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A J Rees

Publications and source records attributed to A J Rees.

At least 73 records · Page 4Linked to original sources
PubMed1991

Interleukin-1 beta stimulates human mesangial cells to synthesize and release interleukins-6 and -8.

Interleukin-1 beta (IL-1 beta) and tumor necrosis factor (TNF) have been reported to stimulate human mesangial cells (HMC) to proliferate and synthesize eicosanoids. We have examined whether they also induce HMC to release cytokines. In this study we show that both IL-1 and TNF stimulate HMC to release IL-6 and IL-8. Cycling and quiescent HMC were stimulated with various concentrations of either recombinant IL-1 beta or TNF for 1 to 24 hours. IL-1 beta at doses as low as 6 pg/ml stimulated mesangial cells to synthesize mRNA for both IL-6 and IL-8 as assessed by Northern analysis; mRNA for tubulin remained constant, which demonstrated a specific increase in mRNA. Secretion of IL-6 and IL-8 into the culture medium increased (4.5 to 18 ng/ml and 4 to 40 ng/ml, respectively) measured by ELISAs. TNF had similar effects but only in high concentrations (greater than 100 ng/ml). IL-1 beta did not stimulate cells to proliferate, as measured by 3H thymidine incorporation. TNF caused proliferation but only in concentrations over 100 ng/ml. We conclude that IL-1 beta is a potent stimulator of human mesangial cell production of IL-6 and IL-8, both of which may influence injury in nephritis. TNF also stimulates mesangial cells but only in pharmacological doses.

Cells, Cultured↗
PubMed1991

Plasma exchange in focal necrotizing glomerulonephritis without anti-GBM antibodies.

To determine whether plasma exchange was of additional benefit in patients treated with oral immunosuppressive drugs for focal necrotizing glomerulonephritis (without anti-GBM antibodies), we performed a randomized controlled trial with stratification for renal function on entry. Forty-eight cases were analyzed, 25 in the treatment group (plasma exchange, prednisolone, cyclophosphamide and azathioprine) and 23 in the control group (drug therapy only). There was no difference in outcome in patients presenting with serum creatinine less than 500 mumol/liter (N = 17), or greater than 500 mumol/liter but not on dialysis (N = 12), all but one of whom had improved by four weeks. However, patients who were initially dialysis-dependent (N = 19) were more likely to have recovered renal function (P = 0.041) if treated with plasma exchange as well as drugs (10 of 11) rather than with drugs alone (3 of 8). Long-term follow-up showed that improvement in renal function was generally maintained. The results of this trial confirm that focal necrotizing glomerulonephritis related to systemic vasculitis responds well to immunosuppressive drugs when treatment is started early, and suggest that plasma exchange is of additional benefit in dialysis-dependent cases.

Adolescent↗
PubMed1991

Anti-neutrophil cytoplasmic antibodies and disease activity during long-term follow-up of 70 patients with systemic vasculitis.

Anti-neutrophil cytoplasmic antibodies (ANCA) have been identified as a diagnostic marker in primary systemic vasculitis, and immunofluorescence assays identify two patterns of binding: cytoplasmic (C-ANCA and perinuclear (P-ANCA). We have examined retrospectively the use of such assays in long-term monitoring of disease activity, in order to determine the relationship between presence of ANCA and relapse, and to assess their suitability as a guide to therapy. Seventy patients were studied over a period of 50 months, using clinical and laboratory criteria for the diagnosis of relapse and the internationally standardised immunofluorescence assay for detection of ANCA. In 19 patients C- or P-ANCA were detectable throughout the study period; six of these (with C-ANCA) relapsed. In 18 patients ANCA were undetectable during long-term follow-up; none of these patients relapsed. In 33 patients C- or P-ANCA were intermittently present; nine of these relapsed and all had C-ANCA detectable at the time of relapse. In six of the nine cases, relapse was accompanied or closely preceded by reappearance of C-ANCA. We conclude that continuing presence and reappearance of ANCA may identify patients who are at risk of relapse and who are most likely to benefit from long-term immunosuppressive therapy.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1991

Immunoreactive endothelin in human plasma, urine, milk, and saliva.

