Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Purification of a basic somatomedin (SM), with similarity to SM-C and insulin-like growth factor, from human plasma Cohn fraction IV-1 enabled development of a RIA based on this SM.SM antiserum was produced by immunizing rabbits with partially purified SM. This antiserum (final dilution, 1:50,000) specifically bound approximately 40% of added [125I]-SM in this RIA. The RIA sensitivity was 2 x 10(-4) U immunoreactive SM (IRSM). Highly purified SM-C, insulin-like growth factor 1, and our SM revealed parallel and approximately equipotent dose-response curves in this RIA; rat SM and multiplication stimulation activity revealed less cross-reactivity. IRSM was detected in sera of all species tested except fish. Acidification of sera, without subsequent chromatography, before assay permitted measurement of total IRSM with either an equilibrium or nonequilibrium RIA technique. Acidification of serum appears to increase SM-binding capacity while decreasing binding affinity of the 20,000--50,000 mol wt proteins in serum. The mean (+/- SEM) IRSM concentrations in sera from normals and patients with acromegaly, hypopituitarism, GH deficiency before/after treatment, and Laron dwarfism were 1.45 +/- 0.17, 5.49 +/- 0.48, 0.19 +/- 0.07, 0.10 +/- 0.02/0.64 +/- 0.45, and 0.25 +/- 0.11 U/ml, respectively, compared to a pooled normal human serum reference standard which was designated to contain 1 IRSM U/ml. Measurements of total IRSM (bound and free) in serum may not accurately reflect SM bioactivity and will require interpretative caution.
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PMID:Radioimmunoassay of a basic somatomedin: comparison of various assay techniques and somatomedin levels in various sera. 3 45

The inability to detect insulin-like growth factor binding protein-3 (IGFBP-3) in some circumstances by Western ligand blot analysis has emphasized the need to characterize IGFBPs by both ligand binding and immunological techniques. In this study, we have: 1) characterized and quantified IGFBP-3 in nonpregnancy, pregnancy, and fetal cord serum, follicular, peritoneal, and amniotic fluid, seminal plasma, cerebrospinal fluid (CSF), and urine; 2) established a new IGFBP-3 RIA that detects both intact and fragments of IGFBP-3; 3) identified both intact and fragments of IGFBP-3 by Western immunoblot techniques; and 4) addressed the discordance between Western ligand blot analysis and RIA by assessing fluids for IGFBP proteolytic activity. All fluids examined, except pregnancy serum, CSF, and amniotic fluid, displayed a 44-34-kilodalton (kDa) IGFBP-3 doublet by Western ligand blot analysis. Western immunoblot analysis using specific IGFBP-3 antiserum showed a 44-34-kDa IGFBP-3 doublet and a 28-kDa fragment in nonpregnancy serum, fetal cord serum, follicular fluid, and peritoneal fluid. The immunoreactive 42-38-kDa doublet was faint in urine and seminal plasma. IGFBPs in CSF did not cross-react with IGFBP-3 antiserum. Pregnancy serum and amniotic fluid contained only the 28-kDa fragment when compared against equal volumes of nonpregnancy serum. With the development of an IGFBP-3 RIA, IGFBP-3 could be accurately measured; urine, CSF, and seminal plasma contained the lowest levels of IGFBP-3 at 27 +/- 3 ng/ml (mean +/- SEM), 110 +/- 26 ng/ml, and 209 +/- 56 ng/ml, respectively. In increasing concentration: fetal cord serum contained 753 +/- 101 ng/ml; peritoneal fluid, 1124 +/- 130 ng/ml; follicular fluid, 2356 +/- 211 ng/ml; nonpregnancy serum, 3556 +/- 508 ng/ml; pregnancy serum, 3718 +/- 842 ng/ml; and amniotic fluid, 5150 +/- 688 ng/ml. The measurable concentrations of IGFBP-3 in CSF and the high concentrations measured in pregnancy serum and amniotic fluid conflicted with Western blot analysis. Thus, fluids were assessed for IGFBP proteolytic activity by incubation with a source of IGFBP-3, either nonpregnancy serum or purified IGFBP-3. All fluids displayed some proteolytic activity with either assay. Fluids with little protease activity (nonpregnancy serum, follicular fluid, and urine) showed a close relationship between immunoassayable IGFBP-3 by RIA and IGFBP-3 band intensity by Western ligand blot. Fluids with high proteolytic activity (pregnancy serum, CSF, seminal plasma, peritoneal fluid, and amniotic fluid) gave discrepant IGFBP-3 values between RIA and Western ligand blot.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Measurement and characterization of insulin-like growth factor binding protein-3 in human biological fluids: discrepancies between radioimmunoassay and ligand blotting. 128 Feb 11

