Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0035078 (renal failure)
 31,970 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 73-year-old man was admitted into the hospital because of lumbago in October, 1986. Laboratory examination on admission showed anemia, an IgA-kappa Bence Jones proteinemia. The bone marrow picture disclosed a marked involvement by the neoplastic cells, followed by leukemic conversion 2 weeks later. The leukemic cells displayed a lymphoblastoid appearance on light microscopy, but rather compatible with plasma cells on electron microscopy, showing some strands of rough endoplasmic reticulum and a prominent Golgi apparatus in the cytoplasm. The cells expressed a wide spectrum of surface markers, including those of plasma cell (PCA-1, OKT10), B cell (B1, sIg) and CALLA. Reverse hemolytic plaque assay disclosed the immunoglobulin production of monoclonal kappa chain, but a heavy chain production was recognized only in a small proportion of the cells. Under the diagnosis of multiple myeloma, he was treated with vincristine, cyclophosphamide, and prednisolone. But he died of renal failure complicating hypercalcemia after only three months of the admission in accordance with previous reports that CALLA-positive myeloma was associated with poor prognosis. This case may also represent the clinical, morphological and phenotypic diversity in multiple myeloma.
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PMID:[CALLA-positive leukemic multiple myeloma of IgA-kappa type]. 250 77

Four patients with common acute lymphoblastic leukemia antigen (CALLA)-positive myeloma are presented. The subclasses of monoclonal protein were IgD kappa (1 case), IgA lambda (1 case), and IgA kappa (2 cases). Bence Jones proteinuria was seen in all cases. The clinical stages were determined as IIA (2 cases) and IIIA (2 cases). All patients died with a median survival time after diagnosis of 62 days due to rapid development of renal failure (3 cases), and renal insufficiency and pneumonia (1 case). According to light microscopic evaluation, these myelomas corresponded to plasmablastic (1 case), immature (2 cases), and intermediate (1 case) types. Both CALLA and a cytoplasmic immunoglobulin identical with the serum monoclonal protein were simultaneously detected in single cells from all cases using immunofluorescent double labeling. These findings suggest that CALLA-positive and plasma-blastic myelomas constitute clinically a subgroup characterized by extremely poor survival but they represent cytologically different subcategories.
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PMID:Clinical features of common acute lymphoblastic leukemia antigen (CALLA)-positive myeloma: report of four cases. 252 31

Endopeptidase 24.11, a widely distributed membrane-bound peptidase is found in low levels in the serum of normal individuals. Although increased levels of the enzyme have been found in sera of patients with sarcoidosis and adult respiratory distress syndrome, the cellular origin of circulating endopeptidase 24.11 remains unknown. As the brush border of the proximal tubular epithelial cells have the highest endopeptidase specific activity, we investigated the possible contribution of the kidney to the release of endopeptidase 24.11 in the systemic circulation. Therefore, we measured serum levels of the enzyme in patients with end-stage renal failure (ESRF) treated by haemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD). Increased serum levels of endopeptidase 24.11 were observed both in HD patients (mean +/- SEM: 74.6 +/- 20.9 ng/ml) and in CAPD patients (mean +/- SEM: 45.1 +/- 8.1 ng/ml) as compared to normal individuals (mean +/- SEM: 13.6 +/- 1.4 ng/ml). Endopeptidase levels remain stable during haemodialysis sessions on two different dialysis membranes. Finally, serum levels of the enzyme in anephric patients tend to be lower than in ESRF patients, suggesting that the kidney may contribute to the generation of the circulating form of endopeptidase 24.11.
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PMID:Increased serum levels of endopeptidase 24.11 ('enkephalinase') in patients with end-stage renal failure. 254 94

A case of plasma cell leukaemia of non-producer type is described. The patient presented with typical clinical features of plasma cell myeloma, including multiple osteolytic lesions, hypercalcaemia, renal failure and reduced polyclonal immunoglobulins, except that M-component was not detected in either the serum or urine. Morphological examinations showed a plasmacytoid appearance of the neoplastic cells, while immunological studies failed to detect cytoplasmic immunoglobulin or secretory capacity. The surface phenotype of CD38+, PCA-1+, DR-, CD20-, CD24-, CD9-, CD10- and surface immunoglobulin- was compatible with mature plasma cells. Chromosomal analysis showed the 14q+ marker due to translocation (6;14) and deletion of the short arm of chromosome 1. Analysis of immunoglobulin genes revealed the presence of heavy chain gene rearrangement, but the light chain genes, both kappa and lambda, remained in germline configuration. Such defective immunoglobulin gene rearrangement may be responsible for the failure of immunoglobulin biosynthesis and secretion by the neoplastic plasma cells. Furthermore, it is suggested that the morphological and phenotypic development of B cells may not necessarily depend on immunoglobulin light chain gene rearrangement, and that the oncogenic event in myeloma may occur at an earlier stage of B cell differentiation.
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PMID:Plasma cell leukaemia of non-producer type with missing light chain gene rearrangement. 313 42