Using a highly sensitive radioimmunoassay, elevated plasma immunoreactive endothelin (ir-ET) levels were found in patients with diabetes mellitus (1.88 +/- 0.12 pmol/L, mean +/- SEM, n = 100), patients undergoing maintenance hemodialysis (4.28 +/- 0.76 pmol/L, n = 14), patients with acute myocardial infarction (3.43 +/- 1.03 pmol/L, n = 6), and patients with subarachnoid hemorrhage (4.92 +/- 0.64 pmol/L, n = 14) (normal controls: 0.54 +/- 0.05 pmol/L, n = 19). ir-ET was also present in urine (2.1 +/- 0.3 pmol/L, n = 12), breast milk (6.8 +/- 1.6 pmol/L, n = 16), and saliva (2.0 +/- 0.2 pmol/L, n = 15) obtained from healthy subjects. Chromatography studies verify the identity of endothelin. Fast protein liquid chromatography (FPLC) showed one peak in the normal plasma extract, three peaks in the plasma extracts from diabetic patients and patients undergoing maintenance hemodialysis, three peaks in the urine extract, four peaks in the milk extract, and five peaks in the saliva extract. When the materials eluting in the void volume on FPLC of urine and saliva extracts were loaded onto a Sephadex G-25 column, the ir-ET was eluted in a higher molecular weight region. Incubation of endothelin-1, endothelin-2, and endothelin-3 in urine for 5 h showed that the total amount of ir-ET decreased to less than 30% of the initial levels, suggesting that endothelins are very unstable in urine.

Adult↗
PubMed1991

Restricted specificity of the autoantibody response in Goodpasture's syndrome demonstrated by two-dimensional western blotting.

The autoantigen in Goodpasture's syndrome is known to be contained within the non-collagenous (NC1) domain of type IV collagen. We have examined the specificity of autoantibodies to glomerular basement membrane (GBM) using the technique of 2-D electrophoresis followed by Western blotting. Protein stains of 2-D gels of collagenase-digested human GBM revealed extensive charge and size heterogeneity. Major components were of mol. wt 24-30 kD and 43-56 kD, corresponding to monomeric and dimeric subunits of NCl. Western blotting of 2-D gels with IgG from patients with anti-GBM disease demonstrated that the most antigenic components migrated as cationic 28-kD monomers (pI 10) and similarly charged dimers, although other components were recognized less strongly. The mobility of the strongly antigenic polypeptides was different to that of the known alpha 1 and alpha 2 chains of type IV collagen. Autoantibodies from all 20 patients studied showed the same pattern of reactivity, regardless of their clinical features (in particular, the presence or absence of pulmonary haemorrhage) or HLA type. A monoclonal antibody (P1) to human GBM bound in a similar pattern, particularly recognizing the cationic components. 2-D gels of affinity-purified GBM from a P1 column showed enrichment of the 28-kD monomers, which were recognized by human autoantibodies on Western blotting. These results demonstrate that the autoimmune response in Goodpasture's syndrome is of restricted specificity, and support the suggestion that the major autoantigenic determinant is present on the novel alpha 3 chain of type IV collagen.

Adolescent↗
PubMed1991

Excretion of metabolites of prostacyclin and thromboxane by rats with nephrotoxic nephritis: effects of interleukin-1.

