific transcripts led to identification and cloning of the full-length cDNA of a novel mammalian 2,052-amino-acid protein (p235) from a mouse adipocyte cDNA library. Analysis of the deduced amino acid sequence revealed that p235 contains an N-terminal zinc-binding FYVE finger, a chaperonin-like region in the middle of the molecule, and a consensus for phosphoinositide 5-kinases at the C terminus. p235 mRNA appears as a 9-kb transcript, enriched in insulin-sensitive cells and tissues, likely transcribed from a single-copy gene in at least two close-in-size splice variants. Specific antibodies against mouse p235 were raised, and both the endogenously and heterologously expressed proteins were biochemically detected in 3T3-L1 adipocytes and transfected COS cells, respectively. Immunofluorescence microscopy analysis of endogenous p235 localization in 3T3-L1 adipocytes with affinity-purified anti-p235 antibodies documented a punctate peripheral pattern. In COS cells, the expressed p235 N-terminal but not the C-terminal region displayed a vesicular pattern similar to that in 3T3-L1 adipocytes that became diffuse upon Zn2+ chelation or FYVE finger truncation. A recombinant protein comprising the N-terminal but not the C-terminal region of the molecule was found to bind 2.2 mole equivalents of Zn2+. Determination of the lipid kinase activity in the p235 immunoprecipitates derived from 3T3-L1 adipocytes or from COS cells transiently expressing p235 revealed that p235 displayed unique preferences for PI substrate over already phosphorylated PI. In conclusion, the mouse p235 protein determines an important novel class of phosphoinositide kinases that seems to be targeted to specific intracellular loci by a Zn-dependent mechanism.
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PMID:Cloning, characterization, and expression of a novel Zn2+-binding FYVE finger-containing phosphoinositide kinase in insulin-sensitive cells. 985 86

The relationship between the rigidity of the liposomal membrane and the absorption of insulin after nasal administration of liposomes modified with an enhancer containing insulin was investigated for the nasal delivery of peptide drugs in rabbits. The rigid liposomal membrane makes liposomes stable, protecting insulin from enzymatic degradation. Soybean-derived sterol (SS) or its sterylglucoside (SG) was used as an enhancer. Dipalmitoylphosphatidylcholine (DPPC) liposomes modified with SG had increased fluidity of the hydrophobic group of the liposome bilayer compared with the liposomes modified with cholesterol (Ch) or SS, as shown by measurements of the steady-state fluorescence anisotropy of 1,6-diphenyl-1,3,5,-hexatriene (DPH); however, the fluidity of the polar group of the liposome bilayer was decreased according to measurements of steady-state fluorescence anisotropy of dansylhexadecylamine (DSHA) at 37 degrees C. These findings suggest that the fluidity of the hydrophobic group of the liposome bilayer is responsible for the increase of liposomal leakage and instability of the liposomes. When insulin was administered nasally to rabbits as a solution, no hypoglycemic effect was observed. The administration of insulin contained in DPPC/SG (7/4, mole) liposomes with high fluidity caused a high glucose reduction of long duration (8 hr). DPPC/SS and DPPC/Ch (7/4) liposomes with low fluidity caused low glucose reductions. These results demonstrated that liposomes modified with SG can be useful as carriers of insulin administered nasally.
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PMID:The relationship between the rigidity of the liposomal membrane and the absorption of insulin after nasal administration of liposomes modified with an enhancer containing insulin in rabbits. 1052 90


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