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)

Marrow transplantation is effective treatment for a number of haematological diseases in patients under the age of 50 who have an HLA-identical sibling donor. It is generally successful when used early in the treatment of aplastic anaemia. It is the only treatment that offers long-term disease-free survival for patients with acute leukaemia who have relapsed at least once, with 10-30 per cent apparent cures. Although still somewhat controversial, it appears also to be the treatment of choice for patients with acute non-lymphoblastic leukaemia in first chemotherapy induced remission and for those with chronic myelogenous leukaemia in the chronic phase since approximately 50-60 per cent of these patients are surviving after marrow transplantation in complete remission, apparently cured. Marrow grafting is the only effective treatment for many patients with inherited immunological-deficiency diseases and certain genetic storage diseases. It is being explored for the therapy of patients with lymphoma, Hodgkin's disease, multiple myeloma, small-cell lung cancer, testicular cancer, ovarian cancer and genetic disorders of haematopoiesis. Cures of congenital Fanconi anaemia, Blackfan-Diamond anaemia, osteopetrosis, and paroxysmal nocturnal haemoglobinuria have been achieved by marrow grafting. Genetic disorders associated with haemolytic anaemia and cyclic neutropenia have been cured by marrow grafting in animals. Target disorders for marrow transplantation in humans are thalassaemia major and sickle cell disease, and, indeed, a first successful transplant for treatment of thalassaemia major has recently been described (Thomas et al, 1982). Marrow transplantation has been limited by the fact that many patients do not have HLA-identical siblings and very few have monozygotic twins. The Seattle team has now explored the use of less well-matched family member donors in more than 80 patients with leukaemia. These donors share one HLA haplotype genetically with the patient and are phenotypically identical at two of the three major HLA loci on the other HLA haplotype (Clift et al, 1979). Overall, the post-transplant survival appears more a reflection of the type and stage of the leukaemia than of the marrow donor. Patients with leukaemia grafted in relapse have a projected survival of 20-30 per cent and those transplanted in remission of 50 per cent. The incidence and severity of GVHD may not be significantly different from that of patients given HLA-identical sibling marrow grafts.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Application of bone marrow transplantation in leukaemia and aplastic anaemia. 635 79

A case of adult Fanconi syndrome is described in which there was urinary excretion of kappa light chains. After 13 years the patient developed overt myeloma. She also developed an adenocarcinoma of the colon and an adenocarcinoma of the parathyroid gland. These findings are discussed in relation to the known association between adult Fanconi syndrome, renal damage, and myeloma.
 ...
PMID:Adult Fanconi syndrome progressing to multiple myeloma. 643 83

Adult Fanconi syndrome has been described as a manifestation of a latent form of myeloma. Since benign monoclonal gammopathy (BMG) is a latent form of myeloma we studied ten patients with this disease with respect to the adult Fanconi syndrome. These patients were selected from a larger group with BMG because of urinary excretion of monoclonal light chains. In no instance could a complete Fanconi syndrome be shown, but one patient, who also had a diabetic nephropathy, had very high levels of urinary beta 2-microglobulins. Two additional patients showed minor features included in the adult Fanconi syndrome. BMG does not seem to be associated with an increased risk of developing adult Fanconi syndrome.
 ...
PMID:Occurrence of adult Fanconi syndrome in benign monoclonal gammopathy. 746 11

Seventy-three BMT procedures (42 allogeneic-BMT, 30 autologous-BMT, 1 syngeneic transplant) were undertaken at the Shariati Hospital in Tehran between March 1991 and November 1993. Allogeneic-BMT was performed for thalassaemia major (n = 23), AML in complete remission (n = 3), severe aplastic anaemia (n = 7), CML (n = 7), dyskeratosis congenita (n = 2) and Fanconi anaemia (n = 1). Conditioning regimens comprised busulphan (BU) plus cyclophosphamide (CY) or CY only. Thirty-two (78%) of the 43 patients remain alive 1-34 months after BMT. Twelve patients died: the causes of death were haemorrhagic cystitis (n = 1), CMV pneumonitis (n = 1), GVHD (n = 3), infection (n = 3), rejection (n = 1), VOD (n = 2) and hepatitis (n = 1). Autologous-BMT was performed for patients with AML in CR (n = 16), ALL in CR (n = 9), lymphoma in relapse (n = 3), Ewing sarcoma (n = 1) and multiple myeloma (n = 1). The median age was 18 years. Conditioning regimens were Ara C plus CY, etoposide plus CY and high-dose melphalan. Sixteen (54%) of the 30 patients survive, 14 in continuous complete remission. The causes of death were relapse (AML (n = 7), ALL (n = 4), lymphoma (n = 1)), VOD (n = 1) and infection (n = 1).
 ...
PMID:Bone marrow transplantation in Iran. 792 Mar 8

