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)

A combination of doxorubicin ('Adriamycin") and B.C.N.U. (1,3 di[2-chloroethyl]-1-nitrosourea) (30 mg/m2 of each intravenously every 3-4 weeks) was used to treat thirteen multiple-myeloma patients who did not respond or were in relapse after remission produced by alkylating-agent/prednisone therapy. All cases were staged according to total-body myeloma-cell number and followed quantitatively for response to therapy. Seven of the thirteen patients responded (54%). Two had complete clinical remissions and a greater than 75% reduction in tumour-cell mass lasting 12 and 16 months. Five others had partial remissions with lesser degrees of tumour-mass reduction and bone pain and improved haemoglobin and serum-albumin concentrations. Toxicity was limited to occasional myelo-suppression, mild alopecia, and nausea. The results indicate the usefulness of doxorubicin/B.C.N.U. for myeloma patients who have relapsed during previously effective alkylating-agent therapy.
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PMID:Doxorubicin/B.C.N.U. chemotherapy for multiple myeloma in relapse. 5 35

The authors report two cases of acute myelo-monocytic leukemia occuring during the course of multiple myeloma treated by local radiotherapy and melphalan. Both patients underwent a complete remission of their myeloma for 27 and 78 months. The myeloma relapsed suddenly in the form of an acute leukemia. In one case, the onset of acute leukemia was preceded by a syndrome of marrow failure with numerous crown-shaped sideroblasts and an excess of myeloblasts in the marrow. This stage lasted two years. The biochemical abnormalities of the red cells usually associated with refractory anemia and preleukemic conditions were present in the other case.
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PMID:[Multiple myeloma and acute leukemia. Simultaneous evolution of plasmacyte and myelomonocytic clones]. 21 59

Using the cytochemical method after Barka and Anderson, activity and localization of lysosomal acid phosphatase (AP) was determined in peripheral-blood lymphocytes from 20 healthy subjects, 10 patients with Hodgkin's disease (HD), 10 patients with plasma cell myeloma (PCM), and 10 patients with primary polycythemia (PP). Total count of AP-positive lymphocytes was lowest in the patients with HD. Moreover, they showed a significant decrease of the absolute count of lymphocytes with well formed and more numerous AP-positive lysosomal granules. Analogous alterations in lymphocytes from patients with PCM and those with PP were much less significant. The authors discuss the importance of the above-mentioned observations for evaluation on a cellular basis of lowered immunity of patients with lympho-proliferative and myelo-proliferative disorders, with special regard to AP as a T-cell marker.
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PMID:Activity and intracellular localization of lysosomal acid phosphatase in lymphocytes from patients with Hodgkin's disease, plasma cell myeloma and primary polycythemia. 102 4

Two cases of IgA multiple myeloma treated with syngeneic bone marrow transplant and a non-total body irradiation (TBI) conditioning regimen are reported. Both patients presented with stage III disease which responded to standard chemotherapeutic management. The myelo-ablative program for transplant consisted of busulfan and cyclophosphamide (Bu/Cy). Evaluation at 40 days post-transplant revealed no evidence of residual myeloma in either patient. One patient died of disseminated Aspergillus fumigatus at day 73 post-transplant. The other patient relapsed at 18 months post-transplant. This conditioning regimen shows efficacy in aggressive myeloma and could be considered earlier in the disease.
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PMID:Syngeneic marrow transplantation in multiple myeloma. 156 44

A series of 217 trephine bone marrow biopsies from adult patients and specimens from 16 fetuses and 5 infants were examined for the presence of stromal myoid cells (MCs) using a monoclonal antibody recognizing alpha-smooth muscle actin. In the normal adult bone marrow, stromal cells did not contain alpha-smooth muscle actin, whereas during fetal life, many alpha-smooth muscle actin-containing MCs were connected with vascular sinusoids in the primitive bone marrow. This cell type reappeared in various characteristic distribution patterns in adult bone marrow during different neoplastic and non-neoplastic conditions including metastatic carcinoma, Hodgkin's disease, multiple myeloma, hairy cell leukemia, acute myeloid leukemia (FAB M4, 5, 7) and chronic myelo-proliferative diseases. In general, the appearance of MCs was associated with a slight to pronounced increase in the deposition of reticulin and collagen fibers. We propose that bone marrow MCs represent a distinct subpopulation of fiber-associated or adventitial reticular cells undergoing cytoskeletal remodeling in response to various stimuli.
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PMID:Alpha-smooth muscle actin is expressed in a subset of bone marrow stromal cells in normal and pathological conditions. 257 Apr 90

