Tetanus as a cause of rhabdomyolysis and acute renal failure.

Acute renal failure developed in an elderly woman with a rapidly progressive illness characterized by nuchal rigidity, limb spasm, repetitive grunting vocalizations without intelligible speech, and risus sardonicus. Eventually she developed characteristic findings of increased tone in her masseter muscles (trismus) and rigid upper and lower extremities, consistent with generalized tetanus. Increasing serum creatinine was temporally associated with rising creatine phosphokinase (CPK) and striking elevations of plasma myoglobin. The patient had marked lability of blood pressure and pulse. She improved briefly after tetanus toxoid and broad-spectrum antibiotics, but died of heart failure after 9 days of hospitalization. A necrotic pelvic tumor was believed to be the source of infection. Tetanus is a preventable disease, which has not been eradicated, even in Western populations. Full-blown tetanus has a high fatality rate, and should be considered in the differential diagnosis of acute renal failure in the setting of rising CPK and continued release of muscle myoglobin.

IgA nephropathy in psoriasis.

IgA nephropathy (IGAN) was first described by Berger and Hinglais in 1968. It is now the most common glomerular disease worldwide. IGAN has been associated with several diseases. Its association with psoriasis has been rarely described. We report a case of IGAN with crescentic changes, associated with psoriasis vulgaris. We review the literature on the association of IGAN with psoriasis and discuss the likely pathogenetic linkage.

Penicillium peritonitis in a patient receiving continuous ambulatory peritoneal dialysis.

We describe herein a case of peritonitis caused by Penicillium species in a patient receiving continuous ambulatory peritonal dialysis (CAPD). This is the first reported case of Penicillium peritonitis complicating CAPD. It is also unusual because Penicillium typically is considered a contaminant and only rarely is it considered a human pathogen.

Complement C5b-9 complex activates phospholipases in glomerular epithelial cells.

In rat membranous nephropathy, formation of the C5b-9 membrane attack complex (MAC) leads to proteinuria in association with glomerular visceral epithelial cell (GEC) injury. These alterations in GEC function and morphology might result from changes in intracellular free Ca2+ concentration [( Ca2+]i) and activation of phospholipases. We demonstrate that in cultured rat GEC, antibody-directed formation of noncytolytic amounts of the MAC induced a rapid and sustained increase in [Ca2+]i that was partly inhibited by ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA). The MAC elevated levels of inositol bis- (IP2) and trisphosphate (IP3), as well as 1,2-diacylglycerol (DAG) and phosphatidic acid (PA). In permeabilized GEC, IP3 released Ca2+ from intracellular stores. Cellular 45Ca2+ uptake was also increased by the MAC. Thus, in GEC, the MAC induced Ca2+ mobilization from intracellular stores secondary to activation of phospholipase C and production of IP3, as well as enhanced Ca2+ influx. In addition, C5b-9 stimulated release of arachidonic acid (AA), prostaglandin F2 alpha, and thromboxane A2. Indomethacin partially inhibited the increase in DAG levels observed with the MAC, whereas the prostaglandin H2/thromboxane A2 analogue U46619 elevated DAG, suggesting that an eicosanoid product of MAC-induced AA release may enhance the activation of phospholipase C. Activation of phospholipases by the MAC may lead to altered GEC function and thereby contribute to the pathophysiological changes that characterize complement-dependent rat membranous nephropathy.

Studies with antibodies to cultured rat glomerular epithelial cells. Subepithelial immune deposit formation after in vivo injection.

To investigate the role of glomerular epithelial cell (GEC) membrane proteins in the in situ formation of subepithelial immune deposits, the authors raised a rabbit antiserum against GEC that had been grown in culture (anti-GEC). By indirect immunofluorescence (IF) on normal rat kidney, anti-GEC stained proximal tubular brush border (BB). After intravenous injection into animals, granular glomerular capillary wall staining for IgG was present by IE and subepithelial immune deposits were identified by standard transmission and immunoelectron microscopy. Using the latter technique, injected anti-GEC IgG was identified beneath slit diaphragms and in endocytic-coated pits and intracellular vesicles of podocytes. Anti-GEC immunoprecipitated gp330 and two other proteins from radiolabeled BB. These proteins also were identified by sheep anti-rat Fx1A, the antiserum responsible for passive Heymann nephritis. Anti-GEC and anti-Fx1A also immunoprecipitated five identical proteins from surface-labeled GEC. Biosynthetically-labeled but not surface-labeled GEC contained immunoprecipitable gp330. Thus, injection into rats of antibodies raised against cultured GEC can produce subepithelial immune deposits, a disease process classically induced by antibodies to BB or its purified components. In addition to gp330, GEC and BB share other antigenic determinants that may contribute to the formation of these immune deposits.

