Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020437 (hypercalcemia)
 10,293 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Secondary hyperparathyroidism is a universal complication of chronic renal failure. It has been proposed that the markedly elevated levels of immunoreactive parathyroid hormone (i-PTH) in uremia may represent a "uremic toxin" responsible for many of the abnormalities of the uremic state. Plasma i-PTH consists of a mixture of intact hormone, a single-chain polypeptide of 84 amino acids, and smaller molecular weight hormonal fragments from both the carboxy- and amino-terminal portion of the PTH molecule. The hormonal fragments arise from metabolism of intact PTH by peripheral organs as well as from secretion of fragments from the parathyroid glands. The structural requirements for the known biological actions of PTH reside in the amino-terminal portion of the PTH molecule. Carboxy-terminal fragments, biologically inactive at least in terms of adenylate cyclase activation, hypercalcemia, or phosphaturia, depend on the kidney for their removal from plasma, and thus accumulate in the circulation in chronic renal failure. It is unknown at the present time if other biological effects of these carboxy-terminal fragments may contribute to some of the biochemical alterations observed in uremia. The most significant consequence of increased PTH levels in uremia is the development of bone disease characterized by osteitis fibrosa. In addition, it would appear that PTH plays an important role in some of the abnormal electroencephalographic patterns observed in uremia. This may be due to a potential role of PTH in increasing calcium content of brain. Parathyroid hormone also has been implicated as a pathogenetic factor in many other alterations present in uremia, i.e., peripheral neuropathy, carbohydrate intolerance, hyperlipidemia, and other alterations. Unfortunately, outstanding clinical research is lacking in this field and conclusive experimental data are practically nonexistent. Further studies are necessary if one is to accept the concept of PTH being a significant "uremic toxin."
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PMID:Parathyroid hormone metabolism and its potential as a uremic toxin. 699 9

Three patients with the watery diarrhea-hypokalemia-achlorhydria (WDHA) syndrome were studied. All had watery diarrhea, hypokalemia and hypercalcemia. Plasma vasoactive intestinal polypeptide (VIP) levels determined by radioimmunoassay were markedly elevated in these patients, indicating that they had VIP-producing tumors. Plasma VIP levels determined serially after the operation indicate that its determination is useful in estimating the effect of a treatment. As for multiple endocrine neoplasia type 1 (MEN1), two out of the three cases belonged to this category. Patient 1 had a brother with insulinoma, and in case 2, even though there was no family history, the autopsy revealed not only multiple tumors of the pancreas but also pituitary adenomas, chief cell hyperplasia of the parathyroid glands, thyroid adenomas and adrenocortical adenomas. VIP and other hormones in the tumors as well as in the plasma were examined extensively in these cases. In case 1, VIP, gastrin and calcitonin were produced in the tumor and only plasma VIP levels were elevated. In case 2, with multiple tumors, tumor 1 produced VIP, glucagon pancreatic polypeptide, gastrin and calcitonin, and tumor 2, VIP, pancreatic polypeptide, gastrin and beta-melanocyte stimulating hormone. In this case, plasma VIP, pancreatic polypeptide and glucagon levels were elevated. In case 3, VIP and calcitonin were produced in the tumor, and plasma VIP and calcitonin levels were elevated. These results indicate that (1) VIP is a good tumor marker for the WDHA syndrome due to VIP-producing tumors; (2) patients with the WDHA syndrome are sometimes associated with MEN1; and (3) VIP-producing tumors are multiple hormone-producing tumors, and VIP predominantly elevated in the plasma results in the WDHA syndrome, although other hormones such as pancreatic polypeptide, glucagon and calcitonin are sometimes found to be elevated in plasma without contributing to the clinical features.
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PMID:Clinical and hormonal aspects of the watery diarrhea-hypokalemia-achlorhydria (WDHA) syndrome due to vasoactive intestinal polypeptide (VIP)-producing tumor. 701 8

Two cases of hypercalcemic infantile renal tumor without macroscopic bone metastases are reported. Optical and ultrastructural characteristics as well as biological and clinical data are sufficiently different from those of other infantile renal tumors to justify the individualization of an original tumor entity. The hypercalcemia is not clearly understood but may be related, in one case, with a high N terminal PTH serum level. Ultrastructural elements (secretory granules) and polypeptide hormone products (glucagon) are discussed in relation with APUD cells characteristics.
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PMID:An original hypercalcemic infantile renal tum or without bone metastasis: heterotransplantation to nude mice: report of two cases. 708 27

