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Biomedical subjects

R C Atkins

Publications and source records attributed to R C Atkins.

At least 181 records · Page 10Linked to original sources
PubMed1988

The relationship of infiltrating renal leucocytes to disease activity in lupus and cryoglobulinaemic glomerulonephritis.

In order to evaluate the contribution of cellular immune mechanisms in the pathogenesis of immune complex-mediated glomerulonephritis, renal biopsies from 18 patients with lupus glomerulonephritis and 26 with cryoglobulinaemic glomerulonephritis were studied. Leucocyte profiles including T cell subsets and 'activated' macrophages within both glomeruli and interstitium were determined, using a panel of monoclonal antibodies as markers, and a sensitive 4-layer peroxidase technique to localize these within tissues. The infiltrating leucocytes were correlated with clinical, histological and immunological parameters of disease activity. Normal glomeruli contained few leucocytes though normal interstitium did (145 +/- 30 mm2), made up predominantly of T lymphocytes and macrophages. There was a significant increase in intraglomerular leucocytes in both systemic lupus erythematosus 4-fold, and essential mixed cryoglobulinaemia 7-fold, as compared to normal. These leucocytes consisted mainly of macrophages, and particularly in cryoglobulinaemia of 'activated' macrophages as demonstrated by their surface expression of the procoagulant tissue factor recognized by the A13 monoclonal antibody. In cryoglobulinaemic glomerulonephritis (GN) there was also a significant increase in T lymphocytes due to a predominance of suppressor-cytotoxic cells (OKT8+). There was a significant increase in interstitial leucocytes in both diseases, lymphocytes (mainly OKT8+ve), and macrophages (mainly 'activated' A13+ve). There were significant positive correlations between disease activity and interstitial leucocyte infiltration including, in lupus nephritis, degree of proteinuria and total leucocytes, hypocomplementaemia and T lymphocytes, increased numbers of monocytes and lymphocytes with a higher histological index of activity, and in cryoglobulinaemic GN of T lymphocytes and proliferative lesions, and T lymphocytes and C1q deposition. This study has demonstrated the importance of the interstitium in the pathogenesis of both diseases, delineated the presence of both T lymphocytes and activated monocytes which make cell-mediated immune mechanisms feasible, and linked the presence of immune mediators to disease activity.

Cell Count↗
PubMed1987

The enhancement of aminonucleoside nephrosis by the co-administration of protamine.

An experimental model of focal segmental glomerular sclerosis (FSGS) was developed in rats by the combined administration of puromycin-aminonucleoside (AMNS) and protamine sulfate (PS). Male Sprague-Dawley rats, uninephrectomized three weeks before, received daily injections of subcutaneous AMNS (1 mg/100 g body wt) and intravenous PS (2 separated doses of 2.5 mg/100 g body wt) for four days. The series of injections were repeated another three times at 10 day intervals. The animals were sacrificed on days 24, 52, and 80. They developed nephrotic syndrome and finally renal failure. The time-course curve of creatinine clearance dropped and showed significant difference (P less than 0.01) from that of each control group, such as, AMNS alone, PS alone or saline injected. Their glomeruli showed changes of progressive FSGS. The ultrastructural studies in the initial stage revealed significant lack of particles of perfused ruthenium red on the lamina rara externa and marked changes in epithelial cell cytoplasm. Therefore, it is suggested that the administration of PS enhances the toxicity of AMNS on the glomerulus and readily produces progressive FSGS in rats resulting in the end-stage renal disease.

Animals↗
PubMed1987

Leukocyte analysis using monoclonal antibodies in human glomerulonephritis.

The leukocyte subpopulations were analyzed within both the glomeruli and the interstitium in renal biopsies from 145 patients with various forms of glomerulonephritis. Cells were identified by monoclonal antibodies to leukocyte cell-surface antigens and immunoperoxidase labelling. Leukocytes, as defined by a monoclonal antibody to the leukocyte common antigen (PHM1), were present in normal, human renal tissue in both glomeruli (2.8 +/- 0.6 cells/glom. cross section) and interstitium (102 +/- 18 cells/mm2). Monocytes constituted the predominant infiltrating cell type in normal glomeruli (1.3 +/- 0.2) and T cells were rarely found (0.3: range 0 to 0.8), whereas both monocytes (34 +/- 10/mm2) and T lymphocytes (33 +/- 14/mm2) were found in the normal interstitium. In the non-proliferative forms of glomerulonephritis there was no significant increase in the number of glomerular inflammatory cells when compared with normal glomeruli. However, significantly increased numbers of T lymphocytes were seen in the interstitium of biopsies with minor non-specific changes (67 +/- 15/mm2), membranous nephropathy (134 +/- 30/mm2), focal glomerulosclerosis (207 +/- 53/mm2), and diabetic nephropathy (198 +/- 81/mm2). In the proliferative forms of glomerulonephritis only crescentic GN and post-infectious GN demonstrated significantly-increased glomerular monocytes and granulocytes. There was no significant increase in the number of glomerular T cells when compared with normal glomeruli. However, there was a significant increase in the number of interstitial T lymphocytes in all forms of proliferative glomerulonephritis when compared with the normal interstitial cell population.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies, Monoclonal↗
PubMed1987

