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

Interleukin-6 (IL-6) is a differentiation and growth factor for a variety of cell types and its excessive production plays a major role in the pathogenesis of multiple myeloma and post-menopausal osteoporosis. IL-6, a four-helix bundle cytokine, is believed to interact sequentially with two transmembrane receptors, the low-affinity IL-6 receptor (IL-6R alpha) and the signal transducer gp130, via distinct binding sites. In this paper we show that combined mutations in the predicted A and C helices, previously suggested to establish contacts with gp130, give rise to variants with no bioactivity but unimpaired binding to IL-6R alpha. These mutants behave as full and selective IL-6 receptor antagonists on a variety of human cell lines. Furthermore, a bifacial mutant was generated (called IL-6 super-antagonist) in which the antagonist mutations were combined with amino acid substitutions in the predicted D helix that increase binding for IL-6R alpha. The IL-6 super-antagonist has no bioactivity, but improved first receptor occupancy and, therefore, fully inhibits the wild-type cytokine at low dosage. The demonstration of functionally independent receptor binding sites on IL-6 suggests that it could be possible to design super-antagonists of other helical cytokines which drive the assembly of structurally related multisubunit receptor complexes.
 ...
PMID:Rational design of a receptor super-antagonist of human interleukin-6. 781 26

Hypercalcemia may be a manifestation of a variety of disorders including hyperparathyroidism, hypervitaminosis D, sarcoidosis, multiple myeloma, hyperthyroidism, acute osteoporosis, metastatic bone disease, and a number of primary malignancies. Hypercalcemia may be seen in as many as 1.5% of all patients with malignant disease, with or without bony metastases. The neoplasms most commonly associated with hypercalcemia include carcinoma of the lung (all cell types), breast cancer, squamous cell carcinomas, hematologic malignancies, and renal cell carcinoma. Observation of a number of instances of hypercalcemia attendant on urologic malignancies prompts the brief report of 4 characteristic cases with documentation of response to therapy. Management of severe and debilitating hypercalcemia is emphasized. Urologists should be aware of new agents available for such treatment.
 ...
PMID:Hypercalcemia and urologic malignancies. 781 68

The bone marrow of the spine, pelvis and proximal femora was examined with MR imaging at diagnosis in 30 cases of multiple myeloma (MM), and during treatment on 69 occasions. The MR pattern was normal, focal or diffuse and correlated to stage. A tumour mass index (TMI) was calculated by estimating the total myeloma mass visualised at MR imaging. The TMI correlated significantly with stage, lytic bone lesions, serum calcium, serum beta-2-microglobulin and survival. No abnormalities were seen at MR investigation in 4 of 6 patients classified as stage II because of osteoporosis only. Therapy efficacy evaluation with MR imaging corresponded to clinical evaluation on 54 of the 69 occasions. MR examination of bone marrow in MM patients can be used for tumour mass assessment, both at diagnosis and during follow-up. Valuable information can be obtained when the tumour mass is difficult to estimate using clinical criteria, e.g. in non-secretory MM or when osteoporosis is the only variable indicating an increase in the tumour mass.
 ...
PMID:MR imaging of multiple myeloma in tumour mass measurement at diagnosis and during treatment. 783 77

Interleukin-6 (IL-6) is a pro-inflammatory cytokine with a wide range of functions. Perhaps the most important physiologically is its role as a mediator of the acute phase inflammatory response. Normally, there is little measurable IL-6 in the circulation, but levels increase abruptly to nanogram amounts during an inflammatory process. During aging, it has been proposed that the tight regulation of IL-6 gene expression becomes less effective and levels are measurable even when there is no evidence for inflammation. Several investigators have identified this cytokine as being involved in the pathogenesis of various disease processes and we have suggested that certain age-associated diseases are directly related. Among these are late-life lymphoma and myeloma, osteoporosis and possibly Alzheimer's disease.
 ...
PMID:The role of interleukin-6 in certain age-related diseases. 783 89

