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Biomedical subjects

A G MacIver

Publications and source records attributed to A G MacIver.

At least 37 records · Page 2Linked to original sources
PubMed1988

Localisation of immunoreactive kininogen and tissue kallikrein in the human nephron.

The cellular localisation of kininogen and its relationships with tissue kallikrein containing cells was studied in the human kidney by the peroxidase-antiperoxidase method using antisera to human LMW kininogen and to human tissue kallikrein. Immunoreactive kininogen was localised in the principal cells of collecting ducts. Immunoreactive tissue kallikrein was detected in the connecting tubule cells, segment of the nephron preceding the cortical collecting ducts. The co-existence of tissue kallikrein and kininogen in the same transitional tubule, but in different cells, was established by the use of serial sections and double immunostaining. This anatomical relationship is in accordance with known studies that describe intermingling of principal cells and connecting tubule cells where connecting tubules merge into cortical collecting ducts in the human nephron. The close relationship between cells that contain tissue kallikrein and its substrate, kininogen, suggests that kinins could be generated in the lumen of distal cortical segments of the human nephron.

Humans↗
PubMed1988

Detection of kidney reactive antibodies at crossmatch in renal transplant recipients.

We have investigated retrospectively sera from 70 renal allograft recipients for the presence of antibodies binding to a preanastomosis biopsy of the donor kidney by an indirect immunoperoxidase technique. All recipients had a negative T cell lymphocytotoxic crossmatch. A positive immunoperoxidase crossmatch for kidney-reactive antibodies was seen in 13/70 (18.6%) recipients--6 reacting with endothelium, 4 with epithelium, and 3 with both cell types. Neither the presence of these antibodies nor their pattern of staining correlated with recipient graft outcome. Following transplantation endothelial reactive antibodies developed in 15/43 (35%) patients, whereas tubular epithelial antibodies occurred in 5/43 (12%). The antibodies were persistent and accompanied graft failure in 10/14 (71%) patients, while transient antibodies were only associated with graft failure in 2/12 (17%) recipients. Development of lymphocytotoxic antibodies did not correlate with the presence of renal reactive antibodies or eventual graft outcome. Smooth muscle and antinuclear antibodies in recipient sera prior to transplantation were associated with improved graft survival. Eluates of 8/14 rejected grafts confirmed the presence of renal reactive antibodies, with patterns of staining similar to those observed in recipient sera. Antibodies in 7/8 recipients were shown by absorption studies to have HLA class I and/or II specificity, the remaining recipient having proximal tubular brush border antibodies.

Adolescent↗
PubMed1988

Expression of polymorphic B-cell antigens on human kidneys.

We have examined the expression on a panel of 22 human kidneys of polymorphic B-cell determinants recognized by mouse monoclonal antibodies. Monoclonal antibodies from a mouse immunized with an antigenic preparation from a DR4 positive B-cell line reacted preferentially with kidneys from DR4 positive donors (p less than 0.005), and the pattern of reactivity with kidney tissues was similar to that of antibodies to monomorphic determinants of class II. However, these antibodies did not show clear specificity for DR4 on lymphocytes in standard serological analyses. These results provide evidence for the expression of polymorphic class II determinants on human kidneys. Reasons for the differences in the apparent specificities of the monoclonal antibodies when tested on kidney sections and lymphocytes are discussed.

Absorption↗
PubMed1987

The natural course of gold nephropathy: long term study of 21 patients.

