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)

The cytokine human interleukin for Da cells/leukemia inhibitory factor (HILDA/LIF) exerts multiple biological effects in vitro. In mice, high circulating levels of HILDA/LIF induce a wide range of pathophysiological events, some of them closely involved with immunological and inflammatory responses. Using a sandwich ELISA recognizing the natural human HILDA/LIF molecule with a threshold of 50 pg/ml in urine and 150 pg/ml in plasma, we monitored the urine and plasma HILDA/LIF levels of 22 patients in their first year after a kidney transplant. HILDA/LIF urine excretion is increased during acute rejection, and infections also trigger heavy HILDA/LIF plasma concentrations or urine excretion. In addition, this study raises the question of HILDA/LIF involvement in post-kidney-transplant phenomena such as hypercalcemia, osteoporosis, or the reversal of anemia.
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PMID:One-year enzyme-linked immunosorbent assay follow-up of human interleukin for Da cells/leukemia inhibitory factor in blood and urine of 22 kidney transplant recipients. 799 61

Hypercalcemia in adult T-cell leukemia has been attributed to increased levels of 1,25-dihydroxyvitamin D (1,25(OH)2D), whereas in other types of leukemia, hypercalcemia has been blamed on direct skeletal invasion by malignant cells, ectopic parathyroid hormone (PTH) production or bone-resorbing cytokines. A 51-year-old man was studied who presented with back pain, circulating myeloblasts, and hypercalcemia. The bone marrow revealed acute myeloblastic leukemia. While the ionized calcium concentration was 8.17 mg/dL (normal, 4.73 to 5.21 mg/dL), the levels of PTH, PTH-related peptide, vitamin D, and thyroxine were normal or subnormal. Bone histomorphometry showed a decreased cortical width with intracortical erosion cavities dissecting into the marrow space. In cancellous bone, the osteoid area, osteoblast perimeter, and tetracycline fluorescence were sparse, whereas the osteoclast perimeter was increased. Persistent marrow fat, the general absence of trabecular narrowing, and the prompt response to calcitonin suggest that the osteoclasts caused the hypercalcemia and lytic lesions, rather than pressure atrophy or osteolysis by leukemic infiltration. Osteoclast activation and subsequent hypercalcemia may have been due to a locally produced cytokine, such as interleukin-1 beta or tumor necrosis factor.
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PMID:Case report: hypercalcemia in acute myeloblastic leukemia is caused by osteoclast activation. 812 79

Burn patients are at risk for bone disease due to aluminum (Al) exposure from use of antacids and albumin, partial immobilization, and increased production of endogenous glucocorticoids. Moreover, severely burned children are growth impaired up to 3 years after the burn. To determine the extent of bone disease, we studied nine men and three women, ages 18-41 years, with greater than 50% body surface area burn. Seven patients underwent iliac crest bone biopsy following double tetracycline labeling, one additional patient expired after a single label, and three others had postmortem specimens obtained for quantitative Al only. Serial serum and urine samples were obtained weekly until biopsy or death. All biopsied patients had reduced bone formation and osteoid area, surface, and width, with mineral apposition rate, osteoblast surface, and osteoclast number with normal eroded surfaces compared to age- and sex-matched normal ambulatory volunteers. Burn patients also had reduced bone formation, mineral apposition rate, osteoid area, and surface compared to age-matched volunteers at short-term bed rest. Serum levels of osteocalcin were low. Most patients had mild hypercalcemia but only a third had hypercalciuria. All patients had elevated Al in blood or urine; urine Al correlated inversely with serum osteocalcin. In 60% significant bone Al was detectable by stain or quantitation. Our data are compatible with burn patients having markedly reduced bone turnover. Al loading, partial immobilization, endogenous corticosteroids, and cytokine production may be among the etiologic factors.
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PMID:Bone disease in burn patients. 845 88

The hypercalcemic syndrome and the relation of serum calcium with the concentration of ionic calcium and albumin are shortly described. The pathogenetic significance of local, cytokine-induced bone destruction and of the osteoclast-stimulating effect by "parathyroid hormone related peptide" leading to "humoral hypercalcemia of malignancy" is underscored. In a hypercalcemic emergency the therapeutic strategy should combine adequate rehydration and induction of calciuresis by furosemide and the intravenous application of a rapid-onset, calcium lowering substance such as calcitonin and, simultaneously, of a slow-onset, long-acting bisphosphonate such as pamidromate, which may be infused as a single dose.
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PMID:[Hypercalcemia as an emergency]. 848 77