To evaluate the diagnostic value of percutaneous vertebral biopsy in noninfectious diseases of the spine, we retrospectively studied 41 cases seen between 1985 and 1992. The level of the lesion was lumbar in 29 cases, thoracic in 11, and cervical in one. There were 19 crush fractures, 11 lytic lesions, six sclerotic lesions, and three mixed lesions. The biopsy was done because of an abnormal magnetic resonance imaging signal in one patient and because of epiduritis in another. The thoracic and lumbar biopsies were done under x-ray guidance using the technique developed by Laredo and Bard. Computed tomography guidance was used for the cervical biopsy. There were no adverse events. The final histological diagnosis was metastatic disease in 17 cases (41.5%), myeloma or plasmacytoma in six cases (14.7%), primary vertebral neoplasia in two cases (4.8%), lymphoma in one case (2.4%), osteoporosis in nine cases (22%), Paget's disease in three cases (7.4%), amyloidosis in one case (2.4%), aseptic osteitis in one case (2.4%), and vertebral necrosis in one case (2.4%). A second biopsy procedure was done in three patients (surgically in two cases and percutaneously in one) because of discrepancies between histological findings and other data. The final diagnosis was metastatic disease in all three patients. Overall, the diagnostic yield of percutaneous vertebral biopsy was 92.6% and varied little with initial roentgenographic or computed tomographic findings. However, yield was only 56% for the diagnosis of tumorous lesions, with variations according to roentgenographic and computed tomographic changes, 90.1% for osteolytic lesions, 66.6% for mixed lesions, 47.4% for crush fractures, and 16.6% for sclerotic lesions.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[Diagnostic value of spinal puncture-biopsy in non-infectious spinal diseases. Apropos of 41 cases]. 783 86

Milk-alkali syndrome can be caused by ingesting large amounts of calcium carbonate. Coincident with the promotion of calcium carbonate as treatment for both dyspepsia and osteoporosis, milk-alkali syndrome is now a common cause of hypercalcemia severe enough to require admission to the hospital. The syndrome accounted for less than 2% of such admissions before 1990, but from 1990 through 1993, it was the cause of hypercalcemia for over 12% of these patients. Only primary hyperparathyroidism and hypercalcemia of malignancy (excluding multiple myeloma) are more common. The diagnosis of milk-alkali syndrome is made almost entirely based on the patient's history; careful attention to dietary practices and over-the-counter drug use is required, as numerous over-the-counter medications contain calcium carbonate. Modern assays for PTH demonstrate the expected suppression of PTH by hypercalcemia. Nonetheless, measurement of PTH must be performed in a timely manner as treatment with intravenous saline may result in hypocalcemia and elevated PTH soon after admission. Given the pathophysiology of milk-alkali syndrome compared to other causes of hypercalcemia, hypocalcemia with rebound hyperparathyroidism is probably unique to milk-alkali syndrome.
 ...
PMID:Milk-alkali syndrome associated with calcium carbonate consumption. Report of 7 patients with parathyroid hormone levels and an estimate of prevalence among patients hospitalized with hypercalcemia. 789 47

A rare case of multiple myeloma associated with severe Coombs-positive hemolytic anemia is described. A 60-year-old woman was hospitalized for acute hemolysis due to an IgG warm autoantibody with pan-agglutinin specificity. Serum and urine electrophoresis revealed the presence of a monoclonal IgGk protein and a BJk protein, respectively. Bone marrow aspirates showed diffuse infiltration with plasma cells, and skeletal survey revealed lytic lesions in the skull and diffuse osteoporosis. Treatment with prednisone, and subsequently with melphalan, cyclophosphamide and vincristine resulted in hematological improvement within two weeks. A reduction of paraprotein below 50% of the initial levels was found after six months of therapy.
 ...
PMID:Multiple myeloma associated with autoimmune hemolytic anemia. 792 76

