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)

[125I]Insulin-like growth factor I (IGF-I) specifically bound to erythrocytes; the binding was saturable, and time and temperature dependent. Steady state binding was reached at 16 h at 4 C, and specific binding averaged 14.3 +/- 0.7% (+/- SEM) at a concentration of 3.6 X 10(9) cells/ml in seven normal subjects. [125I]IGF-I binding to the cells was displaced by unlabeled IGF-I in a dose-dependent manner. Scatchard analysis indicated a linear plot, and Ka and number of binding sites/cell were 1.43 +/- 0.07 X 10(9) M-1 and 20.7 +/- 2.2, respectively. Compared to IGF-I, the relative potencies of multiplication-stimulating activity and insulin for displacing [125I]IGF-I binding were 20% and 1%, respectively. [125I]IGF-I binding to erythrocytes from patients with acromegaly was lower than binding to cells from pituitary dwarfs. An inverse correlation between plasma IGF-I level and the number of IGF-I-binding sites per cell was found (r = -0.75; P less than 0.005). These results demonstrate that [125I]IGF-I binding to erythrocytes can be used for clinical measurement of the IGF-I receptor.
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PMID:Characterization of insulin-like growth factor I receptor on human erythrocytes. 299 58

We have investigated the effects of intravenous administration of a low dose of dopamine (DA) on plasma growth hormone (GH) concentrations in acromegalic patients and normal subjects with the aim of defining the somatotroph responsiveness to peripheral (i.e., outside the blood-brain barrier) specific dopaminergic stimuli. DA (0.02 micrograms/kg/min) was infused for 180 min into 12 acromegalic patients and 10 normal subjects. DA infusion discriminated between two groups of acromegalics. In group I (n = 7), the elevated plasma GH levels (64.1 +/- 29.9 ng/ml, mean basal value +/- SEM) decreased significantly (mean overall GH inhibition, 26% reduction from basal levels; range, 10-49), whereas in group II (n = 5) plasma GH levels (29.8 +/- 12.5 ng/ml) remained elevated (mean GH variation, 8% above baseline; range, 0-15). Plasma GH concentrations showed a significant rebound above baseline values after stopping DA infusion only in group I. In contrast, the responsiveness to TRH was not significantly different between the groups (percentage increase 767 +/- 317% in group I vs. 382 +/- 210% in group II) and they were also comparable with regard to sex, age, glucose tolerance, plasma prolactin (PRL) concentrations and adenoma size. However, the mean duration of the disease was significantly (p less than 0.02) longer in group I (12.8 +/- 2.6 years) than in group II (4.5 +/- 1.5 years). Further, 3 patients with previous radiotherapy for invasive adenomas were nonresponders to DA. In normal subjects, DA infusion had no significant effect on plasma GH levels. It is concluded that: somatotroph responsiveness to DA is not a constant feature of acromegaly.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Somatotroph responsiveness to low dose dopamine infusion in normal subjects and acromegalic patients. 301 Jan 56

1. Somatostatin analogues, such as SMS 201-995 (sandostatin), have been suggested as treatment for a variety of disease states including acromegaly, secretory gastrointestinal tumours and diabetes mellitus. 2. Somatostatin-14 has actions to prolong gastro-intestinal transit time and inhibit intestinal absorption, and we have therefore studied the effects of SMS 201-995 on these processes. Five male subjects received a test meal having been given either saline or 50 micrograms of SMS 201-995 subcutaneously 30 min before ingestion. 3. SMS 201-995 caused a delay in mouth-to-caecum transit time for lactulose assessed by breath hydrogen analysis (316 +/- 17 vs 192 +/- 14 min, mean +/- SEM, P less than 0.01), a delay (234 vs 120 min, P less than 0.05) in the plasma peak of the non-metabolizable glucose analogue 3-O-methylglucose and conversion of the expected postprandial rise in serum triglycerides (with saline 1.02 +/- 0.20 to 1.51 +/- 0.28 mmol/l, P less than 0.05) to a decrease below basal values (with SMS 201-995 0.97 +/- 0.80 to 0.79 +/- 0.11 mmol/l, P less than 0.05). 4. After SMS 201-995, an enhancement of the increase in blood glucose (8.2 +/- 0.7 vs 4.7 +/- 0.2 mmol/l, P less than 0.01) and inhibition and postponement of the postprandial rise in insulin (27.6 +/- 6.7 vs 9.9 +/- 2.1 m-units/l, P less than 0.05) occurred. Furthermore, a rise in non-esterified fatty acids, glycerol and 3-hydroxybutyrate, compared with the decline in concentrations of these metabolites after saline, was observed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of the somatostatin analogue SMS 201-995 (sandostatin) on mouth-to-caecum transit time and absorption of fat and carbohydrates in normal man. 305 74

