Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002871 (anemia)
 52,094 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Multiple peptide hormones can be derived from the single human GH gene. In addition to the full-length 191-amino acid 22-kilodalton (kDa) form, a 20-kDa variant can be produced by alternative splicing, and a 5-kDa variant can be produced by posttranslational cleavage. To more fully appreciate the physiological roles of these proteins, we have made a comparison of transgenic mice that constitutively overexpress one or another of these variants. We have found that both the 22-kDa and the 20-kDa forms of human GH stimulate linear growth and liver hypertrophy. The increase in linear growth in 22-kDa transgenic mice does not, however, correlate with an increase in circulating IGF-I; rather, the increase in IGF-I that does finally occur correlates with marked liver pathology. Both groups of mice also develop glomerulosclerosis and suffer from hyperinsulinemia. Although there are histologically obvious lesions in the livers of both the 22-kDa and the 20-kDa transgenic mice, only the former exhibit hyperalbuminemia and hypercholesterolemia. Both forms of GH lead to anemia, which is normocytic in the 20-kDa transgenic mice and macrocytic in the 22-kDa transgenic mice. Despite the presence of high levels of the 5-kDa N-terminal form of human GH, the transgenic mice that express this protein are indistinguishable from their nontransgenic littermates.
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PMID:An evaluation of the functions of the 22-kilodalton (kDa), the 20-kDa, and the N-terminal polypeptide forms of human growth hormone using transgenic mice. 172 14

In calves with severe iron (Fe) deficiency, insulin-like growth factor (IGF)-I levels and IGF-I responses to exogenous growth hormone (GH) are reduced, while insulin-dependent glucose utilization is enhanced. Blood plasma concentrations of immunoreactive insulin (IRI), IGF-I, IGF-II and GH, and the half-life of blood plasma GH [after an i.v. injection of recombinant bovine GH (rbGH; 100 micrograms rbGH/kg body weight)] were measured in 20 calves at body weights between 160 and 190 kg. Calves were fed milk replacers containing 50 or 10 mg Fe/kg (groups Fe50 and Fe10, respectively). Daily weight gain and feed utilization were similar in both groups. Group Fe10 developed mild Fe deficiency anemia and blood plasma urea-nitrogen concentrations were higher (p < 0.05) than in group Fe50. IGF-I and IGF-II concentrations did not vary consistently over a 10-hour period and were not significantly influenced by different Fe intakes. The IRI concentration increased transiently (p < 0.05) after feed intake, but the total response was (not significantly) smaller in Fe-deficient calves. Plasma GH concentration changed episodically and was similar in both groups. Loss of GH from the circulation after i.v. rbGH injection, estimated by biexponential analysis, during the distribution or alpha phase (first 16 min) was similar in both groups, but during the beta phase was shorter (p < 0.05) in group Fe10 than in group Fe50 (29.9 and 34.2 min, respectively). The increased disappearance rate of GH, seen even in mild Fe deficiency, may contribute to reduced GH levels and IGF-I responses to GH in severe Fe deficiency.
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PMID:Growth hormone concentration and disappearance rate, insulin-like growth factors I and II and insulin levels in iron-deficient veal calves. 771 Feb 63

Correction of anemia with recombinant human erythropoietin (rhEPO) in patients with end-stage renal disease has been associated with improvement of several abnormalities in hypothalamo-hypophyseal functions. The aim of the present work was to evaluate the growth hormone (GH) responses to GH-releasing hormone (GHRH) and clonidine stimulation, as well as the baseline concentrations of insulin-like growth factor I(IGF-I), before and after the correction of anemia with rhEPO in a group of uremic patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Nine clinically stable patients (1 male, 8 female; mean age 55.4 years; mean duration of CAPD 14.1 months) were studied. Twelve normal volunteers were studied as controls. GHRH and clonidine stimulation tests were performed prior to starting rhEPO and again after partial correction of anemia with rhEPO therapy (60-130 U/kg/week, s.c., for 12 weeks). Blood samples for GH were collected during 2 h after GHRH (100 micrograms i.v. in bolus) or clonidine (0.15 mg/m2, p.o.) administration. In basal plasma samples IGF-I concentrations were also measured. Mean (+/- SEM) blood hemoglobin concentration rose from 5.32 +/- 0.25 to 7.22 +/- 0.25 mmol/l (p < 0.001) after rhEPO treatment. GH responses to GHRH were characterized by marked differences in single patients when compared with the control group. However, the GH peak and the area under the secretory curves (AUC) of GH responses in CAPD patients (9.89 +/- 4.01 micrograms/l and 15.06 +/- 6.02 micrograms.h/l, respectively) did not differ from those obtained in control subjects (14.58 +/- 3.25 microgram/l and 16.94 +/- 4.31 microgram.h/l, respectively). The study after correction of anemia showed an evident potentiation of GH values that reached statistically significant values at 60 and 90 min. GH AUC after rhEPO therapy rose to 25.61 +/- 9.25 micrograms.h/l (p = 0.01). In control subjects, clonidine administration was followed by a GH release that reached a maximum at 90 min (7.67 +/- 2.24 micrograms/l). However, CAPD patients exhibited a blunted response to clonidine both before (2.00 +/- 0.78 microgram/l) and after (2.78 +/- 0.76 microgram/l, NS) correction of the anemia with rhEPO. On the other hand, IGF-I concentrations after rhEPO therapy (32.05 +/- 5.52 nmol/l) were not significantly different from those found prior to starting therapy (38.13 +/- 8.44 nmol/l). In conclusion, these results suggest that correction of the anemia with rhEPO therapy potentiates GH responses to direct pituitary stimulation with GHRH although it is unable to restore the blunted response of GH to clonidine that is found in CAPD patients.
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PMID:Growth hormone responses to growth hormone-releasing hormone and clonidine before and after erythropoietin therapy in CAPD patients. 893 79

