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Biomedical subjects

R M McIntosh

Publications and source records attributed to R M McIntosh.

At least 37 records · Page 2Linked to original sources
PubMed1977

Glomerular deposition of renal tubular epithelial antigen in patients with systemic lupus erythematosus: its possible role in lupus nephritis.

Fifty-three renal specimens from 48 patients with SLE were examined for the presence of RTE in the glomeruli. Glomerular RTE, presumably in immune complex form was detected in 60% of the tissues. The deposition of these complexes was related to the severity of histologic changes and activity of SLE. In addition, glomerular localization of RTE was associated with decreased renal function and increased proteinuria. The association between the presence of glomerular RTE antigen, the severity of renal histologic changes and the decreased renal function suggested a possible role for this antigen in the pathogenesis of lupus nephritis.

Adolescent↗
PubMed1976

Experimental autologous immune deposit nephritis in rats associated with mercuric chloride administration.

Serial administration of mercuric chloride to rats was followed by development of antibodies to tubular basement membrane and renal tubular epithelial antigen (RTE) and glomerulonephritis characterized by granular deposits of hosts IgG, C3 and RTE along the glomerular capillary walls. The glomerular fixed antibody was directed against RTE. These studies suggest that tubular injury by mercury may lead to release of RTE and autosensitization and subsequent antibody production to this antigen result in formation of and glomerular deposition of circulating immunopathogenic complexes (RTE-anti-RTE) and glomerular morphologic alterations.

Animals↗
PubMed1976

Autologous immune complex nephritis associated with sickle cell trait: diagnosis of the haemoglobinopathy after renal structural and immunological studies.

A renal tubular epithelial antigen (RTE)--anti-RTE autologous immune complex nephritis associated with sickle cell anaemia (SS) has been reported, but immune complex nephritis has never been described in patients with sickle cell trait (SA). During investigation of a child with "asymptomatic proteinuria" cryoprecipitable complexes of RTE-anti-RTE were detected in the serum and granular deposits of RTE, immunoglobulins, and complement localised on the glomerular basement membranes. Morphological and ultrastructural studies showed increased mesangial matrix, sickled red blood cells in the glomeruli and vessels, and tubular and interstitial abnormalities. These findings prompted haemoglobin electrophoretic studies, which showed previously undiagnosed haemoglobin SA in this patient and her family. These observations suggest that nephritis mediated by similar immunopathogenic mechanisms may be associated with SS and SA haemoglobinopathy. Under some conditions patients with sickle cell trait may experience haemodynamic and oxygenation abnormalities, which may be aetiological factors in the immune complex nephritis associated with SS disease.

Adolescent↗
PubMed1976

The effect of renal hydrodynamics on immune complex deposition.

The role of renal hydrodynamics on renal deposition of immune complexes was evaluated in acute serum sickness. Using i.v. radiolabelled antigen in rabbits under a variety of hydrodynamic alterations, these studies suggested that although intrarenal hydrodynamics influence renal deposition of immune complexes factors other than intrarenal hydrostatic pressure may be important.

Animals↗
PubMed1976

Nephrotic syndrome associated with Fanconi Syndrome. Immunopathogenic studies of tubulointerstitial nephritis with autologous immune-complex glomerulonephritis.

The nature of renal lesions in a patient with simultaneous onset of the Fanconi syndrome and nephrotic syndrome was investigated by immunologic studies of the patient's serum, cryoproteins, and renal tissue. Acute severe tubulointerstitial nephritis and generalized segmental glomerulonephritis were present. Renal tubular epithelial (RTE) antigen, IgG, and Clq were localized in the glomerull and proximal tubules. Cryoprecipitates containing RTE antigen and anti-RTE antigen were isolated from the patient's serum antibody to RTE antigen was detected in the serum of the patient. However, antibody to tubular basement membrane was not found in the cryoproteins or serum. The unusual simultaneous presentation of these two syndromes in our patient possibly represents a common etiology: tubular damage with release of RTE antigen and subsequent development of immune-complex glomerulonephritis mediated by renal tubular epithelial antigen and antibody to this antigen.

