Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
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Plasma GH responses to iv administered synthetic human GH-releasing factor-(1-44)-NH2 (hGRF) and the concentration of endogenous hGRF-like immunoreactivity (hGRF-LI) in the cerebrospinal fluid (CSF) were examined in 16 children with GH deficiency (GHD). Ten patients had idiopathic GHD, and six had GHD secondary to germinoma. An iv bolus hGRF (1 microgram/kg BW) injection test was performed the day before and the day after treatment, with a daily 1-h iv infusion of hGRF (2 micrograms/kg BW) for 3 days. Plasma GH increases (greater than 5 ng/ml) after the first iv bolus injection of hGRF occurred in 2 of the 10 idiopathic GHD children and in 4 of the 6 GHD patients with germinoma whereas the first bolus hGRF injection failed to elicit GH release in the remaining 10 patients. The mean +/- SEM peak plasma GH level after the first bolus hGRF dose in the patients with germinoma (8.2 +/- 2.2 ng/ml) was significantly higher than that in the idiopathic GHD patients (2.9 +/- 0.9 ng/ml; P less than 0.05), but significantly lower than that in normal children with short stature (18.5 +/- 2.5 ng/ml; P less than 0.05). In the 2 patients with germinoma and in 5 of the 8 idiopathic GHD children who did not respond to the first hGRF bolus dose, a significant plasma GH response to hGRF occurred during a daily iv infusion of hGRF for 3 consecutive days, whereas the remaining 3 idiopathic GHD children failed to respond to the daily hGRF infusions. The plasma GH response after the second hGRF bolus dose given after treatment with daily hGRF infusions for 3 days was not different from that after the first hGRF bolus in patients with germinoma or that in the idiopathic GHD children. hGRF-LI was not detected (less than 5.8 pg/ml) in the CSF in any of 5 patients with germinoma, whereas it was present in 5 idiopathic GHD patients (mean, 17.5 +/- 0.9 pg/ml), 3 of whom were nonresponders to daily hGRF infusions. From these results, GHD secondary to destruction of hypothalamic GRF neurons might be defined by the following findings: 1) lack of a GH response to the standard provocative tests acting through the hypothalamus; 2) significant increase in plasma GH after a single bolus and/or repetitive iv administration of hGRF; and 3) undetectable or extremely low levels of endogenous hGRF-LI in the CSF. Most of the idiopathic GHD patients responded to the repetitive hGRF infusion, suggesting insufficient secretion of hypothalamic hGRF as the primary defect. However, since hGRF-LI was detectable in the CSF in some of the idiopathic GHD patients, its pathogenesis must be multifactorial.
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PMID:Idiopathic growth hormone (GH) deficiency, and GH deficiency secondary to hypothalamic germinoma: effect of single and repeated administration of human GH-releasing factor (hGRF) on plasma GH level and endogenous hGRF-like immunoreactivity level in cerebrospinal fluid. 391 56

The effects of intravenously given human growth hormone-releasing hormone (1-44) NH2 (hGRH-44) on growth hormone (GH) secretion were studied in normal men. A wide variability of intersubject GH response to hGRH-44 was observed. The peak plasma GH levels in response to 50, 100 and 200 micrograms hGRH-44 in 7 normal men were 9.1 +/- 3.2 ng/ml (Mean + SEM), 19.3 +/- 3.3 ng/ml and 22.4 +/- 4.0 ng/ml, respectively. Both the mean peak values for plasma GH response to 100 and 200 micrograms were significantly greater than that for 50 micrograms hGRH-44 injection (p less than 0.01), although there was no significant difference of the mean peak plasma GH values and mean concentrations at each time point, except for those at 120 min, when 100 or 200 micrograms hGRH-44 was administered. A significant difference in the mean amount of plasma GH secreted in response to hGRH-44 was observed only between 50 and 200 micrograms hGRH-44 injection (p less than 0.01). Furthermore, a dose-related plasma GH increase in response to hGRH-44 was not always observed in each subject. In contrast to the wide intersubject variability, the difference among responses of plasma GH to 100 micrograms or 200 micrograms of hGRH-44 given at multiple times separated by intervals of at least 1 week in each individual was relatively small.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The inter- and intra-subject variabilities of plasma GH response to human growth hormone-releasing hormone (1-44) NH2 in men. 393 23