To clarify the natural course of gold nephropathy and thereby facilitate its clinical management 21 patients with rheumatoid arthritis who developed proteinuria during treatment with intramuscular sodium aurothiomalate were studied in detail throughout their renal illnesses. Renal biopsies were performed, and creatinine clearance and proteinuria were measured serially for 60 months (range 16-130 months). Ten patients developed proteinuria after six months' treatment, 15 after 12 months, and 18 after 24 months. When treatment was stopped the proteinuria reached a median peak of 2.1 g/day (range 0.7-30.7 g/day) at two months (range 1-13 months) before resolving spontaneously, in eight patients by six months, in 13 by 12 months, and in 18 by 24 months. All patients were free of proteinuria by 39 months, the median duration being 11 months. The median first and last measurements of creatinine clearance showed no significant change (77 ml/minute and 59 ml/minute, respectively), and no patient died from or needed treatment for renal failure. HLA-B8 or DR3 alloantigens, or both, were identified in seven patients. Renal biopsy specimens showed membranous glomerulonephritis in 15 patients, a minimal change nephropathy in two, mesangial electron dense deposits in two, and no appreciable glomerular changes in two. In these 21 patients the proteinuria of gold nephropathy resolved completely when treatment was withdrawn. Renal function did not deteriorate, corticosteroids were unnecessary, and several different renal lesions were seen.

Adult↗
PubMed1985

Varying expression of major histocompatibility complex antigens on human renal endothelium and epithelium.

Pre-anastomosis wedge biopsies from 14 cadaveric donor kidneys were examined for the expression of class I (HLA-ABC) and class II (HLA-DR) antigens in renal tissue. Two monoclonal antibodies to class I antigens and four to class II antigens were used in an indirect immunoperoxidase technique. Consistent expression of both antigens was demonstrated on the surface of glomerular, peritubular capillary and venous endothelial cells. Renal arteries contained only class I antigens. Proximal tubules contained varying amounts of each antigen in their cytoplasm. Sixteen human lymphocytotoxic allo-antisera showed marked variation in their ability to detect HLA antigens on the kidney. The selection of donors for recipients of renal allografts involves the complement-dependent cytotoxicity test and the failure of some lymphocytotoxic antisera to bind to the kidney indicates that some suitable patients may be incorrectly excluded. The use of a binding assay using an immunoperoxidase technique should be included in cross-match techniques particularly for patients who have high levels of circulating cytotoxic antibodies.

Antibodies, Monoclonal↗
PubMed1984

The monocyte/macrophage population of the normal human kidney.

There is continuing controversy over the role of mononuclear phagocytes in glomerulonephritis. It is, therefore, important to know their distribution in normal subjects. Normal kidneys (34) were assessed using three cytoplasmic markers for macrophages employing a trypsin-immunoperoxidase (PAP) technique with antibodies to alpha-1-antitrypsin, muramidase (lysozyme) and a further oligoclonal antibody, serum 22, developed against highly purified preparations of blood monocytes. Serum 22 detected twice as many monocytes/macrophages as anti-muramidase and four times as many as anti-alpha-1-antitrypsin. Most cells that showed positive staining lay in glomerular and intertubular capillaries and were considered to be blood monocytes. There was wide variation in monocyte numbers throughout different glomeruli and up to 14 monocytes could be present in a glomerulus. Not more than 1 per cent lay within the mesangium. Macrophages were virtually never seen in the interstitium, except in areas of scarring. No macrophages were present in the tubules. Monocytes and macrophages are demonstrated in greater numbers within the kidney by antisera to muramidase than to alpha-1-antitrypsin.

Adolescent↗
PubMed1983

Variable localization of blood group antigen in group A kidneys.

The distribution of the blood group A antigen has been examined in 7 Group A kidneys using an indirect immunoperoxidase technique. Monoclonal antibody consistently demonstrated A antigen on the endothelium of all kidneys, particularly peritubular capillary endothelial cells and also the epithelial cells of distal tubules of all but 1 case. Nine hyperimmune anti-A alloantisera gave a variable pattern of staining on different endothelial cells, but no kidney was negative. Epithelial cell staining showed considerable variation both within an individual cell and between adjacent cells. Twenty-six out of 40 alloantisera from normal Group O blood donors failed to bind to endothelial cells of one kidney which was known to show strong expression of A antigen. Absorption was completely achieved using Group A red blood cells but not with a synthetic blood group substance. The variation in reaction intensity using different antisera emphasises that there is variation in antigen expression between cells and indicates the complexity of antibodies directed against the blood group A antigen.