We describe a patient with stage IV non-Hodgkin's lymphoma (NHL) and a t(11;18)(q21;q21) translocation. He presented with a gastric small B-cell lymphocytic lymphoma, expressing IgAL immunoglobulins without expression of CD10, CD5, and CD23 antigens. The lymphoma was the final development of a 6-year history of a monoclonal IgAL increase complicated by severe renal failure due to membranoproliferative glomerulonephritis. The clinical, histological, immunologic, and cytogenetic features of this patient are very similar to those observed in the five other patients with t(11;18) reported to date. This translocation therefore seems to delineate a new subtype of diffuse small B-cell lymphoma with involvement of mucosal sites. Involvement of the BCL2 oncogene on 18q21 could not be detected using molecular techniques with 5' as well as 3' BCL2 probes, indicating that other, so far unknown, genes relevant to lymphoid differentiation could be located in 18q21 and 11q21.
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PMID:t(11;18)(q21;q21) may delineate a spectrum of diffuse small B-cell lymphoma with extranodal involvement. 768 56

Endothelin (ET) is a powerful vasoconstrictor peptide synthesized and secreted by the vascular endothelium. Significant amounts of ET are also produced by nonendothelial cells, mainly tubular-epithelial and mesangial cells. Large amounts of ET are found in the urine compared with the small amounts present in blood. Because most of the ET filtered from plasma is subject to degradation by neutral endopeptidase (EC 3.4.24.11) in the proximal tubule, urinary ET is probably of renal origin. The range of urinary ET excretion in healthy persons is 20 to 90 ng/day. The excretion of endothelin is modulated by several mechanical and chemical stimuli such as angiotensin II, phenylephrine, radiocontrast media, cyclosporine, and cis-platin. In addition, enhanced urinary ET excretion has been found in several forms of renal failure, both acute and chronic, and in diabetes mellitus. Thus, urinary ET has the potential of serving as a marker for renal disease.
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PMID:Urinary endothelin: a possible biological marker of renal damage. 813 95

Atrial natriuretic factor (ANF) has natriuretic, renin-suppressing and chronic hypotensive actions that may be utilized by inhibition of ANF degradation by neutral endopeptidase, E.C.24.11 (NEP). Three groups of 8 male patients [GFR 103 +/- 8 (Normal), 64 +/- 6 (Moderate CRF), and 16 +/- 2 ml/min (Severe CRF)] received 100 mg i.v. bolus of the NEP inhibitor candoxatrilat or placebo in random order in a double-blind crossover study. GFR (51CR-EDTA), ERPF (125I-hippuran). ANF (IRMA), urinary cGMP (RIA) and albumin (RIA) and sodium excretion and flow rate were measured hourly for two hours before and for seven hours after candoxatrilat administration. After candoxatrilat plasma ANF rose two- to threefold from baseline, and remained elevated for 5(N) and 7(M,S) hours (P < 0.01(N,S), P < 0.03(M)) associated with an immediate rise in urine cGMP excretion from 23.5(N), 25.4(M) and 10.4(S) nmol/hr (base) to 51.7(N), 73.8(M) and 27.5(S)(peak) lasting 7(N,M,S) hours (P < 0.01(N,M,S)). There was a marked natriuresis in all three groups, the cumulative sodium excretion at seven hours post-candoxatrilat being 104(N), 140(M), 102(S) mmol (P < 0.05(N,M,S)). This was greatest in those with moderate CRF (moderate CRF vs. normal, P = 0.036, moderate vs. severe CRF, P = 0.01, normal vs. severe CRF, P = 0.74). Following candoxatrilat there was a near doubling of the urine flow rate (P < 0.01(N,S), P < 0.02(M)). Urine albumin excretion increased in patients with renal failure (P < 0.01), but there was no change in GFR, ERPF or systemic blood pressure. We conclude that the marked natriuretic effects of acute NEP inhibition seen in normal subjects are enhanced in the presence of moderate CRF and sustained even in severe renal impairment.
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PMID:Enhanced natriuretic response to neutral endopeptidase inhibition in patients with moderate chronic renal failure. 929 Dec 1