1. To obtain direct evidence of abnormal eicosanoid biosynthesis in rats injected with anti-glomerular-basement-membrane antibodies (a-GBM), products derived from thromboxane A2 (TXA2) and prostacyclin (PGI2) were measured in 24 h urine collections before and after a-GBM. 2. Administration of a-GBM (9.5 mg) caused albuminuria, decreased creatinine clearance, increased numbers of intra-glomerular neutrophils and increased excretion of TXB2, 2,3-dinor-TXB2 (products of TXA2) and 6-oxo-PGF 1 alpha and 2,3-dinor-6-oxo-PGF 1 alpha (products of PGI2) at 24 h. 3. Interleukin-1 (IL-1 beta; 5 micrograms) alone caused an increase in PGI2 metabolite excretion but had no effect on TXA2 metabolites. It had no effect on creatinine clearance but increased numbers of glomerular neutrophils by approximately 4-5 fold compared to a-GBM. 4. Pretreatment of rats with IL-1 beta before a-GBM synergistically increased albumin excretion but only additively increased eicosanoid excretion. Numbers of intra-glomerular neutrophils and creatinine clearance were unchanged compared to IL-1 beta alone. 5. The cyclo-oxygenase inhibitor, ibuprofen (10 mgkg-1 i.p., twice daily for 4 days) inhibited both serum TXB2 production and urinary prostaglandin excretion. It also caused an almost complete attenuation of albumin excretion. Creatinine clearance and glomerular neutrophils remained unchanged after a-GBM/IL-1 beta. 6. We conclude that the 50% inhibition of thromboxane production induced by ibuprofen does not modify the fall in creatinine clearance of accumulation of neutrophils in the glomerulus caused by the a-GBM. This degree of inhibition of eicosanoid production was associated with a striking decrease in proteinuria, but this may reflect a haemodynamic rather than a disease modifying action.

6-Ketoprostaglandin F1 alpha↗
PubMed1991

Small bowel haemorrhage due to cytomegalovirus vasculitis.

A case is described of a life threatening vasculitis of the small bowel leading to massive gastrointestinal haemorrhage which was apparently due to cytomegalovirus inclusion disease. Reactivation of cytomegalovirus probably followed the treatment of Wegener's granulomatosis with corticosteroids and azathioprine. This patient was treated successfully by surgical excision of the affected segment of ileum together with intravenous ganciclovir.

Aged↗
PubMed1991

Evaluation of the in vitro production of tumour necrosis factor by monocytes in dialysis patients.

Modification of the cellular immune response in uraemia is partly responsible for the increased susceptibility to infection found in dialysis patients. In order to study this further we have evaluated the in vitro production of tumour necrosis factor (TNF) by peripheral-blood monocytes (PBMCs) to stimulation by lipopolysaccharide (LPS) from dialysis patients with end-stage renal failure. The patients were subdivided into two groups according to the type of dialysis: those undergoing haemodialysis (HD; n = 12) and continuous ambulatory peritoneal dialysis (CAPD; n = 18). Results were compared with those of controls taken from healthy laboratory staff (n = 7). The experiments show that the secretion of TNF by of TNF by PBMCs in response to LPS is significantly augmented in patients undergoing HD when compared to those on CAPD (81.3 +/- 38.7 vs. 18.2 +/- 13.3 U/ml, mean +/- SD, p less than 0.001) and controls (81.3 +/- 38.7 vs. 18.1 +/- 6.6 U/ml, p less than 0.001). There was no significant difference between the CAPD group and controls. In vitro production of TNF fell slightly following a single HD session (81.3 +/- 38.7 U/ml before HD and 50.5 +/- 28.7 U/ml after HD, p less than 0.05). We conclude from this study that TNF release from PBMCs is augmented in patients with chronic renal failure receiving chronic HD but not in a similar group receiving CAPD, in vitro. TNF release, however, is suppressed immediately following a single HD session. We suggest that HD rather than uraemia per se up-regulates monocyte secretion of TNF in vitro and that this is not an immediate response to activation by membrane polymer.

Adolescent↗
PubMed1991

Ganciclovir treatment for cytomegalovirus infection in immunocompromised patients with renal disease.

The safety and efficacy of a 10-day course of ganciclovir therapy was assessed in 17 consecutive patients with proven cytomegalovirus infection. The patients were receiving immunosuppressive therapy for a variety of non-malignant renal conditions, including renal transplantation (seven patients), small vessel vasculitis (six patients), systemic lupus erythematosus (three patients) and Goodpasture's disease (one patient). Fifteen patients were pyrexial at the time of their cytomegalovirus infection. Twelve patients had pneumonitis manifesting as a pulmonary parenchymal infiltrate or a reduction in gas transfer. Fourteen patients had a significant lymphopenia (lymphocyte count less than 1 x 10(9)/l), nine were leucopenic (white cell count less than 3.5 x 10(9)/l) and nine had abnormal liver biochemistry. One patient had an infection of the ileum and one an infection of the larynx. All these disease manifestations responded completely to a single course of ganciclovir therapy. There were no clinical relapses and no side effects were observed. Ganciclovir is a safe and effective therapy when administered early in the course of cytomegalovirus infection in immunosuppressed patients with renal impairment.