Immunoreactive and receptor-reactive insulin-like growth factor I (IGF-I) was demonstrated in human urine. Thirty percent of the IGF-I immunoreactivity in urine was free, and the remainder was a high mol wt form (approximately 43K). Urinary IGF-I was quantitated by RIA after extraction with octadecylsilyl silica cartridges (Sep-Pak C18 cartridge), a method that measures only free IGF-I. The mean urinary immunoreactive IGF-I levels in normal adults (n = 8) and patients with acromegaly (n = 10) or hypopituitarism (n = 9) were 72 +/- 7 (+/- SEM), 225 +/- 34, and 19 +/- 4 pg/mg creatinine, respectively; these mean values were significantly different from one another. The results indicate that IGF-I is present in human urine and that the quantity in urine is altered in patients with GH excess and deficiency.
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PMID:Demonstration of insulin-like growth factor I in human urine. 357 31

We produced antiserum to insulin-like growth factor I (IGF-I), and developed a specific and sensitive radioimmunoassay (RIA) for IGF-I using the biosynthetic IGF-I. This antiserum to IGF-I was specific for IGF-I; no cross-reactivities with multiplication stimulating activity, porcine insulin or human growth hormone (hGH) were detected. The sensitivity was 10-25 pg/tube with 50% displacement at 125 pg/tube. The intra- and inter-assay coefficients of variation for IGF-I were 5.4 and 9.7%, respectively. The plasma IGF-I levels as determined by RIA in normal adults (N = 46), patients with active acromegaly (N = 31), and pituitary dwarfs (N = 31) were 21.6 +/- 1.0, 157.3 +/- 17.0, and 2.5 +/- 0.3 ng/ml (Mean +/- SEM), respectively, indicating the levels were GH-dependent. The plasma IGF-I levels were significantly increased from 2.2 +/- 0.2 to 26.5 +/- 3.2 ng/ml after hGH administrations for three consecutive days in five pituitary dwarfs. The IGF-I levels were low in patients with hypothyroidism and liver cirrhosis, but were normal in patients with chronic renal failure. These data confirm previous reports and this radioimmunoassay proves useful in evaluating plasma IGF-I levels.
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PMID:Radioimmunoassay for insulin-like growth factor I (IGF-I) using biosynthetic IGF-I. 358 65

