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Biomedical subjects

J J McPhaul

Publications and source records attributed to J J McPhaul.

At least 19 recordsLinked to original sources
PubMed1983

Characterization of B cell antibodies in kidney transplant recipients.

Antibodies against B lymphocytes were found in the serum of the majority of 59 kidney transplant recipients and of 22 eluates obtained from kidney allografts undergoing rejection. To characterize these B cell lymphocytotoxins we have used a mouse monoclonal anti-DR antibody (L227) that inhibits cytotoxicity of antibodies against HLA-DR antigens and a chicken serum against human Ia-like antigens that also inhibits antibodies against DR-related supertypic determinants and other Class II histocompatibility antigens. Three types of B cell cytotoxins were defined: antibodies against HLA-DR, antibodies against Ia-like antigens other than DR, and antibodies against non-Ia-related B cell antigens. Before transplantation, B cell antibodies were detected in about a third of the patients studied. They were inhibited by monoclonal anti-DR more often in recipients who ultimately rejected a kidney allograft (67%) than in those in whom the graft was successful (44%, P less than 0.03). After transplantation, antibodies inhibited by L227 were found in 56% of the patients with functioning grafts and in 94% of the recipients whose grafts had been removed because of rejection (P less than 0.001). B cell antibodies inhibited by monoclonal anti-DR were found in the majority of kidney eluates. However, although 85% of the B cell reactions of kidney eluates were blocked by this antibody, only 55% of the B cell reactions of sera obtained from the same recipients after nephrectomy were similarly inhibited. Thus it appears that antibodies against HLA-DR were bound and concentrated in the transplanted organ and other B cell antibodies were not. These results indicate that anti-DR antibodies blocked by the monoclonal antibody L227 are the most common type of B cell lymphocytotoxins formed in kidney transplant recipients. Their role in kidney allografts undergoing rejection, where they are bound in high concentration, needs to be determined.

Antigens, Surface↗
PubMed1983

Effect of hemodialysis on left ventricular function. Dissociation of changes in filling volume and in contractile state.

Prior studies of the effect of hemodialysis on left ventricular function have not distinguished between the removal of uremic toxins and the change in cardiac filling volume. To separate these effects, left ventricular function was examined by serial echocardiography in five stable hemodialysis patients before and after three different dialysis procedures: (a) hemodialysis with volume Loss, (b) ultrafiltration (volume loss only), and (c) hemodialysis without volume loss. The patients were similarly studied under control conditions and after increased (5 degrees of head-down tilt for 90 min) and decreased (lower body negative pressure) cardiac filling volume. After hemodialysis with volume loss, end-diastolic volume (EDV) decreased from 167 to 128 ml (P less than 0.001) and end-systolic volume (ESV) decreased from 97 to 51 ml (P less than 0.001) without a change in stroke volume (SV). Ejection fraction increased from 42 to 52% (P less than 0.001) and mean velocity of circumferential fiber shortening (VCF) increased from 0.61 to 1.04 circumferences (circ)/s (P less than 0.001). After ultrafiltration, EDV decreased from 167 ml to 124 ml (P less than 0.001) and SV from 73 ml to 39 ml (P less than 0.001), without significant changes in ESV or VCF. In contrast to the maneuvers in which volume loss occurred, after hemodialysis without volume loss ESV decreased from 95 to 66 ml (P less than 0.001) and SV increased from 74 ml to 97 ml (P less than 0.001) without changes in EDV. EF increased from 44 to 59% (P less than 0.001) and VCF increased from 0.64 to 1.26 circ/s (P less than 0.001). Ventricular function curves plotted from data obtained under conditions of altered cardiac filling volume before and after the three dialysis maneuvers demonstrate that ultrafiltration produced a pure Frank-Starling effect, while hemodialysis with or without volume loss produced a shift in the ventricular function curves, which demonstrated an increase in the contractile state of the left ventricle. The changes in left ventricular function produced by regular hemodialysis are the combined effects of a decrease in EDV and an increase in the contractile state of the left ventricle.

Creatinine↗
PubMed1981

Primary tubulointerstitial nephritis caused by antibodies to proximal tubular antigens.

