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E J Lewis

Publications and source records attributed to E J Lewis.

At least 145 records · Page 8Linked to original sources
PubMed1987

Glomerular epithelial cell function and pathology following extreme ablation of renal mass.

The role of the pathologic features and dysfunction of glomerular epithelial cells (GECs) in the pathogenesis of glomerular scarring was studied in the remnant kidney model (RK) (1 and 5/6 nephrectomy) in rats. Three weeks after surgery serum creatinine was greater in the RK than either sham-operation controls (SHAM) or spontaneously hypertensive rats (SHRs). Blood pressure was higher in the RK (181 +/- 26 mm Hg) than in SHAM (129 +/- 17, P less than 0.05) but not SHR (195 +/- 15, P less than 0.05). GEC endocytosis, assessed by protamine heparin aggregate (PHA) disappearance (10), was not different from that in SHAM. Glomerular damage was greater in RK (glomerular damage index, 30 +/- 18) than in SHAM animals (4 +/- 3, P less than 0.05) and SHR (0, P less than 0.05), and 2 of 11 RK animals had fibrinoid necrosis and thrombosis of arterioles and glomeruli. Segmental sclerosis occurred in only 1 RK animal (0.6% of glomeruli). Six weeks after surgery serum creatinine and urinary protein excretion remained higher in the RK than in the SHAM animals. Blood pressure was higher in RK (158 +/- 34 mm Hg) than in SHAM animals (144 +/- 24), but the difference was not significant. PHA disappeared from the glomerulus at a slower rate in RK than in SHAM animals (outside the 95% confidence limits of SHAM). Glomerular pathology was more widespread in RK than in SHAM animals (glomerular damage index, 73 +/- 62 versus 3 +/- 8, P less than 0.05), and 4 of 11 animals had acute hypertensive injury in arterioles and glomeruli. Segmental glomerular sclerosis was only seen in the animals with necrotic glomeruli. GEC dysfunction is not demonstrable until long after proteinuria and hypertension are established, and it only occurs in the context of severe, acute glomerular injury when the epithelial cells separate from the capillary wall and undergo severe degenerative changes and necrosis. The acute glomerular and vascular lesions in the RK model are morphologically similar to malignant nephrosclerosis in humans. Segmental glomerular sclerosis occurs only after proteinuria is well established in the context of severe glomerular injury, and it appears to represent, at least partially, progression of more proximate glomerular capillary injury.

Animals↗
PubMed1986

Short-term prognosis of severe proliferative lupus nephritis.

The prognosis of systemic lupus erythematosus (SLE) is considerably worse when accompanied by renal involvement. In order to study the outcome within a year of histologic diagnosis of severe lupus nephritis, we obtained data on 25 patients from nine participating centers. All these patients fulfilled clearly defined histologic criteria of severe lupus nephritis, thus enabling us to evaluate a homogeneous group of patients. During a mean follow-up period of 9.4 months, there appeared to be an equal probability that the renal function would improve, remain stable, or worsen as assessed by changes in serum creatinine concentration. One patient died and another patient reached end-stage renal disease (ESRD), a combined crude mortality plus ESRD rate of 8% for 9.4 months. As both these patients had serum creatinine values of less than 2 mg/dL at the time of diagnosis of severe lupus nephritis, it appears that normal or mildly impaired renal function at the time of diagnosis does not ensure benign outcome. These features should be considered when new studies on SLE nephritis are planned or any new therapeutic modality is evaluated.

Adolescent↗
PubMed1986

Demonstration and characterization of C3 receptors on rat glomerular epithelial cells.

Receptors for C3 have been demonstrated on the glomerular podocyte in humans. There is conflicting evidence regarding the presence of C3 receptors on rat glomerular cells. Even when shown to be present, the ligand specificity of the receptor has not been determined. Decapsulated rat glomeruli obtained from male Sprague-Dawley rats weighing 50 to 100 g were placed in enriched culture media. On days four to eight, cells of epithelial morphology were observed growing out of glomeruli. Receptors for C3 were detected by rosette formation of sheep erythrocytes (E) coated with antibody (A) and complement (EAC) around the glomerular epithelial cells in culture. The EACs were prepared by incubating antibody-coated sheep erythrocytes with C5-deficient mouse serum or with individual components of complement. Results indicate the presence of two types of C3 receptors on glomerular epithelial cells--CR1 for C3b and CR2 for C3d. The functional roles of these receptors remain to be elucidated.

Animals↗
PubMed1986

The prognosis of focal segmental glomerular sclerosis of adulthood.