As with spontaneous growth, the height gain achieved by stimulation with recombinant human growth hormone (rhGH) in children with chronic renal failure appears to be inversely related to the degree of renal dysfunction. The secondary complications of CRF that may independently interfere with growth, such as metabolic acidosis, anaemia, and secondary hyperparathyroidism, do not explain the poorer response to rhGH in children with end-stage renal failure. Certain abnormalities of the somatotropic hormone axis, the severity of which is related to the degree of renal dysfunction, are more likely to explain the dependence of the rhGH treatment response on glomerular filtration rate. These derangements include partial GH receptor deficiency, increased plasma binding of IGF-I, and accumulation of non-competitive inhibitors of IGF-I action. Strategies to optimise growth-promoting treatment in end-stage renal failure will depend on the relative contribution of these different somatotropic hormone axis alterations to uraemia.
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PMID:Pathogenic mechanisms underlying the variable response to recombinant human growth hormone in children with chronic renal failure. 899 24

In neonatal calves besides adaptations in organ function there are marked metabolic and endocrine changes. The growth hormone (GH)-insulin-like growth factor (IGF) axis is basically functioning, but needs maturation. Various metabolic and endocrine traits do not exhibit marked ontogenetic changes after the first week of life, but others remain different from the adult stage. Thus, plasma oxytocin or an oxytocin-like substance and nitrate concentrations are elevated for months. The ability to digest colostrum (C) and milk involves great alterations in structure and function of the gastrointestinal (GI) tract. C intake is important for passive immunity, provision of nutrients, minerals and vitamins, and contains biologically active substances. IGF-I, present in C in high amounts, appears to enhance GI tract development and function. For sufficient absorption not only of immunoglobulins, but also of fatty acids and fat-soluble vitamins, C should be ingested immediately after birth. The amino acid pattern and the glutamine/glutamate ratio depends greatly on whether C is fed or not. Effects on insulin, IGF-I, and IGF binding proteins depend on time-point and amounts of C fed. After the colostral period calves are almost exclusively fed milk and milk substitutes or weaned. Low iron intake, required for the production of pale meat, besides anemia causes metabolic and endocrine adaptations, such as enhanced insulin-dependent glucose utilization and appears to reduce IGF-I responses to GH. Metabolic and endocrine changes, such as insulin resistance and disturbed glucose metabolism, can be observed in part in association with high feeding intensity in veal calves.
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PMID:Endocrine and metabolic aspects in milk-fed calves. 1052 25

We evaluated a short, prepubertal 13.9 year-old boy with Blackfan-Diamond anemia and significant liver iron stores due to multiple blood transfusions and found him to have several endocrine abnormalities, including hypothyroidism, hypoparathyroidism, primary and secondary hypogonadism and IGF-I insufficiency. Growth velocity was poor despite treatment with levothyroxine, calcitriol, calcium and aggressive therapy with chelating agents. After 25 months of treatment with rhGH his growth velocity, height for age and PAH increased significantly, suggesting a degree of sensitivity to GH despite his liver damage.
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PMID:Multiple endocrine abnormalities in a child with Blackfan-Diamond anemia and hemochromatosis. Significant improvement of growth velocity and predicted adult height following growth hormone treatment despite liver damage. 1071 60

