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J Michael

Publications and source records attributed to J Michael.

At least 19 recordsLinked to original sources
PubMed1996

Glomerular vascular cell adhesion molecule-1 expression in renal vasculitis.

AIMS: To study the expression of cell adhesion molecules in the renal biopsy specimens of patients with systemic vasculitis and Henoch-Schönlein purpura (HSP); to correlate this with the severity of glomerular inflammation. METHODS: Renal biopsy specimens obtained from eight patients with untreated systemic vasculitis (four with Wegener's granulomatosis and four with microscopic polyarteritis), eight with HSP and nine controls (four with normal histopathology and five with thin glomerular basement membrane disease) were stained using the alkaline phosphatase anti-alkaline phosphatase method with monoclonal antibodies directed against intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin. RESULTS: Biopsy specimens of normal kidneys expressed ICAM-1 in glomerular endocapillary cells, Bowman's capsule epithelium, interstitial cells and interstitial vascular endothelium, and VCAM-1 in Bowman's capsule epithelium, proximal tubular epithelium and interstitial vascular endothelium. No staining with antibody directed against E-selectin was seen in any of the biopsy specimens. Biopsy specimens of patients with a vasculitic glomerulonephritis (segmental necrotising glomerulonephritis) expressed VCAM-1 in glomerular endocapillary cells (four of eight patients with systemic vasculitis; two of eight patients with HSP). In patients with a systemic vasculitis glomerular VCAM-1 expression was associated with a more severe renal lesoin (44, 50, 60, and 65% of glomeruli involved) than in those not showing glomerular VCAM-1 expression (3, 3, 11, and 39% of glomeruli involved). CONCLUSION: Expression of VCAM-1 by glomerular endocapillary cells in renal biopsy specimens raises the possibility that recruitment of VLA-4 bearing leucocytes may contribute to glomerular injury in Wegener's granulomatosis and microscopic polyarteritis.

Adolescent↗
PubMed1996

Low calcium dialysate and hyperparathyroidism.

A low calcium dialysate reduces hypercalcemia from calcium-containing phosphate binders and makes phosphate control possible without the use of aluminum salts. We asked whether this might, however, lead to hyperparathyroidism. We prospectively studied serum concentrations of parathyroid hormone levels (by an immunoreactive intact molecule assay) in 173 patients on continuous ambulatory peritoneal dialysis (CAPD) who were started on a low calcium dialysate (Ca2+ 1.25 or 1.00 mmol/L) because of hypercalcemia. Median follow-up was 13.2 months (range 1-28). Initial serum parathyroid hormone was [median(range)]: 70(5-1043) ng/L pre low calcium dialysate, and this rose to 130(5-914) ng/L at 0-6 months; 130(5-1030) ng/L at 6-12 months; 170(170-1400) ng/L at 12-18 months; and 130(5-1200) ng/L at 18-24 months (p = 0.0006). Twenty-two patients required a parathyroidectomy because of a sustained rise in parathyroid hormone that was not responsive to alfacalcidol and hypercalcemia. Initial serum parathyroid hormone was significantly higher in these patients at 359 (5-1073) ng/L as compared to a level of 69.5 (6-1147) ng/L in patients who did not have a parathyroidectomy (p = 0.0009). There was a significant sustained fall in mean serum corrected calcium from 2.77 (2.37-3.51) mmol/L to 2.53 (1.39-3.20) mmol/L at three months (p = 0.0006), a nonsignificant rise in mean serum alkaline phosphate from 179 (47-1858) mmol/L to 191 (55-1821) mmol/L (p = 0.15), and a fall in mean serum phosphate levels from 1.87 (0.59-3.18) mmol/L to 1.68 (0.45-3.6) mmol/L (p = 0.76). Our data suggest that the benefits of a low calcium dialysate in CAPD patients are balanced by an increased risk of hyperparathyroidism, and that this risk is higher in patients with an initially high serum parathyroid hormone level.

Adult↗
PubMed1994

Anti-idiotypic activity against anti-myeloperoxidase antibodies in pooled human immunoglobulin.

