Biomedical subjects

D C Mathews

Publications and source records attributed to D C Mathews.

9 recordsLinked to original sources

PubMed1991

Localisation of complement components in association with glomerular extracellular particles in various renal diseases.

Intraglomerular extracellular microparticles including so-called virus-like particles and striated membranous structures have been observed in various renal diseases. The presence and localisation of complement components in these extracellular bodies was studied using the protein A-gold electron microscopy method. Ultrastructurally these particles were differentiated into microspherical structures (MSS) and thread-like structures (TS). Both structures showed weak to moderate diffuse labelling with C1s, whilst the intense labelling found with C3d and C9 was confined to individual membrane-like structures of both MSS and TS. Labelling with IgA, IgG, fibrinogen and the complement components C1q, C1r, C3c C4 and C5 showed negative or trace results. There were no differences between the immunolabelling patterns of MSS and TS, nor among different renal diseases in which these structures were found. These findings raise the possibility that formation of so-called virus-like particles such as MSS and TS may be associated with complement activation.

Complement System Proteins↗

PubMed1991

Platelet-derived growth factor mesangial deposits in mesangial IgA glomerulonephritis.

Platelets may play a role in the pathogenesis of IgA glomerulonephritis (IgAGN). Ultrastructural labelling of platelet antigens might identify activated platelets, and localisation of platelet antigens may assist in understanding the role of platelets in glomerular disease. We examined renal biopsies from eight patients with mesangial IgAGN using protein A-gold immunoelectron microscopy. Serial sections were stained with antisera against platelet-derived growth factor (PDGF), platelet factor 4, beta-thrombolglobulin, platelet glycoprotein IIb-IIIa complex, and fibrinogen, as well as antisera against IgA, IgG, IgM and C3c. Platelets, including activated and degranulated platelets, were detected in capillaries in five of eight biopsies. PDGF was detected in mesangial deposits in five of eight cases. In one case immunolabelling was as intense as IgA labelling. Fibrinogen labelling was present in six of eight. Less intense labelling or negative results were obtained with the other antisera. There was no correlation between intensity of immunolabelling and any clinical or morphological features reflecting severity of glomerular lesions. The role of platelets in the pathogenesis of IgAGN remains unclear. The documentation of frequent deposit of PDGF should stimulate further interest in PDGF participation in this condition.

Blood Platelets↗

PubMed1991

Atypical structured glomerular deposits: an immunohistochemical study.

Atypical structured glomerular deposits were identified in sub-epithelial, sub-endothelial and mesangial areas in biopsy tissue from a female, aged 33, who presented with anaemia and was found to have proteinuria and microscopic haematuria. Histological examination showed that the deposits were periodic acid Schiff positive and silver negative whilst stains for amyloid were negative. Immunofluorescent staining for all immunoglobulins was negative, and only C3 showed moderate labelling. Conventional electron microscopy revealed that all deposits contained microtubular structures of variable length but with an average diameter of 25 nm and a periodicity of approximately 16 nm. The glomerular basement membrane was interrupted in many areas by deposits, and also contained 'myelin-like' structures. Free microtubular structures were also seen in the urinary space. Immunoelectron microscopy using protein-A-gold confirmed the immunofluorescent findings with immunoglobulins and fibrinogen, showed marked positive labelling of deposits with C1s and C3d and also intense labelling of coiled microtubular structures with C9. Other complement components C1q, C1r, C3c, C4 and C5 showed weak or negative results. Although these organised glomerular deposits contain complement components, their pathogenesis remains uncertain.

Adult↗

PubMed1989

Modified immunogold labelling applied to the study of protein droplets in glomerular disease.

Glomerular protein droplets have been observed in human glomerular epithelial cells, peripolar cells and mesangial cells, particularly in the preeclamptic lesion. Although morphologically similar, their functional role is uncertain. Whilst previous electron microscopic studies have shown these droplets to be generally uniform in electron density, our immunoelectron microscopy study of 10 biopsies, one showing lesions of preeclampsia, and the remaining 9 showing different forms of glomerular disease, generally displayed two distinct patterns of electron density and immunolabelling, when using a less severe fixation regime. An electron dense inner core was strongly positive to anti-fibrinogen, whilst a less dense peripheral zone was positive to anti-IgM. All other immunoglobulins, C3c, and albumin showed a less specific immunolabelling pattern. Protein droplets were also observed in proximal tubules in 7 out of 10 biopsies. In droplets found in most tubular cells immunolabelling was not partitioned, the most prominent findings being diffuse labelling for fibrinogen and albumin. In most instances where glomerular droplets were found adjacent to intraglomerular deposits, the marker identified within the deposit could also be seen in either the core area or the peripheral zone of the droplets. These findings raise the possibility that these droplets may be involved in protein adsorption from the deposits through a damaged glomerular basement membrane.