Plasma fibronectin concentration was determined by electroimmunodiffusion and laser nephelometry in 40 healthy persons and 321 patients with myelo- and lymphoproliferative diseases and other malignancies. Decreased fibronectin concentrations were found in patients with leukemia, Hodgkin's and non-Hodgkin's lymphomas, myelofibrosis, polycythaemia rubra vera and angioimmunoblastic lymphadenopathy. Elevated fibronectin level was detected in patients with multiple myeloma. In patients with cancer of the lung, stomach and colon, fibronectin level was found in the normal range. Decreased fibronectin concentration was observed in patients with cancer of the breast and prostate. Lower plasma fibronectin concentrations were detected in all groups of patients with infectious septical complications as compared to the patients without infections.
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PMID:[Determination of plasma fibronectin in myeloproliferative and lymphoproliferative diseases and other malignancies]. 308 43

The serum concentration of free kappa and lambda light chains of immunoglobulins were measured in 114 patients with myelo- and lymphoproliferative disorders including multiple myeloma. Increased concentrations of a single light chain type, suggesting monoclonal origin, were found with high frequency in B-cell diseases only. Thus 6 out of 9 patients with chronic lymphatic leukaemia and 24 of 28 patients with multiple myeloma had increased concentrations of a single chain type. The highest values reported in chronic lymphatic leukaemia were approximately 10 and in multiple myeloma 1000 times normal mean. Cytostatic treatment of chronic lymphatic leukaemia was followed by a decrease in the light chain levels. The levels were, however, not correlated to the number of circulating lymphocytes, the lymphatic infiltration of tissue or clinical activity. Increased concentrations of both chain types, suggesting a polyclonal origin, were found in both of 2 patients with acute monocytic leukaemia, 6 of 7 with acute myelomonocytic leukaemia, 2 of 23 with acute myeloid leukaemia and 1 of 7 with acute lymphoblastic leukaemia. The highest levels of light chains in these groups were 5 times normal mean. All patients with myeloproliferative disorders revealed normal values of both light chain types.
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PMID:Free light chains of immunoglobulins in serum from patients with leukaemias and multiple myeloma. 681 Apr 51

Uric acid is the end-product of purine nucleotide metabolism in man. The renal handling of urate is a complicated process, resulting in a fractional clearance of 8.2-10.3%. The anhydrous form is thermodynamically the most stable uric acid crystal. Uric acid is a weak acid that ionizes with a Pka at pH 5.75. At the normal acidic region, uric acid solubility is strongly increased by urinary pH. The prevalence of uric acid stones varies between countries, reflecting climatic, dietary, and ethnical differences, ranging from 2.1% (in Texas) to 37.7% (in Iran). The risk for uric acid stone formation correlates with the degree of uric acid supersaturation in the urine, depending on uric acid concentration and urinary pH. Hyperuricosuria is the major risk factor, the most common cause being increased purine intake in the diet. Acquired and hereditary diseases accompanied by hyperuricosuria and stone disease include: gout, in strong correlation with the amount of uric acid excreted, myelo- and lymphoproliferative disorders, multiple myeloma, secondary polycythemia, pernicious anemia and hemolytic disorders, hemoglobinopathies and thalassemia, the complete or partial deficiency of HGPRT, superactivity of PRPP synthetase, and hereditary renal hypouricemia. A common denominator in patients with idiopathic and gouty stone formers is a low urinary pH. Uric acid nephrolithiasis is indicated in the presence of a radiolucent stone, a persistent undue urine acidity and uric acid crystals in fresh urine samples. A radiolucent stone in combination with normal or acidic pH should raise the possibility of urate stones.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Uric acid nephrolithiasis. 778 6