We investigated the ability of six different pooled human immunoglobulin (PHIG) preparations to inhibit the binding of anti-myeloperoxidase (MPO) antibodies to MPO. All six PHIG preparations inhibited the binding of anti-MPO antibodies from six sera to MPO in a concentration-dependent manner in the concentration range 0.016-10 mg/ml. There was considerable variation in the ability of each PHIG preparation to inhibit the binding of anti-MPO antibody in a given serum. Further differences were seen in the ability of a given PHIG to inhibit anti-MPO binding in different sera. F(ab')2 fragments from two PHIG preparations also inhibited in a concentration-dependent manner anti-MPO binding to MPO in all six sera in the concentration range 0.002-2.65 mg/ml, with a maximum inhibition of 42%. Little inhibition was seen with F(ab')2 of normal human IgG from individual donors (1.8-12.2% at the maximum concentration of 2 mg/ml). F(ab')2 fragments from three anti-MPO containing sera and two affinity-purified anti-MPO antibodies were eluted by affinity chromatography from Sepharose-bound PHIG F(ab')2 and showed anti-MPO antibody activity. We have shown that PHIG and F(ab')2 fragments of PHIG inhibit anti-MPO binding to MPO, and further that F(ab')2 fragments of PHIG bind to F(ab')2 fragments of anti-MPO antibodies. These observations indicate binding between the variable regions of PHIG and the antigen binding site of anti-MPO antibodies, and are consistent with an anti-idiotypic reaction. The variability seen in the inhibitory effect of the different PHIG preparations in anti-MPO-positive sera implies differences in their anti-idiotype content, while the variability of the inhibitory effect of a particular PHIG preparation between different sera suggests heterogeneity in the idiotypic repertoire of anti-MPO antibodies. Such variations in the inhibitory effect of different PHIG preparations on antibody binding may be an important determinant of their therapeutic effect.

Animals↗
PubMed1994

Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) expression and function on cultured human glomerular epithelial cells.

Glomerular epithelial cells are involved in extracapillary inflammation (crescents) but the mechanisms of this extracapillary accumulation of macrophages, epithelial cells and occasional lymphocytes are unknown. Human glomerular parietal epithelial cells express ICAM-1 and VCAM-1 on immunohistological stains of renal biopsies. We studied the expression of these cell adhesion molecules on cultured human glomerular epithelial cells (HGEC), their regulation by pro-inflammatory cytokines, and their role in mediating the adhesion of concanavalin A (Con A)-activated peripheral blood mononuclear cells. Human glomerular epithelial cells in culture constitutively express ICAM-1 and VCAM-1. The expression of ICAM-1 was not significantly altered by tumour necrosis factor-alpha (TNF-alpha) (P = 0.32), IL-1 beta (P = 0.24), interferon-gamma (IFN-gamma) (P = 0.66) or IL-4 (P = 0.85). VCAM-1 expression was increased by all four cytokines, but only significantly so by IL-4 (P = 0.0001). Con A-stimulated, monocyte-depleted peripheral blood lymphocytes bound to human glomerular epithelial cells, median 28.9% (range 14.5-37.9%). This adherence was significantly inhibited by anti-ICAM-1 (P = 0.03) and anti-LFA-1 (P = 0.02), but not by anti-VCAM-1 (P = 0.13) or by antibody to von Willebrand factor (P = NS). The interaction between ICAM-1 on HGEC and LFA-1 on mononuclear cells may be important in the pathogenesis of extracapillary inflammation in glomerulonephritis.

Cell Adhesion↗
PubMed1994

Interdependence of contractile responses of rat small mesenteric arteries on nitric oxide and cyclo-oxygenase and lipoxygenase products of arachidonic acid.

1. We have examined the effects of nitric oxide inhibition, indomethacin and the dual lipoxygenase/cyclo-oxygenase inhibitor, 3-amino-1-[m-(trifluoromethyl)-phenyl]-2-pyrazoline (BW755C), on the responses of small mesenteric arteries of Wistar rats, with and without endothelium, to noradrenaline, potassium chloride, endothelin-1, acetylcholine and sodium nitroprusside. 2. Noradrenaline, potassium chloride and endothelin-1 caused concentration-dependent contraction of small mesenteric arteries. Indomethacin (14 microM) attenuated the contractile response to both noradrenaline and potassium chloride. The inhibitory action of indomethacin persisted in vessels treated with CHAPS. 3. Acetylcholine produced concentration-dependent relaxation in these vessels. Indomethacin (14 microM) had no significant effect on the acetylcholine concentration-response relationship. 4. NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) potentiated the contractile response to both noradrenaline and potassium chloride and inhibited acetylcholine-induced relaxation. Indomethacin attenuated the effects of L-NAME. 5. BW755C inhibited the contractile response to noradrenaline and potassium chloride but not to endothelin-1. The inhibitory effects of BW755C persisted in the presence of indomethacin and in vessels treated with CHAPS. 6. BW755C enhanced endothelium-dependent relaxation, as assessed by the response to acetylcholine. In the presence of indomethacin, BW755C produced a shift to the right of the concentration-response curve to acetylcholine. 7. Inhibition of nitric oxide synthase with L-NAME, reversed the inhibitory effect of BW755C on noradrenaline- and potassium-induced contraction. L-NAME and BW755C in combination resulted in a shift to the right of the concentration-response curve to acetylcholine. 8. Sodium nitroprusside produced concentration-dependent relaxation of the vessels. Endothelium removal reduced the maximum relaxation to nitroprusside. BW755C did not alter the response to sodium nitroprusside in vessels with or without endothelium.9 .These data support the existence of two vasoconstrictor products of arachidonic acid released during contraction of small mesenteric arteries with noradrenaline and potassium chloride: a cyclo-oxygenase product and a lipoxygenase product both of which appear to be largely endothelium-independent.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1994

Relative roles of nitric oxide and cyclo-oxygenase and lipoxygenase products of arachidonic acid in the contractile responses of rat renal arcuate arteries.

