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Biomedical subjects

R M McIntosh

Publications and source records attributed to R M McIntosh.

At least 19 recordsLinked to original sources
PubMed1980

Cryoglobulinemia and decreased monocyte chemotaxis is malignant melanoma.

The sera fromm 13 patients with malignant melanoma were evaluated for immune complexes by cryoprecipitation and the 125I Clq binding assay. Cryoprecipitates were identified in 12/13 patients (92%) and cryoimmunoglobulins in 7/13 patients (54%). Either cryoimmunoglobulin or elevated Clq binding was identified in 8/13 patients (62%). Incubation of normal monocytes with the resuspended cryoimmunoglobulin of 7 melanoma patients produced greater than 50% reduction in the ability of th monocytes to respond to chemotactic stimuli (p < .01). Similar inhibition was seen with cryoimmunoglobulin from erythema multiforme patients, but not with 'medium alone, albumin, heat aggregated albumin or heat aggregated-IgG in similar concentrations. No soluble factors produced in vitro could be demonstrated to produce this inhibition. Inhibition of monocyte function by immune complexes may be an important component of impaired host response to malignant melanoma, or alternatively may represent an important mechanism for the accumulation of monocytes at sites of inflammation, analogous to migration inhibition factor.

Adolescent↗
PubMed1980

Characterization of the glomerular antibody in acute poststreptococcal glomerulonephritis.

Glomerular-fixed antibody was eluted from the kidney of a 17-year-old patient who died 2 weeks after the onset of acute poststreptococcal glomerulonephritis. Elevated titers of antibodies to streptococcal enzymes were found in the serum but not in the glomerular eluate. Streptococcal M protein and anti-M protein reactivity were not detected in the eluate. Immunoglobulin G was the only serum protein demonstrated in the eluate, and it was found to have anti-IgG activity highly concentrated with respect to the serum. These studies appear to indicate that anti-IgG is involved in the immune pathogenesis of acute poststreptococcal glomerulonephritis. Native IgG may be rendered autoimmunogenic by the streptococcus with subsequent antibody production to the neoautoimmunogen. Alernatively, anti-IgG may be produced to the IgG incorporated in an exogenous streptococcal antigen-antibody complex.

Adolescent↗
PubMed1980

Circulating immune complexes and serum immunoglobulins in acute poststreptococcal glomerulonephritis.

Acute poststreptococcal glomerulonephritis (APSGN) is a disease thought to be induced by the renal deposition of circulating immune complexes. In order to test this possibility, serum samples from 119 patients with APSGN were studied for Clq binding activity (ClqBA), levels of IgG, IgM, IgA, C3 and antibody titers to streptococcal enzymes. These parameters were analyzed in relation to the clinical and laboratory data of the acute nephritic syndrome and with respect to the time elapsed from streptococcal infection and from the onset of nephritis. Elevated ClqBA was found in 66.7% of the patients in the first week of the disease and this frequency decreased progressively to 17.6% after the second week. Normal ClqBA was found in patients after the third week of nephritis. Serum levels of IgG and IgM were elevated in over 95% of the patients. Levels of IgG in excess of 2400 mg/dl were detected in 71.1% of the cases. No correlation could be found between the ClqBA and the clinical or immunoserological findings of the disease. The data support the hypothesis that circulating immune complexes are responsible for the nephritis that follows streptococcal infection.

Acute Disease↗
PubMed1980

Antibodies to human glomerular basement membrane: modified methodology for detection in human serum.

A new radioimmunoassay for detection of circulating antibodies to human glomerular basement membrane (GBM) is described. GBM was isolated, purified, and an antigenic component extracted by 8 M urea incubation. The 8 M urea extract was radiolabelled, separated on Sephadex G-150, and employed as GBM antigen for detection of binding in a double antibody radioimmunoassay (RIA). Three groups of sera were studied: (a) 40 normal subjects bound a mean of 0.5% +/- 3.4% (s.d.), (b) 12 patients with glomerulonephritis with non-linear immune deposits in direct immunofluorescent staining of kidneys bound a mean of 0.2% +/- 4.4% (s.d.), (c) 14 patients with Goodpasture's syndrome or glomerulonephritis with linear deposits in direct immunofluorescent staining of kidneys bound a mean of 23% +/- 9.1% (s.d.). Serial dilutions of sera from patients with Goodpasture's syndrome showed a progressive reduction in binding while binding of positive sera was inhibited by increasing quantities of unlabelled GBM. The GBM antigen extracted with 8 M urea is convenient to prepare and conditions for performance of the RIA are reproducible. Hence, this may represent a valuable on-site aid for diagnosis and management of patients with anti-GBM mediated glomerulonephritis.