To study the potential contribution of glycine toxicity in the transurethral resection syndrome, we evaluated hemodynamic and visual evoked potential responses to glycine infusion (1 g/kg) in 22 dogs anesthetized with halothane (1.0-1.2% end tidal. Three dogs received 5% glucose in normal saline without glycine; three received arginine (4 mg/kg) in normal saline without glycine; three received arginine (4 mg/kg) in normal saline without glycine; 10 received glycine (1 g/kg), then arginine (4 mg/kg) 120 min after the completion of glycine infusion; and six received arginine 30 min after the completion of glycine infusion. Arginine was infused to evaluate potential antagonistic effects of glycine toxicity. Blood levels of glycine, ammonia, arginine, urea, and formate were determined after infusions of glycine or arginine. All animals received about 5 ml X kg-1 X hr-1 of normal saline during the 2-4 hr of study. Immediately after glycine infusion, cardiac output increased 57%, whereas systemic vascular resistance and mean arterial pressure decreased 32% and 8%, respectively. Later cardiac output and mean arterial pressure were 41% and 18% less than control levels, whereas systemic vascular resistance returned to control levels. Both amplitude and latency of visual evoked potential waveforms were altered in the animals receiving glycine infusion but not in the control animals. These responses were associated with elevations of blood glycine (149 +/- 5 to 9591 +/- 809 microM/L, mean + SEM) and blood NH3 (10.5 +/- 2.8 to 100.0 +/- 13.6 microM/L), but not with formate levels.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of glycine on hemodynamic responses and visual evoked potentials in the dog. 405 Dec 5

Peptidyl glycine alpha-amidation activity has been detected in human plasma and in several human tissues known to synthesize biologically active alpha-amidated peptides. Activity was monitored by measuring conversion of mono-[125I]-D-Tyr-Val-Gly into mono-[125I]-D-Tyr-Val-NH2. The plasma alpha-amidation activity is dependent on molecular oxygen, copper, and ascorbic acid and appears to recognize a variety of peptide substrates which contain carboxyl terminal glycine residues. Kinetic analyses demonstrated Michaelis-Menten kinetics with a Km of 14 mumol/L for D-Tyr-Val-Gly. Based on gel filtration, the apparent molecular weight of the peptidyl glycine alpha-amidation activity in human serum is 60,000. The level of peptidyl glycine alpha-amidation activity in adult plasma (N = 17) was 106 +/- 3 pmol/mL/h (Mean +/- SEM) with no difference between male and female subjects (range 84 to 126 pmol/mL/h). In subjects under 15 years old (N = 10), mean plasma activity was 128 +/- 10 pmol/mL/h, higher than values for adult control plasma (P less than .05). In serum from hypothyroid adults (N = 13), mean serum activity was 141 +/- 11 pmol/mL/hr, higher than euthyroid controls (P less than .025). The most striking elevations in alpha-amidation activity occurred in plasma from patients with peptide-secreting tumors. Patients with medullary thyroid carcinoma (N = 19) had a mean plasma peptidyl glycine alpha-amidation activity of 142 +/- 52 pmol/mL/h (range 84 to 435 pmol/mL/h). The level of plasma alpha-amidation activity in one patient with metastatic carcinoid tumor was 560 pmol/mL/h.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of a peptide alpha-amidation activity in human plasma and tissues. 405 9

