Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The hypercalcaemia of malignancy is multi-factorial, even within individual tumours. In most cases, hypercalcaemia is due to a combination of increased bone resorption associated with decreased renal capacity to excrete the increased extracellular fluid calcium. In solid tumours such as carcinoma of the lung, tumour-derived growth factors are probably primarily responsible for the increased bone resorption, and a separate family of factors which interact with some parathyroid hormone (PTH) receptors cause increased renal tubular calcium reabsorption. PTH production by non-parathyroid tumours rarely if ever occurs. In contrast, haematological malignancies such as myeloma and T-cell lymphomas produce locally acting bone resorbing lymphokines in excessive amounts. Some T-cell lymphomas in addition have the capacity to metabolize 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D. In myeloma, impaired glomerular filtration frequently contributes to the pathogenesis of hypercalcaemia by impairing renal compensatory mechanisms for maintaining normal serum calcium concentrations in the presence of increased bone resorption.
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PMID:Pathogenesis of hypercalcaemia of malignancy. 300 48

1. This paper describes the production and characterization of monoclonal antibodies against bovine parathyroid hormone (bPTH)-(1-84). 2. Spleen cells from A/J mice successfully immunized with bPTH-(1-84) were fused with SP2/O myeloma cells using PEG 4000 as fusogen. The screening method employed microtiter plates coated with sheep antimouse IgG and the presence of specific monoclonal antibodies was demonstrated by the binding of 125I-bPTH-(1-84). 3. A detailed study of the specificity of the three viable monoclonals with highest affinity showed that two (6FH6 and 6CD4) were amino-terminal specific and the other (5BG9) carboxyl-terminal specific. The two amino-terminal monoclonal antibodies appear to recognize the same antigenic site. 4. The monoclonal antibodies produced are potentially useful reagents for the development of new methods for the measurement of PTH in biological fluids, studies on the interaction of PTH with its receptor, as well as localization of PTH producing cells.
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PMID:Monoclonal antibodies to bovine parathyroid hormone: production and characterization. 324 28

Monoclonal antibodies against the biologically active N-terminal fragment of human parathyroid hormone, hPTH (1-34), were produced. The procedure included the use of novel secondary immunization in vitro of mouse spleen cell cultures. Dissociated spleen cells from primary immunized Balb/c mice, were cultured for five days in the presence of thymocyte conditioned media (TCM) and synthetic hPTH (1-34). Contrary to previous findings by other workers, in our hands Balb/c mice responded well. Following immunization the spleen cells were fused with NSl myeloma cells and cultured for eleven days before screening for antibody. Using an enzyme linked immunosorbent assay (ELISA) a number of positive clones were detected. Positive cells were cloned by limiting dilution and fifteen specific monoclonal hybridomas were produced. The immunoglobulin class of the different monoclonal antibodies was found to be IgGl. The immunocytochemical reaction was tested with chief cell carcinoma tissue and found to be clearly positive.
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PMID:Monoclonal antibodies to human parathyroid hormone (1-34) and their use in the immunocytochemical detection of parathyroid tumours. 362 82

Serum concentrations of immunoreactive parathyroid hormone (iPTH) measured with a mid-region specific radioimmunoassay and total calcium were correlated in 300 healthy subjects and 158 patients with surgically verified primary hyperparathyroidism (HPT). All the healthy individuals could be separated from the patients by a monoexponential declining curve in which iPTH at concentrations of 0.60 micrograms/l and 0.33 micrograms/l corresponded to calcium concentrations of 2.20 mmol/l and 2.60 mmol/l, respectively. In 22 patients more than one sample was analysed and serum iPTH and calcium were inversely correlated. In contrast, three patients with parathyroid carcinoma showed no reciprocal fluctuations between serum iPTH and calcium. Of 75 patients with hypercalcaemia due to malignant diseases (metastatic mammary carcinoma, bronchial carcinoma, renal carcinoma, myelomatosis), 62 had a normal iPTH/calcium relationship. Two patients with myelomatosis had a temporary elevation of serum iPTH and calcium due to renal impairment. One patient with bronchial carcinoma probably had ectopic production of iPTH. The remaining 10 patients (six mammary carcinomas and four bronchial carcinomas) were found in the pathological iPTH/calcium range. In conclusion, we have demonstrated that an inverse relationship exists between serum iPTH and calcium in patients with non-malignant, primary HPT. Evaluation of iPTH and calcium in the same serum sample gave a correct diagnosis in more than 90% of patients with primary HPT.
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PMID:Improved diagnosis of primary hyperparathyroidism by defining the inverse relationship between serum immunoreactive parathyroid hormone and calcium. 374 90

