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Biomedical subjects

B H Spargo

Publications and source records attributed to B H Spargo.

At least 55 records · Page 3Linked to original sources

Immune complex nephropathy in mixed connective tissue disease.

Initial reports on the clinical spectrum of mixed connective tissue disease (MCTD) indicated that renal involvement was uncommon. Four of 20 patients with MCTD underwent renal biopsy and all showed evidence of immune complex trapping with a membranous glomerulonephritis in three patients. Clinically evident renal disease was absent in two patients. These findings suggest that renal involvement in MCTD may be more prevalent than previously indicated.

Adolescent↗

Idiopathic membranous glomerulopathy preceding the emergence of systemic lupus erythematosus in two children.

An idiopathic nephrotic syndrome associated with membranous glomerulopathy antedated the subsequent emergence of systemic lupus erythematosus in two patients (7-year-old and 14-year-old girls). At the onset of INS, there was neither clinical evidence of multisystem disease nor unequivocal serologic evidence of SLE. The only early possible indication of SLE was the presence of microtubular inclusions in glomerular endothelial cells on electron microscopy. In each instance (one year and three years after onset of INS), a second renal biopsy showed transformation of the membranous glomerular lesion to a more florid type with glomerular subendothelial dense deposits. One patient died of overwhelming pulmonary infection while she was receiving prednisone and cyclophosphamide; the other developed progressive renal failure despite steroid treatment. SLE should be considered in patients presenting with apparent idiopathic MG, in whom nephrotic syndrome persists. Intraendothelial cell microtubular inclusions may be an early clue to later emergence of SLE.

Adolescent↗

The differential diagnosis of crescentic glomerulonephritis. The pathology of specific lesions with prognostic implications.

Combined findings from light and electron microscopy with immunofluorescence studies make a definitive diagnosis possible in most cases of crescentic glomerulonephritis. The patient's prognosis and pattern of response to therapy are matters of immediate concern in the light of recent developments in nephrology. The frequency of crescentic lesions varies depending on the specific types of disease, but the idiopathic lesion is seldom seen.

Anti-Glomerular Basement Membrane Disease↗

Phospholipid metabolism during renal regeneration after acute tubular necrosis.

Renal function, structure, and membrane metabolism were studied during regeneration of proximal tubular cells in rats. A reversible syndrome of nonoliguric acute renal failure was induced by the intravenous administration of a low dose of mercuric chloride (1.0 mg Hg/kg). At day 1 there was a marked increase in serum urea nitrogen concentration (SUN), decrease in food intake, and a zone of proximal tubular cell necrosis in the inner cortex. By day 3 low cuboidal epithelial cells were seen, indicating that regeneration had been initiated despite decreased food intake and increasing SUN. Phospholipid synthesis for new membrane formation in regenerating cells was studied by using [14C] choline as a precursor of phosphorylcholine and cytidine diphosphocholine (CDP-choline), which are intermediates in the synthesis of renal choline-containing phospholipid. The rate of [14C]choline incorporation into phospholipids in inner cortical slices was lowest 1 day after mercury administration, then increased constantly for the next 4 days to reach a maximal value 104% above control. The rate declined slowly for the next 11 days and returned to normal by 28 days. The increased rate represented choline phosphoglyceride synthesis, since degradation was unchanged. The entire increment in choline radioactivity in regenerating tissue 2 and 3 days after mercury administration was in phospholipid or CDP-choline, which suggests that the increased number of choline molecules entering the growing cells were trapped in these two forms. The results indicate that renal regeneration is associated with a specific enhancement of the synthesis of choline-containing phospholipids. This anabolic response of the kidney occurs in the presence of systemic catabolism and progressive renal functional insufficiency.

Acute Kidney Injury↗

Stimulation of renal phospholipid formation during potassium depletion.

Potassium depletion induces increased membrane phospholipid formation and renal growth in rats. To determine the mechanism by which potassium depletion augments phospholipid formation, the metabolism of radioactive choline, a precursor of choline-containing phospholipids, was studied in renal slices. Cortical and medullary tissue from potassium-depleted and control animals accumulated extracellular choline and sequentially converted it to phosphorylcholine, cytidine diphosphocholine (CDP-choline), and choline phosphoglyceride, thereby demonstrating that renal cells can utilize the Kennedy pathway for phospholipid synthesis. [14C]Choline uptake into intracellular fluid was increased in cortical slices from potassium-depleted animals. The apparent Km and Vmax of the kinase reaction which converts entering [14C]choline to [14C]phosphorylcholine were unchanged during potassium depletion. The rate of [14C]phosphorylcholine conversion to [14C]CDP-choline was also unchanged. In contrast, the Vmax of [14C]choline phosphoglyceride formation from [14C]CDP-choline was increased, whereas the apparent Km for this reaction was unchanged. These results indicate that increased renal choline phosphoglyceride formation during potassium depletion can occur via the Kennedy pathway and appears to be mediated by increases in choline uptake and the rate of CDP-choline incorporation into phospholipid, the first and last steps of the pathway.