The goal of this investigation was to identify the metabolic abnormalities in a group of colon cancer patients before and during 5-fluorouracil chemotherapy. Twenty-two colon cancer patients were prospectively enrolled into a Clinical Research Center for measurement of counter regulatory hormones, fasting hepatic glucose production (HGP), intravenous glucose tolerance test, plasma leucine appearance (LA), and leucine oxidation (LO). Both the cancer group and the normal volunteers were matched for nutrition status (109 +/- 5% of ideal body weight vs 104 +/- 4%, mean +/- SEM, respectively) and history of weight loss (6.3 +/- 2.6 kg vs 4.4 +/- 4.8). Plasma growth hormone was significantly elevated in the colon cancer patients (3.22 +/- 0.62 ng/mL vs 0.73 +/- 0.18, p < .05) despite the fact that insulin-like growth factor-1 levels were not different. Plasma glucose, insulin, cortisol, glucagon, epinephrine, and norepinephrine levels were not significantly different than those of the normal volunteers. Fasting HGP rates were slightly but not significantly elevated in the group of colon cancer patients compared with the normal volunteers (2.09 +/- 0.11 mg/kg per minute vs 1.79 +/- 0.10, p = .10). Plasma LA was not significantly elevated in the colon cancer group (63.3 +/- 3.0 mumol/kg per hour vs 57.7 +/- 4.2; p = .25). Five days of continuous 5-fluorouracil chemotherapy was associated with a significant elevation in both the fasting glucose level (97 +/- 3 mg/dL vs 106 +/- 5, p < .05), and HGP (2.09 +/- 0.11 mg/kg per minute vs 2.27 +/- 0.10; p < .05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Metabolic response to chemotherapy in colon cancer patients. 128 27

Non-nutritive sucking in premature infants accelerates weight gain for unclear reasons. The effects of non-nutritive sucking on enteral hormone secretion may augment digestion and/or absorption of nutrients. Blood concentrations of gastrin, motilin, insulin and insulin-like growth factor-1 were measured before and 72 h after the initiation of nasogastric feedings in 21 premature infants randomly assigned to either a non-nutritive suckling or control group. Gastrin and motilin concentrations increased significantly after feedings in all infants (mean +/- SEM) (gastrin, 41 +/- 4 to 73 +/- 9 pg/ml, p < 0.01; motilin, 141 +/- 5 to 181 +/- 3 pg/ml, p < 0.01) Pre- and post-feed insulin concentrations were greater in the non-nutritive sucking group receiving bolus feeds than in control infants who were bolus-fed (P < 0.01). Non-nutritive sucking in premature infants does not appear to alter blood concentrations of motilin, gastrin, insulin or insulin-like growth factor-1 three days after initiation of feedings. If changes in the secretion of these hormones are induced by non-nutritive sucking, they may be at a local paracrine level.
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PMID:Non-nutritive sucking does not increase blood levels of gastrin, motilin, insulin and insulin-like growth factor 1 in premature infants receiving enteral feedings. 129 Aug 61

Obesity may be characterized by abnormal sex steroid secretion and reduced sex hormone binding globulin (SHBG) which in turn is related to fat distribution and insulin secretion. Recent in-vitro and in-vivo evidence suggests that insulin is the common mechanism regulating the secretion of SHBG and insulin-like growth factor small binding protein (IGFBP-1). IGFBP-1 appears not only to be a carrier for insulin growth factors (IGFs) but also to play an active role in growth processes, independent of growth hormone secretion. We have examined the possible relationship between fasting insulin, SHBG, testosterone, IGF-1, IGFBP-1 and fat distribution in 25 extremely obese, menstruating women (mean weight 107 +/- 3 kg) with normal glucose tolerance. Fat distribution was assessed from measurements of the waist to hip ratio (W/H). The obese women showed an elevated fasting insulin (mean +/- SEM; 21 +/- 2 mumol/l), a normal IGF-1, but reduced IGFBP-1 (14.6 +/- 2 micrograms/l); in 15 women IGFBP-1 levels were undetectable by the present assay. In addition, SHBG levels were reduced in the obese women (24 +/- 2 nmol/l) but total testosterone values (1.9 +/- 0.1 nmol/l) were normal. The elevated fasting insulin levels were positively correlated with increasing upper segment obesity as expressed by a rising W/H ratio (P less than 0.01, r2 = 0.306) and inversely correlated with SHBG (P less than 0.01, r2 = 0.483). Similarly, reduced SHBG values showed an inverse correlation with increasing W/H ratio (P less than 0.001, r2 = 0.383). No correlation was found between IGFBP-1 and W/H ratio but a strong positive correlation was seen between IGFBP-1 and SHBG (P less than 0.001, r2 = 0.466). Furthermore, an equally significant inverse correlation was found between IGFBP-1 and insulin levels (P less than 0.001, r2 = 0.474).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Decreased sex hormone binding globulin (SHBG) and insulin-like growth factor binding protein (IGFBP-1) in extreme obesity. 170 70