Peptidyl-glycine alpha-amidation activity has been detected in human cerebrospinal fluid (CSF) and in several regions of the central nervous system. Activity was monitored by measuring conversion of mono-125I-D-Tyr-Val-Gly into mono-125I-D-Tyr-Val-NH2. The alpha-amidation activity in CSF is dependent on molecular oxygen, copper ions and ascorbic acid and appears to recognize a variety of peptide substrates which contain carboxyl terminal glycine residues. Kinetic analyses demonstrated Michaelis-Menten kinetics with a Km of 4.6 microM for D-Tyr-Val-Gly. The level of peptidyl-glycine alpha-amidation activity in 14 samples of CSF averaged 43 +/- 5 pmol/ml/h (mean +/- SEM; range 11-85 pmol/ml/h) or 1.9 +/- 0.2 pmol/Mg protein/h. No difference was noted between samples from male and female subjects. Extracts of central nervous system tissue contained alpha-amidation activity. The highest levels of enzyme activity were found in the hypothalamus with lower levels in the neurohypophysis and the cerebral cortex. Still lower but detectable activity was found in the cerebellum and pons. Human peptidyl-glycine alph-amidation activity is found in central nervous system tissues known to synthesize alpha-amidated neuropeptides and may be secreted from these tissues along with alpha-amidated peptides into CSF.
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PMID:Characterization of peptide alpha-amidation activity in human cerebrospinal fluid and central nervous system tissue. 408 90

Immunoreactive growth hormone-releasing factor was detected in extracts of acetone preserved human stalk median eminence utilizing an antiserum against human GRF-(1-44)-NH2, isolated from a pancreatic tumor. The antibody is highly specific for the C-terminus of GRF-(1-44)-NH2, and has a cross-reactivity less than 0.02% with GRF-(1-40) free acid, a peptide isolated from a different pancreatic tumor. The mean concentration of IR-GRF in 5 pools of 10-15 stalk-median eminence fragments was 57.7 +/- 7.2 ng/mg protein (mean +/- SEM, range 42.5-75.8 ng/mg protein). Gel filtration chromatographic analysis showed that 97% of the IR-GRF coeluted with synthetic hpGRF-(1-44)-NH2 and eluate inhibition of binding in the radioimmunoassay was parallel to that of hpGRF-(1-44)-NH2. These data strongly suggest that human hypothalamic tissue contains a peptide that is similar to hpGRF-(1-44)-NH2.
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PMID:Immunoreactive growth hormone-releasing factor in human stalk median eminence. 642 65

The concentration of the NH2-terminal fragment of gastrin-17 in serum was determined by radioimmunochemistry. Two antisera were used, one specific for the COOH-terminus and the other for the NH2-terminus of gastrin-17. The NH2-terminal gastrin-17 immunoreactivity in unfractionated serum correlated well with the amount of fragment found after gel filtration of the same sera (p less than 0.001). In healthy subjects (no. = 100), the NH2- and COOH-terminal gastrin immunoreactivity was 8 +/- 1 and 20 +/- 1 pmol/l (mean +/- SEM), respectively. In patients with acute duodenal ulcer (no. = 30) and acute gastritis (no. = 10) the NH2-terminal immunoreactivity was fourfold increased compared with in healthy subjects (p less than 0.001), whereas the COOH-terminal was identical, the NH2- and COOH-terminal concentrations being 33 +/- 7 and 22 +/- 2 pmol/l in duodenal ulcer and 35 +/- 6 and 21 +/- 1 pmol/l in acute gastritis. Other groups of patients had NH2- and COOH-terminal gastrin concentrations in serum similar to those measured in healthy subjects. The results suggest that gastrin cells process gastrin-17 abnormally during the acute phase of duodenal ulcer and gastritis.
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PMID:Increased concentrations of the NH2-terminal fragment of gastrin-17 in acute duodenal ulcer and acute gastritis. 667 84