Animals↗

Renal disease.

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Amyloidosis↗

Formation of renal medullary lysosomes during potassium depletion nephropathy.

The biochemical correlates of droplet formation in renal inner medullary cells of potassium-deficient rats were studied. An increase in the activities of five hydrolytic enzymes typical of lysosomes was associated with an increase in the number and size of droplets observed during progressive potassium depletion. Acid phosphatase activity increased 7-fold whereas beta-glucuronidase, beta-galactosidase, cathepsin, and acid DNase increased 2- to 4-fold in medullary homogenates at 25 days of depletion. Following potassium repletion the activities returned to normal at a rate dependent upon the duration of potassium depletion. The decreases in enzyme activities were associated with a concomitant rapid disappearance of the droplets from medullary cells. Protein synthesis for new droplet enzyme formation was studied by measuring the rate of [14C]leucine incorporation into protein in medullary slices. The rate increased at 1 day of depletion and reached a maximum which was 139 per cent higher than control after 7 days of depletion. In droplets isolated from medullary tissue during progressive potassium depletion the rate of protein labeling with [14C]leucine and acid phosphatase specific activity increased in parallel. When droplet proteins were separated by gel electrophoresis, acid phosphatase activity was detected in a protein band which had been labeled with [14C]leucine, thereby suggesting new enzyme protein formation. The increase in enzyme and protein synthesis and a previously demonstrated increase in phospholipid synthesis and membrane formation indicate that potassium depletion induces specific alterations in renal inner medullary cell metabolism which result in increased lysosome formation.

Acid Phosphatase↗

C-type virus expression in systemic lupus erythematosus.

Kidneys from patients with lupus nephropathy, non-lupus immune-complex glomerulonephritis and other renal diseases were examined by indirect immunofluorescence for antigens related to a C-type virus from human cells (HEL-12 virus). All 11 specimens of lupus nephropathy contained HEL-12 virus antigens deposited in the same pattern as the immune complexes. The intensity of immunofluorescence with anti-HEL-12 virus serum correlated with the extent of immune-complex deposition. In contrast, nine renal lesions other than lupus nephropathy and seven normal tissues did not react with anti-HEL-12 virus serum. Antibody eluted from one kidney with lupus nephropathy reacted by indirect immunofluorescence with human and dog cells infected with HEL-12 virus but not with uninfected control cells. These findings demonstrate a specific association of lupus nephropathy with a C-type viral antigen that is deposited as antigen-antiviral antibody complex.

Antibodies, Viral↗

Reversible renal failure from isolated granulomatous renal sarcoidosis.

A patient presented with a 6 month history of progessive renal failure. Serum creatinine was 7.1 mg/100 ml, creatinine clearance 4 ml/minute and hematocrit 22%. Skin tests for tuberculosis, trichophyton, SK/SD and candida were all unreactive and all cultures were negative or showed normal growth. A renal biopsy revealed non-caseating epithelial granulomas and foreign body multinucleated giant cells. No deposits or micro-organisms were seen on electron microscopy. Bone marrow and lymph node biopsies were unremarkable and no lung pathology was present. Therapy with systemic prednisone produced a dramatic improvement with serum creatinine diminishing to 1.3 mg/100 ml, creatinine clearance increasing to 81 ml/minute and hematocrit improving to 39%. A search of the literature has failed to reveal similar reports of reversible renal failure from isolated granulomatous renal sarcoidosis.

Adult↗

Zonal changes in renal structure and phospholipid metabolism in potassium-deficient rats.

Morphologic alterations and membrane metabolism were studied in the kidneys of rats fed a low potassium diet. Transmission and scanning electron microscopy following perfusion-fixation of kidneys revealed that the earliest morphologic change occurs in cells of the papillary tip in which multivesicular bodies, a specific type to lysosome, appear after 1 day. Increased depletion leads to extension of the lesion to all cells of the papilla. After 1 week, a narrow band of hyperplasia in the inner red medulla appears; this band is characterized by adenomatous proliferation of intercalated and light cells and partial obstruction of collecting tubules. These alterations and cortical growth in the normal pattern result in increased renal weight. New membrane formation for lysosomes and growing cells was studied by measuring the rate of [14C]choline incorporation into phospholipid in slices from five zones of the kidney. In the papilla the rate increased 39 per cent after 18 hours, the earliest change detected. After 36 hours the rate increased in inner red medulla by 28 per cent, inner cortex by 25 per cent and outer cortex by 40 per cent. [14C]choline was a specific precursor of the three renal phospholipids, phosphatidylcholine, lysophosphatidylcholine, and sphingomyelin. The relative distribution of the label did not change with growth induced by potassium depletion. The results indicate that potassium depletion induces early increases in the formation of cell membrane phospholipid which correlate with specific morphologic changes in different zones within the kidney.