Fanconi syndrome is characterized by some absorptive defects of proximal renal tubules. It is observed either primarily, or secondarily to various diseases. A case of multiple myeloma complicated by Fanconi syndrome is reported. The patient was a 62-year-old female. The serum total protein was elevated, and monoclonal IgG-kappa protein was found on serum immunoelectrophoresis. Urinary Bence Jones protein was positive. Bone marrow aspiration disclosed increased dysplastic plasma cells, which led to the diagnosis of multiple myeloma. A diagnosis of Fanconi syndrome was based on renal glycosuria, hypophosphatemia, hypokalemia, and panaminoaciduria due to abnormal excretion from the kidney, and metabolic acidosis. After chemotherapy for multiple myeloma, serum IgG level and urine sugar decreased, and serum potassium level was corrected.
 ...
PMID:[A case of IgG-kappa type multiple myeloma complicated by Fanconi syndrome]. 793 67

An extracted Bence Jones lambda protein from a Japanese patient with myeloma-associated Fanconi syndrome was found to contain 5 components, including the dimer and the monomer of the entire light-chain, the dimer and the monomer of the constant domain, and monomer of the variable domain. The entire amino acid sequence of this lambda chain was completed. The protein, containing 5 components, was injected intraperitoneally in C3H mice, 20 mg for 13 days and 200 mg for 3 days. Both groups of C3H mice showed a renal proximal tubular deposition of variable domain fragment of the Bence Jones protein by immunoperoxidase staining. Other control Bence Jones proteins of the lambda type and serum albumin were negative in terms of deposition in the epithelial tubular cells. It is also shown that the proximal tubules of the biopsied kidney from the patient had a deposition of variable domain fragment of Bence Jones protein. Thus, the myeloma-associated Fanconi syndrome could be included in the spectrum of light-chain associated disease or monoclonal Ig deposition disease. This is the first case of lambda type Bence Jones protein with a complete amino acid sequence analysis found in Fanconi syndrome with myeloma, demonstrating the deposition of the variable domain in the proximal tubules of the kidney.
 ...
PMID:V-domain deposition of lambda Bence Jones protein in the renal tubular epithelial cells in a patient with the adult Fanconi syndrome with myeloma. 968 6

Plasma cell dyscrasias may be responsible for Fanconi's syndrome, due to the toxicity of a free monoclonal kappa light chain toward kidney proximal tubules. Eight cases of Fanconi's syndrome were analyzed. We compared the structures of VkappaI variability subgroup V domains from five cases of Fanconi's syndrome and one myeloma without renal involvement. Among Fanconi cases, four putative structures were obtained after molecular modeling by homology, and the other had previously been refined by X-ray crystallography. The complete sequences of one VkappaI, one VkappaIII and N-terminal sequences of two VkappaI light chains, from patients with different forms of Fanconi's syndrome, were compared with four previously studied sequences. All three kappa chains responsible for a 'classical' form with intralysosomal crystals and a low mass myeloma, were encoded by the LCO2/O12 germline gene and had an unusual non-polar residue exposed to the solvent in the CDR-L1 loop. Of both VkappaI light chains from patients with Fanconi's syndrome without intracellular crystals, one derived from LCO2/O12 and the other from LCO8/O18 gene. Another feature that could be related to non-crystallization was the absence of accessible side chains in the CDR-L3 loop which is known to be implicated in dimer formation.
 ...
PMID:Kappa light chain-associated Fanconi's syndrome: molecular analysis of monoclonal immunoglobulin light chains from patients with and without intracellular crystals. 1032 8