Adult↗
PubMed1979

Simultaneous immunologic studies of skin and kidney in systemic lupus erythematosus clinicopathologic correlations.

Thirty-two biopsies of kidneys and of normal skin were performed simultaneously on patients with systemic lupus erythematosus (SLE) to determine whether the deposition of immune reactants in skin was correlated with the severity of renal injury or with several serologic measures of systemic disease activity. Immunofluorescent deposits at the dermal-epidermal junction (lupus band test) did not correlate with any clinical or histologic measures of glomerulonephritis or with serologic abnormalities. Immune deposits in dermal venules were found in 56% of the skin biopsies and were correlated with hypocomplementemia and higher levels of immune complexes in serum, and possibly with glomerular subendothelial electron dense deposits. Azathioprine therapy was correlated with absence of both sub-epidermal and vascular immune deposits. Immuno-fluorescent findings on serial skin biopsies on 13 patients were highly inconsistent. It is concluded that the lupus band test is clinically useful only as a diagnostic aid but not helpful in assessing renal or serologic activity of lupus, and that dermal vascular deposits of immunoglobulin or complement are more frequent than previoulsy recognized and correlate with measures of circulating immune complexes.

Adolescent↗
PubMed1979

Acute poststreptococcal glomerulonephritis in Maracaibo. II: Studies on the incidence, nature, and significance of circulating anti-immunoglobulins.

Antiglobulins were measured in the sera of 82 patients with acute poststreptococcal glomerulonephritis and correlated with C1q binding activity, serum levels of immunoglobulins and C3, site of infection, antibody titres to streptococcal enzymes, and the duration of the nephritis and interval from infection. Raised serum antiglobulins were found in 89.2% of the patients. In addition, raised titres were detected at any time during the course of the disease and very early after streptococcal infection. The finding of antiglobulins soon after the infection suggests the possibility that they appear as a primary event in the disease.

Acute Disease↗
PubMed1979

Immune deposit nephritis and single-component cryoglobulinemia associated with chronic lymphocytic leukemia. Evidence for a role of circulating IgG-anti-IgG immune complexes in the pathogenesis of the renal lesion.

2 patients developed the nephrotic syndrome several years after diagnoses of chronic lymphocytic leukemia. In both cases light microscopy showed membranoproliferative glomerulonephritis. Electron microscopy and immunofluorescent staining revealed electron-dense deposits and deposition of immunoglobulins and C3. Both patients had single-component IgG cryoglobulinemia. The eluted glomerular-bound protein contained IgG only. IgG in patients' sera, cryoglobulins, and kidney eluate had kappa light chains only. Immune complexes were detected in the sera and in the cryoglobulins by the Clq binding test. Immunoadsorption studies revealed anti-IgG antibodies in the patients' sera, cryoglobulin, and kidney eluate. Direct immunofluorescent studies using the patients' sera, cryoglobulins, and kidney eluate on frozen sections of patients' kidneys were positive, providing additional evidence for the immune complex nature of the glomerulonephritis. The immunohistochemical studies of our patients are suggestive of the presence of circulating IgG-anti-IgG immune complexes and their possible involvement in the pathogenesis of the glomerulonephritis and the nephrotic syndrome in these 2 cases.

Antigen-Antibody Complex↗
PubMed1979

Etiologic variability of nephropathy in juvenile diabetes mellitus.

Clinicopathologic studies of four patients with juvenile diabetes mellitus and renal disease demonstrated the pathogenetic variability of nephropathy in diabetic patients. Only in one patient was the clinical nephropathy associated with the typical diabetic glomerulosclerosis. Another patient had steroid responsive nephrotic syndrome superimposed on minimal diabetic glomerulosclerosis. A third patient had steroid resistant nephrotic syndrome associated with mild diabetic glomerulosclerosis and with later appearance of Grave's disease. The fourth patient, in addition to moderate diabetic glomerulosclerosis had prominent tubulointerstitial nephritis, the latter probably being responsible for the rapidly declining renal function. The poor prognosis associated with diabetic nephropathy warrants a careful search for other potentially treatable causes of nephropathy in patients with juvenile diabetes mellitus.

Adolescent↗
PubMed1978

Small vessel vasculitis caused by hepatitis B virus immune complexes. Small vessel vasculitis and HBsAG.