Widespread, progressive skin necrosis developed in a 42-year-old male with a 5-year history of osteosclerotic myeloma. Biopsy of the necrotic lesions demonstrated a leucocytoclastic vasculitis with extensive vascular calcification. Radiological investigations demonstrated widespread arterial calcification. Clinical improvement of the established skin lesions followed the institution of a forced calciuresis and parathyroid hormone suppression by induced hypermagnesaemia and phosphate depletion. No further cutaneous necrosis developed. Subsequent treatment with oral immunosuppressive therapy and the diphosphonate, EHDP, has been associated with a complete 18-month remission. The relationship of this apparently unique pathological process to the osteosclerotic myeloma is discussed, together with the rationale for the therapeutic regime instituted.
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PMID:Osteosclerotic myeloma complicated by diffuse arteritis, vascular calcification and extensive cutaneous necrosis. 392 May 44

A prospective survey was carried out to determine the incidence of hypercalcemia in hospitalized patients with lymphoma. Serum calcium determinations were carried out during 440 admissions on 152 patients, most of whom had widespread lymphoma. Forty-one of the 152 patients died, all having had calcium levels recorded on that admission. Two of the 152 patients (1.3%) were found to have hypercalcemia. By comparison hypercalcemia occurred in 6 of 34 patients (17.6%) with multiple myeloma.Hypercalcemia is uncommonly associated with lymphoma but may be seen particularly in centres where many patients with this disease are treated. Hypercalcemia readily responds to therapy and is a reversible cause of morbidity, but when associated with lymphoma it usually indicates widespread disease. The mechanism of hypercalcemia is unknown but there is strong evidence for humoral factors that may or may not be related to parathyroid hormone.
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PMID:Lymphoma with hypercalcemia. 460 55

Dichloromethylene diphosphonate (Cl2MDP) a potent inhibitor of osteoclast-mediated bone resorption, lowers serum calcium in hypercalcemia associated wit malignancies and with primary hyperparathyroidism, and reduces excess calcium mobilization from bone in multiple myeloma and in Paget's disease. We have evaluated the effectiveness of intravenously administered Cl2MDP in five patients with parathyroid carcinoma, a disorder characterized by severe hypercalcemia, very high parathyroid hormone (PTH) levels, and marked osteoclast-mediated bone resorption. All patients had biopsy-proved metastatic parathyroid carcinoma and hypercalcemia which persisted after multiple surgical procedures and other attempts at management. During a three-day observation period, each patients continued to demonstrate stable or progressive hypercalcemia despite infusion with saline solution and furosemide. Cl2MDP was administered over 2 hours at 2.5 mg/kg on day 1 and 5 mg/kg on days 2 through 7. Response was noted in all five patients; there was a gradual decline in the average serum calcium from 16.0 +/- 1.1 mg/dl (SEM) to 11.1 +/- 0.9 mg/dl by the eighth day (p less than 0.01). There were concomitant reductions in urinary calcium excretion, from 798 +/- 153 mg/g creatinine to 350 +/- 96 mg/g creatinine (p less than 0.05) and in the urinary hydroxyproline excretion, from 155 +/- 38 mg/g creatinine to 94 +/- 29 mg/g creatinine (p less than 0.02). Serum PTH levels remained markedly elevated (460 +/- 141 micrograms eq/ml to 493 +/- 169 micrograms eq/ml). In three patients, all indices returned to pretreatment levels by 10 days after the last infusion. In two of these patients there was a response to retreatment with Cl2MDP with a fall in calcium from 16.9 +/- 0.5 mg/dl to 12.4 +/- 1.5 mg/dl. There was no response in one patient. No adverse reactions to Cl2MDP were observed. The decrease in serum calcium and concomitant declines in urinary calcium and hydroxyproline suggest that Cl2MDP can effectively inhibit the excessive bone resorption associated with parathyroid carcinoma.
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PMID:Therapy of hypercalcemia due to parathyroid carcinoma with intravenous dichloromethylene diphosphonate. 621 78