We describe 46 adults with idiopathic focal segmental glomerular sclerosis (FSGS). The mean age was 36.9 years (range, 15 to 80 years). Males represented 61%, and 65.2% were white. Hypertension was a presenting feature in 63% and 32.6% had microscopic hematuria. Twenty-nine patients had nephrotic proteinuria (greater than or equal to 3.0 g/24 h) at presentation, and 13 had renal insufficiency (serum creatinine concentration greater than 1.5 mg/dl). A mean follow-up of 59.8 months (range, 3 to 255 months) was obtained. In addition to segmental sclerosis, glomerular hyalinosis was observed in 65.3% of biopsies, and this was similar irrespective of the severity of proteinuria. Sixteen of the 29 patients with nephrotic proteinuria received prednisone therapy (60 mg/day) for at least 1 month. Three received cytotoxic agents in addition. A response to therapy was observed in 50%, 5 achieving a complete remission and 3 a partial remission. No patient with non-nephrotic proteinuria received prednisone therapy. The clinical course of each patient was evaluated based on the slope calculated by the linear regression method using the inverse of serum creatinine from the time of presentation to follow-up. Patients with non-nephrotic proteinuria had a better prognosis than nephrotics (P less than .05). Nephrotic patients responding to therapy had a better course than non-responders or patients not treated (P less than 0.01). At the time of last follow-up, 8 patients had progressed to end-stage renal disease, 6 of whom had presented with nephrotic proteinuria. No patient responding to therapy had progressed to end-stage renal disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Glomerular epithelial cell structure and function in chronic proteinuria induced by homologous protein-load.

The pathogenesis of glomerular scarring in proteinuric diseases is unknown, but glomerular epithelial cell (GEC) injury has been implied by the glomerular pathology seen in patients with focal segmental glomerular sclerosis and the nephrotic syndrome. We studied the effect of proteinuria on glomerular histology and GEC structure and function in rats made proteinuric for up to 8 weeks by the daily parenteral injection of homologous serum albumin. Proteinuria in the albumin-injected rats peaked at a mean level of 131 +/- 12 mg/24 hours (mean +/- SD) during the 1st week. It subsequently plateaued at 41 +/- 6 mg/24 hours but remained significantly greater than the saline-injected controls throughout the study. The albumin-injected rats developed slight but significant increases in blood pressure, serum albumin, plasma volume, and urine urea nitrogen compared to the saline injected controls. The serum creatinine was not different from controls. In the albumin-injected rats no glomerular scarring was observed after 8 weeks of proteinuria. The GEC developed albumin reabsorption droplets and signs of activity including increased numbers of organelles, vacuoles, and cytoplasmic hypertrophy, but there were no signs of irreversible GEC damage. The GEC foot processes were quantitated morphometrically, and there was no evidence of effacement after eight 4 or 8 weeks of proteinuria. GEC endocytic function, evaluated by the technique of protamine heparin aggregate disappearance, was not different from the saline injected controls. Proteinuria caused by the chronic administration of homologous serum albumin for 8 weeks is regularly associated with increased blood pressure, plasma volume, and serum albumin and ultrastructural changes in the GEC. These morphologic changes in the GEC apparently represent a normal response to proteinuria and are not evidence for irreversible cell damage. Despite their avid endocytosis of filtered plasma proteins, GEC endocytic function remains normal. These experimental results imply that glomerular sclerosis is not a consequence of proteinuria per se.

Animals↗
PubMed1986

Necrotizing glomerulonephritis in rheumatoid arthritis.

Rheumatoid arthritis may be associated with several glomerular lesions including amyloidosis, mesangial proliferation and membranous glomerulonephritis. Systemic vasculitis is a well-recognized extra-articular complication of rheumatoid arthritis, but necrotizing glomerulonephritis, the glomerular expression of vasculitis, has been described infrequently. This report comprises four patients with rheumatoid arthritis who underwent renal biopsy for declining renal function, proteinuria and active urine sediments. Pathology revealed that three patients had segmental necrotizing glomerulonephritis without significant glomerular immunoglobulin deposition. The fourth had segmental necrosis associated with diffuse membranous glomerulonephritis. We conclude that necrotizing glomerulonephritis is part of the spectrum of glomerular lesions seen in patients with rheumatoid arthritis. Because of therapeutic considerations involving the use of cyclophosphamide, necrotizing glomerulonephritis should be a diagnostic consideration in the rheumatoid arthritis patient with signs of glomerulonephritis and rapidly deteriorating renal function.

Adult↗
PubMed1985

Trans-synaptic increase in RNA coding for tyrosine hydroxylase in a rat sympathetic ganglion.

