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Biomedical subjects

E J Lewis

Publications and source records attributed to E J Lewis.

At least 163 records · Page 9Linked to original sources
PubMed1984

Laryngeal complications in a patient with inactive systemic lupus erythematosus.

Laryngeal complications in systemic lupus erythematosus (SLE) are rarely described. They range from hoarseness to life-threatening respiratory distress. To our knowledge, previous reports describe laryngeal involvement with SLE occurring only during periods of active disease. We saw a patient with inactive SLE in whom hoarseness and exertional dyspnea developed as a result of arytenoiditis and vocal cord paresis during steroid tapering. The condition responded dramatically to readjustment of her steroid dosage. Involvement of the larynx with SLE is a potentially life-threatening complication and may occur in patients with either active or inactive disease. It is an indication for close observation and steroid therapy in patients with SLE.

Airway Obstruction↗
PubMed1983

Regulation of tyrosine hydroxylase mRNA by glucocorticoid and cyclic AMP in a rat pheochromocytoma cell line. Isolation of a cDNA clone for tyrosine hydroxylase mRNA.

Treatment of a subclone of the PC12 pheochromocytoma cell line, PC8b, with either dexamethasone or 8-bromo cyclic AMP resulted in increased translational activity of tyrosine hydroxylase mRNA (mRNATH). Poly(A+)-containing RNA from cells treated with both inducers was used to construct a cDNA library. Double-stranded cDNA was inserted into the PstI site of pBR322 using GC tailing, and plasmids were used to transform Escherichia coli HB101. Colonies containing plasmids with inserted sequences were initially screened by DNA dot hybridization, and those positive colonies were then screened by hybrid selected translation. One plasmid, pTH.4, was identified as containing a 400-base pair sequence complementary to mRNATH. Nick-translated pTH.4 DNA was used to identify mRNATH as containing approximately 1800 nucleotides by Northern blot analysis. PC8b cells treated with either dexamethasone or 8-bromo cyclic AMP yielded greater mRNATH hybridization on Northern blot analysis and accumulated higher molecular weight tyrosine hydroxylase RNA species. Following treatment of cells with inducers, the temporal increase in tyrosine hydroxylase enzyme activity was associated in all cases with an increase in the translational activity and relative amount of mRNATH, and the fold increase in the latter two parameters was equal to or greater than the increase in enzyme activity.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1983

Differential characteristics of immune-bound antibodies in diffuse proliferative and membranous forms of lupus glomerulonephritis.

Diffuse proliferative (PGN) and membranous (MGN) glomerulonephritis represent contrasting histologic lesions in systemic lupus erythematosus (SLE). Serum, cryoglobulins, and renal biopsies in 8 SLE patients with PGN and 8 with MGN were studied in order to determine whether variations in the properties of immune-bound antibodies correlate with the pattern of glomerular involvement. Several immunologic parameters suggested differences in complement activation between the two groups. PGN cryoglobulins demonstrated immunoglobulin G (IgG) anti-native DNA (nDNA) subclass heterogeneity with highest titers of IgG3. These findings contrasted with the observation that MGN was characterized by a predominance of IgG4 in cryoglobulins. The major glomerular IgG subclasses in PGN were IgG3 and IgG1, while MGN biopsies demonstrated IgG4 in largest amount. Serum C1q was lower in PGN than in MGN. Serum anti-nDNA antibodies, solid-phase C1q-binding IgG immune complexes, and cryoglobulin protein concentrations were higher in PGN sera. Cryoglobulin complement component and control protein concentrations were greater in PGN than in MGN, while cryoglobulin Ig and immune-bound anti-nDNA were not different. In vitro C3 fixation by cryoglobulin anti-nDNA was greater in PGN than in MGN. Glomerular C1q, C4-binding protein (C4bp), and C3c were present in comparable amounts to IgG deposits in PGN biopsies, while in MGN IgG was demonstrable in greater quantities than C1q, C4bp, and C3c. In contrast, glomerular C3d (alpha 2d), C5, C6, P, and H were comparable in the two groups. It was concluded that immune-bound antibodies in cryoglobulins and in glomerular immune deposits in SLE PGN appear to activate complement via the classical and alternative pathways, while complement activation in MGN appears to occur predominantly via the alternative pathway. These differences in IgG subclass composition may account for the differential complement activation and may explain the contrasting histologic expression of immune aggregate localization in glomerular capillaries in these variants of lupus nephritis.