Careful examination as well as biochemical and hormonal investigations should be performed in men suffering from vertebral crush fractures, in order to detect a destructive skeletal process (multiple myeloma, bone metastatic lesions, lympho and myeloproliferative disorders), a mineralization defect (osteomalacia) or a secondary osteoporosis: primary hyperparathyroidism, hypogonadism, hyperthyroidism, renal hypercalciuria, alcoholism and tobacco smoking. The diagnosis of idiopathic osteoporosis should be made only after these causes have been excluded; the pathogenesis of the disease is unclear but risk factors have been identified: family history of osteoporosis, low dietary calcium intake, delayed puberty, ethanol use, tobacco smoking, inactive lifestyle and lean body build. Correction of risk factors, calcium supplementation, regular program of weight bearing physical activity, in some instances correction of testosterone deficiency may be of benefit to reduce bone loss. Severe osteopenia or osteoporosis may require sodium fluoride therapy.
 ...
PMID:[Male osteoporosis]. 793 30

The pleiotropic cytokine interleukin 6 (IL-6) plays a role in the pathogenesis of various diseases, such as multiple myeloma, autoimmune and inflammatory diseases and osteoporosis. Therefore, specific inhibitors of IL-6 may have clinical applications. We previously succeeded in developing receptor antagonists of IL-6 that antagonized wild-type IL-6 activity on the human Epstein-Barr virus (EBV)-transformed B cell line CESS and the human hepatoma cell line HepG2. However, these proteins still had agonistic activity on the human myeloma cell line XG-1. We here report the construction of a novel mutant protein of IL-6 in which two different mutations are combined that individually disrupt the association of the IL-6/IL-6 receptor (R) alpha complex with the signaltransducing "beta" chain, gp130, but leave the binding of IL-6 to IL-6R alpha intact. The resulting mutant protein (with substitutions of residues Gln160 to Glu, Thr163 to Pro, and replacement of human residues Lys42-Ala57 with the corresponding residues of mouse IL-6) was inactive on XG-1 cells and weakly antagonized wild-type IL-6 activity on these cells. By introducing two additional substitutions (Phe171Leu, Ser177Arg), the affinity of the mutant protein for IL-6R alpha was increased fivefold, rendering it capable of completely inhibiting wild-type IL-6 activity on XG-1 cells. Moreover, this mutant also antagonized the activity of IL-6, but not that of leukemia inhibitory factor, oncostatin M, or GM-CSF on the human erythroleukemia cell line TF-1, demonstrating its specificity for IL-6. These data demonstrate the feasibility of developing specific IL-6R antagonists. The availability of such antagonists may offer an approach to specifically inhibit IL-6 activity in vivo.
 ...
PMID:Development of an interleukin (IL) 6 receptor antagonist that inhibits IL-6-dependent growth of human myeloma cells. 796 14

Though vertebral fractures were required to make the diagnosis of osteoporosis prior to the advent of methods for accurate bone measurement, osteopenia is readily defined by a decrease of bone mineral density by 2 to 2.5 SD from the peak bone density. After excluding other metabolic bone diseases such as primary hyperparathyroidism, osteomalacia, renal osteodystrophy, multiple myeloma and tumor metastases by means of X-ray studies and biochemical studies on serum and urine, by far the largest proportion of patients with osteopenia are usually found to have osteoporosis. Primary osteoporosis is found in males and females after middle age, and secondary osteoporosis at any age with definite causes such as corticosteroid excess, immobilization, rheumatoid arthritis or vitamin C deficiency. Estrogen withdrawal in young women is classified as secondary osteoporosis, but postmenopausal osteoporosis with similar cause is usually classified into primary osteoporosis, creating a confusion. Rapid bone loss occurring only during a few years after menopause should be clearly distinguished from the life-long process of bone loss common to males and females and should not be classified as a "type" of osteoporosis.
 ...
PMID:[Osteoporosis--concept, classification and epidemiology]. 796 67


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>