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Biomedical subjects

R B Nagle

Publications and source records attributed to R B Nagle.

At least 127 records · Page 7Linked to original sources

A quantitative light- and electron-microscopic study of type IV nuclear bodies in crescentic glomerulonephritis.

Type IV nuclear bodies were found in all renal biopsies obtained from 14 patients with crescentic glomerulonephritis (CGN) and in 8 of 43 control patients studied by light and electron microscopy. The mean ratio of Type IV nuclear bodies per 10 tubular cross-sections examined was 0.67 +/- 0.27 for the CGN cases, which was significantly different from 0.09 +/- 0.26 obtained for the controls (P less than 0.05). Type IV nuclear bodies were most commonly seen in the epithelial cells of proximal tubules but were also seen occasionally in interstitial fibroblasts and cells of a collecting duct and a developing crescent.

Acute Kidney Injury↗

Nephrotoxicity of halogenated vinyl cysteine compounds.

S-(1,2-dichlorovinyl) cysteine (DCVC), is a potent nephrotoxin. In order to determine if other vinyl cysteine conjugates were nephrotoxic, halogenated vinyl cysteines, HVC-1 and HVC-2, were prepared from chlorotrifluoroethylene (CTFE), a fluorocarbon monomer, or chlorotifluoroethylene, a metabolite of halothane, respectively. Three days after receiving DCVC (5-10 mg/kg), CD-1 mice developed focal renal tubular necrosis. Mice treated with HVC-1 or HVC-2 (5-10 mg/kg) also developed renal necrosis by 3 days post exposure. HVC-1 was not as potent as DCVC with the necrosis limited to the pars recta. At equivalent doses HVC-2 caused less necrosis of the pars recta than HVC-1. The degree of nephrotoxicity by all three compounds exhibited a dose-response from 1-25 mg/kg. Doses greater than 25 mg/kg were often lethal within 3 days and the mice had a complete zonal necrosis of the renal cortex and a two-fold increase in kidney weight. Structural analogues, S-(chlorethyl) or S-(hydroxyethyl) cysteine, did not cause renal necrosis in mice at doses up to 200 mg/kg. These studies indicate that the enzymes reportedly responsible for converting DCVC to a nephrotoxic intermediate will also bioactivate other halogenated vinyl cysteines.

Animals↗

Massive nontraumatic hematuria: a challenge demanding immediate action.

Massive nontraumatic hematuria threatens the life of the patient and presents a complex management problem for the clinician. A rational approach to the condition demands rapid initial assessment followed by specific diagnosis of the cause of bleeding and appropriate corrective steps.

Aged↗

Pathology of experimental African trypanosomiasis in rabbits infected with Trypanosoma rhodesiense.

The pathologic response of New Zealand White rabbits to experimental infection with Trypanosoma rhodesiense is described. Autopsies of 18 rabbits killed from 30-44 days after infection revealed focal perivascular inflammation of the ears, eyes and testes. Examination by electron microscopy revealed extravascular trypanosomes in the dermis of the ear and interstitium of testes. Deposits of IgG, IgM and C3 were in renal glomeruli associated with glomerular hypercellularity; proteinuria was present as evidenced by an increase in tubular hyaline droplets. There was marked hyperplasia of lymph nodes and spleen with generalized increase in the number of macrophage and plasma cells. In contrast there was thymic atrophy. The findings suggest an immunologic host response associated with severe localized vascular injury.

Animals↗

Variable severity of glomerulonephritis in inbred rats infected with Trypanosoma rhodesiense. Correlation with immunoglobulin class-specific antibody responses to trypanosomal antigens and total IgM levels.

Five strains of inbred rats (ACI, BUF, F344, WF and WL) were infected with Trypanosoma rhodesiense and killed at 28 days for renal pathology and serological studies. The BUF strain demonstrated the most consistent and severe glomerulonephritis, accompanied by high titer IgM antibodies to trypanosomes and high total IgM levels. The WL strain demonstrated mild glomerulonephritis but prominent PAS (+) intracytoplasmic inclusions in proximal convoluted tubules, accompanied by low titer IgM antibodies and slightly elevated total IgM levels. All strains had low to medium titer IgG1 and IgGa antibodies to trypanosomes. Serial serologic studies in BUF rats showed peak titers of IgM, IgGa and IgG1 antibodies to trypanosomal antigens at 10 days. Immune complexes as measured by a C1q binding assay were elevated at 10 days, 3 days following the first detectable antibody responses, and remained so through the 30th day.

Animals↗

Complement receptors on normal human lymphocytes containing parallel tubular arrays.