Acute oliguric renal failure requiring hemodialysis developed in a 59-year-old man who had myasthenia gravis. A renal biopsy on day 21 was diagnostic of tubulointerstitial nephritis. Despite regular hemodialysis, the patient died of complications 17 weeks after the onset of oliguria. At post-mortem examination, a thymoma was found, and renal histopathology indicated tubulointerstitial nephritis and concomitant generalized epimembranous and intramembranous electron-dense deposits of glomerular capillary walls. By direct immunofluorescence, immunoglobulins and C'3 were visualized in peritubular granular deposits around proximal tubules, but not on glomeruli. The renal acid-eluate contained immunoglobulins that bound to proximal tubule brush border, intracellular cytoplasmic granules, and a granular antigen probably associated with basement membrane of proximal tubule cells of normal human kidney and the patient's kidney, whereas the patient's serum apparently contained antibodies only to proximal tubule brush border. The renal eluate did not bind to normal or the patient's glomeruli, and partial elution of the patient's kidney did not expose new binding sites for the eluate. The data indicate a unique instance of tubulointerstitial nephritis caused by antibodies to multiple proximal tubule antigens apparently forming immune complexes in situ.

Autoantibodies↗
PubMed1981

Interstitial nephritis caused by methicillin. Studies in a case complicating staphylococcal sepsis with acute glomerulonephritis.

A 16-year-old student was admitted with acute, oliguric renal failure complicating staphylococcal sepsis. During treatment with methicillin drug hypersensitivity was suspected, and antibiotic was changed to vancomycin; by day 19 hemodialysis was discontinued. Renal biopsy showed two pathologic processes: acute exudative glomerulonephritis and widespread tubulointerstitial nephritis. In addition to glomerular immunoglobulin and C'3 deposits, interstitial and focal tubular basement membrane deposits of IgG were seen. Antiserum to DPO (methicillin) haptens localized apparently to the same tubular sites, as did fluorescein-conjugated antibodies from the patient's serum. The data suggest that interstitial nephritis was caused by serum antibodies to methicillin which bound to sites in renal tubules to which methicillin also had fixed. The acute tubulointerstitial nephritis complicated acute oliguric glomerulonephritis of staphylococcal sepsis.

Adolescent↗
PubMed1981

Specificities of antibodies eluted from human cadaveric renal allografts. Multiple mechanisms of renal allograft injury.

The purpose of the present experiments was to evaluate the role of circulating antibodies in the rejection of human renal allografts and to study the apparent target(s) for antibody binding. Eluates obtained from surgical biopsy and nephrectomy specimens of rejecting, cadaveric human renal allografts were tested for antibodies directed to structural antigens of normal kidney and for cytotoxic antibody activity against mononuclear cell populations. By indirect immunofluorescence 23 of 35 eluates contained immunoglobulin that bound to normal kidney. Staining was in smooth muscle only in 10 patients, in smooth muscle and other structures such as tubular basement membranes, proximal cells, or brush border in 9 patients, and in structures other than smooth muscle in 4 patients. All 16 eluates tested contained antibodies cytotoxic for cells derived from a panel of normal volunteers. Six were cytotoxic to T cells and 10 to B cell and monocyte-enriched preparations. Absorption of eluates with pooled buffy coat cells, platelet concentrates and packed, cultured B cells removed antibodies reactive with vascular wall smooth muscle and endothelium, but not antibodies to tubular basement membranes, proximal or distal tubular cells, brush border, or other structures of kidney sections. Two of five eluates containing antikidney antibodies were found to bind to rat kidneys in vivo. These results suggest that circulating antibodies participate in cadaveric renal allograft destruction and demonstrate that they can be recovered directly from the allograft. Moreover, the data indicate that there are different antibody populations involved: some clearly directed to allo-specific differences and others that are apparently kidney-specific.

Antibody Specificity↗
PubMed1981

Cryoimmunoglobulinaemia in patients with renal disease. II attempts to demonstrate-that cryoprecipitate contain autoantibodies and/or antigen.