Autoantigens↗
PubMed1976

Immune-complex disease with unilateral renal vein thrombosis.

The sequence of events in the relationship between membranous nephropathy and renal vein thrombosis is controversial. We postulate that occasionally, the thrombosis may precede the nephropathy and that release of autologous antigens from renal tissue damaged by occlusion of the vein may incite an autologous immune-complex disease. In a case of membranous nephropathy associated with renal vein thrombosis, renal tubular epithelial antigen (RTE) was localized in the glomerulus, along with the host immunoglobulins and complement components. Cryoproteins isolated from the serum contained RTE and anti-RTE. In addition, immunoglobulin eluted from the diseased glomeruli showed antibody activity to RTE. The membranous nephropathy was demonstrated to be secondary to an autologous immune-complex nephritis. Although the sequence of events is inconclusive, it is possible that the renal vein thrombosis preceded and was involved in the etiopathogenesis of the autologous immune-deposit nephropathy.

Adult↗
PubMed1976

Acute immune complex disease associated with hepatitis. Etiopathogenic and immunopathologic studies of the renal lesion.

Immune deposit glomerulonephritis has been associated with hepatitis B antigenemia. Immune complexes of this antigen and its antibody have been implicated in the pathogenesis of the renal disease. A boy had acute immune complex disease with glomerulitis in which cryoprecipitable complexes of HbsAg and its antibody were isolated from serum. HbsAg was concentrated in the cryoprecipitate and localized in a granular pattern along the glomerular basement membrane in association with immunoglobulins. Glomerular fixed antibody was eluted and shown to be directed against HbsAg. The level of antibody activity to HbsAg was higher in the eluate than the serum, suggesting immunopathogenic specificity of the antibody. The study demonstrates that the nephritis was mediated by immune complexes of HbsAg and its antibody, and the presence of immunoglobulin on the kidney did not represent trapping from the circulation.

Child↗
PubMed1976

Leukocytoclastic vasculitis.

Patients with leukocytoclastic vasculitis have purpuric, palpable lesions, most commonly on the lower part of the legs. Systemic involvement, particularly of the kidneys, is found frequently. Characteristic pathological features include necrosis of small vessels within the dermis, infiltration by polymorphonuclear leukocytes within and around the vessel walls, hemorrhage, and occasionally thrombosis. Immunofluorescence study frequently shows granular deposits of immunoglobulins and complement in vessel walls. Etiologic agents that have been implicated include infection, foreign proteins, chemicals, drugs, and a variety of diseases. The mechanism causing tissue damage is thought to be mediated by immune complexes, although specific antigens have only occasionally been unequivocally identified. Treatment includes bedrest, corticosteroids, and sometimes, cytotoxic agents.

Animals↗
PubMed1975

Nephropathy associated with sickle cell anemia: an autologous immune complex nephritis. II. Clinicopathologic study of seven patients.

A variety of renal structural and functional abnormalities have been associated with sickle cell disease. To define the relationship between the hemoglobinopathy and glomerular disease, clinicopathologic correlations, renal morphologic, ultrastructural immunohistologic and functional studies were performed on seven patients with clinical and laboratory evidence of glomerular disease. In addition, immunologic studies including isolation and characterization of cryoprecipitable immune complexes, and determination of immunoglobulin, total complement and complement component levels, and antibody titers to several antigens were performed in an attempt to define the etiologic and pathogenic mechanisms of the renal disease and its relationship to sickle cell anemia. Proteinuria was presnet in all patients. The nephrotic syndrome, hypertension, hematuria and renal insufficiency were found in more than one half the patients. All patients had membranoproliferative glomerulonephritis of varying degree; glomerular basement membrane splitting, electron dense deposits in the glomerulus; interstitial fibrosis, tubular atrophy and hemosiderin deposits were frequent. Immunoglobulin complement components (classif complement pathway) and renal tubular epithelial antigen were distributed in a granular pattern along the glomerular basement membranes of all patients studied by these methods. Cyroprecipitable complexes of renal tubular epithelial antigen-antibody to renal tubular epithelial antigen as well as antibody to renal epithelial antigen were detected in the circulation of some patients. There was no serologic evidence of activation of the alternate complement pathway. These studies demonstrated an immune deposit normocomplementemic nephritis associated with sickle cell anemia; they further support our hypothesis that the relationship is more then coincidental, and is mediated by glomerular deposition of immune complexes of renal tubular epithelial antigen-antibody to renal tubular epithelial antigen, the antigen possibly released after tubular damage secondary to oxygenation and hemodynamic alterations related to sickle cell disease.