Insulin-like growth factor II and insulin-like growth factor binding protein-1 were identified and quantified in the urine of 23 healthy subjects between 17 and 76 years of age. IGF-II was measured after separation by gel chromatography at low pH and compared with IGF-I levels in the same samples, whereas IGF binding protein-1 was measured in dialysed urine. Urinary IGF-II was found at much higher concentrations than IGF-I (mean +/- SEM: 717 +/- 69 vs 110 +/- 5 ng/mmol creatinine). The chromatographic profile indicates that pro-IGF-II may also be present. The concentrations of IGF-II appear to be less variable than the other reported parameters. The mean IGF binding protein-1 concentrations in these urine samples was 414 +/- 83 ng/mmol creatinine. IGFs in the urine are in part bound to binding proteins.
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PMID:Immunoreactive insulin-like growth factor II in urine. 170 9

The decidualized endometrium during the first trimester of pregnancy synthesizes and secretes a 32-kDa insulin-like growth factor-binding protein (termed hIGFBP-1) at high levels. IGFBP-1 is the major soluble protein product of this tissue and is principally localized to the differentiated endometrial stromal cell, the decidual cell. In the present study long term culture of stromal cells from the nonpregnant endometrium have been employed to elucidate the hormonal requirements for IGFBP-1 production. Immunoreactive IGFBP-1 was undetectable in control cultures. However, inclusion of medroxyprogesterone acetate (MPA) induced rates of 0.35 +/- 0.09 microgram/0.1 mg cell DNA.day (mean +/- SEM; n = 5) after 20-30 days. In these cultures cells exhibited morphological changes consistent with decidual cell differentiation. In all cultures removal of MPA after exposure for 10-16 days, with or without subsequent inclusion of relaxin (RLX), increased production of IGFBP-1 450- to 4600-fold to rates of 150-710 micrograms/0.1 mg cell DNA.day or 26-131 micrograms/10(6) cells.day on days 24-26. The rates tended to be higher with the inclusion of RLX and were sustained in contrast to cultures without RLX, where rates fell by day 30. Individual cultures responded differently to RLX when added from the initiation of culture, with either a response similar to MPA alone or a cyclical change in production, achieving maximal rates of 190-290 micrograms/0.1 mg cell DNA.day. Cultures in which RLX alone induced high IGFBP-1 high production were obtained from endometrium during the progesterone-dominated luteal phase. In cultures exhibiting high rates of immunoreactive IGFBP-1 production, the protein represented their major secretory protein product. This was confirmed by [35S]methionine incorporation and the presence of IGFBP-1 as the predominant protein in serum-free culture medium. The immunoreactive IGFBP-1 isolated from culture medium was found to be identical, by a number of criteria, with IGFBP-1 derived from decidual tissue. These results were consistent with a primary role of progestin exposure, whether in vivo or in vitro, in converting endometrial stromal cells to cells potentially able to exhibit the high rates of IGFBP-1 production typical of the decidualized endometrium of pregnancy.
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PMID:Regulation of insulin-like growth factor-binding protein-1 synthesis and secretion by progestin and relaxin in long term cultures of human endometrial stromal cells. 170 79