Quantitation of intraglomerular mononuclear phagocytes in experimental glomerulonephritis in the rat using specific monoclonal antibodies.

Intraglomerular mononuclear phagocytes were quantitated, in normal Sprague-Dawley rats and in animals with diffuse proliferative glomerulonephritis, using recently described specific monoclonal antibodies (ED1, ED2, ED3) and a 4-layer immunoperoxidase technique. Results obtained with the immunoperoxidase technique were compared with estimates of glomerular mononuclear cellularity based upon glomerular histochemistry and glomerular cell culture. Normal animals (n = 12) had no significant glomerular mononuclear phagocyte population by immunoperoxidase [0.01 macrophages per glomerular cross section (MO/gcs)], histochemistry (+0.2 +/- 0.1 staining intensity) or glomerular cell culture [0.10 +/- 0.02 MO/glomerulus (MO/glom)]. Evolution of diffuse proliferative glomerulonephritis was associated with a progressive rise in glomerular mononuclear phagocyte infiltration using all three techniques. Immunoperoxidase staining (ED1) at the time of maximal macrophage infiltration of glomeruli revealed 6.21 +/- 1.78 MO/gcs (n = 12) using the ED1 macrophage marker. This correlated with histochemical (+3.8 +/- 0.2 staining intensity) and glomerular cell culture (17.6 +/- 4.5 MO/glom) estimates of the glomerular mononuclear phagocyte population. In addition, significant numbers of intraglomerular monocytes possessed the ED2 and ED3 macrophage differentiation antigens (0.82 +/- 0.41 and 0.24 +/- 0.15 MO/gcs respectively). Thus these specific monoclonal antibodies provide a reliable and readily reproducible means for the quantitation of intraglomerular mononuclear phagocytes. In addition, they provide evidence for intraglomerular macrophage differentiation in experimental glomerulonephritis in the rat.

Animals↗
PubMed1987

Monoclonal antibody-ricin conjugate cytotoxic to cells expressing the common acute lymphoblastic leukemia antigen (CALLA).

The monoclonal antibody PHM-6, which is specific for the common acute lymphoblastic leukemia antigen (CALLA), was conjugated to the plant toxin ricin. Binding of the PHM-6-ricin conjugate to cells via the ricin molecule was blocked by the presence of 100 mM lactose. The IC50 (concentration resulting in 50% inhibition) of the PHM-6-ricin conjugate for the CALLA-positive KM-3 cell line was 280-fold greater than for bone marrow stem cells, indicating the potential of this conjugate for immunological purging of autologous remission marrow.

Antibodies, Monoclonal↗
PubMed1986

Immunohistological studies with A1-3, a monoclonal antibody to activated human monocytes and macrophages.

A wide variety of monoclonal antibodies (mAb) have now been produced which recognize cell surface antigens on human peripheral blood monocytes. However, few of these mAb demonstrate specificity for monocytes, and fewer still recognize antigens exclusively on monocytes activated by one or more stimuli and/or block specific monocyte functions. The mAb A1-3 binds to lipopolysaccharide (LPS)-stimulated monocytes but not to resting blood monocytes, and inhibits the procoagulant activity of these LPS-activated cells. By using this mAb, we examined the reactivity of monocytes/macrophages (MO) in a broad range of normal and inflammatory tissues by means of a sensitive, four-layer immunoperoxidase technique. Cells of the MO system, in addition to lymphocytes and dendritic cells resident in lymphoid tissues, liver, lung, and other organs, were nonreactive with the A1-3 mAb. In contrast, intense staining of inflammatory MO was found in biopsies from patients with renal allograft rejection, acute glomerulonephritis, or granulomatous diseases. This apparent restriction of A1-3 binding to inflammatory, "activated" MO suggests that A1-3 mAb will be useful for the analysis of MO "activation" in many pathologic processes.

Animals↗
PubMed1986

Clinicopathological associations in mesangial IgA nephropathy.