The measurement of whole body protein turnover in the preterm infant has been investigated with an intragastric infusion of L-[1-13C]-leucine and with sampling of the urinary leucine pool. Measurements have been made in seven preterm infants with body weights averaging 1733 g, fed with either human breast milk (n = 3) or proprietary formulae (n = 4), giving intakes of 541 (+/- 25) kJ/kg and 465 (+/- 42) mg of N day-1 kg-1 and growing satisfactorily (14.7 +/- 2.6 g day-1 kg-1). The measurement of the enrichment of urinary leucine was well within the capability of gas chromatography-spectrometry, and similar values for the enrichment of plasma and urinary leucine were observed (plasma/urinary ratio was 0.93 +/- 0.04, mean +/- 1 SEM, n = 13). Isotopic equilibrium, as indicated by a plateau in the urinary leucine and expired CO2 enrichment, was obtained within 8 h and was maintained for at least 48 h. Nitrogen retention, measured by nitrogen balance, was similar to that calculated from the leucine retention (determined as the leucine intake--oxidation), i.e. 310 +/- 45 and 301 +/- 38 mg of N day-1 kg-1 (means +/- 1 SEM). Because of this it is suggested that in this specific type of study the direct measurement of nitrogen retention dispenses with the need for measurement of leucine oxidation, thereby simplifying the measurements. From the leucine flux, leucine intake and nitrogen retention, rates of whole body protein synthesis and degradation were shown to be 11.32 (+/- 0.78) and 9.54 (+/- 0.55) g day-1 kg-1.
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PMID:The measurement of whole body protein turnover in the preterm infant with intragastric infusion of L-[1-13C]leucine and sampling of the urinary leucine pool. 669 51

In 10 patients with active gastroenterological disease and protein-malnutrition (weight: 77.3 +/- 2.6 (mean +/- SEM) percent of ideal body weight, serum-albumin levels: 2.59 +/- 0.17 mg/100 ml) a randomized crossover study was performed to assess the effects of two energy:nitrogen ratios on body cell replenishment. After at least 3 days for equilibration, the total parenteral nutrition (TPN) study carried out with 354 +/- 5 mg of casein hydrolysate-nitrogen/kg/day, divided in two 7-day periods during which two nonprotein calorie supplies of 47 +/- 1 kcal/kg/day and 81 +/- 4 kcal/kg/day were given. The same 50 +/- 5% dextrose and fat emulsion energy sources were used in the two periods. Nitrogen (Kjeldahl method) and potassium retention, and weight and serum albumin concentration gains were all significantly better (Student t test) during the hypercaloric regimen than during the normocaloric regimen. In the 10 patients, the protein-sparing effect of nonprotein calories "added" during the hypercaloric regimen was demonstrated and represented 17% of the constant infused nitrogen. The more catabolic patient was prior to TPN, the more energy-dependent was the protein-sparing effect observed (r = +0.638). Preliminary data obtained with 3-methylhistidine urine determination suggests that the protein-sparing effect of "added" calories was due to an increased protein synthesis. Finally, body cell replenishment was better with the higher 230 +/- 6 energy:nitrogen ratio than with the lower 132 +/- 4 energy:nitrogen ratio, which suggests that the hypercaloric TPN regimen was useful in such patients.
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PMID:Effects of two energy: nitrogen ratios in patients with gastroenterological disease and malnutrition. 677 8

Six purified amino acid diets containing 6.0 g cystine/kg and the following levels of L-methionine (g/kg diet): 2.1, 2.7, 3.3, 3.9, 4.5, 9.0 were presented to twelve weanling kittens (six male and six female) for six periods of 10 d each. Kittens were assigned to the diets in accordance with a 6 x 6 balanced Latin-square design. Body-weight gains of males and females attained apparent plateaux at 3.3 g methionine/kg diet and were respectively (mean +/- SEM) 22 +/- 4 and 18 +/- 2 g/d. Daily food intakes attained apparent plateaux at 2.7 g methionine/kg diet for male and female kittens and were 63 +/- 10 and 49 +/- 4 g/d respectively. Nitrogen retentions (calculated as dietary-N intake minus faecal- and urinary-N excretion) attained apparent plateaux at 3.9 g methionine/kg diet for both male and female kittens and were 0.85 +/- 0.15 and 0.65 +/- 0.05 g/d respectively. Previous work has shown that the kitten's L-methionine requirement, in a diet lacking cystine, is 7.5 g/kg diet. Our results indicate that the kitten's L-methionine requirement is 3.9 g/kg diet when 6.0 g cystine/kg is provided, thus approximately 50% of the animal's sulphur amino acid requirement can be met by cystine.
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PMID:Methionine requirement of kittens given amino acid diets containing adequate cystine. 686 Jun 23


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