Recently, the effects of interleukin-1 (IL-1) on bone resorption in organ culture have been shown to be inhibited by an interleukin-1 receptor antagonist (IL-1RA), a novel monocyte cytokine in the IL-1 family. IL-1RA, which binds to IL-1 receptors and inhibits many of the effects of IL-1 alpha and beta, has been purified, cloned, and expressed. We used IL-1RA to investigate its effects on calcium homeostasis in vivo. After confirming that IL-1RA completely inhibited the effects of IL-1 on bone resorption in organ cultures, we tested the effects of IL-1RA on hypercalcemia mediated by IL-1 in normal mice and found that prolonged hypercalcemia provoked by IL-1 was completely inhibited by IL-1RA. The initial transient decrease in blood ionized calcium observed following an injection of IL-1 was also abrogated. IL-1RA had no effect alone on blood ionized calcium or on hypercalcemia mediated by parathyroid hormone (PTH) or PTH-related protein (PTHrP). These data suggest that antagonists to the IL-1 receptor may provide a useful therapeutic approach to osteoclastic bone resorption and hypercalcemia that is IL-1 dependent.
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PMID:Interleukin-1 receptor antagonist inhibits the hypercalcemia mediated by interleukin-1. 851 85

Multiple myeloma (MM) remains incurable. Despite many chemotherapy programs for large numbers of patients, there has been little improvement in outcome during the past 25 years. For many years, intermittent courses of melphalan and prednisone have represented the standard chemotherapy for newly diagnosed symptomatic MM. Many other drug combinations have been assessed, including regimens using multiple alkylating agents, and programs with vincristine, or an anthracycline, and have failed to show any superiority to melphalan-prednisone. Interferon alpha (IFN alpha) inhibits plasma cell growth and has induced responses in approximately 15% of previously untreated patients. This cytokine may have a role when used in those patients who have reached a good "plateau phase" with low tumor burden at the end of a chemotherapeutic program or after a transplantation procedure. The results of myeloablative therapy with allogenic or autologous marrow transplantation are promising and suggest possibility of a cure in some patients. Important problem in the management of MM patients is the treatment of complications, especially bone destruction, hypercalcemia, anemia and infections. Experimental modalities, especially immunotherapy, hold promise for use in humans and may also provide further insights into the pathogenesis of MM.
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PMID:[Treatment of multiple myeloma--present status and perspectives]. 862 44

A case of humoral hypercalcemia of malignancy in cutaneous squamous cell carcinoma is reported. An 82-year-old male underwent surgery for cutaneous squamous cell carcinoma (SCC) of the left hand in 1992. He subsequently developed clouding of consciousness with remarkable hypercalcemia, a high parathyroid hormone related protein (PTHrP) level, and elevated plasma cytokine levels [tumor necrosis factor alpha (TNF alpha), interleukin-6 (IL-6)]. Diagnosis of humoral hypercalcemia of malignancy (HHM) was made on the basis of these findings. He died of renal insufficiency due to this hypercalcemia in spite of several replacement therapies and chemotherapies. The PTHrP might have derived from the SCC and have been responsible for the HHM in conjunction with IL-6 and TNF alpha.
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PMID:Humoral hypercalcemia of malignancy with elevated plasma PTHrP, TNF alpha and IL-6 in cutaneous squamous cell carcinoma. 877 24