On hundred and fifteen renal biopsies performed in 112 patients with mesangial IgA nephropathy were reviewed and the histological disease patterns correlated with the clinical features at the time of initial biopsy. To determine the significance of macroscopic haematuria in this disease, specific comparisons were made between patients with a history of episodes of macroscopic haematuria and those with only microscopic haematuria. The mean age at initial biopsy was 38.3 years (90 males, mean 40.3 years; 22 females, mean 30.2 years). Histological examination showed 9 patients (8%) with class I disease (mesangial matrix expansion alone); 43 patients (38%) with class II disease (diffuse mesangial proliferation); 60 patients (54%) with class III disease (focal and segmental proliferation), including subsets of 20 patients (16%) with segmental sclerosis and/or synechiae and 23 patients (21%) with crescent formation. Class III disease and crescent formation correlated with an increased frequency of capillary loop IgA and glomerular fibrin deposition and with the presence of subendothelial and subepithelial deposits. The degree of renal impairment and the incidence of hypertension were increased in class III disease. Macroscopic haematuria patients were younger (mean 31.1 vs. 43.0 years; p less than 0.001), had less severe renal impairment (mean creatinine 116.2 vs. 213.3 mumol/l; p less than 0.001) and less class III disease (48 vs. 58%; p less than 0.05). The incidence of crescentic disease was equal in macroscopic (17%) and microscopic (23%) haematuria. Eventual progression to end-stage renal failure occurred in 12 patients (11%) and correlated with crescentic disease, renal impairment, hypertension and heavy proteinuria at the time of diagnosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1986

Identification of a major sialoprotein in the glycocalyx of human visceral glomerular epithelial cells.

Glomerular visceral epithelial cells are endowed with a sialic acid-rich surface coat (the "glomerular epithelial polyanion"), which in rat tissue contains the sialoprotein podocalyxin. We have identified a major membrane sialoprotein in human glomeruli that is similar to rat podocalyxin in its sialic acid-dependent binding of wheat germ agglutinin and in its localization on the surface of glomerular epithelial and endothelial cells, as shown by immunoelectron microscopy, using the monoclonal antibody PHM5. Differences in the sialoproteins of the two species are indicated by the discrepancy of their apparent molecular weights in sodium dodecyl sulfate gels, by the lack of cross reactivity of their specific antibodies, and by the lack of homology of their proteolytic peptide maps. It is therefore possible that the human glomerular sialoprotein and rat podocalyxin are evolutionarily distinct, but have similar functions.

Animals↗
PubMed1986

Monoclonal antibody to rat ovarian inhibin.

Ovaries from rats treated with pregnant mare serum gonadotrophin were used as a source of inhibin for raising monoclonal antibodies. The antisera were screened for binding to rat ovarian tissue sections and examined for their ability to neutralize inhibin bioactivity in vitro, i.e. the ability to abolish the suppressive action of rat inhibin on pituitary FSH secretion. Two monoclonal antibodies to rat ovarian inhibin were raised, one exhibiting complete (antibody PHM15) and the other incomplete (antibody MCA-3) neutralizing ability. Both antisera bound well to antral granulosa cells, as judged by the degree of staining using an indirect horseradish peroxidase technique. Ascites fluid from mice injected with hybridoma cells secreting antibody PHM15 also showed inhibin-neutralizing ability, and was effective against inhibin prepared from ovarian follicular fluid of rats, sheep, pigs and cows. The latter observation indicates the potential application of this antibody to the preparation and measurement of inhibin from several animal species.

Animals↗
PubMed1985

Immunohistological analysis of serial biopsies taken during human renal allograft rejection. Changing profile of infiltrating cells and activation of the coagulation system.

This immunohistological study investigated two aspects of the mechanisms underlying human renal allograft rejection. First, because rejection is a dynamic, complex process, we sought to delineate any changes in the types of cells mediating graft destruction by evaluating the cellular infiltrates in sequential renal biopsies from 14 patients with rejection. Second, because macrophage accumulation and fibrin deposition are major features of kidney rejection, the membrane characteristics of intragraft macrophages were analyzed to determine whether these cells could indeed cause the fibrin deposition frequently observed. Thirty-six biopsies, performed for assessment of renal failure posttransplantation (post-Tx), were studied using a panel of monoclonal antibodies and a 4-layer immunoperoxidase technique. Biopsies were divided into 3 groups depending upon the time post-Tx. Comparison of biopsies taken on days 2-3 post-Tx with those taken either at days 10-12, or later than 30 days, showed similar proportions of T cells, T cell subsets, B cells and macrophages. By contrast, the proportion of natural killer (NK) cells was significantly increased at days 2-3 (P less than .01), and the proportion of activated T cells bearing interleukin-2 receptors was significantly increased at days 10-12 (P less than .01). Granulocytes were restricted to biopsies that displayed areas of infarction, regardless of the time at which this occurred. In addition, various proportions of intragraft macrophages exhibited the membrane phenotype of activated macrophages, as a result of their expression of the procoagulant molecule termed human-tissue-factor--related antigen (HTF:RAg). The proportion of graft macrophages exhibiting HTF:RAg was significantly increased in biopsies on days 10-12 (P less than .05) compared with biopsies on days 3-4, and remained elevated thereafter. Interstitial and perivascular collections of HTF:RAg+ macrophages were closely associated with fibrin deposits and, in two cases, mononuclear cells harvested from rejected grafts were shown to contain significant procoagulant activity in vitro. These studies demonstrate a major temporal variation in the types of cells contributing to human kidney rejection.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Monoclonal↗
PubMed1985

