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Biomedical subjects

E J Lewis

Publications and source records attributed to E J Lewis.

At least 127 records · Page 7Linked to original sources
PubMed1988

Recurrent nephrotic syndrome in renal allografts.

We describe the clinicopathologic course of two patients with recurrent focal segmental glomerular sclerosis (FSGS). In both patients, FSGS was initially demonstrated during the evaluation of proteinuria. After progressing to end-stage renal disease, each patient received a living-related renal transplant. Shortly after transplantation, proteinuria recurred in both patients, progressing to the nephrotic syndrome. Serial renal biopsies were obtained from each patient. These initially demonstrated focal segmental epithelial proliferation (the "cellular lesion"), but focal segmental scars were observed in subsequent biopsies. None of the biopsies demonstrated immunoglobulin, complement deposition, or diffuse epithelial cell foot process fusion. These findings suggest that the scarring lesion in recurrent FSGS may be the result of a primary process involving damage to a limited number of visceral epithelial cells.

Adult↗
PubMed1988

Effect of puromycin aminonucleoside on HSPG core protein content of glomerular epithelial cells.

It has been suggested that the glomerular basement membrane heparan sulfate proteoglycan (HSPG) is an important determinant of the glomerular permselectivity barrier. Derangements in the content of basement membrane heparan sulfate have been implicated in alterations in glomerular permselectivity seen in many glomerular diseases such as aminonucleoside nephrosis. The cellular origin and metabolism of the glomerular basement membrane HSPG have not been studied in detail. We have detected the expression of the proteoglycan by cloned glomerular visceral epithelial cells of the rat by employing a specific antibody against the core protein of HSPG isolated from the rat glomerular basement membrane. These findings suggest that in the rat in vivo glomerular visceral epithelial cells are one source of heparan sulfate present in the glomerular basement membrane. The effect of puromycin aminonucleoside (PAN) on the HSPG core protein content of the cloned glomerular epithelial cells was studied. By a quantitative immunoperoxidase method, the aminonucleoside caused a 28% reduction in the core protein content of the epithelial cells (P less than 0.01) following 72 h of incubation. However, the content of Heymann nephritis-related antigen, Fx1A was unchanged. Studies employing [3H]leucine incorporation showed that PAN was a weak inhibitor of de novo protein synthesis at 24 h of incubation, with complete recovery at 48 and 72 h. These data suggest that PAN effect on heparan sulfate core protein cannot be attributed to generalized inhibition of protein synthesis. The precise mechanism underlying the aminonucleoside effect on heparan sulfate core protein remains to be elucidated.

Aggrecans↗
PubMed1988

The importance of sample size in the interpretation of the renal biopsy.

The number of abnormal glomeruli present in a renal biopsy can be viewed as a binomial distribution. Recognition of this fact permits a quantitative assessment of the effect of biopsy sample size in renal biopsy interpretation. If the percent of glomerular involvement in a biopsy is used to determine the severity of a focal glomerular lesion, a small biopsy sample size will lead to considerable misclassification of disease severity. In addition, a small biopsy sample size will make the exclusion of focal disease difficult.

Biopsy↗
PubMed1988

Minimal-change glomerulopathy of adulthood.

We describe 40 adults with idiopathic minimal-change glomerulopathy. They consisted of 27 females and 13 males, mean age 40.7 +/- (SD) 19.8 years (range 15-78 years). Twenty patients were less than 40 years of age at presentation. They presented with significantly (p less than 0.05) lower serum creatinine (0.9 +/- 0.2 vs. 1.3 +/- 0.5 mg/dl) and serum albumin (1.9 +/- 0.8 vs. 2.4 +/- 0.7 g/dl) levels than patients greater than 40 years. Only 7 patients (18%) presented with a decrease in renal function (serum creatinine greater than 1.3 mg/dl). All patients had nephrotic-range proteinuria at the time of presentation or biopsy. There was no significant difference in presenting proteinuria (8.7 +/- 5.7 g/24 h) or length of follow-up (mean 63.5, range 4-176 months) between the two age groups. Microscopic hematuria and hypertension were each present in 21% of the patients. Thirty-four patients received therapy with prednisone. A complete remission was obtained in 91% of the patients treated with prednisone. The response occurred within 16 weeks in 77% of the patients. The response to prednisone therapy was similar for patients less than 40 years when compared to those greater than 40 years, with a complete remission being obtained in 88 and 94%, respectively. The rate of response, however, differed significantly with 73% of patients less than 40 years versus 32% of patients greater than 40 years achieving a complete remission by 8 weeks. Twenty patients initially responding to prednisone therapy (64.5%) relapsed. A relapse occurred within 3 months of attaining a complete remission in 70% of the patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Identification and cell type specificity of the tyrosine hydroxylase gene promoter.