Intracellular immunoglobulin crystal formation within plasma cells is an uncommon finding in multiple myeloma and other lymphoplasmacytic tumors. We present 12 cases of plasmacytic tumors with prominent crystal formation, including myeloma (5 cases), lymphoplasmacytic lymphoma (6 cases), and a nonneoplastic plasma cell proliferation. In all cases, crystal formation was associated with the proliferation of variable numbers of histiocytes containing similar inclusions. These cases showed a variety of appearances, sometimes obscuring the underlying plasma cell tumor and raising the differential diagnosis of a storage disorder, hemophagocytosis, or a mesenchymal lesion. In cases of lymphoplasmacytic lymphoma, patients typically presented with marked paraproteinemia and symptoms of hyperviscosity. Crystal-storing histiocytosis was not associated with other immunoglobulin deposition disorders, including amyloidosis, Mott cell tumors, or kappa-light chain deposition. In our cases and those previously reported, we found an overwhelming association of crystal-storing histiocytosis (CSH) with tumors expressing immunoglobulin kappa light chain with no consistent association with a particular heavy chain. These results suggest that CSH results from the ingestion of crystals produced by plasma cell tumors that either overproduce kappa light chain or express a structurally aberrant molecule. CSH persists in the marrow and other sites throughout the course of the disease and in our series was not highly associated with development of the adult Fanconi syndrome or rapid clinical deterioration.
 ...
PMID:Crystal-storing histiocytosis: a disorder occurring in plasmacytic tumors expressing immunoglobulin kappa light chain. 1066 22

Fifty-seven cases of Ig light chain-associated Fanconi syndrome (FS) have been reported so far, mostly as isolated reports. The pioneering work by Maldonado and associates (35), who reviewed the first 17 cases in 1975, led to the unifying concept that patients with FS and Bence Jones proteinuria have a special form of plasma cell dyscrasia characterized by slow progression of the tumor and by prominent crystal formation in proximal tubule cells, in the absence of myeloma casts in the distal tubule. We carefully reappraised these characteristics in a series of 11 patients. Ten renal biopsy specimens were available for electron microscopy, adding to the 15 previously reported cases with ultrastructural studies. Moreover, 10 of the kappa light chains could be entirely or partially sequenced and tested for their resistance to cathepsin B, a lysosomal protease present in proximal tubule cells. Our series showed an unexpected clinicopathologic heterogeneity. Seven patients presented with the typical clinical and pathologic features of FS and low-mass myeloma or monoclonal gammopathy of undetermined significance (MGUS), in keeping with Maldonado et al's description. Crystals in bone marrow cells were detected in patients of this group, only. Three patients who presented with full-blown FS exhibited, however, the characteristic features of myeloma cast nephropathy in the setting of high-mass myeloma. One patient of this group also had numerous crystals in proximal tubule cells. The eleventh patient had complete FS with MGUS, but no crystals in proximal tubule cells even after electron microscopy. Contrasting with the clinicopathologic heterogeneity, genetic and biochemical analyses of the light chains showed a striking homogeneity. First, they all were of the kappa type. Second, 8 of 9 belonged to the V kappa I variability subgroup, which indicates that FS light chains are related by the sequence of their variable regions. Third, the 8 V kappa I light chain sequences most likely originated from only 2 germline genes, LCO2/012 and LCO8/018. Fourth, all 5 LCO2/012-derived sequences presented an unusual hydrophobic or nonpolar residue at position 30. These sequence peculiarities may account for unusual physicochemical properties of the light chains including the resistance of their variable domain V kappa to proteolysis by cathepsin B, observed in 7 of 9 patients in our series, while light chains isolated from patients with myeloma cast nephropathy are completely digested. Resistance of V kappa to proteolysis in FS patients can explain the accumulation of the light chain in the endocytotic compartment of the proximal tubule cells, leading to impairment of proximal tubule functions.
 ...
PMID:Adult Fanconi syndrome secondary to light chain gammopathy. Clinicopathologic heterogeneity and unusual features in 11 patients. 1084 34

Multiple myeloma is associated with a wide array of renal diseases that include myeloma cast nephropathy, monoclonal immunoglobulin deposition disease, amyloidosis, cryoglobulinemia, tubular dysfunction, pyelonephritis, nephrocalcinosis, urate nephropathy, and infiltration by atypical plasma cells (or myeloma cells). Filtered immunoglobulin light chains may affect both the distal and, more frequently, the proximal tubule. Tubular abnormalities in patients with plasma cell dyscrasia may be more frequent than previously thought. A patient with a plasma cell dyscrasia is described, who presented with biochemical features consistent with Fanconi syndrome. Immunoelectron microscopy performed on the renal biopsy confirmed the presence of kappa light chain immunoglobulin in intracytoplasmic crystals in proximal tubular epithelial cells. This report is one of a few demonstrating the presence of light-chain immunoglobulin in intratubular crystals in a human renal biopsy obtained from a patient with a plasma cell dyscrasia and Fanconi syndrome.
 ...
PMID:Clinical, biochemical, and pathological features in a patient with plasma cell dyscrasia and Fanconi syndrome. 1101 62


<< Previous 1 2 3 4 5 6 7 Next >>