Adolescent↗
PubMed1991

Proximal cutaneous necrosis associated with small vessel calcification in renal failure.

Cutaneous necrosis with microvascular calcification is a rare and serious complication of chronic renal failure and has been given the sobriquet of 'calciphylaxis'. We describe four dialysis-dependent patients with proximal cutaneous necrosis who presented with this distinctive clinical syndrome. All of the patients were women aged between 40 and 68, and all developed widespread livedo reticularis followed by painful subcutaneous nodules which progressed to eschar-like lesions of the skin. Microvascular calcification was seen on radiographs of the limbs, especially at the sites of the cutaneous lesions. Serum phosphorus concentrations were increased in all the patients (maximally to between 2 and 3.6 mmol/l), but serum calcium concentrations were mildly increased in only two patients and only one patient had hyperparathyroidism. Histological examinations of skin biopsies in two patients showed cutaneous infarcts. Three patients died despite a reduction in serum phosphorus concentration and one patient improved. The proximal form of 'calciphylaxis' constitutes a distinct syndrome which can be recognized clinically.

Adult↗
PubMed1990

Towards a more rapid diagnosis of rapidly progressive glomerulonephritis.

An attempt was made to provide simple practical guidelines to alert general practitioners to the diagnosis of rapidly progressive glomerulonephritis and lead to early referral to hospital. The duration of illness before referral to this hospital and its effect on outcome in patients with crescentic nephritis were assessed retrospectively from the case notes of 24 patients referred over two years. Four patients had Goodpasture's syndrome, 11 Wegener's granulomatosis, seven microscopic polyarteritis, and two idiopathic progressive glomerulonephritis. The duration of symptoms before referral to the local hospital was similar in the four groups of patients and varied from one week to 28 months (mean 10 months). The duration of stay in the local hospital was two, nine, 11, and 180 days in the patients with Goodpasture's syndrome and a mean of four days (range one to eight) in those with Wegener's granulomatosis and 10 days (one to 18 days) in those with microscopic polyarteritis. In the local hospital the diagnosis was based on the results of renal biopsy and detection of antibodies to glomerular basement membrane in two patients with Goodpasture's syndrome and on the results of renal biopsy in seven of the other patients aided by the detection of antibodies to the cytoplasm of neutrophils (ANCA) in 10. Three of the 24 patients died and four required maintenance haemodialysis. Patients who present to their general practitioners with persistent non-specific symptoms should have a urine dipstick test and then blood tests and emergency referral to hospital if necessary. Hospital physicians should be aware of the speed and accuracy with which current assays can confirm a diagnosis of rapidly progressive glomerulonephritis.

Adult↗
PubMed1990

Serum sickness and acute renal failure after streptokinase therapy for myocardial infarction.

A patient developed serum sickness and acute renal failure following therapy with streptokinase for myocardial ischaemia. There was a previous history of a cellulitic infection of the leg, and antibodies to streptokinase were measurable in a serum sample taken from the patient before therapy. A cryoglobulin was detected at the time of presentation with serum sickness. This contained polyclonal IgG (with anti-streptokinase activity), streptokinase, and C3. Circulating immune complexes were demonstrated by C1q-binding assay. Deposition of C3 was observed in skin and renal biopsies, and bound to erythrocytes. Renal histology, however, showed acute tubular necrosis, with no vasculitis or inflammatory cell infiltrate. This case provides an unusual example of the characterization of an immune complex comprising a specific antibody and an exogenous antigen, and has clinical implications for the use of streptokinase.

Acute Kidney Injury↗