Genomic DNA encoding the rat tyrosine hydroxylase (TH) gene was isolated from a lambda phage library using a nick-translated fragment from a cDNA clone for rat TH. We have determined the initiation site for TH RNA synthesis and have sequenced 1100 bases of the primary transcript and 5' flanking region. The 5' end of the transcript is the same in several rat tissues in which TH is expressed as well as in rat pheochromocytoma cells (PC). RNA prepared from PC cells that had been stimulated with dexamethasone also mapped to the same transcription start site. Sequence upstream from the initiation site contains the canonical TATA box, but no apparent CAAT box. When a portion of the 5' flanking region of the TH gene (-773 to + 27) is fused to the chloramphenicol acetyltransferase (CAT) gene, it promotes expression of CAT in pheochromocytoma cells and GH4 cells, but not in two neural tumour lines, RT4-D and B103, nor in several non neural cell lines. This suggests that this region of the TH gene has features that confer tissue-restricted expression on the TH promoter.

Adrenal Gland Neoplasms↗
PubMed1987

Persistence of clinical and serologic activity in patients with systemic lupus erythematosus undergoing peritoneal dialysis.

To determine whether patients with systemic lupus erythematosus undergoing long-term peritoneal dialysis have persistent clinical and serologic remissions, the clinical courses of eight patients with end-stage renal disease in whom peritoneal dialysis was begun at Rush-Presbyterian-St. Luke's Medical Center between 1981 and 1986 were analyzed. Patients were followed for a mean of 90.1 +/- 28.8 months before dialysis and 20.8 +/- 4.7 months after the initiation of dialysis. Disease activity was quantified for each individual in terms of "flares" per year before and after the initiation of peritoneal dialysis, the means of which were 0.66 +/- 0.46 and 0.94 +/- 0.28, respectively. Comparison of these rates showed no statistical difference. Seven of the eight patients had at least one flare while receiving peritoneal dialysis, all of which required prednisone therapy (mean 31.3 mg per day). The clinical manifestations included fever, rash, myalgias, anemia, leukopenia, serositis, and cerebritis. Eighty-eight percent of these flares had associated worsening of serologic results. Prednisone was discontinued in only one patient at any time during peritoneal dialysis. This experience reveals that patients with lupus continue to show clinical and serologic disease activity and require maintenance prednisone therapy while receiving long-term peritoneal dialysis.

Adult↗
PubMed1987

Histologic features that correlate with the prognosis of patients with lupus nephritis.

This study stresses the significance of accurate assessment of renal biopsy material in patients with lupus nephritis in order to determine prognosis. The size of the biopsy sample is important because of the focal nature of the disease. The number of glomeruli that must be present to judge the extent of focal involvement was computed. The correct categorization of a patient's disease is essential to avoid "stage migration." Class III lupus nephritis (focal, segmental) should be divided into mild, moderate, and severe. The amount of prednisone administered was calculated, and it was found that the severity of the renal lesion was of greater prognostic significance than the choice of treatment given. While a classification that includes consideration of chronicity appears useful, this study indicates that the amount of acute inflammatory change in the glomeruli is also an important prognostic indicator.

Biopsy↗
PubMed1987

Glomerular epithelial cell, polyanion neutralization is associated with enhanced prostanoid production.

We have studied the effect of neutralizing the surface charge of rat glomerular epithelial cells (GEC) in culture on prostanoid production. Incubation of rat GEC with polycations poly-L-lysine (PL) resulted in a dose dependent increase of 6-keto-PGF1 alpha (up to 8 to 10-fold) and PGE2 (up to 7 to 8-fold) production. Other polycations such as protamine sulfate (PS) and lysozyme (LY) produced a similar effect. The stimulation of prostaglandin (PG) production by PL treated GEC was prevented by the addition of polyanions such as bovine serum albumin (BSA) and heparin (HP). The effect of PL on prostaglandin (PG) synthesis by GEC was suppressed by the cyclooxygenase inhibitor sulindac sulfide. Addition of exogenous arachidonic acid (C20:4) increased the basal production of PG and under these conditions the effect of PL was masked. We conclude that neutralization of the surface charge of rat GEC by polycations results in profound increase of prostanoid synthesis. The polycation caused increase in PG synthesis appears to be the result of increased availability of intracellular C20:4.

Animals↗
PubMed1987

The prognosis of segmental glomerulonephritis in systemic lupus erythematosus.