Seventeen patients found to have cryoimmunoglobulinaemia (CIG) while undergoing diagnostic renal biopsy and two patients with CIG without renal disease were studied. The cryoprecipitates (CP) from four of seven patients tested contained enhanced concentrations of autoantibodies: to vascular smooth muscle, autologous skeletal muscle, nuclear antigen and cardiac muscle. Antisera were made in rabbits against each of the 19 CP; six antisera contained antibodies to sarcolemma of skeletal muscle, nuclear antigen, elastin, reticulin, renal eluate and autologous kidney immune deposits respectively. Although one anti-CP antiserum bound to renal deposits, eight others tested on autologous renal biopsies did not. The data suggest that CP frequently may contain enhanced concentration of circulating autoantibodies and/or tissue antigens, possibly as immune complexes. In only one case was it possible to demonstrate that there was a common immunological identity between CP and renal Ig deposits.

Antigen-Antibody Complex↗
PubMed1978

Cryoimmunoglobulinaemia in patients with primary renal disease and systemic lupus erythematosus. I. IgG- and DNA-binding assessed by co-precipitation.

Sera were tested for cryoglobulin precipitates from 206 consecutive patients with renal disease, ninety-eight normals and sixteen patients with systemic lupus erythematosus (SLE) without evident renal disease. Cryoprecipitates were detected in 17% of test subjects overall and 2% of normals; the incidence was highest in patients with SLE, regardless of detectable renal disease. Cryoprecipitates usually were comprised of IgG and IgM or IgG, IgM, and IgA in thirty-six out of forty-two instances, although a single immunoglobulin class was detected in five patients. Co-precipitation experiments showed IgG-binding by virtually all sera forming cryoprecipitates; isolated cryoprecipitates bound radiolabelled homologous IgG, and Fc fragment and sometimes IgG subclass proteins preferentially. Freshly forming cryoprecipitates sometimes co-precipitated DNA, whereas all isolated cryoprecipitates co-precipitated DNA from dilute solutions. The data are compatible with the current hypothesis that cryoimmunoprecipitates are immune complexes that are insoluble in vitro in the cold, that they usually comprise mixed immunoglobulins with anti-IgG activity, and may contain a mixture of antigens and antibodies.

Adult↗
PubMed1977

IgA-associated glomerulonephritis.

In summary, IgA-associated glomerulonephritis is an interesting clinical problem. The immunohistochemical identification of renal IgA deposits is the sine qua non of its diagnosis, although most of the patients reported have had hematuric syndromes, particularly recurrent gross hematuria. The importance of this immunopathologic entity devolves from the crucial use of special stains to identify IgA, the enigmatic role of IgA, the usual mesangioapthic expression of histologic response, and the ill-defined relationship of this clinical problem to nephropathies associated with systemic diseases that also have glomerular IgA deposits. Although still unproven, it is likely that the usual instance of IgA-associated glomerulonephritis is due to deposition of circulating immune complexes containing IgA. The nature of the exciting antigen(s), quantitative measures and characteristics of such complexes, and the role of mediating systems, including coagulation, have not yet been elucidated.

Complement System Proteins↗
PubMed1977

Treatment of autologous immune complex glomerulonephritis with vasoactive amine antagonists.

AIC nephritis produced in rats by a single injection of FxIA in CFA was treated by agents with known antihistamine and antiserotonin activity. The effect of this drug regimen in altering the deposition of Ag-Ab complexes in the glomerulus was assessed by light, immunofluorescent, and electron microscopy. The vasoactive amine antagonists Chlortrimeton, Vistaril, Azatadine, and Sansert, when given singly or in combinations which completely abrogated histamine and serotonin-induced skin wheal formation, were unsuccessful at reducing apparent glomerular deposition of the circulating immune complexes of AIC nephritis.

Animals↗
PubMed1976

Glomerulonephritis mediated by antibody to glomerular basement membrane. Immunological, clinical, and histopathological characteristics.