ABO Blood-Group System↗
PubMed1983

Renal dysplasia and duplex kidneys.

34 children with double ureters (n = 26), bifid ureters (n = 7) or bifid renal pelvis (n = 1) had heminephrectomy, leaving a normal portion of kidney. Patients with ectopic ureteroceles and ectopic ureters had upper pole lesions (18 of 18) whilst the lower pole was more often involved in those with vesico-ureteric reflux (9 of 11). Histological changes of renal dysplasia were present in both upper and lower pole lesions, being generally less severe at the lower pole. These findings suggest that prolonged urinary obstruction plays a major role in the formation of dysplasia in developing kidneys.

Child↗
PubMed1982

Immunoperoxidase techniques in human renal biopsy.

Immunoperoxidase techniques can be easily performed on formalin fixed renal tissue after incubation in trypsin. The sensitivity of the PAP technique on fixed tissue is as good as immunofluorescence methods using frozen sections. The method provides permanent preparations with clear localization of deposited immunoproteins giving accurate classification of renal disease and assessment for treatment. The availability of this technique for retrospective and centralized studies is a major advantage. Infectious agents are rendered harmless and can be specifically identified. The development of the trypsin-immunoperoxidase technique is an important and exciting advance in renal immunopathology.

Antigens↗
PubMed1982

Protein AA amyloidosis in Nigeria.

Eight cases of multi-system amyloid have been found in 4235 autopsies (0.2%) performed at University College Hospital, Ibadan, Nigeria between 1970 and 1979. Blocks and sections of seven cases showed the organ distribution associated with secondary amyloid, involving kidney, spleen and liver. Potassium permanganate oxidation prior to Congo Red staining showed that all seven cases contained protein AA amyloid. Five patients had tuberculosis but in two patients there was no recognized cause, idiopathic AA amyloid. Patients usually presented with nephrotic syndrome or renal failure and hypertension was absent. There appears to be a low incidence of amyloidosis in Africans, despite the occurrence of a large number of potential amyloidogenic stimuli, indicating the importance of individual host reactivity and failure of amyloid degradation in the causation of amyloidosis.

Adult↗
PubMed1979

The loin-pain/haematuria syndrome.

Nine patients with the loin-pain/haematuria syndrome are described. The previously reported clinical features of severe recurrent loin pain and tenderness in young women, the relationship of symptoms to use of oral contraceptives, and the demonstration of intrarenal vascular abnormalities by angiography are confirmed. Histology revealed minor non-specific abnormalities, and electron microscopy showed fibrin in the afferent arteriole and in glomerular capillaries of one patient only. No diagnostic changes were found on renography. In all patients except one the heparin-thrombin clotting-time was abnormal, suggesting increased platelet activity or release and providing further evidence of a vascular disorder.

Adult↗
PubMed1976

Liver abnormalities and gallstones: a prospective combined clinical, histological and surgical study.

In a prospective study of 57 patients coming to elective cholecystectomy for gallstone disease, clinical, biochemical and immunological features have been correlated with the histological changes in core biopsies of the liver obtained at surgery. Only 13 liver biopsies were normal. Ten biopsies showed changes of acute duct obstruction, 16 showed minimal portal tract abnormalities and 10 showed moderate portal tract inflammation and scarring. Histological changes were more marked in male patients. Clinical and biochemical investigations were not useful in predicting histological appearance, apart from cases with jaundice at the time of operation where changes of acute duct obstruction were usually, but not invariably, seen. Atuo-antibodies were present in 50 per cent of cases tested and all persisted for at least 6 months after operation. They were commoner in patients with more marked histological changes. Operative cholangiography was of little use in predicting histological change. These findings suggest that the possibility of gallstones should be considered in the interpretation of any abnormal liver biopsy irrespective of clinical symptoms or biochemical investigations.

Adult↗