Severe segmental glomerulonephritis (Seg GN) (greater than or equal to 50% involvement) in systemic lupus erythematosus (SLE) is classified as diffuse GN (DPGN) in the WHO classification. We tested the validity of the assumption that severe Seg GN and DPGN have the same prognosis by determining the proportion of glomeruli involved by active segmental inflammation in a series of 127 patients and by comparing the prognosis in various categories of Seg GN with patients with DPGN. In Seg GN we found mild involvement (1 to 19%) in 19 patients, moderate involvement (20 to 49%) in 9 patients and severe involvement (greater than or equal to 50%) in 17 patients. There were 28 cases of DPGN. The actuarial five-year survival of patients with mild and moderate Seg GN was 82%. The survival of patients with severe Seg GN and DPGN were 59 and 53%, respectively. The incidence of adverse outcomes, including death, end-stage kidney disease, and deterioration of renal function was similar in patients with severe Seg GN and DPGN, and greater than in patients with mild and moderate Seg GN. Although there was a trend associating increasing glomerular involvement with elevated urinary protein excretion and serum creatinine and decreased serum C3 and C4, the differences were not significant. Cumulative prednisone dose and prednisone given in the first and second years following biopsy were not different in the various categories of Seg GN and DPGN, suggesting that differences in outcome were not related to the amount of prednisone therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy↗
PubMed1987

Transcriptional regulation of the tyrosine hydroxylase gene by glucocorticoid and cyclic AMP.

Glucocorticoid and cyclic AMP increase tyrosine hydroxylase (TH) activity and mRNA levels in pheochromocytoma cultures. The transcriptional activity of the TH gene, as measured by nuclear run-on assay, is also increased when cultures are treated with the synthetic glucocorticoid dexamethasone or agents that increase intracellular cyclic AMP, such as forskolin and 8-BrcAMP. Both inducers effect transcriptional changes within 10 min after treatment and are maximal after 30 min for forskolin and after 60 min for dexamethasone. The 5' flanking sequences of the TH gene were fused to the bacterial gene chloramphenicol acetyltransferase (CAT), and the hybrid gene was transfected into pheochromocytoma cultures and GH4 pituitary cells. In both cell lines, a region of the TH gene containing bases -272 to +27 conferred induction of CAT by cyclic AMP, but not by glucocorticoid. The same results were found when a region of the TH gene containing -773 to +27 was used. Thus, the sequences required for induction of TH by cyclic AMP are contained within 272 bases of 5' flanking sequence, but sequences sufficient for glucocorticoid regulation are not contained within 773 bases.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1987

Relationship between renal pathology and the size of circulating immune complexes in patients with systemic lupus erythematosus.

Sera from 35 patients with biopsy-proven diffuse proliferative (WHO class IV) or membranous (WHO class V) lupus nephritis were analyzed for the presence and size of circulating immune complexes. Elevations of the C1q solid-phase assay (C1qSP) for immune complexes were found in sera from all patients with diffuse proliferative nephritis, with a mean +/- 1 SEM of 166.8 +/- 42.0 micrograms/AHG-equivalents/ml serum, and in 71.4% of the patients with membranous nephritis (83.1 +/- 26.7, p = 0.06). Using the WHO criteria for subclasses of membranous lupus nephritis, we also designated renal biopsies as nonproliferative (WHO classes Va and Vb) or proliferative (WHO classes IV and Vc). Employing the latter groupings, we observed significant differences between C1qSP results of patients with nonproliferative (30.3 +/- 8.8) and proliferative (172.8 +/- 36.8, p less than 0.001) lupus nephritis. These data suggest that the presence of C1q-binding material in serum is pathophysiologically related to proliferative glomerular lesions, and that levels of C1qSP binding reflect renal lesions in SLE patients. Sucrose density gradient ultracentrifugation was performed on each serum, and gradient fractions analyzed for C1qSP-binding and total IgG, using techniques to minimize losses of immune complexes. The predominant peak of C1qSP activity sedimented with the 6.6S monomeric IgG. The 6.6S C1q-binding IgG was increased only in 1 of 10 patients with membranous lupus nephritis without proliferative changes, and was elevated in 16 of 25 patients with proliferative lesions (WHO classes IV and Vc). A significant negative correlation was found between the presence of this C1q-binding material and subepithelial electron-dense deposits, suggesting that the presence of this material contributed to the absence of subepithelial immune deposits. Large-molecular-weight C1qSP-binding material was also present, mainly in sera from patients with proliferative lesions. Furthermore, highly positive correlations were found between immune deposits in interstitial blood vessels and peritubular areas, and the concentrations of C1qSP-binding IgG and rapidly sedimenting IgG in density gradient analysis. Overall, these findings are consistent with the hypotheses that circulating immune complexes contribute to the pathogenesis of glomerulonephritis and interstitial nephritis in patients with SLE, and that 6.6S C1q-binding IgG plays a role in the proliferative lesions of lupus glomerulonephritis.