To begin examining molecular mechanisms underlying trans-synaptic regulation, tyrosine hydroxylase (TH) and its messenger RNA (mRNA) were examined in the superior cervical sympathetic ganglion (SCG) of adult rats. Basal levels of TH mRNA were detectable in control ganglia by RNA dot hybridization, using the 32P nick translated PstI-KpnI restriction fragment of pTH.4 as a probe. Reserpine induced a 3-fold rise in TH activity per microgram protein, and a simultaneous 3-fold increase in ganglion TH mRNA. As expected, ganglion decentralization (denervation) prevented the trans-synaptic induction of TH. In addition, decentralization prevented the increase in TH mRNA, suggesting that the increase in message was dependent on trans-synaptic stimulation. Northern blot analysis indicated that the cDNA (complementary DNA) probe hybridized to a single band of approximately 1900 nucleotides, which was the same size in all ganglia. Our observations indicate that induction of TH is associated with a trans-synaptic increase in mRNA coding for the enzyme. Consequently, trans-synaptic increases in impulse activity may induce TH by increasing neuronal levels of TH mRNA in the SCG.

Animals↗
PubMed1985

Focal segmental glomerular sclerosis: the cellular lesion.

The pathological features of 59 renal biopsy specimens with focal segmental glomerular sclerosis (FSG) were correlated with the patient's clinical and laboratory findings at the time of biopsy. Two morphologic patterns were identified: thirty-nine biopsy specimens had only focal segmental scars which were frequently associated with hyaline deposits. In 20 scars which were frequently associated with hyaline deposits. In 20 biopsy specimens with FSG, the glomeruli also contained a cellular lesion. It consisted of hypercellularity in the involved portion of the glomerulus, increased cells in the surrounding Bowman's space, and reactive and proliferative changes in the associated glomerular visceral epithelial cells. The cellular lesion was seen overlying glomerular capillaries with minimal histologic abnormalities and adjacent to scars. However, it was usually superimposed upon a segmental scar or a portion of the glomerulus with collapsed capillaries and wrinkled, folded basement membranes. Immunofluorescence and electron microscopy did not demonstrate significant immune reactants or electron-dense deposits in the glomeruli. Nineteen of 39 patients with only segmental scars had proteinuria equal to or greater than 3.0 g/day, and nine had the nephrotic syndrome. Eighteen of 20 patients with the cellular lesion had proteinuria equal to or greater than 3.0 g/day, and 14 had the nephrotic syndrome. The interval between the onset of proteinuria and biopsy was much shorter in patients with the cellular lesion (3.4 +/- 3 vs. 71.9 +/- 87 months, mean +/- SD, P less than 0.01). This difference was also significant when only those with nephrotic range proteinuria were compared (3.4 +/- 3 vs. 45.6 +/- 73 months, mean +/- SD, P less than 0.01). Patients with FSG, with or without the cellular lesion, were similar with respect to male/female ratio, age, serum creatinine, and diastolic blood pressure. From these observations, we believe that glomerular injury, evidenced by segmental proliferative lesions with signs of epithelial cell injury, is a significant factor in the pathogenesis of FSG.(ABSTRACT TRUNCATED AT 250 WORDS)

Biopsy, Needle↗
PubMed1985

The development of screening tests for D-penicillamine-like antirheumatic activity based on in vivo interactions with copper.

Injections of labile copper complexes such as copper II bisglycinate [Cu(II)gly] induce marked inflammatory responses in rats in contrast to stable copper complexes like copper II bishistidinate which are nonirritant. The antirheumatic drugs D-penicillamine, mercaptopyridoxine, thiola and captopril, inhibit Cu(II)gly-induced cutaneous vascular permeability when given intravenously and show oral cupriuretic activity. Inhibition of Cu(II)gly inflammation alone or cupriuretic activity alone do not appear predictive of clinical antirheumatic activity since L-cysteine methylester and trien, which are active in the former and latter tests, respectively, are devoid of clinical antirheumatic activity. Indomethacin and aspirin are inactive in these tests, thus discounting the concept that such drugs act in part through their copper complexes. The mechanisms by which labile copper induces inflammation and by which D-penicillamine-like drugs modulate the response are discussed. It is suggested that copper can generate free radicals in vivo and that D-penicillamine may act by neutralization of labile copper complexes and/or by formation of copper complexes with the capacity to catalyse the dismutation of superoxide anion.

Animals↗
PubMed1985

Immunotactoid glomerulopathy.