1. We have examined the effects of inhibition of nitric oxide synthase, cyclo-oxygenase and lipoxygenase on the responses of renal arcuate arteries of Wistar rats, with and without endothelium, to noradrenaline, potassium chloride, endothelin-1, acetylcholine and sodium nitroprusside. 2. Noradrenaline, potassium chloride and endothelin-1 caused concentration-dependent contraction of the vessels. Indomethacin (14 microM) attenuated the contractile response to noradrenaline and to potassium chloride. The inhibitory effect of indomethacin persisted following endothelial removal. 3. Acetylcholine produced concentration-dependent relaxation of the vessels which was potentiated by indomethacin (14 microM). 4. NG-nitro-L-arginine methyl ester (L-NAME, 100 microM) did not affect the contractile response to either noradrenaline or potassium chloride but abolished relaxation to acetylcholine. In addition, L-NAME abolished the affects of indomethacin on acetylcholine-induced relaxation and noradrenaline- and potassium chloride-induced contraction. 5. BWC755C attenuated noradrenaline and potassium chloride-induced contraction. This effect persisted in the presence of indomethacin. 6. In vessels pretreated with CHAPS, BW755C inhibited both noradrenaline and potassium chloride-induced contraction. In these vessels BW755C had no additional inhibitory effect to indomethacin on noradrenaline- and potassium-induced contraction. 7. Inhibition of nitric oxide synthase with L-NAME (100 microM) attenuated the effect of BW755C on noradrenaline- and potassium-induced contraction. 8. BW755C alone did not affect endothelium-dependent relaxation as assessed by the response to acetylcholine. However, in the presence of indomethacin, BW755C inhibited acetylcholine-induced relaxation. 9. BW755C did not affect endothelium-independent relaxation as assessed by the response to sodium nitroprusside in vessels with or without endothelium. 10. These data support the existence of two vasoconstrictor products of arachidonic acid released during contraction of renal arcuate arteries with noradrenaline and potassium chloride. A cyclooxygenase product which appears to be endothelium-independent and the other an endothelium dependent lipoxygenase product.

4,5-Dihydro-1-(3-(trifluoromethyl)phenyl)-1H-pyraz↗
PubMed1994

Circulating soluble adhesion molecules in systemic vasculitis.

The plasma levels of soluble intercellular adhesion molecule-1 (sICAM-1), E-selectin (sE-selectin), and vascular cell adhesion molecule-1 (sVCAM-1), might reflect endothelial activation and injury and would therefore be useful markers of disease activity in vasculitis. To investigate this we measured the levels of sICAM-1, sE-selectin, and sVCAM-1 by two-site ELISAs in the plasma of patients with (a) active vasculitis (n = 16), (b) vasculitis in remission (n = 15), (c) chronic renal failure (CRF) (n = 10), and (d) normal healthy controls (n = 10). Plasma sICAM-1 levels were significantly higher in patients with active vasculitis, 323 ng/ml (193-607) compared with patients with inactive vasculitis, 199 ng/ml (131-297); P = 0.0006 and healthy controls, 188 ng/ml (138-259); P = 0.0002. Plasma sE-selectin levels were also significantly higher in the patients with active vasculitis, 45 ng/ml (15-65) compared with patients with inactive vasculitis, 25 ng/ml (15-55); P = 0.027 but not when compared with healthy controls, 35 ng/ml (20-55); P = 0.16. There was no difference in plasma sVCAM-1 levels between patients with active vasculitis, OD 0.56 (0.45-0.85) and inactive disease, OD 0.58 (0.47-0.79) (P = 0.12) or with healthy controls OD 0.49 (0.42-0.68) (P = 0.48). There were no significant differences between the plasma levels of any of the soluble adhesion molecules between patients with active vasculitis and patients with chronic failure.(ABSTRACT TRUNCATED AT 250 WORDS)

C-Reactive Protein↗
PubMed1994

Knowledge of renal histology alters patient management in over 40% of cases.