Decay accelerating factor regulates complement activation on glomerular epithelial cells.

Epithelial cells of the glomerular capillary are the site of C5b-9 mediated injury in rat membranous nephropathy. We investigated the regulation of C activation by cultured glomerular epithelial cells (GEC). Rat and human GEC were more resistant to C injury by homologous C than heterologous C. In human GEC homologous C cytotoxicity was enhanced by antiserum to decay accelerating factor (DAF) indicating that homologous C activation was, at least in part, restricted by membrane DAF. Anti-DAF immunoprecipitated a 67-kDa protein from human glomeruli. In rat GEC, pronase and phosphatidylinositol-specific phospholipase C (which are known to inactivate human DAF) enhanced cytotoxicity by homologous C. Thus, DAF is present on human GEC in culture and in human kidney glomeruli, and a DAF-like protein is present on cultured rat GEC. These proteins regulate C activation in vitro and may play a role in controlling C activation on GEC in vivo.

Anti-Fx1A induces association of Heymann nephritis antigens with microfilaments of cultured glomerular visceral epithelial cells.

Binding of anti-Fx1A to Heymann nephritis antigens (HA) on rat glomerular epithelial cells (GECs) in culture leads to capping and disappearance of antigens from the cell surface. This process may contribute to the formation of glomerular subepithelial immune deposits in vivo. The authors differentially extracted GECs to determine whether HA redistribution is mediated by cytoskeletal components. Observations were made by phase-contrast and immunofluorescence microscopy on primary and passaged GECs in monolayer culture and by spectrofluorimetry on GECs in suspension. GEC-bound sheep anti-Fx1A IgG was detected by fluoresceinated anti-sheep IgG. Microfilaments were identified by rhodamine-phalloidin staining of F-actin. After cross-linking HA on GECs by anti-Fx1A IgG at 0 C, GECs remained polygonal in shape and had diffuse granular IgG staining of their plasma membranes. Treatment of GECs at 0 C with hypotonic buffer containing 0.5% Triton X-100 produced microfilament-rich cytoskeletons that retained the shape of unextracted GECs. Further incubation with DNase I at 37 C removed microfilaments (mean fluorescence declined by 90%) and resulted in the rounding of cytoskeletons. After Triton X-100 treatment, 85% of initial GEC-bound anti-Fx1A IgG remained, but only 29% remained after DNase I. In contrast to intact IgG, detergent-extraction resulted in the complete loss of GEC-bound anti-Fx1A Fab'. Anti-Fx1A IgG did not bind to GECs pretreated with Triton X-100. Thus, cross-linking of HA by anti-Fx1A converts HA from a detergent-soluble, membrane-associated form to an insoluble, cytoskeleton-bound form. Attachment of cross-linked HA to the cytoskeleton is mediated by microfilaments.

Sex difference in reward asymmetry and effects of cocaine.

Male and female rats with bilaterally implanted electrodes in the lateral hypothalamus were tested daily for self-stimulation of each side of the brain, and rotation (circling behavior) was recorded concomitantly. All rats rotated in a preferred direction, regardless of the side of the brain stimulated, and all rats had asymmetries in the sensitivity for self-stimulation (thresholds and rate-intensity functions) related to the direction of rotation. However, the direction of the asymmetry of self-stimulation was sex-dependent: the side of the brain contralateral to the preferred direction of rotation was the more sensitive side in female rats, as reported previously, whereas the ipsilateral side was the more sensitive side in male rats. In both sexes, cocaine acted predominantly on the contralateral side: that is, cocaine lowered the thresholds and shifted the rate-intensity functions to the left on both sides of the brain, but the effects were much greater on the side of the brain contralateral to the preferred direction of rotation. When compared to baseline parameters, cocaine enhanced the asymmetry of self-stimulation in female rats, but reduced or reversed the asymmetry of self-stimulation in male rats; similar effects were produced by d-amphetamine. It is suggested that at least two separate systems (both lateralized) mediate self-stimulation of the lateral hypothalamus, that the relative importance of these systems differs between the sexes and that cocaine selectively affects one of these systems.

A simple and rapid technique for preparing histological sections of brain.

A rapid technique for preparing histological sections of rodent brain is described. Sectioning and staining may be completed within two hours of sacrifice.