Antibodies, Antinuclear↗
PubMed1983

Necrotizing glomerulitis of systemic lupus erythematosus.

The authors report four cases of systemic lupus erythematosus (SLE) with severe, active glomerulonephritis. Associated with histologic evidence of glomerular inflammation were focal, predominantly mesangial immune reactants. This finding contrasts with reports that massive subendothelial electron-dense deposits are the ultrastructural feature that correlates best with the severity of glomerular inflammation. The patients studied had significantly fewer subendothelial electron-dense deposits than did other patients with SLE with comparable glomerular lesions (8 +/- 3 per cent versus 42 +/- 14 per cent of glomerular capillaries involved, respectively; P less than 0.05). In addition, serologic evidence of disease activity, assessed by measurement of serum levels of C3, C4, circulating immune complexes (cryoglobulins), and serum antinative DNA activity, was either normal or only mildly abnormal. The lack of correlation between the severity of glomerular lesions on the one hand and the paucity of glomerular immune reactants and mild serologic abnormalities on the other may be interpreted as questionable evidence that these cases of glomerulonephritis were mediated by immune complexes. In the light of recent clinical and experimental studies that support a possible role for cell-mediated immunity in the pathogenesis of glomerulonephritis, the authors propose that a role for cell-mediated hypersensitivity be considered.

Glomerulonephritis↗
PubMed1982

Pathologic changes in the renal tubule in systemic lupus erythematosus.

Interstitial nephritis may be prominent morphologic feature in systemic lupus erythematosus (SLE), but there are limited data relating the pathologic findings to renal function impairment. We studied 69 biopsy specimens from 55 patients by light, fluorescence, and electron microscopy and compared the results with the serum creatinine levels. The relative interstitial volume, a measure of tubular damage and interstitial expansion, was the only morphologic feature that correlated well with renal function (serum creatinine level). Fifty-nine per cent of the biopsy specimens studied by fluorescence microscopy and 31 per cent of the biopsy specimens studied by electron microscopy had extraglomerular deposits. Ultrastructural studies determined that the sites of the deposits were the tubular basal lamina in five cases, the peritubular capillaries in four, and both in 12. In addition, the deposits were irregularly deposited along the nephron, with examples of isolated proximal and distal tubular involvement. Ultrastructural changes in the tubular basal lamina were interpreted as reparative responses to injury. Tubular pathologic features included reduplicated basal lamina and the apparent incorporation of electron-dense deposits and cellular debris. These data support the concept of a role for immune deposits in the pathogenesis of the tubulointerstitial lesion in SLE.

Creatinine↗
PubMed1982

Impairment of glomerular clearance of macroaggregates in immune complex glomerulonephritis.

Autologous immune complex glomerulonephritis (AICGN, Heymann nephritis) in rats is characterized by the accumulation of immune deposits in a subepithelial location. Protamine-heparin aggregates with similar localization are normally cleared by glomerular epithelial cell endocytosis. The kinetics of protamine-heparin aggregate clearance from the lamina rara externa of the glomerular basement membrane in rats with AICGN were investigated. In the early stages of AICGN, the baseline numerical density of protamine-heparin aggregates at sites of immune deposit accumulation was 37.8 +/- 8.4 (mean +/- SEM) aggregates per 100 mu, significantly lower than the 71 +/- 6.9 aggregates per 100 mu in the normal appearing, immune deposit free, zone of the glomerular basement membrane (P less than 0.05). The aggregates localizing along the normal appearing parts of the lamina rara externa disappeared according to first order kinetics, similar to their clearance in normal animals. The numerical density after 3 hr in this zone of the membrane was 21.7% +/- 3.5 of the baseline at 5 min. By contrast, at sites of immune deposit accumulation, the aggregates were not cleared and actually accumulated to 160.9% +/- 12.4 of the baseline at 3 hr. It is proposed that there is impaired epithelial cell endocytic function in early AICGN, which could contribute to the perpetuation of the immune-deposit mediated lesion.