We present 11 patients with immunotactoid glomerulopathy, a new syndrome characterized clinically by proteinuria (11/11), microscopic hematuria (9/11) and hypertension (9/11). The patients consisted of six females and five males, aged 25 to 59 years (mean, 44.6). Proteinuria was the presenting feature and the reason for renal biopsy in all patients. The diagnosis of immunotactoid glomerulopathy was established at renal biopsy by the presence of glomerular extracellular microtubules composed of immune reactants. All the biopsies studied by immunofluorescence (10 cases) had glomerular deposits of IgG and C3. In three biopsies studied with IgG subclass specific antisera, only one patient had monoclonal immunoglobulin deposits (IgG3 kappa). In six cases the glomerular deposits were analyzed for light chains. In three the deposits contained kappa only, and three consisted of both kappa and lambda. In two cases the immune aggregates were confined to the mesangium, and in the remaining eight cases, the deposits were present in the mesangium and the glomerular basement membranes. Electron-dense deposits composed of microtubules were present in the same distribution within the glomerulus as the immune reactants. The microtubules had a uniform diameter in each biopsy, but they varied in size from case to case. They were approximately the same size in eight cases (mean, 22.3 +/- 3 [SD] nm). Three cases had much larger microtubules: 34.2 nm, 35.4 nm, and 48.9 nm in diameter. Although the 22.3-nm microtubules resembled amyloid in their appearance, glomerular distribution and random orientation in the tissue, they were more than twice the diameter of amyloid (8.9 nm), and Congo red and thioflavin T stains for amyloid were negative. Similar microtubular structures have been described in patients with cryoglobulinemia, SLE and paraproteinemia, but these diseases were excluded in our patients on clinical, serologic and in some cases histologic grounds. More important, none of our patients had clinical or histochemical evidence of amyloidosis, an entity which may be confused with immunotactoid glomerulopathy on a morphologic basis. Follow-up, from 22 to 94 months (mean, 52.6) was obtained in all 11 patients, and 2 clinical courses were noted. Six patients had progressive deterioration of renal function, with five requiring dialysis. This group had severe hypertension (4/6) and nephrotic-range proteinuria (5/6) at some point in their course. The remaining five patients with stable renal function had proteinuria of less than 2.0 g/24 hr in most cases (4/5), and none had severe hypertension. This dichotomy correlated with the distribution of immunotactoids.(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1985

Elevation of RNA coding for tyrosine hydroxylase in rat adrenal gland by reserpine treatment and exposure to cold.

When rats are treated daily with reserpine or maintained at 4 degrees C, the level of a specific RNA coding for tyrosine hydroxylase is elevated in the adrenal gland. The increase in this specific RNA temporally precedes and is quantitatively equal to the increase in adrenal tyrosine hydroxylase enzyme activity elicited by these treatments. These results suggest that prolonged stress may lead to changes in the levels of specific RNA species in the adrenal gland.

Adrenal Glands↗
PubMed1985

Transient nephrogenic diabetes insipidus associated with pregnancy.

The coexistence of diabetes insipidus and pregnancy is uncommon and can be associated with worsening of the diabetes insipidus. We report a patient who developed a transient nephrogenic diabetes insipidus associated with a pregnancy complicated by preeclampsia. The diabetes insipidus resolved spontaneously within several days after delivery.

Adult↗
PubMed1984

Immune complex deposition and coronary vasculitis in systemic lupus erythematosus. Report of two cases.

Extramural coronary arteries were examined in two patients with systemic lupus erythematosus (SLE). Coronary vasculitis was found in both patients. One patient with clinically and serologically inactive SLE had died suddenly and was found to have a myocardial infarction secondary to the coronary vasculitis. Immunopathologic studies demonstrated immune reactants in the walls of inflamed and noninflamed arterial segments in a pattern consistent with immune complex aggregates. Immunologic injury secondary to immune complex deposition may be responsible for the development of coronary disease in patients with SLE. This has been demonstrated in experimental animals but not in humans. Although this is an uncommon complication of SLE, it represents a cause of sudden death and a potentially treatable lesion in this patient population. Its occurrence may be related to the deposition of immune aggregates in the walls of coronary vessels.

Adult↗
PubMed1984

Evaluation of hypervitaminosis A in the rat by measurement of tibial bone breaking strain.

Using etretinate as a model compound, the bone changes characteristic of hypervitaminosis A were evaluated in the rat in terms of tibial bone-breaking strain. Dose-related effects were observed in the dose range of 5-30 mg/kg p.o. for 15 days. The model proved a simple and precise means of assessing hypervitaminosis A in this species. Isotretinoin also showed a small but significant reduction in tibial breaking strain, but with a shallow dose-response curve in the range of 50-150 mg/kg.

