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)

Possibilities and limits of radiotherapy are described in a survey in the following diseases: Undifferentiated cell leucoses: The radiotherapy of the central nervous system brings an increase of the 5-year survival rates, since the localisations in this region existing in 45-70% are only insufficiently reached by the cytostatic substances because of the defective blood-liquor passage. On the other hand, other indications to radiotherapy recede into the background. Chronic leucoses: In the foreground of the application is the ray-therapy of the spleen, of which, apart from the local effect on the splenic tumour, also an improvement of the remission rates is expected. At adequate indication also the ray-therapy of infiltrates in the lymph nodes and other localisations achieves good palliative results. The extra-corporeal irradiation of blood is a method, the usability of which must still be proved. With the introduction of the modern cytostatic drugs the exposure of the whole body has lost significance. Lymphogranulomatosis: In this disease the radiotherapy has caused a decisive change: In these cases the recognition of the local development of the disease and its continuous spreading was decisive, and issuing from this also the simultaneous irradiation of the defluxion areas and the application of an oncolytic dose. According to the stage with or without combination of cytostatic drugs an exact plan of therapy is made. Here healing rates of 70-80% in stage I are to be expected. Myeloma: Here the radiotherpy has palliative tasks, with correct indication good effects are to be expected. Polycythaemia vera: In this disease radiotherapy in form of incorporation of radioactive phosphorus is the remedy of choice.
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PMID:[Radiotherapy of hematologic diseases]. 6 Aug 34

32P is effective therapy for polycythemia and primary thrombocytosis. The Polycythemia Vera Study Group is comparing radioactive phosphorus with alkylating agents to determine relative efficacy. Less well investigated is the effectiveness of 32P vs. busulfan in chronic granulocytic leukemia. Endolymphatic administration of radiopharmaceuticals may play a role in the therapy of infradiaphragmatic lymphoma. Among the radionuclides that have at times been used in hematology are 32P, 198Au 24Na, 76As, 89Sr, 52Mb, 54Mn, 91Y, 95Zr, 95Cb, 111Ag, 109Pd, 131I, 185W, and 192Ir. As stated, 32P has proven single most efficacious agent. The hematologic diseases that have been treated include both malignant and benign conditions. Among the malignant conditions are polycythemia vera, agnogenic myeloid metaplasia, thrombocythemia, leukemia, Hodgkin's disease, and multiple myeloma. Hemophilia, and Osler--Weber--Rendu disease are among the benign entities in which the agents have been tried. Polycythemia and thrombocythemia remain those in which the greatest success has been achieved.
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PMID:Radionuclide therapy of hematologic disorders. 48 47

The pKa values of the three histidine residues in the Fv fragment (variable region of the heavy and light chains) of the mouse myeloma protein MOPC 315, measured by high resolution n.m.r. (nuclear magnetic resonance), are 5.9, 6.9 and 8.2. The perturbation of the pKa of one of the histidines (pKa 6.9) on the addition of hapten and the narrow linewidth of its proton resonances suggests that it is at the edge of the combining site. References to the model of the Fv fragment [Padlan, Davies, Pecht, Givol & Wright (1976) Cold Spring Harbor Symp. Quant. Biol. 41, in the press] allows assignment of the three histidine residues, histidine-102H, histidine-97L and histidine-44L. The determination of the pKa of the phosphorus group, by 31P n.m.r., of a homologous series of Dnp- and Tnp- (di- and tri-nitrophenyl) haptens has located a positively charged residue. Molecular-model studies on the conformations of these haptens show that the residue is at the edge of the site. The model suggests that the positively charged residue is either arginine-95L or lysine-52H.
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PMID:Specificity of interactions of hapten side chains with the combining site of the myeloma protein MOPC 315. 92 46

A 74-year-old white man with established polycythemia vera was treated with radioactive phosphorus after phlebotomies alone failed to control his disease. About 2 3/4 years later he died of multiple myeloma. The mutagenic effect of radioactive phosphorus may have caused or possibly accelerated preexisting myeloma. Basic nonmalignant disease deserves careful consideration before radiation or radiomimetic agents are used. One might consider a probably less mutagenic drug such as hydroxyurea in patients with polycythemia vera when phlebotomy alone does not give good control of red cell mass and thrombocytosis.
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PMID:Multiple myeloma on polycythemia vera following radioactive phosphorus therapy. 101 58

A 59-year-old woman with kappa light-chain myeloma had Fanconi's syndrome characterized by renal glycosuria, generalized aminoaciduria, bicarbonaturia and decrease of phosphorus and uric acid reabsorption. A bone marrow biopsy showed the presence of 27% of dystrophic plasma cells; the cytoplasm of these cells was intensely stained with anti-kappa light-chain monoclonal antibodies. By light microscopy, the renal biopsy revealed a tubulointerstitial nephritis without glomerular lesions and with intratubular casts. By immunofluorescence, no deposits were observed along the glomerular and tubular basement membranes, but a positivity with anti-kappa light chain was noticed in some tubular epithelia and casts. By electron microscopy, fibrils (35-nm diameter) were observed in the cytoplasm of proximal tubular cells. These fibrils were situated in vesicles (100- to 600-nm diameter) in the luminal side of tubular cells. In the basal pole of the cell, fibrils seemed to group in crystals (120- to 200-nm diameter). Only kappa light-chain protein was demonstrated in these fibrils and crystals by an immunoelectron microscopic technique. These data suggested the pathogenic role of the fibrils and crystals present in tubular epithelium in the tubular proximal syndrome.
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PMID:Fanconi's syndrome, kappa light-chain myeloma, non-amyloid fibrils and cytoplasmic crystals in renal tubular epithelium. 166 55

