Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0033687 (proteinuria)
 24,015 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Renal amyloidosis was diagnosed in 14 young Chinese Shar Pei dogs, all of which were related. Clinical signs were those of renal failure and included vomiting, anorexia, lethargy, polydipsia, polyuria, weight loss, and dehydration. Some dogs had a history of intermittent fever and joint swelling. Laboratory findings also were compatible with renal failure and included azotemia, hyperphosphatemia, low total CO2 content in serum, isosthenuria, proteinuria, and hypercholesterolemia. All dogs had medullary deposition of amyloid, and 9 of 14 (64%) had glomerular involvement. The remaining renal lesions were typical of end-stage renal disease. In some dogs, amyloid deposits were found in other tissues (eg, liver, spleen, stomach, small intestine, myocardium, lymph node, prostate gland, thyroid gland, and pancreas). Amyloid deposits were sensitive to potassium permanganate oxidation, suggesting the presence of amyloid protein AA.
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PMID:Familial renal amyloidosis in Chinese Shar Pei dogs. 221 Dec 93

The purpose of the study was to determine if danazol was efficacious in the treatment of lupus MRL/MpJ (lpr) mice, as measured by longevity, proteinuria and serum amyloid protein (SAP) levels. Danazol, administered at an oral dose of 100 mg/kg, significantly prolonged survival of female MRL/MpJ (lpr) mice but had no effect on the mortality of their male counterparts. Medication with danazol began 40 days after birth of the mice and resulted in a significant decrease in proteinuria in female but not male lupus mice. The concentration of SAP, an acute phase reactant, was significantly decreased in danazol-treated female lupus mice at 80, 100, 120, 140 and 160 days of age when compared to vehicle-treated control mice. SAP levels in male lupus mice treated with danazol were significantly lower than normal control levels only at the 120 and 160 day time points. Measurements of mortality, proteinuria and SAP concentration indicate that danazol at 100 mg/kg is orally active in the treatment of MRL/MpJ (lpr) female, but not male mice.
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PMID:The effect of danazol in the MRL/lpr mouse model of autoimmune disease. 318 43

A 22-year-old woman, who had been diagnosed as having rheumatoid arthritis (RA) 2 years before, was admitted to our hospital complaining of watery diarrhea (several times/day). She had been treated with low dose prednisolone (PSL) and auranofin in out-patient clinic. On admission, laboratory data showed moderate proteinuria (0.3 g/day) and positive CRP (2.7 mg/dl). Although the activity of RA was controlled by the administration of low dose methotrexate (7.5 mg/week) in addition to PSL, watery diarrhea and proteinuria did not improve. The biopsy of the stomach, rectum and kidney revealed the deposition of AA type amyloid protein, resulting in the diagnosis of secondary amyloidosis. Secondary amyloidosis has been reported as one of the common complications in RA patients, especially in old patients with a long history of RA. To our knowledge, however, there have been few reported cases who developed secondary amyloidosis so early during the course of RA as our case. We should be careful for the development of secondary amyloidosis even in young RA patients with short history of RA, when the disease is active.
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PMID:[A young woman with rheumatoid arthritis who rapidly developed secondary amyloidosis]. 755 43

Primary or AL amyloidosis occurs in patients with monoclonal plasma cell-related disorders and is typically associated with the systemic deposition as amyloid fibrils of the light-chain portion of the immunoglobulin molecule. Recently, the discovery that heavy chains could be involved in amyloid formation led to the designation of this type of disease process as AH amyloidosis. We have now identified a second example of heavy chain-associated amyloidosis in a patient (MAD) who had a serum IgG monoclonal gammopathy and Bence Jones proteinuria. In this case, the renal and splenic amyloid deposits consisted solely of the VH-D-encoded portion of the heavy polypeptide chain, in contrast to the first case, where the amyloid contained an immunoglobulin component composed of the entire heavy-chain variable and third constant domains. In this respect, the chemical composition of the amyloid protein MAD differed not only from that of the first reported case of AH amyloidosis but from all other structurally abnormal components found in patients with heavy chain-associated disease. The discovery that certain forms of heavy chains, as well as light chains, can form amyloid provides further information on the chemical basis of amyloidogenicity and the diverse nature of this disease.
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PMID:Primary amyloidosis associated with a novel heavy-chain fragment (AH amyloidosis). 814 Nov 23