Antigen-Antibody Complex↗
PubMed1987

Regulated expression of the tyrosine hydroxylase gene by epidermal growth factor.

The addition of epidermal growth factor (EGF) to cultures of the rat PCG2 pheochromocytoma cell line increased the level of RNA coding for tyrosine hydroxylase (TH). A region of DNA containing 5'-flanking sequences of the TH gene was fused to a heterologous gene and transfected into a rat anterior pituitary cell line, GH4. The TH gene sequences from +27 to -272 contained information sufficient for the induction of TH by EGF. Two regions within this TH DNA were extensively homologous to the EGF regulatory element of the rat prolactin gene.

Animals↗
PubMed1987

Effect of nutritional iron deficiency on acute and chronic inflammation.

Mild nutritional iron deficiency significantly reduced the severity of adjuvant induced joint inflammation assessed by histology, microfocal radiography, and subjective scoring. Other indices of adjuvant induced inflammation, such as increased levels of serum acute phase reactants, characteristic pathological changes in the inguinal lymph nodes, and granuloma formation at the site of adjuvant injection, were not different from those of control animals. The level of iron deficiency used did not affect the acute inflammatory response to a range of irritants and was not sufficient to suppress immune function. Both the hypersensitivity reaction to oxazalone and lymphocyte tritiated thymidine incorporation were normal. These observations support the view that iron has a selective influence on joint mediated inflammation.

Acute-Phase Proteins↗
PubMed1987

Renal autoregulation and vulnerability to hypertensive injury in remnant kidney.

The remnant kidney model is characterized by moderate hypertension, proteinuria, and progressive glomerular scarring, which are ameliorated by a low-protein diet or antihypertensive drugs. The role of renal autoregulation, in determining vulnerability to hypertensive injury was investigated. After right nephrectomy and infarction of two-thirds of the left kidney, rats were fed an isocaloric normal (NP) or low-protein (LP) diet. After 3-4 wk blood pressure was not significantly different between NP and LP rats (171 +/- 8 vs. 155 +/- 6 mmHg), but urinary protein excretion was higher in NP rats (32.3 +/- 7.3 vs. 7.0 +/- 1.2 mg/24 h P less than 0.05). Measurement of renal plasma flow and glomerular filtration rate (GFR) after graded changes in renal perfusion pressure (100-160 mmHg) demonstrated poor autoregulation in NP but not in LP rats. Morphological evidence of severe injury in the form of fibrinoid necrosis and thrombosis of arterioles and glomeruli was largely confined to NP rats and became more severe after 6-8 wk. We conclude that remnant kidney rats fed NP diet autoregulate poorly, which may account for the malignant hypertensive injury to "unprotected" glomeruli, despite only moderate systemic hypertension, and contribute to the progressive nephron loss that is encountered.

Animals↗
PubMed1987

Eosinophilia in the diagnosis of atheroembolic renal disease.

We report 6 patients with eosinophilia and atheroembolic renal disease. Histologic examination of biopsy of kidney or skin revealed extensive atheroembolic in the vasculature. However, no evidence of vascular or tubulointerstitial inflammation was observed. Eosinophil count ranged from 540 to 2,000 cells/mm3. Upon review of the literature, 80% (29 out of 36) of patients with adequately reported total and differential leukocyte counts had eosinophilia in association with atheroembolic disease. In contrast, review of the clinical records of 40 consecutive patients with acute renal failure seen during an 18-month period uncovered only 1 case of eosinophilia (2.5%). This latter patient was established as having acute interstitial nephritis. Thus eosinophilia appears to be a helpful diagnostic clue to the presence of atheroembolic renal disease.

Acute Kidney Injury↗
PubMed1987

Angiotensin-converting enzyme inhibitors: considerations regarding proteinuria.

The effects of captopril on renal function are evaluated in hypertensive patients with impaired renal function previously entered in a worldwide surveillance study. For the overwhelming majority of patients, control of BP was accompanied by stable or improved renal function. To date, the major adverse renal reactions have been a somewhat increased risk of worsening proteinuria among these patients and the well-documented acute decrease in renal function that may occur in patients with bilateral renal artery stenosis.

Angiotensin-Converting Enzyme Inhibitors↗