Parathyroid hormone-like protein (PLP) was originally identified from tumors associated with hypercalcemia. Recently, it has been found to be expressed in a stretch-responsive manner in several types of smooth muscle. We studied adult rat heart muscle for the presence of the PLP. Using immunohistology and the PCR, we demonstrated the presence of PLP and its mRNA in all heart chambers. Immunoelectron microscopy demonstrated PLP in secretory vesicles of atrial mycocytes. Using immunoassay, we demonstrated that atria contained a higher concentration of PLP than ventricles. Furthermore, primary cultures of both chambers released PLP into conditioned medium, with atria secreting more than ventricles. Considered with studies of the role of PLP in other tissues, our observations suggest that the production and secretion of PLP by cardiac myocytes represents a calcium-related regulatory function for this stretch-responsive polypeptide in the cardiovascular system. PLP in the heart may be the calcium counterpart for the atrial natriuretic-sodium regulatory axis of the cardiovascular system.
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PMID:Parathyroid hormone-like protein is a secretory product of atrial myocytes. 834 12

We have isolated a human cDNA clone encoding the mammalian homolog of stanniocalcin (STC), a calcium- and phosphate-regulating hormone that was first described in fishes where it functions in preventing hypercalcemia. STC has a unique amino acid sequence and, until now, has remained one of the few polypeptide hormones never described in higher vertebrates. Human STC (hSTC) was found to be 247 amino acids long and to share 73% amino acid sequence similarity with fish STC. Polyclonal antibodies to recombinant hSTC localized to a distinct cell type in the nephron tubule, suggesting kidney as a possible site of synthesis. Recombinant hSTC inhibited the gill transport of calcium when administered to fish and stimulated renal phosphate reabsorption in the rat. The evidence suggests that mammalian STC, like its piscine counterpart, is a regulator of mineral homeostasis.
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PMID:Human stanniocalcin: a possible hormonal regulator of mineral metabolism. 870 Aug 37

Feeding problems, anorexia and vomiting are common in infants and children with chronic renal failure (CRF), and play a major role in the growth failure often found in this condition. However, the gastroenterological and nutritional aspects of CRF in children have received little attention, hence therapeutic interventions are usually empirical and often ineffective. Gastritis, duodenitis and peptic ulcer are often found in adults with CRF on regular haemodialysis and following renal transplantation. Despite persistent hypergastrinaemia, gastric acid secretion is decreased rather than increased in most of these patients, and active peptic disease appears to be promoted by the removal of the acid output inhibition (neutralisation of gastric acid by ammonia) that follows active treatment. Helicobacter pylori, on the other hand, does not seem to play a significant role in the pathogenesis of peptic disease in CRF. Gastro-oesophageal reflux has been found in about 70% of infants and children with CRF suffering from vomiting and feeding problems, and thus appears to be a major problem in these patients. In a number of symptomatic patients with CRF, gastric dysrhythmias and delayed gastric emptying have also been found; hence there appears to be a complex disorder of gastrointestinal motility in CRF. Serum levels of several polypeptide hormones involved in the modulation of gastrointestinal motility [e.g. gastrin, cholecystokinin (CCK), neurotensin] and the regulation of hunger and satiety (e.g. glucagon, CCK) are significantly raised as a consequence of renal insufficiency, and can be reverted to normal by renal transplantation. Furthermore, several other humoral abnormalities (e.g. hypercalcaemia, hypokalaemia, acidosis, etc.) are not uncommon in CRF. By directly affecting the smooth muscle of the gut or stimulating particular areas within the central nervous system, all these humoral alterations may well play a major role in the gastrointestinal dysmotility, anorexia, nausea and vomiting in patients with CRF. Specific pharmacological and nutritional interventions should thus be considered for the treatment of vomiting and feeding problems in CRF.
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PMID:Gastrointestinal function in chronic renal failure. 874 22