Membrane complement receptors have been identified on a subpopulation of normal lymphocytes containing cytoplasmic inclusions called parallel tubular arrays (PTA) using two different rosetting techniques. The first technique utilizes as indicator cells erythrocytes that were coated with complement by the classic pathway of complement activation (EAC rosettes). The second technique utilizes as indicator cells Salmonella typhi, which were coated with complement by the alternate pathway of complement activation (FBC rosettes). In the latter technique, lipopolysaccharide material in the bacterial cell wall directly activates complement without the use of a sensitizing antibody. This eliminates binding of marker particles by lymphocytes having Fc receptors. The presence of PTA lymphocytes at the center of EAC rosettes and FBC rosettes was demonstrated by electron microscopy, indicating that the PTA lymphocyte has a complement receptor. Examination of FBC rosettes revealed that the adherent complement-coated bacteria were usually partially surrounded by pseudopodal extensions of the PTA lymphocyte. In addition, some PTA lymphocytes phagocytized the complement-coated bacteria but not the complement-inactivated bacteria. These phagocytic cells were placed in the lymphocytic series instead of the monocytic series by virtue of complete lack of endogenous peroxidase activity.

Bone Marrow↗

The human thymus. I. Partial characterization of nonlymphoid cells.

Human thymus was disrupted by mechanical and enzymatic techniques yielding tissue fragments and single-cell suspensions. Cell types and their distribution were determined before and after density separation. Single-cell suspensions produced by both separation procedures yielded comparable percentages of lymphoid and monocytic cells, whereas only the enzyme-treated tissue yielded epithelial cells. Less than 1% of all monocytic cells were mature. Monolayer cultures were established from fragments as well as unfractionated cells and gradient fractions. Analysis of these cultures showed that: (1) gradient separation of mechanically-prepared cell suspensions produced cultures enriched for macrophages, while epithelial cell cultures could be produced from fractionated enzyme treated tissue; (2) spindle-shaped cells may be fibroblasts or epithelial cells; (3) explant cultures have a growth pattern characteristic of other epithelial cells in vitro; (4) macrophages constitute a definite population of explanted cells and their percentages increase with time in culture; (5) macromolecular synthesis by epithelial cells in culture may be donor age dependent. Nonlymphoid cells of the human thymus can be identified by a variety of separation techniques and after monolayer culture. Characteristics of these cells are defined which may affect cell-cell interaction studies of the thymus.

Aging↗

Morphological study of the desert heteromyid kidney with emphasis on the genus Perognathus.

The renal morphology of three species of desert dwelling Perognathus rodents were compared to Dipodomys and two species of sympatric cricetid rodents. Perognathus has a highly adapted unipolar kidney capable of urine concentration up to 7,500 mOsm/KgH2O. Two major modifications were observed in these kidneys. (1) There is elongation of both the inner and outer medulla. When the thickness of the regions in P. penicillatus are factored by kidney weight it is found that the outer medulla is 3.8 and the inner medulla is 2.2 times greater in length than the extensively studied Dipodomys merriami. (2) There is great variance in glomerular size with approximately 20% of the glomeruli being very large and located in the juxta medullary region. These glomeruli are 1.5--1.6 times greater in diameter than the more numerous superficial glomeruli. These structural modifications are quantitated and the functional implications are discussed particularly in relation to urine concentrating ability in these desert inhabitants.

Animals↗

Isolation and characterization of human placental chorionic villar extracellular matrix.

The cell-free extracellular matrix of human placental chorionic villi has been prepared by a procedure employing extraction of the terminal villar fragments with the detergents Triton X-100 and sodium deoxycholate. The isolated human placental extracellular matrix retains an intact, but collapsed, histoarchitecture, as observed by scanning and transmission electron microscopy. It remains intact, in large part because of the presence of continuous sheets of villar basement membranes and associated interstitial collagen fibers and scattered patches of fibrin. The staining charcteristics and chemical composition of the isolated human placental extracellular matrlix are similar to those reported for basement membranes in several tissues and indicate the presence of collagen-like and glycoprotein components in this preparation. Gel electrophoresis of urea-SDS-mercaptoethanol extracts of the matrix showed that it consists of several polypeptide components of various molecuar weights, some of which are associated into high molecular weight complexes by disulfide bonds.

Amino Acids↗

Inhibition of in vitro synthesis of the second (C2) and fourth (C4) components of complement in guinea pig peritoneal macrophages by a soybean oil emulsion.