Animals↗

The morphologic relationship of light and dark cells of the collecting tubule in potassium-depleted rats.

The luminal surface of collecting tubule cells in the inner stripe of the renal medulla in normal and potassium-depleted rats was studied by scanning electron microscopy. In normal rats the luminal surfaces were of two types. One cell type was sparsely covered with small bulbous microvilli and had either a single or double cilium. This type corresponds to the light cell seen in transmission electron microscopy. The second cell type was covered by prominent microplicae and represents the dark cell observed in transmission electron microscopy. In potassium-depleted animals, numerous cells with a morphologic appearance of intermediate forms were identified. By scanning electron microscopy, the luminal surface of these cells was covered by a mixed population of villi and microplicae in different stages of development and often showed cilia, which were previously considered to exist only on light cells. On the basis of these morphologic findings, we conclude that the dark and light cells are not different cell types but rather represent different forms of a single type of cell.

Animals↗

Practical use of electron microscopy for the diagnosis of glomerular disease.

In the past few years many clinically significant new glomerular lesions have been reported from observations made on renal biopsy specimens by electron microscopy. The clinical applicability of electron microscopy is illustrated by examples of specific ultrastructural patterns of glomerular reaction making possible a more accurate diagnosis, prognosis, and prediction of the response to treatment.

Amyloidosis↗

Experimental glomerulonephritis in the guinea pig. II. Ultrastructural lesions of the basement membrane associated with proteinuria.

Humoral immune processes mediate alterations in glomerular basement membrane (GBM) permeability by two mechanisms. One requires complement and polymorphonuclear leukocytes and the second is complement- and polymorphonuclear leukocyte-independent. The structural basis for enhanced GBM permeability induced by anti-GBM antibody is not clear. Experimental anti-GBM glomerulopathy was induced in guinea pigs by immunization with human GBM in complete Freund's adjuvant. Control animals received injections of complete Freund's adjuvant alone. Light, immunofluorescent, and electron microscopic studies were done on eight heavily proteinuric animals, four immunized nonproteinuric animals, three controls, and two normal animals. All animals that received injections of GBM had intense linear deposits of gamma2 anti-GBM antibody. Complement deposition was not demonstrable in vivo, and anti-GBM antibody deposits did not fix complement in vitro. Histologic abnormalities in proteinuric animals were confined to the GBM, which was of variable density and had a characteristic beaded thickening, with numerous areas of electron lucency most prominent in the outer aspect of GBM in peripheral portions of capillary loops. The inner margin and endothelium were normal. Ultrastructural tracer studies with ferritin demonstrated increased permeability confined to portions of GBM demonstrating ultrastructural lesions. The urine protein excreted by animals with ultrastructural GBM lesions was largely albumin. The absence of complement deposition accompanying anti-GBM antibody deposits in vivo and the unique GBM lesion in this model differ from the findings in nephritis induced by most heterologous nephrotoxic antibodies and suggest that GBM injury in this model is mediated by autologous antibody through complement-independent mechanisms. The selective proteinuria and ultrastructural lesions suggest a derangement in glomerular permeability functionally localized to the epithelial side of the GBM and could reflect an antibody-mediated abnormality in GBM biosynthesis.

Animals↗

Renal biopsy in pregnancy-induced hypertension.

Percutaneous renal biopsy, introduced 20 years ago, has revolutionized our understanding of many diseases affecting the kidney. In studies performed in nonpregnant subjects substantial progress in defining the mechanism, prognosis and treatment of a host of renal diseases was achieved by correlating clinical findings and renal function with light, electron and immunofluorescent microscopy. In the early 1960's investigators described the renal lesions associated with preeclampsia and made initial clinicopathological correlations, but relatively few studies combining light, electron and immunofluorescent findings in pregnant women have appeared to date. This is because clinical circumstances rarely justify even the minimal risks of biopsy during gestation, and after the disease has regressed, nephrology consultation is not requested in the puerperium. In addition, a report of excessive bleeding and other complications in gravidas, although not encountered by other groups (and personal experience of the authors), has contributed to the lack of enthusiasm for renal biopsy on obstetrical services and to the belief that this procedure is not advisable both during gestation and the immediate puerperium. This article reviews the renal morphology of preeclampsia and described those aspects of it in which current knowledge is still incomplete. Indications, benefits, and risks of kidney biopsy during pregnancy or puerperium will be discussed, with emphasis on the prognostic information to be expected from the procedure which may help in predicting the outcome of future pregnancies.

Adolescent↗