The morbidity and lethality of AL amyloidosis is caused by the deposition of lg light chains as fibrillar amyloid protein in vital organs, disrupting their function, and not by the generally low burden of clonal plasma cells that produce the paraproteins. Survival of patients with AL amyloidosis is no more than 1 to 2 years from the time of diagnosis with current management approaches. Clearly, more effective therapies are needed for this rapidly lethal disease. Five patients were treated with dose-intensive melphalan and blood stem cell support and followed for a period of 1 year. Patients were diagnosed with AL amyloidosis by tissue biopsy and categorized by performance status and organ involvement. Their plasma cell dyscrasias were evaluated with immunofixation electrophoresis of serum and urine specimens, quantitative serum lgs, and immunohistochemical staining of bone marrow biopsy specimens. After treatment with dose-intensive intravenous melphalan followed by infusion of autologous growth-factor-mobilized blood stem cells, clinical evaluations and plasma cell studies were repeated at 3 and 12 months. Three men and 2 women aged 38 to 53 years were treated. Median performance status (SWOG) was 2 (1 to 3), and clinical presentations included nephrotic syndrome (n = 1), symptomatic cardiomyopathy (n = 1), gastrointestinal involvement with polyneuropathy (n = 2), and hepatomegaly (n = 1). With a median follow-up of 13 months (12 to 17 months), all five patients are well and have shown stable or improved performance status and clinical remission of organ-related dysfunction, including a 50% reduction in daily proteinuria with no change in creatinine, reversal of symptoms of cardiomyopathy and reductions of posterior wall and septal thickening, reversal of polyneuropathy and gastric atony, and resolution of hepatomegaly by computed tomographic scan. In 3 of the 5 patients (60%) at 12 months after treatment, plasma cell dyscrasias could not be detected. Dose-intensive chemotherapy with intravenous melphalan and growth-factor-mobilized blood stem cell support is feasible therapy for patients with AL amyloidosis, even when there is clinical evidence of cardiac involvement. At least some patients with AL amyloidosis achieve complete remission of their plasma cell dyscrasia, improvement in performance status, and clinical remission of organ-specific disease after this form of treatment.
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PMID:Dose-intensive melphalan with blood stem cell support for the treatment of AL amyloidosis: one-year follow-up in five patients. 883 79

Although systemic AA amyloidosis complicating Crohn's disease has been found in 0.5 to 6% in America and Europe, it is relatively rare in Japan. We report a case of systemic AA amyloidosis complicating Crohn's disease. In 1979, a 26-year-old Japanese man presented with diarrhea, melena and perianal abscesses, and was diagnosed as having Crohn's disease. He was treated with oral prednisolone, salazosulfapyridine and diet therapy. However, the gastrointestinal symptoms recurred and he was hospitalized several times. In 1991, his thyroid gland was found to be swollen, but with normal thyroid function, and his thyroid gland became larger subsequently. In October 1995, he showed renal dysfunction (blood urea nitrogen 33.2 mg/dl; serum creatinine 1.5 mg/dl) with proteinuria. His renal function had been deteriorating rapidly. On September 13, 1996, he was admitted to the Tsukuba University Hospital. At the time of admission, his renal function showed a blood urea nitrogen of 129.5 mg/dl with a creatinine of 5.4 mg/dl. The urine contained 0.8 g of protein per 24 hours. He presented with diarrhea for several days before admission and was treated with central venous hyperalimentation. Despite supportive care, he developed end-stage renal failure, then hemodialysis was initiated on October 7. His condition was complicated by a complete auriculoventricular block on October 18. He died of hemoperitoneum on October 25. On postmortem examination, extensive amyloid deposits were found in multiple organs including kidneys, intestine, heart, thyroid gland, lungs, liver, spleen, pancreas, gall bladder, adrenal glands, testis, prostate, bone marrow and parathyroid glands. Analysis of amyloid protein in the autopsy specimens showed type AA.
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PMID:[A case of systemic AA amyloidosis complicating Crohn's disease]. 965 12