Calcitonin gene-related peptide (CGRP), a potent vasodilator neuropeptide, plays a counterregulatory role in subtotal nephrectomy-salt (SN-salt)-induced hypertension, reflecting a stimulation of the efferent vasodilator function of perivascular sensory nerves. To determine the effect of omapatrilat, a dual ACE and neutral endopeptidase inhibitor, on blood pressure and the potential antihypertensive role for CGRP, 24 male Sprague-Dawley rats were separated into 4 groups: (1) SN-salt, (2) SN-salt plus omapatrilat (80 mg. kg(-1). d(-1) in the drinking water), (3) sham-operated plus salt, (4) sham-operated plus salt and omapatrilat. After 11 days the mean arterial pressure was higher in the SN-salt group (174+/-10 mm Hg) versus the sham-operated-salt (109+/-4 mm Hg) and sham-operated-salt plus omapatrilat (105+/-3 mm Hg) groups. Omapatrilat treatment of the SN-salt rats significantly decreased the mean arterial pressure to 123+/-7 mm Hg and significantly reduced the heart-to-body weight ratio. Intravenous administration of a specific CGRP receptor antagonist produced a significant 10+/-2 mm Hg mean arterial pressure increase in the untreated SN-salt hypertensive rats but was without effect in the other groups. This indicates that CGRP does not contribute to the antihypertensive actions of omapatrilat. In addition, CGRP mRNA and protein content in dorsal root ganglia were decreased approximately 25% in the SN-salt plus omapatrilat rats. Thus, omapatrilat not only markedly reduces the blood pressure in this model of renal failure-induced hypertension but may also prevent the abnormal compensatory stimulation of the vasodilator activity of the peripheral sensory nervous system.
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PMID:Omapatrilat in subtotal nephrectomy-salt hypertension: role of calcitonin gene-related peptide. 1156 59

Blockade of the renin-angiotensin-aldosterone cascade is now recognised as a very effective approach to treat hypertensive, heart failure and high cardiovascular risk patients and to retard the development of renal failure. The purpose of this review is to discuss the state of development of currently available drugs blocking the renin-angiotensin system, such as angiotensin converting enzyme (ACE) inhibitors, renin inhibitors and angiotensin II receptor antagonists, with a special emphasis on the results of the most recent trials conducted with AT(2) receptor antagonists in heart failure and Type 2 diabetes. In addition, the future perspectives of drugs with dual mechanisms of action, such as NEP/ACE inhibitors, also named vasopeptidase inhibitors, are presented.
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PMID:Novel angiotensin II inhibitors in cardiovascular medicine. 1177 99

Since the original discovery of atrial natriuretic peptide (ANP) nearly 20 years ago and the subsequent realisation of the existence of a family of natriuretic peptides, there has been considerable progress in the elucidation of the physiological and pathophysiological significance of these peptides. This review has examined two potentially important practical aspects arising from natriuretic peptide research - the significance of measurement of plasma levels of ANP and of brain natriuretic peptide BNP for cardiovascular disease and the therapeutic potential of targeting the natriuretic peptide system. Several situations where the measurement of plasma ANP and BNP may be of benefit in the overall assessment and prognosis of cardiac disease have been discussed. The measurement of plasma levels of these peptides appears to have limited value as a specific diagnostic tool and is unlikely to replace well-established procedures to assess cardiac function. Nevertheless, given the strong negative predictive value, the value of the measurement of plasma natriuretic peptides particularly BNPs, in people with suspected heart disease, rests on the evidence that a normal value indicates a low risk of cardiac impairment. Moreover, a consistently elevated plasma level of BNP after myocardial infarction is associated with a distinctly poor prognosis. In turn, this may help to select those with high plasma levels for subsequent detailed investigation of cardiac dysfunction. This may be an important option, especially where the facilities for the more invasive cardiological procedures are not available. Intriguingly, recent research also suggests the possibility that plasma levels of natriuretic peptides may have an important role in guiding more effective therapy for heart failure. The potent cardiovascular and renal effects of ANP and BNP provide an important therapeutic potential for hypertension and for conditions associated with volume overload. A number of approaches which have been used to enhance endogenous activity of these peptides have been highlighted. The use of the native peptides ANP and BNP may well be valuable in some circumstances, such as in critically ill individuals with congestive heart failure or renal failure. However, the limitations of the use of peptides, especially for long-term treatment, are obvious. In view of this, considerable effort has been devoted to the development of orally active agents to enhance endogenous natriuretic peptides by inhibition of breakdown by neutral endopeptidase. This research has led to the development of vasopeptidase inhibitors - dual inhibitors of both endopeptidase and angiotensin-converting enzyme - to enhance endogenous natriuretic peptide function on a background of reduced angiotensin II activity. The broad spectrum of action and the potentially important target-organ protection of these inhibitors offer potential benefits which may well go beyond existing treatment of hypertension and of conditions associated with overt volume overload.
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PMID:Practical implications of current natriuretic peptide research. 1196 16


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