After surgical resection for rectosigmoid carcinoma a 63-year-old man had secretory diarrhea causing severe metabolic acidosis, hypokalemia, hypercalcemia and dehydration. Subsequent investigations revealed a mass measuring 4 x 5 cm in the uncinate process of the pancreas and an elevated vasoactive intestinal polypeptide concentration. The diarrhea responded to treatment with the somatostatin analogue. Sandostatin, and remained under control during a prolonged preoperative period. The patient underwent a Whipple procedure with immediate lessening of his diarrhea. This report illustrates a classic case of vipoma and demonstrates the need to consider this condition in the differential diagnosis of secretory diarrhea, even in the presence of other gastrointestinal lesions. The effectiveness of somatostatin analogues in stabilizing the diarrhea preoperatively is also well illustrated.
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PMID:Surgical treatment of pancreatic cholera: a case report. 876 28

Leukemia inhibitory factor (LIF) is a single-chain polypeptide that previously was shown in mice to produce hypercalcemia and influence skeletal growth and turnover. We performed dose-response studies to determine if LIF alters the serum calcium or histomorphometry of the tibia in growing male rats. Forty animals were divided into five groups of eight animals each. Recombinant human LIF, 0.01, 0.1, 1, or 10 microg/100 g body wt, or vehicle was administered daily S.C. for 3 weeks. Compared with controls it was found that LIF increased mean serum calcium at the two highest doses (11.4 +/- 0.1 versus 10. 8 +/- 0.1 mg/dl, P = 0.0005 by one-way analysis of variance (ANOVA) but did not alter static or dynamic measurements of histomorphometry or length of the tibia. We conclude that in growing rats, high systemic concentrations of LIF result in hypercalcemia with no changes in bone turnover.
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PMID:Leukemia inhibitory factor produces hypercalcemia in rats without altering bone histomorphometry of the tibia. 878 Oct 56

G proteins couple receptors for many hormones and neurotransmitters to effectors that regulate second messenger metabolism. G protein-coupled receptors comprise a superfamily with the common structural feature of a single polypeptide with seven membrane-spanning domains. G proteins themselves are heterotrimers with an alpha subunit that binds guanine nucleotides. In the basal state, G proteins tightly bind GDP; receptor activation allows exchange of bound GDP for GTP that activates the G protein and causes it to modulate effector activity. An intrinsic GTPase activity hydrolyzes bound GTP to GDP thereby deactivating the G protein. The effects (cholera, whooping cough) of bacterial toxins that target G proteins for covalent modification signal the potential importance of G protein dysfunction as a cause of human disease. Conceptually, G protein dysfunction could involve gain or loss of function. For Gs, examples of both types have already been defined. Mutations in G protein-coupled receptors have also been identified in several human diseases. Germline loss of function mutations in rhodopsin, cone opsins, the V2 vasopressin receptor, ACTH receptor, and calcium-sensing receptor are responsible for retinitis pigmentosa, color blindness, nephrogenic diabetes insipidus, familial ACTH resistance, and familial hypocalciuric hypercalcemia, respectively. Missense mutations that cause constitutive receptor activation have been identified in the TSH and LH receptors.
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PMID:Defects in G protein-coupled signal transduction in human disease. 881 89

Parathyroid hormone-related protein (PTHrP) is an important causal factor of hypercalcemia associated with malignancy. PTHrP also modulates cell growth and differentiation of normal cells through mechanisms that include binding to cell surface-specific receptors as well as by possible intracellular routes. To understand the regulation of intracellular PTHrP expression, post-translational processing of PTHrP was investigated. Using cell-free translations it was shown that PTHrP can be ligated efficiently to multiple ubiquitin moieties. Both conjugation to ubiquitin and degradation of prepro-PTHrP synthesized in vitro were ATP-dependent. Translation in vitro in the presence of the proteasome inhibitor MG-132 abolished the degradation of PTHrP. Treatment of cells, cotransfected with hemagglutinin-tagged ubiquitin and histidine-tagged prepro-PTHrP, with MG-132, led to the accumulation of ubiquitinated prepro-PTHrP. Deletion mutagenesis experiments indicated that both the prepro secretory domain and a PEST (amino acid residues Pro (P), Glu (E), and/or Asp (D), Ser (S), and Thr (T)) motif in the COOH-terminal region of the protein were not required as cis-acting determinants for ubiquitination. This is the first report of a wild-type secretory polypeptide serving as a substrate of the ubiquitin proteolytic pathway. These results suggest that the ubiquitin-dependent proteolytic pathway is involved in regulating the metabolic stability of intracellular PTHrP, and this regulation may be an important mechanism for modulating its effects on cell growth and differentiation.
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PMID:Preproparathyroid hormone-related protein, a secreted peptide, is a substrate for the ubiquitin proteolytic system. 904 3


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