Interleukin-6 (IL-6) is a multifunctional cytokine that is produced not only by a variety of normal cells but also by cancer cells. IL-6 produced by cancer cells stimulates the proliferation of these cancer cells in an autocrine/ paracrine manner and causes paraneoplastic syndromes including hypercalcemia, cachexia, and leukocytosis. We have reported previously that a human oral squamous cancer associated with hypercalcemia produces large amounts of IL-6, that animals bearing this cancer exhibit elevated levels of plasma IL-6, and that neutralizing antibodies to human IL-6 reverse hypercalcemia in tumor-bearing animals, indicating an important role of IL-6 in the hypercalcemia in this model. Because these cancer cells overexpress epidermal growth factor receptors (EGFR) with intrinsic tyrosine kinase (TK) activity similar to many other squamous cancers, we examined the effects of herbimycin A, a tyrosine kinase inhibitor, on IL-6 production and hypercalcemia in animals bearing this cancer to develop a new approach to treat the hypercalcemia associated with malignancy. Intraperitoneal administration (once a day for 2 days) of herbimycin A to cancer-bearing hypercalcemic mice reduced the plasma levels of human IL-6 and impaired the hypercalcemia. During 2-day treatment with herbimycin A, no changes were observed in tumor size. Of interest, plasma levels of mouse, but not human, soluble IL-6 receptors were also elevated. However, herbimycin A showed no effects on plasma levels of mouse soluble IL-6 receptors. Herbimycin A suppressed the tyrosine autophosphorylation of EGFR and IL-6 mRNA expression and production, all of which were stimulated by EGF. The data raise the possibility that TK inhibitors may be potential mechanism-based therapeutic agents for the treatment of hypercalcemia associated with squamous cancers which overexpress EGFR.
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PMID:Herbimycin A, a tyrosine kinase inhibitor, impairs hypercalcemia associated with a human squamous cancer producing interleukin-6 in nude mice. 879 10

Remodeling the cyclical replacement of old bone by new, serves to maintain its mechanical and metabolic functions. In each cycle a circumscribed volume of bone is removed by osteoclastic resorption and subsequently replaced by osteoblastic formation at the same location. Remodeling is carried out by elongated structures known as basic multicellular units (BMU) that travel through or across the surface of bone. Each BMU lasts about six months, with continued sequential recruitment of new osteoclasts and osteoblasts. Abnormal bone remodeling involves some combination of loss of directional control, increase in number of remodeling cycles and incomplete replacement. In metastatic bone disease, tumor cells find the hematopoietic bone marrow conducive to their survival and growth, because they can manipulate the local cytokine network to increase recruitment of osteoclasts from local precursors and so increase bone resorption. The effect on bone formation is biphasic; an initial increase is due partly to the normal evolution of the BMU, and partly to the induction of reparative woven bone formation. Later, normal BMU-based bone formation may fall to subnormal levels. In some tumors, a generalized increase in osteoclast recruitment and decline in bone formation are the systemic responses to one or more agents released by tumor cells into the circulation, of which the most frequent is parathyroid hormone-related peptide, but in both metastatic and non-metastatic disease, the cellular events in bone are essentially the same. Cancer-related bone disease is amenable to treatment with drugs that inhibit osteoclast recruitment, of which the bisphosphonates are the most effective. Treatment should be started before there has been irreparable damage to bone structure and before the onset of hypercalcemia. Although bisphosphonates remain in bone for a long time, adverse effects are very unlikely within the patient's lifetime.
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PMID:Bone remodeling, normal and abnormal: a biological basis for the understanding of cancer-related bone disease and its treatment. 885 18

Cytokine messenger RNA expression was studied using the reverse transcription/polymerase chain reaction in 23 patients with multiple myeloma (MM), 16 with monoclonal gammopathy of undetermined significance (MGUS), 12 with post menopausal osteoporosis, (OP) and 12 normal controls. Messenger RNAs for IL-1 alpha, IL-1 beta, TNF-alpha, TNF-beta, IL-6 and M-CSF were sought in view of their reported pathogenic role in myeloma. Transcripts for IL-1 beta, TNF-alpha, TNF-beta and M-CSF were found frequently in all four groups of patients. The only significant difference in cytokine expression between the groups was for IL-6 which was expressed in 17% of controls compared with 87% of patients with MM (p < 0.001), 62% of patients with MGUS (p < 0.02) and 67% of patients with osteoporosis (p < 0.02). Further analysis of IL-6 expression by quantitative PCR showed significantly higher IL-6 mRNA levels in MM compared with MGUS (p < 0.006). There was no correlation however between expression of individual cytokines and clinical features of myeloma such as osteolytic bone disease or hypercalcaemia. We conclude that expression of IL-6 mRNA is significantly enhanced in multiple myeloma when compared with MGUS. However, since MGUS and osteoporosis were also associated with a high prevalence of IL-6 expression when compared with controls it is probable that factors other than IL-6 are responsible for the local osteolytic lesions which characterise MM, but which are not seen in MGUS or osteoporosis.
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PMID:Cytokine expression in multiple myeloma and monoclonal gammopathy: analysis by reverse transcription/polymerase chain reaction and quantitative PCR. 904 67


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