Life-threatening sepsis complicating heavy metal chelation therapy with desferrioxamine.

A case of severe Yersinia enterocolitica septicemia in a hemodialysis patient receiving desferrioxamine (DFX) therapy is reported. The association between systemic yersiniosis and DFX chelation therapy is reviewed. The increasing application of DFX chelation, in iron overload states and for aluminium overload in dialysis patients, provides an increasing number of patients at risk for this unusual drug side effect. An awareness of the association between Yersinia sepsis and DFX therapy allows appropriate therapeutic intervention which may prove lifesaving.

Adult↗
PubMed1985

The clinical spectrum of acute glomerulonephritis and lung haemorrhage (Goodpasture's syndrome).

The aetiology, clinical features and outcome of 40 patients presenting with Goodpasture's syndrome (glomerulonephritis with haemoptysis and pulmonary infiltrates) are reviewed. The diseases of the patients studied could be divided into three groups: antiglomerular basement membrane (anti-GBM) antibody-induced disease (7/40); systemic vasculitis (22/40) and idiopathic Goodpasture's syndrome (i.e. no systemic disease or anti-GBM antibody detected) (11/40). Overall mortality was 57.5 per cent (anti-GBM disease 4/7; systemic vasculitis 15/22; and idiopathic Goodpasture's syndrome 4/11). Most patients died of disease progression or infection. End-stage renal failure developed in 26 patients (anti-GBM (7), vasculitis (14) and idiopathic Goodpasture's syndrome (5). End-stage renal failure developed in 23 of 24 patients presenting with a creatinine of greater than 600 microM/l regardless of the aetiology of Goodpasture's syndrome or treatment used. Review of renal histology showed that all had proliferative nephritis, with 80 per cent of patients having more than 30 per cent crescents. Thus Goodpasture's syndrome was associated with a wide variety of underlying disease. It had a poor prognosis, with the degree of renal impairment at presentation, the extent of crescent formation and the nature of the underlying disease being the major determinants of outcome.

Adult↗
PubMed1984

Renal involvement in systemic lupus erythematosus.

A review of 28 cases of biopsy-proven lupus nephritis seen in Prince Henry's Hospital, Melbourne, in the last 12 years from 1971 to 1982 is reported. The mean follow-up period was 51 months. Renal histopathological changes were categorized according to the WHO classification of lupus nephritis. The majority of our patient population fell into two of the seven possible histological subgroups - Class IV (diffuse proliferative) disease (53.6%) and Class IIb (mesangial proliferative) disease (28.5%). Treatment with prednisolone alone or with a prednisolone/azathioprine combination resulted in an equal five-year survival (82%) and a similar overall preservation of renal function. The major single cause of death was opportunistic infection (60%). Despite overrepresentation of the more severe forms of lupus nephritis in a nephrology-unit population, there was a satisfactory outcome from therapy with either prednisolone alone or with a prenisolone /azathioprine combination. However, there were significant rates of morbidity and death associated with immunosuppressive therapy, primarily from opportunistic infection.

Acute Kidney Injury↗
PubMed1984

"Long-term" survival in light-chain myeloma with dialysis therapy alone.

We report a case of a 59 year old woman who presented in end-stage renal failure with lambda (lambda) light-chain myeloma (LLCM). Despite a large tumour burden, and refusal to accept cytotoxic chemotherapy, she was commenced on continuous ambulatory peritoneal dialysis (CAPD). With dialysis therapy alone she has shown considerable hematological improvement and remains well 18 months after diagnosis. The extremely poor prognosis attributed to light-chain myeloma is largely due to death from uremia. As the natural history of this disease in patients offered dialysis therapy is unknown, dialysis should not automatically be withheld from patients with LLCM.

Bone Neoplasms↗