Recently a soybean oil emulsion (Intralipid) (IL) has been released in the United States for use as a parenteral nutrient. The study reported here was undertaken to determine the effect of ingestion of IL on the synthesis and secretion of the second (C2) and fourth (C4) components of complement by guinea pig peritoneal macrophages in vitro. Cells exposed to IL had extensive Oil Red 0-positive granular-appearing accumulations of neutral lipid within the cytoplasm. Control cells did not stain with Oil Red 0. Incubation of the cells with concentrations of IL from 2.3--37.5 mg/100 ml resulted in a significant decrease in the production of both C2 and C4, which could not be explained by variability between plates. The decrease in total C2 or C4 production by cells incubated with IL for 4 hr was similar to the decrease in production by cells incubated with IL for 48 hr. Several lines of evidence indicated that the decrease of C2 or C4 was the result of decreased synthesis of these proteins and not interference of IL with the detection of the proteins or their secretion from the cells. Exposure of the cells to IL at all concentrations caused reduction of the number of cells having pseudopodia and a rounding-up of the cells. IL did not affect the rate of detachment of the cells from the plates through the 48-hr incubation period or the ability of the cells to exclude trypan blue. Total protein synthesis and total lysozyme production by control and IL-treated cells was similar.

Animals↗

Alteration of the structure and function of guinea pig peritoneal macrophages by a soybean oil emulsion.

Studies in humans who have received Intralipid (IL) have demonstrated the presence of a fat pigment and fat droplets in reticuloendothelial phagocytic cells. Clinical data and in vitro studies suggest that these cells do not function normally. We have studied the effect of IL on the morphology and function of guinea pig peritoneal macrophages in vitro. Starch-induced macrophages were exposed to IL for up to 48 hours. Ingestion of increasing amounts of IL over the 48-hour period was confirmed by transmission electron microscopy and by oil red O stain. The uptake of the IL was associated with marked morphologic changes characterized by a decreased ability of the cells to spread and by a decrease in the number and degree of complexity of the membrane ruffles. The ingestion of IL also resulted in decreased capacity of the cells to associate with latex beads (5.7 mu in diameter) or Candida albicans and decreased capacity to adhere to and ingest sheep erythrocytes coated with IgG. After ingestion of latex beads 0.46 mu in diameter, which are similar in size to IL particles, macrophages had normal morphology and function, indicating that neither the morphologic nor functional abnormalities were due to a nonspecific effect of ingestion of small particles. Alterations of human reticuloendothelial macrophage function similar to the effects observed here could compromise host defense against infection.

Animals↗

The nature of the receptor for complement (C3b) in the human renal glomerulus.

The physicochemical nature of the human glomerular complement receptor was studied. Receptor activity was measured by determining the avidity of glomeruli of normal human renal tissue for fluorescein-labeled bacteria (S.typhi) coated with C3b. Maximal binding of C3b-coated bacteria to normal human glomeruli took place in phosphate-saline buffers of pH 6.5 and 0.08 to 0.15 mu ionic strength. Pretreatment of renal tissue with neuraminidase enhanced receptor activity. On the other hand, binding of C3b-coated bacteria to the glomeruli was diminished by pretreatment of the tissue with proteolytic enzymes, phospholipase C and certain lipid solvents. The binding of C3b-coated bacteria to the glomeruli was also diminished by pretreatment of the tissue with fluid-phase C3b, or by pretreatment of the bacteria with C3b inactivator. Normal human serum and purified fluid-phase C3 or the absence of magnesium and calcium ions had little effect on glomerular complement receptor activity.

Binding Sites, Antibody↗

Proliferative glomerulonephritis, hypocomplementemia, and nucleic acid antibodies in rats infected with Trypanosoma rhodesiense.

Host immunologic responses were studied in Sprague-Dawley rats infected with a human isolate of Trypanosoma rhodesiense. Retro-orbital sinus bleedings were obtained on days 0 and 14 and at 21 or 28 days. Infected and control rats were sacrificed on day 21 or 28 of the infection. Mild glomerulitis, as assessed by increased cellcularity and/or widening of the mesangial region, was apparent in 6 of 7 infected animals. Finely granular deposits of IgM and IgGl were found in most glomeruli with less prominent deposits of IgGa and IgA. Focal cortical mononuclear interstitial infiltrates were present in 2 of 7 rats. Subepithelial or mesangial electron dense deposits were present in the glomeruli of infected rats. Hypocomplementemia was present by day 21 and involved both the classical and alternative pathways of complement activation. Antibodies to native DNA and single-stranded RNA were present by day 21. These studies indicate the feasibility of studying trypanosomal glomerulonephritis in rats and will provide a convenient model for detailed immunologic and morphologic investigation of host immune responses in African trypanosomiasis.

Animals↗