The CD34 antigen is a glycosilated transmembrane protein with a molecular weight of 105-120 kDs, whose molecular function is still unknown. At present different epitopes of this antigen are recognized by more than 20 monoclonal antibodies. By flow cytometry is quite simple to identify and enumerate the CD34+ cells, present in physiological conditions on 1-3% of normal bone marrow, 0,1-0,5% of cord blood and 0,001-0,01% of peripheral blood cells. The concomitant expression of other monoclonal antibodies allows the identification of different subsets, lineage negative or already lineage "committed", so that CD34+ cells represent an heterogeneous population with only a small number of undifferentiated progenitors. The number of circulating progenitors has highly increased in peripheral blood for few hours during the fast hematopoietic recovery after high dose chemotherapy. Growth factors are able to mobilize CD34+ cells if used alone in a short treatment schedule and the effect is amplified by combining growth factors with chemotherapy. With this treatment CD34+ cells can increase in peripheral blood up to 100-1000 fold the baseline concentration. Collection of large scale of peripheral stem cells is now possible using different models of continuous-flow blood cell separators. The vast majority of the cells harvested by apheresis are constituted by "committed" elements, myeloid peroxidase positive cells (40%), T lymphocytes (30%), monocytes (20%), B lymphocytes (1-2%), the CD34+ representing not more than 3-4% of the total cells collected. The main biological characteristic of the CD34+ cells is the capacity to reconstitute the myelo and lymphopoietic system after a myeloablative treatment. For this reason in the last few years there has been an increasing interest in using these particular stem cells in many clinical settings. Peripheral blood autografting is widely used in a large number of trials for the treatment of chemosensitive tumors. At present peripheral blood allogeneic transplants have been done in a number of patients sufficient to conclude that it is safe and able to give rise to a sustained marrow engraftment. Moreover, due to the fact that circulating stem cells are a mixture of indifferentiated progenitors and "committed" cells, the hematopoietic recovery is significantly faster both in autologous and allogeneic transplant setting. The increasing use of peripheral blood stem cells for autografting has raised the problem of tumoral contamination. The role of reinfused tumoral cells in promoting the relapse had been proved in the past. Attempts to "purge" the bone marrow of patients affected by low-grade non-Hodgkin lymphoma were done several years ago at Dana Farber Institute, strongly suggesting the importance of tumor cells left in the inoculum in modifying the prognosis. In certain tumors, such as myeloma for example, using a PCR based method, the contamination was found in all the aphereses tested. Similar data were found in samples derived from advanced breast cancer or small-cell lung cancer patients. These findings have brought to the development of different systems of stem cell "purging" or CD34+ positive selection. At present at least two or three different methods are available on the market for small and large scale bone marrow or peripheral blood stem cell processing. The ongoing trials will clarify the clinical utility. In the end the availability of large amount of enriched CD34+ cells have suggested to several investigators a possible target for gene therapy. The first data seem to suggest this is a good way to pursue, even if a clinical application remains still far from being satisfying.
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PMID:[CD34+ cells: biological aspects]. 892 36

Thalidomide was developed in the 1950s as a sedative drug and withdrawn in 1961 because of its teratogenic effects, but has been rediscovered as an immuno-modifying drug. It has been administered successfully for the treatment of erythema nodosum leprosum, aphthous ulceration in HIV disease, inflammatory bowel diseases, and multiple myeloma. So far, investigations into the mode of action of thalidomide have focused on lymphocytes and vascular endothelial cells and have shown that this agent inhibits the production of tumor necrosis factor (TNF)-alpha and is an inhibitor of tumor angiogenesis. Recently, other immunological effects of this drug have been gaining attention, including attenuation of neutrophil activation and inhibition of myelo-proliferative responses. In autoimmune diseases, inflammation is characterized by an influx of granulocytes, and the association of granulocytes with gastrointestinal ulcer formation or rheumatic arthritis has been well documented. The suppressive effect of thalidomide on the activation of the nuclear transcription factor NF-(kappa)B may explain these effects of thalidomide. NF-(kappa)B is retained in the cytoplasm with I(kappa)B(alpha), and is activated by a wide variety of inflammatory stimuli including TNF, IL-1 and endotoxin followed by its translocation to the nucleus. Constitutive activation of NF-(kappa)B has been detected in various inflammatory diseases, while angiogenesis and organogenesis also require NF-(kappa)B activation. Thalidomide, on the other hand, has been shown to selectively suppress NF-(kappa)B activation induced by inflammatory mediators. NF-(kappa)B is known to be located downstream of proliferative and/or survival signaling induced by growth factors, which regulate anti-apoptotic genes. Myeloid cells in vitro, however, have been found to proceed to apoptosis as the result of the treatment with thalidomide and subsequent inactivation of NF-(kappa)B. These findings are consistent with clinical symptoms that showed the recovery from leukocytosis and/or neutrophilia after the administration of thalidomide. These findings shed new light on the anti-inflammatory properties of thalidomide and suggested that they may inhibit granulocyte-mediated tissue injury.
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PMID:Thalidomide as an immunotherapeutic agent: the effects on neutrophil-mediated inflammation. 1572 33


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