Animals↗
PubMed1982

Differences in rates of tyrosine aminotransferase deinduction with cyclic AMP and glucocorticoids.

As an indirect test of the possibility that cyclic AMP produces its stimulatory effects on the synthesis of tyrosine aminotransferase (L-tyrosine:2-oxoglutarate aminotransferase, EC 2.6.1.5) by stabilizing its mRNA, the kinetics of decline in the rate of synthesis of this enzyme was measured in rat hepatoma cells following inducer removal or addition of RNA synthesis inhibitors. In all cases in which cells were previously exposed to cyclic AMP, the decline in enzyme synthesis after removal of inducer or addition of inhibitors of RNA synthesis was 4 to 5 times more rapid than in cells exposed to a glucocorticoid (dexamethasone) which also induces the aminotransferase. Thus, it seems unlikely that cyclic AMP had been acting by stabilizing the mRNA that directs the synthesis of the aminotransferase. Possible explanations for these paradoxical results are suggested. A more rapid decline in enzyme synthesis was also seen in cells induced with both cyclic AMP and glucocorticoid, suggesting direct interaction between the two inducers.

Animals↗
PubMed1981

A serum C3-activating factor: its characterization and its presence in glomerular deposits.

A non-IgG C3 activating factor (C3AF) isolated from the serum and plasma of a patient with membranoproliferative glomerulonephritis with subendothelial and subepithelial deposits (type III) was studied to define its molecular structure, functional characteristics, and presence in renal biopsies. Alternative complement pathway (ACP) activation of C3 was comparable to that of zymosan, but significantly less than that of IgG C3 nephritic factor (C3NeF). Functionally active isolate contained beta 1H globulin (beta 1H) and the C3AF protein, which had a gamma-electrophoretic migration. beta 1H present in the isolate exhibited an altered gamma-beta electrophoretic mobility. The function of this complex is heat labile. Time/temperature studies demonstrated that inactivated preparations of this isolate show a return to the normal beta migration of beta 1H followed by the development of an alpha 2 electrophoretic migration of the previously gamma-migrating material of functionally active isolate. Normal human serums contain an alpha 2 protein that shows complete antigenic identity with the gamma protein of C3AF, but this alpha 2 protein lacks C3 activating function. On polyacrylamide gel electrophoresis, the C3AF isolate contains a high m.w. protein of 500,000 to 590,000 that is composed of 2 major subunits. Carbohydrate is not demonstrable, and the protein is antigenically distinct from plasma fibronectin. Immunofluorescence studies of renal biopsies of patients with types I and III MPGN revealed the presence of C3AF antigen in granular deposits in 10 of 16 cases. The presence of this antigen in glomerular deposits was associated with C3 and beta 1H, but was independent of Ig. These studies suggest that the mechanism of ACP activation by C3AF results from interference with beta 1H function. The presence of this material in renal biopsies from some MPGN patients further suggests a pathogenetic role in mediating glomerular pathology.

Chemical Precipitation↗
PubMed1981

Evidence of glomerular epithelial cell endocytosis in vitro.

The disappearance rate of protamine-heparin aggregates (PHA) from the lamina rara externa of the glomerular basement membrane was determined in vitro to better characterize the clearance mechanism. Sprague-Dawley rats were injected intravenously with protamine, followed by a neutralizing dose of heparin, and the glomeruli were isolated and incubated in Dulbecco's tissue culture medium. After obtaining a baseline sample, aliquots were taken every 10 minutes for an hour. The samples were processed for electron microscopy, and the numerical density of PHA in the lamina rara externa was determined using a computerized morphometric technique. Disappearance curves for PHA were constructed by expressing the numerical density at each point as a percentage of the baseline value and plotting the logarithm against time. At 37 degree C., the disappearance of PHA was rapid (t 1/2 = 24 minutes), followed first order kinetics (R2 = 0.9948), and was almost complete by 1 hour. The epithelial cells took up PHA by an endocytic process. Significant inhibition of PHA disappearance was achieved when the glomeruli were incubated at 4 degree C. and with 10(-3) M NaF. These data indicate that PHA disappearance is an energy-dependent cell function, and it was concluded that glomerular epithelial cell endocytosis is the principal mechanism of PHA clearance.

Animals↗