Adolescent↗
PubMed1975

Nephropathy associated with sickle cell anemia: an autologous immune complex nephritis. I. Studies on nature of glomerular-bound antibody and antigen identification in a patient with sickle cell disease and immune deposit glomerulonephritis.

The nature of the glomerular-bound antibody and the putative antigen was investigated in one of the patients with sickle cell disease and immune deposit membranoproliferative glomerulonephritis by immunohistologic and glomerular antibody elution. Renal proximal tubular epithelial antigen was localized in association with immunoglobulins G (IgG), M (IgM), Clq fraction of the first component of complement (Clq) and the third component of complement (C3) in a granular pattern along the glomerular basement membrane of the patient's kidney. IgG and IgM were eluted from glomeruli. These immunoglobulins fixed to the proximal tubules of normal human kidney by direct immunofluorescence. This localization was abolished by absorption of the eluted immunoglobulins with renal tubular epithelial (RTE) antigen. The IgG eluted from the glomeruli blocked the fixation of rabbit anti-RTE antigen to normal proximal tubular brush border. These studies suggest that the nephritis in this patient was due to deposition of complexes or RTE antigen and specific antibody. An autologous immune complex nephritis may develop in some patients with sickle cell anemia secondary to RTE antigen released possibly after renal ischemia or some other phenomenon causing renal tubular damage.

Adolescent↗
PubMed1975

Human necrotizing vasculitis: immunoglobulins and complement in vessel walls of cutaneous lesions and normal skin.

Immunoglobulins and C3 were detected by immunofluorescence in the blood vessel walls of biopsies of clinically normal skin in patients with active necrotizing vasculitis. Of the 13 patients studied, 9 had C3 and 6 of these had IgM or IgA in biopsies of lesions of vasculitis. In adjacent clinically normal skin, 7 patients had C3 and 3 of these also had IgM or IgA. These findings support the hypothesis that immunoglobulins and complement are present in vessels of some patients prior to chemotaxis of polymorphonuclear leukocytes and the resulting inflammatory purpuric lesions so characteristic of necrotizing vasculitis.

Antigen-Antibody Complex↗
PubMed1975

Neuraminidase treated homologous IgG and immune deposit rental disease in inbred rats.

Immune deposit renal disease followed intravenous or intraperitoneal injections of neuraminidase treated homologous IgG or neuraminidase alone. No alterations were associated with several groups of controls. This preliminary study suggests that one mechanism by which microogranisms may be involved in the development of immune renal disease is by chemical alteration of immunoglobulin.

Animals↗
PubMed1975

Acute and chronic effects of chemically induced unilateral renal disease in rats.

Chemically induced unilateral renal disease was associated with a high incidence of proteinuria, diuresis, a morphological spectrum ranging from perinephritis to acute tubular or cortical necrosis, and unilateral or bilateral glomerular fibrinogen deposition during the first 2 wk after induction. Later, a decrease in proteinuria and return to normal urine output was not infrequently followed by recurrent proteinuria, hypergammaglobulinemia, morphological alterations, and deposition of IgG and beta1C on the glomerular basement membranes and mesangium of the contralateral kidney and the treated kidney. Intercapillary deposition of fibrinogen in association with IgG and beta1C was occasionally observed in one or both kidneys. The morphologic, immunohistologic, serologic, and chemical findings suggest that this model may be useful for further defining the course and prognosis of unilateral renal disease produced by vascular insufficiency.