In a comprehensive study of 80 patients with vasculitis, 4 had concurrent hepatitis B virus (HBV) infection. Polyarteritis nodosa was present in 2 and in the other 2, cutaneous vasculitis, presenting clinically as palpable or Henoch-Schönlein purpura. In one of these patients skin biopsies demonstrated granular deposits of IgM, C3, C4, and the hepatitis B surface antigen (HBsAg) and electron-dense deposits of aggregated 20-nm particles resembling HBsAg in postcapillary venules. Evidence for circulating HBsAg-immune complexes included increased serum Clq binding activity, decreased serum complement, and a cryoprecipitate containing both HBsAg and IgM anti-HBs. Aggregated 20-nm particles resembling intact HBsAg were also seen by negative staining electron microscopy of the serum cryoprecipitate. This patient fulfills all the criteria for a specific immune complex vasculitis caused by his immune response to a chronic HBV infection. These findings emphasize that HBV infection may be associated with small vessel vasculitis as well as polyarteritis nodosa, mixed cryoglobulinemia, and glomerulonephritis. A similar immune response to other viral infections may be expressed as palpable (Henoch-Schönlein) purpura also.

Adult↗
PubMed1978

Evidence of an autologous immune complex pathogenic mechanism in acute poststreptococcal glomerulonephritis.

Clinical and experimental studies have suggested a role for antiimmunoglobulins in the pathogenesis of glomerulonephritis associated with streptococcal infection. We attempted to localize anti-IgG in the kidneys of 22 patients who had renal biopsies performed 7 to 66 days after the onset of acute poststreptococcal glomerulonephritis (APSGN). In addition to routine localization of immunoglobulins and C3, specimens were stained with neuraminidase-treated, heat-aggregated, and unmodified IgG. Twelve biopsies showed staining with fluorescein-labeled human neuraminidase-treated IgG. A lesser number gave positive staining with the other IgG preparations. Following treatment of slides with 0.01 M citrate buffer, seven previously negative biopsies showed positive staining with neuraminidase-treated IgG. The demonstration of anti-IgG by these methods was possible in 19 out of 22 biopsies. It correlated best with the presence of C3 and IgG, and to a lesser extent with IgM, in the renal glomerulus. These results and our previous finding of elevated levels of serum anti-IgG early in the course of APSGN, and as early as 8 days following the antecedent streptococcal infection, support a role for anti-IgG in the immune pathogenesis of APSGN. Although our series of studies support the hypothesis that anti-IgG is formed to an IgG modified enzymatically by streptococcal product, the formation of this autoantibody to IgG incorporated in an exogenous (streptococcal antigen-antibody) complex can not be ruled out.

Adolescent↗
PubMed1978

Acute nephritis and pulmonary alveolitis following pneumococcal pneumonia.

Acute glomerulonephritis developed in a man with pneumococcal pneumonia. Serum complement studies revealed decreased levels of C4, properdin, and C3. Renal immunofluorescence studies demonstrated pneumococcal antigen, C1q, C4, C3 proactivator, properdin, C3, IgG, and IgM. Circulating cryoglobulin contained pneumococcal antigen and antibody, C3, and immunoglobulins. Serial pneumococcal antigen and antibody levels did not display patterns that were characteristic of classical immune elimination, but the patterns may have been influenced by the reentry of antigen. A diffuse, pulmonary alveolitis also developed in the patient. Lung immunofluorescence studies revealed pneumococcal antigen, IgG, and C3 in alveolar walls and capillary basement membranes. The glomerulonephritis and alveolitis resolved after a prolonged course. These findings provide presumptive evidence for pneumococcal, immune complex glomerulonephritis with complement activation via both classical and alternative pathways and suggest an immunologic pathogenesis for the pulmonary alveolitis.

Adult↗
PubMed1977

Severe steroid-responsive nephrosis associated with hypersensitivity.

Sensitivity to cow's whole milk investigated in six patients with the idiopathic nephrotic and an elemental diet was given. After proteinuria had decreased to less than or equal to 500 mg/24 hours on consecutive days patients were challenged with cow's milk. This resulted in the return of significant proteinuria, oedema, and decreased urine volume together with a decrease in serum-IgG concentrations in four patients. Acute alteration of plasma C3 complement component accompanied milk challenge in all 6 patients. There were no consistent alterations in other immunoglobulin concentrations. Intradermal skin testing with cow's milk extract was positive in all patients. These results suggest that in some individuals clinical and biochemical manifestations of the nephrotic syndrome of childhood may be related to hypersensitivity of food products.

Adolescent↗