We present a 68-year-old woman with Ig A-K multiple myeloma and a laboratory report of extreme hyperphosphatemia (29 mg/dl), but no clinical manifestations attributable to such a high serum phosphorus. The hyperphosphatemia was demonstrated to be spurious and due to interference of monoclonal immunoglobulin with the phosphomolybdate calorimetric assay for phosphorus of some automated systems. In this case, after removal of serum proteins phosphorus values were normal. Normal values of phosphorus were also obtained with the phosphomolybdate calorimetric assay after reduction of paraprotein levels in this patient by chemotherapy. Knowledge of this phenomenon may obviate unnecessary testing and treatment. It may also suggest the presence of dysproteinemia.
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PMID:[Spurious hyperphosphatemia in multiple myeloma]. 179 58

A 66 year-old woman with multiple myeloma developed hypoparathyroidism during combination chemotherapy with melphalan, prednisolone, and alpha-interferon (INF). Seven weeks after commencement of the therapy, the serum calcium (Ca) level decreased to 7.4 mg/dL, and the phosphorus (P) level increased to 7.2 mg/dL; parathyroid hormone (PTH) was at a critically low level. By 13 weeks after discontinuation of alpha-INF, the levels of Ca, P, and PTH had returned to normal values: 8.6 mg/dL, 4.5 mg/dL, and 310 pg/ml, respectively. These changes suggest a strong correlation between hypoparathyroidism and the administration of alpha-INF. Autoantibodies against the parathyroid gland cell were not present in the serum of this patient by indirect immunofluorescent techniques. The mechanism of hypoparathyroidism by alpha-INF could not be identified, but this is the first case of this condition during alpha-INF therapy.
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PMID:Hypoparathyroidism during alpha-INF therapy in a patient with multiple myeloma. 262 20

We report the case of a patient with IgG multiple myeloma and pseudohyperphosphatemia, and the case of another patient in whom unexplained hyperphosphatemia led to the diagnosis of monoclonal gammopathy. The pseudohyperphosphatemia was due to the interference of monoclonal immunoglobulins with the phosphomolybdate colorimetric assay for phosphorus determination widely in use with some automated systems. Ultrafiltration of these patients' serum samples resulted in normalization of the elevated phosphorus values. Knowledge of this phenomenon may obviate confusion, unnecessary testing, and expenditure. It may also provide clinicians with a clue as to the presence of a dysproteinemia.
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PMID:Pseudohyperphosphatemia and dysproteinemia. 367 8

Three patients presented with encephalopathies: an undiagnosed degenerative disease of the brain, a degenerative cerebral disease in a patient with a myeloma but without a myelomatous deposit in the CNS and a malignant astrocytoma. Perivascular pallidal deposits (vascular siderosis) containing chromium, phosphorus and calcium plus sometimes traces of other elements were present in the three cases. Such deposits were present in the pallidal parenchyma and around vessels in the cerebellum in one case. Calcium and phosphorus are always present in any CNS calcification but the presence of chromium has not been reported. Chromium and its compounds (ingested, injected or inhaled) are toxic to humans and animals in trace doses. Approximately 900 cases of chromium intoxication have been reported and usually have had dermatological or pulmonary lesions (including cancer) but there is no report of involvement of the CNS. Sublethal doses of chromium nitrate injected intraperitoneally in rats and rabbits results in the presence of chromium in the brain. A thorough investigation was made to find the source of the chromium in these patients. Chromium was found to be present in trace amounts in the radiological contrast agents administered to these patients and in the KCl replacement solution and in mylanta, an antacid, given to one case. The evidence that chromium induced pathological changes in these three brains is circumstantial but shows that chromium can penetrate the human brain. This study indicates that vascular siderosis found in the brains of the majority of middle-aged and elderly humans is not simply an anecdotal pathological curiosity, but that it can serve as a route of entry for toxic products into the brain.
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PMID:Abnormal deposits of chromium in the pathological human brain. 395 42

Phosphorus-31 nuclear magnetic resonance (NMR) studies on the two phosphorus nuclei of the phosphonium analogue (Me3P+CH2CH2OPO3(2-)) of phosphocholine are used to monitor the charged subsites in the phosphocholine-binding immunoglobulin A mouse myeloma M603. Comparison of the 270-MHz 1H NMR difference spectrum on addition of either this analogue or phosphocholine to M603 and the almost identical changes in the pKa values of the phosphate groups on binding to M603 confirm that the analogue is a good model for phosphocholine. The pKa of the phosphate groups is decreased by 0.5 unit on binding to M603, which is consistent with the phosphate group being hydrogen bonding to Tyr-33H and Arg-95L, as suggested from the X-ray structure, and also implies that the binding energies for the mono- and dianion are similar. The P+Me3 moiety is used to probe the electrostatic interactions in the choline subsite. Titration of the chemical shift of the phosphonium phosphorus reflects a group on the protein that has a pKa value of less than or equal to 5, which from the refined X-ray structure (D.R. Davies, personal communication) of the site is assigned to Asp-97L. The choline subsite is monitored by using 1H NMR difference spectra, which indicates that the subsite is highly aromatic as expected from the crystal structure that places Trp-107H and Tyr-100L in this subsite. The ring current interactions from these rings can account for the 1H NMR chemical shift data on choline.
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PMID:A combined proton and phosphorus-31 nuclear magnetic resonance investigation of the combining site of M603, a phosphocholine-binding myeloma protein. 629 93


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