The renal excretion of radioimmunoassayable somatomedin-C/insulin-like growth factor I (Sm-C/IGF-I) was measured in 12-h overnight urine samples obtained from 88 subjects, aged 3-19 yr. The participants included 34 healthy children (group 1), 29 children with idiopathic growth failure and normal GH stimulation tests (group 2), and 25 GH-deficient subjects (group 3). The mean (+/- SEM) urinary Sm-C/IGF-I excretion in group 1 (28.4 +/- 2.1 mU/kg) was significantly greater than that in group 2 (8.1 +/- 1.6 mU/kg) or group 3 (8.6 +/- 1.3 mU/kg). Twenty-two of the 29 subjects in group 2 had urinary Sm-C/IGF-I values less than 8 mU/kg. After the administration of biosynthetic GH to 12 GH-deficient subjects, urinary Sm-C/IGF-I excretion rose from 10.3 +/- 2.3 to 21.4 +/- 4.2 mU/kg within 12 h (P less than 0.05), indicating that renal excretion of Sm-C/IGF-I is GH dependent. One woman with acromegaly had markedly elevated urinary Sm-C/IGF-I excretion (420 mU/kg). The authenticity of urinary Sm-C/IGF-I was confirmed by high pressure liquid chromatography (HPLC). Assay of serial dilutions of urinary Sm-C/IGF-I demonstrated a direct proportionality between concentration and dilution. Although it is not possible to identify whether urinary Sm-C/IGF-I reflects local or generalized synthesis of the peptide, we hypothesize that quantitation of Sm-C/IGF-I in timed urine collections will yield additional information about GH production and action in children with normal and abnormal growth.
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PMID:Quantitation of urinary somatomedin-C in children with normal and abnormal growth. 368 Apr 79

Determination of plasma IGF-I concentrations is not easily accessible to clinical use at present because of extremely limited supply of purified natural IGF-I essential for its assay system. Thus, an alternative method has recently been introduced by the development of a specific radioimmunoassay (RIA) for IGF-I (26-46). We examined the specificity and sensitivity of this assay system, and then investigated the changes in plasma concentrations of IGF-I in normal children, adults and in patients with various endocrine and metabolic diseases. Each plasma sample was subjected to acid-ethanol treatment before assay to separate IGF-I from its binding protein. The recovery rate of known amount of IGF-I (26-46) added to untreated plasma sample was more than 90%. The coefficients of variation of intra- and interassay were 9.0% and 13.6%, respectively. This assay system was able to detect IGF-I as low as 10 pg/tube. When plasma sample of a patient with active acromegaly was applied to Sephadex G-75 column, immunoreactive IGF-I was eluted at the position of 7,000 molecular weight. An inhibition curve of plasma extract from an acromegalic patient was parallel to that of IGF-I (26-46), indicating that the RIA could detect IGF-I. There was no remarkable difference between IGF-I values of plasma and serum from the same individual. The value of IGF-I concentration of cord plasma was considerably low (144 +/- 6.7 pg/ml, M +/- SEM) as compared with that of sera of 49 normal children aged 7-12 12 years (320 +/- 14.3 pg/ml). The highest value (460 +/- 54 pg/ml) was attained at the age of 13 years, followed by gradual decrease toward adult age. Plasma IGF-I concentration of normal adults between 20 and 69 years of age was 290 +/- 10 pg/ml. When plasma IGF-I values of adult males and females were separately plotted against age group of each decade, the value declined gradually with age in males while in females there was a remarkable increase in plasma IGF-I concentration at 4th and 5th decades, suggesting the effect of hormonal change at menopause on plasma IGF-I levels. There was a good correlation between disorders of GH secretion and plasma IGF-I concentrations. In 10 cases of active acromegaly the level was 506 +/- 67 pg/ml (285-970 pg/ml). On the other hand in 20 patients with pituitary dwarfism it was only 180 +/- 15 pg/ml.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Studies on plasma insulin-like growth factor (IGF)-I levels in normal subjects and in patients with various endocrine and metabolic diseases using radioimmunoassay for synthetic IGF-I (26-46)]. 369 96

The pharmacokinetics of oral terguride 1 mg was evaluated in a single-dose study in 8 patients with a prolactinoma and one with acromegaly. A radioreceptor assay was used to measure the plasma levels of terguride. The peak plasma concentration (2.3 +/- 0.7 ng/ml, mean +/- SEM) was attained within 1 h of drug administration. Moment analysis gave a mean residence time of 4.3 +/- 0.6 h. Plasma prolactin was also determined by radioimmunoassay. The plasma prolactin was reduced to 30 +/- 3% of its pretreatment value after 4 h.
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PMID:Pharmacokinetics of oral terguride in patients with a prolactinoma. 373 77