1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] induces differentiation and inhibits proliferation in many cell types including bone cells. These effects may be mediated by the modulation of the insulin-like growth factor (IGF) regulatory system. Therefore we investigated the effects of 1,25-(OH)2D3 on transcript and protein levels of both IGF-I and IGF binding proteins (IGFBPs) in clonal mouse osteoblasts. Subconfluent cultures were treated in serum-free medium with 1,25-(OH)2D3. Secreted IGF-I was measured using a RIA under conditions eliminating the interference of IGFBPs. 1,25-(OH)2D3 (10(-11)-10(-8) M) inhibited IGF-I release in a dose dependent manner at 24 h (maximally to 30 +/- 5% of control, mean +/- SEM of seven independent experiments). In a time course study IGF-I increased in the media of control cultures over a 48-h period, while IGF-I secretion was completely prevented from 6 h onward in 1,25-(OH)2D3 treated cultures. Northern blot analysis revealed four IGF-I transcripts of 0.9, 1.8, 4.4, and 7.5 kilobases (kb). 1,25-(OH)2D3 decreased levels of the 7.5 kb IGF-I transcript from 4-48 h, with maximal inhibition occurring at 24 h (25% of control). Western ligand blots of the culture medium demonstrated secretion of a 25-kilodalton IGFBP, which comprised greater than or equal to 90% of the secreted IGFBPs. The 25-kilodalton IGFBP had previously been shown to have sequence similarity with IGFBP-4, a binding protein which inhibits the action of IGFs on bone cells. 1,25-(OH)2D3 treatment increased secretion of IGFBP-4 up to 14-fold over 24 h. 1,25-(OH)2D3 also increased IGFBP-4 (2.2 kb) transcript levels within 30 min, with the maximal stimulation of 8-fold occurring after 8 h. [3H]Thymidine incorporation into cells was inhibited by 1,25-(OH)2D3 both under basal and serum-stimulated conditions. Our results are consistent with the hypothesis that the effects of 1,25-(OH)2D3 on osteoblast proliferation may be mediated in part by decreased levels of IGF-I and increased concentrations of inhibitory IGFBP-4. It is proposed that this alteration in the IGF system may be an important functional autocrine or paracrine switch in the transition of osteoblasts from states of proliferation to differentiation.
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PMID:1,25-Dihydroxyvitamin D3 differentially regulates the production of insulin-like growth factor I (IGF-I) and IGF-binding protein-4 in mouse osteoblasts. 172 89

Growth factor-induced changes of cytosolic free calcium ion concentration ([Ca2+]i) and phosphatidylinositol (PI) turnover in cultured human retinal pigment epithelial (RPE) cells were studied, and their temporal relationship was compared. After a 24-hr serum depletion, RPE cells were loaded with fura-2/AM, and [Ca2+]i was analyzed using a digital imaging microscopy system. The resting [Ca2+]i in a single cultured human RPE cell was 153 +/- 1.5 nM (mean +/- the standard error of the mean [SEM], n = 105). The percentage of reactive cells that had Ca2+ transients induced by various growth factors were: epidermal growth factor, 18%; basic fibroblast growth factor (bFGF), 5%; nerve growth factor, 15%; platelet-derived growth factor (PDGF), 70%; insulin-like growth factor, 0%; fibronectin, 0%; insulin, 3%; and fetal bovine serum (FBS), 100%. The PDGF showed a peak concentration of 237 +/- 4.7 nM (mean +/- SEM, n = 67) and FBS, 774 +/- 34.5 nM (mean +/- SEM, n = 52). Chelation of the extracellular Ca2+ by EGTA made the resting and peak concentration lower. The Ca2+ transients occurred within 60 sec and lasted less than 5 min after the application of the growth factors. However, measurements of phosphoinositides in 24-hr serum-starved RPE cells revealed that growth factor-induced PI turnover was much slower than Ca2+ transients. In addition, FBS, bFGF, and PDGF increased the contents of inositol phosphate, inositol biphosphate, and inositol triphosphate (IP3) in RPE cells slowly up to 60 min except that PDGF showed a peak of IP3 at 15 min after stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Growth factor-induced cytosolic calcium ion transients in cultured human retinal pigment epithelial cells. 191 91

Serum insulin-like growth factor (IGF) and IGF-binding protein (IGF-bp) levels were studied in 92 constitutionally short children and adolescents (height less than mean for age -2 SD) and in 13 subjects after completion of growth. IGF levels increased with age in a manner similar to that in normal subjects, but at lower levels (P less than 0.001). The values were 0.41 +/- 0.03 SEM U/ml in 1 to 5 year old children, 0.72 +/- 0.03 U/ml in 6- to 16 year old prepubescent children and 0.95 +/- 0.05 U/ml during puberty. IGF-bp levels developed in a similar way, the values being 0.45 +/- 0.06, 0.61 +/- 0.04 and 0.85 +/- 0.06 U/ml, respectively, for the three periods considered. Both IGF and IGF-bp levels in each of the three groups were significantly lower than those in normal subjects at the same stage of development. After fusion of the epiphyses, IGF and IGF-bp levels were within the normal range. A longitudinal study was undertaken in 15 subjects, showing increases in height corresponding with increases in IGF levels. For all the subjects studied during their growth period, there was a correlation between height age and IGF levels (r = 0.64, P less than 0.001). All the subjects exhibited a normal rise in GH levels following stimulation. Although the possibility of quantitative or qualitative disorders of GH biosynthesis cannot be excluded in some of the cases, our data are compatible with the hypothesis that the growth retardation observed in constitutionally short children results, at least in part, from insufficient IGF production during post-natal growth.
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PMID:Serum levels of insulin-like growth factor (IGF) and IGF-binding protein in constitutionally short children and adolescents. 242 88


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