There is great debate as to whether the benefit gained from the knowledge of renal histology outweighs the risk to the patient from the biopsy procedure. We conducted a prospective study of 276 native renal biopsies performed on 266 patients from a single centre in 1991 to assess the effect of the knowledge of renal histology on patient management. Biopsies were performed under ultrasound guidance using the Trucut biopsy needle. The indications for biopsy were: non-nephrotic proteinuria alone (25), haematuria and proteinuria (28), nephrotic range proteinuria (28), acute renal failure (31), haematuria alone (36), and chronic renal failure (128). Two hundred and sixty-three biopsies were successful. The mean number of glomeruli obtained was 23, range 0-115. Eight patients developed macroscopic haematuria of which two required blood transfusion. The result of the biopsy altered management in 24/28 (86%) of cases of nephrotic range proteinuria, 22/31 (71%) of cases of acute renal failure, 58/128 (45%) of cases of chronic renal failure, 9/28 (32%) of cases with haematuria and proteinuria, 3/25 (12%) of cases with non-nephrotic proteinuria alone, and 1/36 (3%) of cases with haematuria alone. management was altered in 42% of cases overall. These data suggest that knowledge of renal histology is essential in the management of patients with renal disease.

Adolescent↗
PubMed1994

Classical versus non-renal Wegener's granulomatosis.

We investigated whether 'limited' or 'non-renal' Wegener's granulomatosis (WG) differs from classical or 'renal' WG. Renal WG is characterized by necrotizing granulomatosis of the upper and or lower respiratory tract, accompanied by systemic vasculitis and focal segmental necrotizing glomerulonephritis. This last feature is absent in non-renal WG. In a prospective follow-up study of all identified cases presenting to a single teaching hospital, we reviewed 22 patients with non-renal WG, and compared their presentation and outcome with that of 28 patients with renal WG. Clinical and laboratory assessment of disease activity, frequency of death, relapse and end-stage renal disease were assessed. The two groups differed in clinical presentation, laboratory features and outcome. The group with non-renal WG had less cutaneous and pulmonary disease; the haemoglobin, white cell count and platelet count tended to be normal. Residual mortality was confined to the renal group. However, the groups shared many features, particularly their requirement for immunosuppressive therapy, since WG causes major tissue destruction regardless of whether it is a localized or widespread process. At the immunopathological level, the two groups appear to be part of a single disease spectrum. Importantly, the non-renal WG group may change the pattern of their disease to involve the kidney. Long-term follow-up of such patients is therefore essential.

Adult↗
PubMed1993

Pooled human IGG (PHIG) inhibits the binding of anti-myeloperoxidase antibodies to myeloperoxidase.

This study demonstrates that pooled human immunoglobulin (PHIG) contains anti-idiotypes to anti-myeloperoxidase (MPO) antibodies and can inhibit the binding of anti-MPO to MPO. The variability seen in the inhibitory effect of different PHIG preparations in the same and also in different patient sera suggests heterogeneity in the idiotypic repertoire of anti-MPO antibodies.

Antibodies, Anti-Idiotypic↗
PubMed1993

Little evidence for anti-endothelial-cell antibodies in microscopic polyarteritis and Wegener's granulomatosis.

Sera from patients with a vasculitis and controls were investigated for the presence of anti-endothelial cell antibodies(AECA), anti- neutrophil cytoplasmic antibodies(ANCA) and anti-myeloperoxidase (MPO) antibodies. Only 19% of patients with Wegener's granulomatosis and 2% of patients with microscopic polyarteritis had AECA. Our data suggests that AECA are a minor antibody system in vasculitis.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed1993

Relapses in patients with a systemic vasculitis.

Treatment with cyclophosphamide and steroids has greatly improved survival in patients with systemic necrotizing vasculitis but does not always provide a complete cure. There are as yet few data on the incidence, pattern and outcome of relapses in these diseases. We studied relapses in 150 consecutive patients with an idiopathic necrotizing vasculitis: 12 with classical polyarteritis (CPAN); 95 with microscopic polyarteritis (MPA); 28 with Wegener's granulomatosis (WG); and 15 with limited Wegener's granulomatosis (LWG). The relapse rates and median time to relapse in months were: CPAN, 41.7%/33; MPA, 25.4%/24; WG, 44%/42; LWG, 52%/18. The clinical features of relapse were similar to or more aggressive than those of the original presentation in CPAN and LWG and included renal disease for the first time, but in MPA and WG, relapse involved less renal involvement in the majority of cases. Laboratory tests, although often positive at relapse, were unhelpful in its prediction. The considerable accumulative non-fatal relapse rate contrasts with the very good long-term survival rates, and confirms the importance of long-term follow-up in systemic vasculitis.

Adult↗