Animals↗
PubMed1975

Cryoglobulins. III. Further studies on the nature, incidence, clinical, diagnostic, prognostic, and immunopathologic significance of cryoproteins in renal disease.

Serial serum samples from a large number of patients with immunologic renal disease, normal healthy controls, acute infections as well as non-immunological renal disease were studied for the presence, nature and properties of cryoproteins, and these correlated with serial renal functional, morphologic, immunohistologic and clinical fingings as well as serologic observations. A high incidence of cryoproteins were found in renal disease thought to be mediated by immune complexes. Cryoprecipitates were not detected in the other patients. The presence of fibrinogen in a serum cryoprecipitate was always associated with rapidly progressive disease and poor prognosis. An association between the detection of cryoproteins and the clinical and morphological activity of disease was observed. Persistence of cryoproteinemia was associated with progression and apparent disappearance with resolution or progression to end stage renal disease. In patients with hematuria or proteinuria of questionable significance cryoprotein detection was always associated with immune complex nephritis. Renal transplantation in the presence of cryoproteinemia was associated with recurrent nephritis in the graft. Cryoproteins were found to have biologic properties attributable to antigen-antibody complexes, to contain immune complexes of antigen and antibody and to have serologic factors concentrated. The detection of serum cryoglobulins was found to be a better index of clinical and morphologic activity of immune complex renal disease than was serum complement. As in our previous studies, these proteins appear to be of diagnostic and prognostic value in renal disease and provide a method of antigen identification in these disorders.

Animals↗
PubMed1975

Pancreatic transplantation in diabetic rats: renal function, morphology, ultrastructure, and immunohistology.

Serial renal morphologic, ultrastructural immunohisotlogic and functional studies were done on diabetic Lewis rats to evaluate the course of nephropathy and to study the effects of early pancreatic isografts on renal disease associated with streptozotocin diabetes. Three groups of experimental animals and one group of agematched controls were used. Group 1 consisted of 12 animals which were made diabetic with streptozotocin and which did not receive transplants. Early in the course of diabetes, these animals developed an increase in mesangial matrix, electron-dense material in themesangium, with immunoglobulin G, C3, and occasionally fibrinogen deposits in the glomerular mesangium. Alterations were progressive and mesangial bars, proximal tubular degeneration, tubular vacuolization, and myeloid figureswere present later. Progressive increase in protein excretion and increase in glomerular filtration rate were observed. Persistent glycosuria, hyperphosphaturia, andhypercalcuria. In contrast, only an occasional animal from Groups 2 and 3 with a pancreatic transplant showed renal in age-matched controls. These studies have demonstrated the evolution of renal glomerular and tubular changes in streptozotocin diabetic rats, and they have showed functional, and immunohistochemical changes.

Animals↗
PubMed1975

The human choroid plexus and autoimmune nephritis.

The choroid plexus resembles the glomerular basement membrane (GBM) and may be a site of injury or source of antigen in Goodpasture syndrome. Immunohistologic studies were performed on the choroid plexus of a patient with auto-immune nephritis and pulmonary hemorrhage. The studies showed linear deposition of host IgG, IGM, and beta1c. Antibody eluted from the diseased kidney fixed in a linear pattern to normal choroid plexus and could be absorbed by either choroid plexus or GBM. Antibody to choroid plexus fixed to GBM and the linear staining was no longer observed after absorption with GBM or choroid plexus. Antibody to GBM fixed to normal choroid plexus and was obsorbed by both choroid plexus and glomerular basement membrane. The studies suggest an immunologic relationship between choroid plexus and GBM and a role for the choroid plexus in autoimmune nephritis.

Animals↗