High doses of GH, used to induce anabolism in prolonged critically ill patients, unexpectedly increased mortality. To further explore underlying mechanisms, a valid animal model is needed. Such a model is presented in this study. Seven days after arterial and venous cannulae placement, male New Zealand White rabbits were randomly allocated to a control or a critically ill group. To induce prolonged critical illness, a template controlled 15% deep dermal burn injury was imposed under combined general and regional (paravertebral) anesthesia. Subsequently, critically ill rabbits received supplemental analgesia and were parenterally fed with glucose, insulin, amino acids, and lipids. On d 1 and d 8 after randomization, acute and chronic spontaneous hormonal profiles of GH, TSH, and PRL secretion were obtained by sampling blood every 15 min for 7 h. Furthermore, GH, TSH, and PRL responses to an iv bolus of GH-releasing peptide 2 (GHRP-2) + TRH were documented on d 0, 1, and 8. Hemodynamic status and biochemical parameters were evaluated on d 0, 1, 3, 5, and 8, after which animals were killed and relative wet weight and water content of organs was determined. Compared with controls, critically ill animals exhibited transient metabolic acidosis on d 1 and weight loss, organ wasting, systolic hypertension, and pronounced anemia on d 8. On d 1, pulsatile GH secretion doubled in the critically ill animals compared with controls, and decreased again on d 8 in the presence of low plasma IGF-I concentrations from d 1 to d 8. GH responses to GHRP-2 + TRH were elevated on d 1 and increased further on d 8 in the critically ill animals. Mean TSH concentrations were identical in both groups on d 1 and 8, in the face of dramatically suppressed plasma T(4) and T(3) concentrations in the critically ill animals. PRL secretion was impaired in the critically ill animals exclusively on d 8. TSH and PRL responses to GHRP-2 and TRH were increased only on d 1. In conclusion, this rabbit model of acute and prolonged critical illness reveals several of the clinical, biochemical, and endocrine manifestations of the human counterpart.
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PMID:A novel in vivo rabbit model of hypercatabolic critical illness reveals a biphasic neuroendocrine stress response. 1186 95

The insulin-like growth factor (IGF) system regulates proliferation and differentiation of hematopoietic cells. IGFs exert their effects through specific receptors on growing and differentiating blood cells as they emerge from their small pool of ancestral stem cells. The IGF system is complex as both stimulating and inhibiting effects occur by interaction of IGFs and IGF-binding proteins (IGFBPs). IGFs stimulate erythrocytes and lymphocytes but also promote leukemic hematopoietic cell proliferation. IGF-I appears to be correlated with hemoglobin levels in anemia and could also be of benefit for patients with bone marrow aplasia after transplantation. Hypersensitivity to IGF-I has been implicated as an underlying cause of polycythemia vera. Loss of imprinting of IGF-II is found in acute myeloid leukemia and myelodysplastic syndrome. Apoptosis of hematopoietic cells is significantly reduced by IGF-I involving an intriguing signal transduction pathway. IGFs could therefore, although not classical hematopoietic growth factors, be of benefit for patients with diverse hematopoietic disorders.
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PMID:The insulin-like growth factor system in hematopoietic cells. 1200 50

Thalassemia/hemoglobinopathy is a hereditary disease that causes chronic anemia and increased erythropoiesis. Consequently, an expansion of bone marrow spaces may contribute to osteopenia/osteoporosis. However, the pathogenesis of bone changes is not yet known. We, therefore, carried out the study on bone histomorphometry and biochemical and hormonal profiles in children and adolescents with suboptimally treated beta-thalassemia disease with the hope of gaining some new insight into the cellular and structural alterations of thalassemic bone. Seventeen patients underwent iliac crest bone biopsy for histomorphometric analyses. Bone mineral density (BMD) measurements were performed by dual energy x-ray absorptiometry. Most patients had growth retardation and delayed bone age. BMD was low especially at the lumbar spine. Serum IGF-I levels were almost always low. Bone histomorphometry revealed increased osteoid thickness, osteoid maturation time, and mineralization lag time, which indicate impaired bone matrix maturation and defective mineralization. In addition, iron deposits appeared along mineralization fronts and osteoid surfaces. Moreover, focal thickened osteoid seams were found together with focal iron deposits. Dynamic bone formation study revealed reduced bone formation rate. These findings indicate that delayed bone maturation and focal osteomalacia are the pathogenesis of bone disease in suboptimally blood-transfused thalassemics with iron overload. Iron deposits in bone and low circulating IGF-I levels may partly contribute to the above findings.
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PMID:Bone histomorphometry in children and adolescents with beta-thalassemia disease: iron-associated focal osteomalacia. 1291 94

Geriatric and cancer-afflicted patients often experience decreased quality of life with cachexia, anemia, anorexia, and decreased activity level. We have studied the possibility that a myogenic plasmid that expresses growth hormone releasing hormone (GHRH) can prevent and/or treat these conditions. We administered plasmid to 17 geriatric and five cancer-afflicted companion dogs with an average age of 10.5+/-1.0 and 11.3+/-0.6 years at enrollment, respectively. Effects of the treatment were documented for at least 180 days post-treatment, with 10 animals followed for more than 1 year post-treatment, on average 444+/-40 days. Treated dogs showed increased IGF-I levels, and increases in scores for weight, activity level, exercise tolerance, and appetite. No adverse effects associated with the GHRH plasmid treatment were found. Most importantly, the overall assessment of the quality of life of the treated animals increased. Hematological parameters such as red blood cell count, hematocrit, and hemoglobin concentrations were improved and maintained within their normal ranges. We conclude that intramuscular injection of a GHRH-expressing plasmid is both safe and capable of improving the quality of life in animals for an extended period of time in the context of aging and disease. The observed anabolic and hematological responses to a single dose of this plasmid treatment may also be beneficial in geriatric patients or patients with cancer-associated anemia and/or cachexia.
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PMID:Long-term effects of plasmid-mediated growth hormone releasing hormone in dogs. 1507 11


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