Supernatant fluids from the cultures of bone marrow cells from 10 of 12 patients with multiple myeloma (MM) caused bone resorption in organ cultures of fetal rat calvaria. In four patients, the marrow cells were cultured with and without indomethacin (1 muM). The supernatant fluids from indomethacintreated marrow cultures caused significantly less bone resorption than supernatant fluids of cell cultures without indomethacin. This inhibition of release of bone resorbing factor(s) by myeloma cultures is similar to the previously observed indomethacin-induced inhibition of osteoclast-activating factor (OAF) production by activated human leukocytes. None of the MM supernatants had any effect on cyclic (c)AMP accumulation in resorbing bone in vitro. Four separate preparations of partially purified OAF obtained from phytohemagglutinin-stimulated peripheral human leukocytes were tested for their ability (a) to cause bone resorption in organ cultures of fetal rat and neonatal mouse calvaria and (b) to cause accumulation of cAMP in rat and mouse skeletal tissue in vitro. Those dilutions of OAF that caused bone resorption had no effect on accumulation of cAMP in rat or mouse calvaria incubated in vitro. In addition, no stimulation of adenylate cyclase activity in membranes prepared from fetal rat calvaria could be found. Bone cell populations isolated by sequential collagenase digestion of fetal rat calvaria also showed no cAMP response to these dilutions of OAF. Parathyroid hormone caused a clear response in all three systems. Furthermore, no cAMP response to OAF was observed in calvaria in the presence of cholera toxin (1 mug/ml) and isobutyl-methylxanthine (0.3 mM). These observations demonstrate that (a) supernatant fluids from MM marrow cultures stimulate bone resorption but do not increase cAMP accumulation in vitro; (b) indomethacin interferes with the release of bone resorbing factors by MM bone marrow cultures suggesting that this process requires prostaglandins; and (c) Sephadex G100 or G75 purified OAF does not stimulate adenylate cyclase or increase cAMP accumulation at equivalent bone resorbing concentrations in rat and mouse skeletal tissue. The resorptive action of MM culture fluids is similar to that of partially purified OAF from activated cultured leukocytes, but different from those of other bone resorbing factors, parathyroid hormone and prostaglandin E(2), which stimulate cAMP production in skeletal tissue.
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PMID:Observations on the mechanism of bone resorption induced by multiple myeloma marrow culture fluids and partially purified osteoclast-activating factor. 626 78

A patient with multiple myeloma and hypercalcemia responded to cytotoxic chemotherapy. However, hypercalcemia persisted. Because of the absence of lytic bone lesions, the presence of a low serum phosphate level, and a family history of possible primary hyperparathyroidism, the patient was evaluated for this disorder. Serum parathyroid hormone and urinary cyclic adenosine monophosphate levels were elevated. Exploration of the neck disclosed two enlarged parathyroid glands (1,850 mg and 210 mg), which were excised. After surgery, the patient's serum calcium levels remained normal for one year. Progressive myeloma bone disease developed that eventually resulted in recurrent hypercalcemia and death. Autopsy revealed only evidence of myeloma.
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PMID:Coexistent multiple myeloma and primary hyperparathyroidism. 627 81

Total and ionized calcium and other related parameters were measured in 34 patients with multiple myeloma. Hypercalcemia was not a major feature of the group of patients studied with only three patients exhibiting marked increases in total (Ca total) and ionized (Ca++) calcium concentrations. The Ca++/Ca total ratio was also maintained within relatively narrow limits. No major differences were found in the calcium fractions of patients with different types of multiple myeloma. Serum immunoreactive parathyroid hormone showed no consistent relationship with either the total or ionized calcium concentration. There were no correlations between increased total protein or reduced serum albumin concentrations and changes in total and ionized calcium fractions or Ca++/Ca total ratios. These results imply that in this group of myeloma patients, there was no significant binding of calcium by the monoclonal immunoglobulins.
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PMID:Frequency of calcium binding by monoclonal immunoglobulins in multiple myeloma. 646 28


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