It is not clear whether dopamine (DA) has a central stimulating activity on GH secretion in patients with acromegaly, as it does in normal subjects. To clarify this, we compared the GH inhibitory potencies of DA, which does not cross the blood-brain barrier (BBB), and L-dopa or bromocriptine, which do cross the BBB, in 23 patients with acromegaly. Further, we examined the central effects of L-dopa after selectively blocking peripheral (median eminence and pituitary) DA receptors with domperidone (a DA D2 receptor blocker which does not cross the BBB). After the administration of DA (5 micrograms/kg X min, iv, for 90 min), L-dopa (500 mg, orally), or bromocriptine (2.5 mg, orally), the mean plasma GH decrease was greatest after DA [maximum decrement, 71.9 +/- 3.8% (+/- SEM); n = 21] compared to L-dopa (44.1 +/- 5.6%; n = 23; p less than 0.001) or bromocriptine (58.9 +/- 5.0%; n = 20; p less than 0.02). Eleven of these patients received a single infusion of domperidone (0.22 mg/min, iv, for 180 min) or a combination of domperidone and L-dopa. Mean plasma GH levels did not change during domperidone alone. However, plasma GH levels in these patients increased significantly when L-dopa was administered 30 min after the start of domperidone infusion (vs. control study: at 90 min, 137.3 +/- 10.8% vs. 100.2 +/- 3.9%, p less than 0.01; at 120 min, 138.8 +/- 19.7% vs. 106.5 +/- 3.1%, p less than 0.05). In contrast, one patient who had a distinct plasma GH increase in response to the domperidone-L-dopa test had no increase in plasma GH when given L-dopa 30 min after the start of a sulpiride infusion (DA D2 receptor blocker which crosses the BBB; 1.1 mg/min, iv, for 180 min). Unlike GH, plasma PRL responses to domperidone infusion were not modified by the additional administration of L-dopa. These results suggest that in acromegaly, DA has not only direct suppressive effects on the pituitary tumor somatotrophs, but also indirect stimulatory effects via the hypothalamus; therefore, the hypothalamic GH-releasing system is not entirely suppressed by excessive tumor GH secretion.
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PMID:Growth hormone inhibitory and stimulatory actions of L-dopa in patients with acromegaly. 379 48

Patients with acromegaly have alterations in mineral metabolism. To determine the effect of correction of excess GH secretion on calcium metabolism, we studied 12 acromegalic patients before and 3-4 weeks after pituitary adenomectomy. Treatment of acromegaly resulted in significant decreases in both serum calcium [from 9.3 +/- 0.2 to 8.7 +/- 0.1 mg/dl (mean +/- SEM); P less than 0.01] and urinary calcium excretion (from 200 +/- 24 to 88 +/- 12 mg/24 h; P less than 0.0002). Serum phosphate also decreased significantly (P less than 0.01) from 4.8 +/- 0.2 to 4.3 +/- 0.2 mg/dl. Both serum immunoreactive PTH and calcitonin levels were normal initially and did not change after surgery. The mean serum 25-hydroxyvitamin D (25OHD) level was significantly (P less than 0.01) lower and the 1,25-dihydroxyvitamin D [1,25-(OH)2D] level was significantly (P less than 0.0001) higher in acromegaly compared with measurements in 25 normal subjects. After surgery, the serum 25OHD level did not change; however, the serum 1,25-(OH)2D concentration fell significantly (P less than 0.0001) from 60 +/- 4 to 43 +/- 2 pg/ml. A positive correlation was found between the decrements in urinary calcium excretion and the serum 1,25-(OH)2D level when the comparison was made between the decrements as percentages of pretreatment values (r = 0.64; P less than 0.05). The accumulated data suggest that the hypercalciuria in acromegaly might be due to intestinal calcium hyperabsorption, which could be attributed to the elevated circulating 1,25-(OH)2D level. Excessive GH secretion might stimulate the production of 1,25-(OH)2D and might also directly stimulate calcium absorption.
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PMID:Changes in calcium homeostasis in acromegaly treated by pituitary adenomectomy. 383


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