Animals↗
PubMed1984

Clinical and pathological features of membranous glomerulonephritis of systemic lupus erythematosus.

The prognostic significance of glomerular inflammation in patients with lupus membranous glomerulonephritis (MGN) was evaluated by classifying 100 renal biopsies from lupus patients according to World Health Organization (WHO) criteria and correlating the histology with clinical data. There were 22 cases of MGN: in 3 the lesion was pure MGN (Va); in the remainder, diffuse MGN was modified by superimposed mesangial proliferation in 6 (Vb), segmental glomerulonephritis (GN) or sclerosis in 10 (Vc), and diffuse GN in 3 (Vd). Patients in the four categories had similar clinical presentations. When the 4 patients with active proliferative glomerulonephritis (PGN) were grouped and compared to those without PGN, they had more active serologies. Quantitation of glomerular electrondense deposits in MGN showed variation in the percentage of basal lamina covered by subepithelial deposits, segmental subepithelial deposits in 4 cases, focal segmental subendothelial deposits in most cases and massive subendothelial deposits in 5 biopsies. 4 of the latter patients had active PGN, suggesting that only extensive subendothelial deposits are pathogenetically significant. The predicted 5-year survival for all MGN patients was 90%, and the only 2 deaths were not related to renal failure. Thus, it appears valid to include mixed lesions in the membranous category, but it is our impression that the immediate course and prognosis of SLE and associated PGN depends upon the extent and reversibility of the inflammatory lesions.

Glomerulonephritis↗
PubMed1984

Review of the overall experience of captopril in hypertension.

The pharmacologic profile of the angiotensin-converting enzyme inhibitor, captopril, is described. After reviewing the total clinical experience of captopril from the world literature and manufacturer's files, a small subgroup of clinically complex patients at particular risk of side effects and in whom the drug must be used with caution is characterized. Evidence is available that demonstrates that lower doses (150 mg/day or less, with modest doses of diluretic agents) are effective in both short- and long-term therapy, while the incidence of side effects is substantially reduced. With this background information, the benefit-risk ratio is substantially improved and the use of captopril as a primary agent in the management of hypertension may be considered.

Captopril↗
PubMed1984

Inhibition of glomerular visceral epithelial cell endocytosis during nephrosis induced by puromycin aminonucleoside.

Puromycin aminonucleoside (PA), injected intravenously into rats in a single dose, causes proteinuria and ultrastructural pathology reminiscent of human lipoid nephrosis (puromycin aminonucleoside nephrosis (PAN]. Glomerular epithelial cell (GEC) endocytosis was studied in this model and in rats with protein-overload proteinuria using ultrastructural morphometry. Disappearance curves were constructed for protamine-heparin aggregates (PHA), which localized in the subepithelial region of the glomerular basal lamina following intravenous injection of protamine followed by heparin. Five groups were studied: (a) preproteinuric PAN, 4 days after PA (mean 4.5 +/- 1.5 mg of urinary protein/24 hours); (b) proteinuric PAN, 10 days after PA (mean 128 +/- 9.6 mg/24 hours); (c) recovery from PAN (mean 12.5 +/- 1.5 mg/24 hours); (d) protein-overload proteinuria, induced by injecting albumin intraperitoneally (mean 211 +/- 15.9 mg/24 hours); and (e) saline-injected controls (mean 1.2 +/- 0.2 mg/24 hours). Only the proteinuric PAN animals (group 2) had altered GEC endocytosis with a PHA half-disappearance time different from the group 5 saline controls (143.2 versus 72.6 minutes, p less than 0.05). The half-disappearance times in groups 1, 3, and 4 were 74.6, 80.7 and 86.5 minutes, respectively. Altered GEC function was further characterized by comparing PHA disappearance with the abundance of albumin-filled vacuoles in the GEC. Prolongation of PHA disappearance in group 2 correlated with the virtual absence of vacuoles; they were abundant in nonproteinuric phases of PAN and in animals with overload proteinuria. We conclude (a) GEC endocytosis is reduced only during the proteinuric phase of PAN, (b) GEC endocytosis is active during the preproteinuric phase of PAN and is a factor that may account for the absence of protein in the urine despite abnormal GBM permeability, (c) decreased GEC endocytosis during proteinuric PAN reflects abnormal cell metabolism due to PA and is not simply a consequence of albuminuria, as overload proteinuria did not produce diminished PHA or albumin uptake.

Animals↗