A prospective study was undertaken to establish the incidence of glomerular basement membrane (GBM) antibody-mediated glomerulonephritis and its histopathological characteristics in a clinical group of patients presenting with renal disease. Biopsies from 43 of 409 consecutive patients technically satisfactory for direct immunofluorescent (IF) examination had diffuse and generalized linear localization of host immunoglobulin (Ig); two other badly scarred kidneys tested negative to IF although GBM antibodies were eluted. Confirmatory evidence of GBM antibody-mediated disease in these patients came from whole kidney or biopsy elutions (15 patients), serologic assays for circulating GBM antibodies by indirect IF (9 of 38 patients), radioimmunoassay (26 of 34), and hemagglutination (31 of 32). Although sera were not tested from six patients, circulating antibodies were demonstrated by some test in 36 of 39 of the remainder. Histologically, half of the patients had minor and nonspecific glomerular abnormalities or mild focal proliferative glomerulonephritis. More severely involved kidneys had focal necrotizing (17%), rapidly progressive (7%), and chronic, usually sclerosing, glomerulonephritis (27%). Clinical courses of these patients comparably were quite variable, ranging from indolent microhematuria and/or gross hematuric bouts to progressive renal failure; nephrotic syndrome was observed in 11 patients. GBM antibody-mediated glomerulonephritis may be a relatively mild disease with apparently stable renal function, although 16 patients have experienced functional deterioration, and 11 have progressed to dialysis, renal transplantation, or death.

Adolescent↗
PubMed1976

Single and multiple drug therapy in autologous immune complex nephritis in rats.

Autologous immune complex (AIC) nephritis is a form of chronic renal disease with remarkable similarities to idiopathic membranous nephropathy occurring in man. AIC nephritis was induced in 160 gram Lewis rats with a single footpad injection of tubular brush-border antigen (FxIA) in complete Freund's adjuvant. When killed at 8 weeks, 85 per cent of the rats demonstrated typical diffuse glomerular deposits of immunoglobulin G and B1C (C1/3 component of complement) by immunofluorescent microscopy, and subepithelial electron-dense deposits by electron microscopy. Both immune complex disease and significant proteinuria occurred in two-thirds of these animals. An attempt to modify the natural course of established AIC nephritis using large doses of potent glucocorticoids (methyl-prednisolone), anti-inflammatory agents (acetylsalicylic acid, indomethacin, and cyproheptadine), and immunosuppressive drugs (cyclophosphamide, azathioprine) was begun 4 weeks after initial immunization and continued for 4 more weeks. None of the single drug nor multiple drug protocols employed was of demonstrable benefit in ameliorating the immune events operating in AIC nephritis. Cyclophosphamide and indomethacin, when used singly, were associated with significant mortality in the animals studied. All combined drug protocols involving glucocorticoids and antimetabolites were associated with unacceptable mortality as well. Of interest, immune complexes could not be demonstrated in the vascular choroid plexus of any rat with AIC nephritis. This failure to modify the course of established renal disease (AIC) in an experimental animal with generally available pharmacologic agents, is similar to the usual results of such treatment in chronic renal disease (idiopathic membranous nephropathy) in man. It is possible that new and more potent anti-inflammatory agents employed singly or in various combinations, will permit more successful manipulation of the host's immunologic system to prevent or modify immune injury of the renal glomerulus.

Animals↗
PubMed1975

Immunopathologic findings in idiopathic renal hematuria.

Eighty patients had idiopathic renal hematuria and normal renal function. Renal biopsy showed minimal changes or focal glomerulonephritis in two thirds of the patients. The remainder exhibited diffuse proliferative glomerulonephritis and included nine patients with segmental glomerular sclerosis. Electron microscopy disclosed alterations of the capillary loop in 23 biopsy specimens and electron-dense deposits in 11. Immunofluorescent microscopy identified glomerular-bound immunoglobulins, C3, or fibrinogen in 58% in a generalized distribution. IgG was the immunoglobulin seen most commonly. IgA and IgM were present in 14 and 13 biopsy specimens, respectively. These findings suggest that idiopathic renal hematuria is a clinical syndrome rather than a single disease with varying underlying renal findings. Both immunologic and nonimmunologic mechanisms may be involved, and the prognosis is favorable even in patients followed up for 11 years.

Creatinine↗