Light chain-associated amyloidosis is characterized by the deposition as fibrils of monoclonal light chain-related components consisting predominately of the variable domain (VL) or the VL plus up to approximately 60 residues of the constant domain (CL). Here, we describe a patient (designated BIF) with light chain-associated amyloidosis and kappa Bence Jones proteinuria in whom, notably, >80% of the amyloid deposits were comprised of CL-related material. The extracted amyloid protein consisted of 99 aa residues identical in sequence to the main portion of the Ckappa region (positions 109-207) of the precursor Bence Jones protein. Remarkably, the CLs from both molecules contained a Ser-->Asn substitution at position 177. This heretofore undescribed Ckappa alteration did not result from somatic mutation but rather was germline encoded. When tested in our in vitro fibrillogenic kinetic assay, Bence Jones protein BIF was highly amyloidogenic. Notably, endopeptidase treatment of amyloid fibrils prepared from the native light chain revealed the VL to be markedly susceptible to enzymatic digestion, whereas the CL was protease-resistant. Our findings provide evidence that the fragmented light chains typically present in this disease result from proteolytic degradation and suggest that, in this case, conformational differences in VL/CL packing within the fibrils may account for the unusual composition of the amyloid deposits. Additionally, we posit that the previously unrecognized Asn177 substitution represents yet another Ckappa allotype, provisionally designated Km4.
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PMID:Light chain-associated amyloid deposits comprised of a novel kappa constant domain. 968 17

A French family with hereditary renal amyloidosis (HRA) was studied. The disease presented in 7 of the 8 affected individuals with proteinuria or the nephrotic syndrome. The age of onset was in the fifth decade of life. There is currently no sign of extrarenal involvement in any affected individual. However, the nephropathy in this family is progressive and led to terminal renal failure in 4 patients. Immunohistochemistry studies of glomerular amyloid deposits suggested that the amyloid protein was the fibrinogen A alpha chain. Direct DNA sequencing revealed a G 4993 T transversion and subsequently Arg 554 Leu mutation in the fibrinogen A alpha chain. This is the first description of this fibrinogen A alpha chain mutation in Europe. This family is of French descent and cannot be related to the previously reported Peruvian/Mexican and African-American kindreds.
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PMID:Fibrinogen A alpha chain mutation (Arg554 Leu) associated with hereditary renal amyloidosis in a French family. 1003 86

A fifteen-year-old boy was admitted to our hospital because of lower abdominal pain, watery diarrhea and mucobloody stool. Two years before admission, he was diagnosed to have Still's disease presenting with polyarthritis, sore throat, remittent fever and typical skin rash. He had been treated with non-steroidal anti-inflammatory agents, oral prednisolone and low-dose methotrexate. Although he was almost free of symptoms during the next two years, serum C-reactive protein (CRP) levels continued to be elevated moderately. He began to complain of lower abdominal pain and loose stool in May 1997 and came down with mucous-bloody diarrhea in June. Laboratory data on admission showed an elevated level of serum CRP (13.9 mg/dl). The biopsy of the stomach, ileum, sigmoid colon and rectum revealed the deposition of amyloid protein of AA type, which confirmed the diagnosis of secondary amyloidosis. The dose of prednisolone was increased and dimethyl sulfoxide per os or rectum was instituted, which improved his gastro-intestinal symptoms to some extent. However, fever, arthritis and diarrhea recurred along with tapered prednisolone dosage. In addition to gastro-intestinal symptoms, arrhythmia and proteinuria appeared. These symptoms were considered to reflect general deposition of amyloid in his body. He is now on immunosuppressive agent and high-dose prednisolone. Several studies report the higher frequency of gamma-allele of SAA 1 gene in the cases of rheumatoid arthritis with AA-amyloidosis than in those without. In the patient presented here, molecular biological analysis revealed that his SAA 1 gene was composed of beta- and gamma-allele. The presence of gamma-allele in his SAA 1 gene might be one of the factors that predisposed him for generalized deposition of amyloid protein in such a short period of time.
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PMID:[Rapidly progressed secondary amyloidosis in a patient with Still's disease with gamma-allele in his SAA 1 gene]. 1092 Jun 89

Demonstration of amyloid deposits in biopsy specimens is the only means of confirming the diagnosis of amyloidosis. In experienced hands, nonsurgical biopsies of the rectal mucosa or, preferably, of the abdominal fat pad or labial salivary glands provide the diagnosis in 80 to 85% of cases. Immunolabeling studies help to determine the histological type of amyloidosis but are not performed routinely in everyday practice. In patients with a family history of amyloidosis, studies of the genome and amyloid protein can identify the protein variants capable of causing systemic amyloidosis. Once the diagnosis of amyloidosis is established, the extent of systemic involvement with amyloid should be evaluated by performing renal and hepatic function tests, a proteinuria assay, and an echocardiogram. Scintigraphy with radiolabeled serum amyloid P (SAP) component is a rapid and specific investigation that provides a map of the amyloid deposits. Deposits are usually seen in the liver and spleen. SAP component scintigraphy can provide support for the diagnosis of amyloidosis in patients with negative histological studies. Tissue retention of radioactivity predicts survival.
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PMID:Diagnostic tools for amyloidosis. 1253 60


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