Antigens↗

PubMed1988

Morphometric analysis of pre-eclampsia in women biopsied in pregnancy and post-partum.

The importance of endothelial cell swelling and subepithelial deposits in producing capillary wall thickening in women with pre-eclampsia is controversial. In this study renal biopsy tissue from 16 women with a diagnosis of pre-eclampsia was analyzed morphometrically. Women biopsied during pregnancy (N = 6) showed substantial, electron-dense subendothelial deposits in capillary loops, but these were rare or absent in women (N = 10) biopsied post-partum (P less than 0.01). Endothelial cell swelling was present in both groups of patients to an equal degree. Mesangial cell interposition occurred but was not the dominant feature, and was similar in both pregnancy and post-partum biopsies. The median percentage per patient occupied by basement membrane was similar for both groups. Subendothelial deposits appear to resolve early in the post-partum period.

Adult↗

PubMed1987

Silver methenamine impregnation: a useful adjunct to renal electron microscopy.

The application of silver methenamine impregnation (SMI) to renal electronmicroscopy (EM) has been relatively neglected, but the technique has proved to be a useful aid in renal biopsy diagnosis. Tissues for SMI were fixed in glutaraldehyde/osmium and were embedded in either L.R. White resin or Epon. En-bloc staining of tissue with uranyl acetate was undertaken, but this procedure is considered optional. In our hands the technique has been valuable in the rapid assessment of renal ultrastructure in "routine" biopsies and especially in the diagnosis of complex or subtle changes in a variety of subtypes of glomerulonephritis, including the early membranous, familial-Alport type, mesangiocapillary and difficult to classify categories.

Glomerulonephritis↗

PubMed1987

Rapid development of diffuse crescents in post-streptococcal glomerulonephritis.

A 14-year-old boy presented with 3 days of hematuria and oliguria following impetigo. Renal biopsy showed diffuse endocapillary proliferative glomerulonephritis with subendothelial electron dense deposits but no crescents. Due to recrudescence of clinical abnormalities after initial improvement, the patient was re-biopsied 10 days later. This biopsy showed circumferential crescents in 83% of the glomeruli. Treatment with intensive plasma exchange, prednisolone, cyclophosphamide and dipyridamole was accompanied by prompt improvement in renal function. The need to carefully monitor the course in patients with acute post-streptococcal glomerulonephritis is emphasized.

Adolescent↗

PubMed1985

Immunoelectron microscopic localization of glomerular IgA deposits using a protein A-colloidal gold probe.

Currently there is increasing interest in the localization and accurate determination of the composition of protein deposits involved in the pathogenesis of human glomerulonephritis using immunoelectron microscopy. Previous studies have largely relied on capricious immunoperoxidase techniques applying both the preembedding and postembedding methods to renal tissue. Both methods identify a single antigen, but preservation of ultrastructure is suboptimal, and there is the potential problem of imprecise localization of antigen due to diffusion of the peroxidase reaction product. A less demanding method of ultrastructural antigen identification for renal tissue has been employed with success in clearly localizing glomerular deposits of IgA. The technique involves fixation of tissue in periodate-lysine-paraformaldehyde, embedding in L. R. White resin, and labeling by an indirect immunologic reaction using protein A-gold as an electron-dense marker. This technique provides an accurate marker for the localization of glomerular antigen while retaining optimal tissue morphology, and we predict that this method will have wide application in human and experimental renal disease.

Glomerulonephritis↗

PubMed1975

Glomerular lesions after renal transplantation.

Significant changes in glomeruli on light microscopy has been observed in 27 of 109 cadaveric renal allografts which functioned beyond 6 months. Tissue was available for study from all but two allografts. The histologic lesions were classified as follows: recurrent glomeruloneophritis, 9 cases (3 focal scierosis, 2 mesangial immunoglobulin A[IgA] disease, 2 mesangiocapillary glomerulonephritis, 1 dense deposit disease, 1 familial nephritis); de novo glomerulonephritis, 1 case (diffuse proliferative glomerulonephritis with crescents); and glomerular change of uncertain etiology, 17 cases (10 mesangiocapillary, 5 focal scierosis, 1 focal proliferative and 1 mesangial proliferative). These lesions were not distinguishable on light, fluorescent and electron microscopy from those in patients with spontaneous renal disease. All patients with glomerular lesions had proteinuria, and all but 3 had microscopic hematuria. Glomerular lesions were not significantly associated with early clinical rejection episodes or HLA compatibility. Presensitization of HLA antigens was significantly related to the occurence of a nonrecurrent glomerular lesion. Vescoureteral reflux was significantly more frequent in those with glomerular change (14 of 24) than in those without (13 of 48). Glomerular lesions were associated with a higher rate of graft loss due to renal transplant failure; renal function in survivors was significantly worse than in those without glomerular lesions.

Adolescent↗