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A J D'Apice

Publications and source records attributed to A J D'Apice.

At least 19 recordsLinked to original sources
PubMed2000

The pig analogue of CD59 protects transgenic mouse hearts from injury by human complement.

BACKGROUND: It has been proposed that hyperacute rejection (HAR) of pig-to-primate vascularized xenografts is due in large part to ineffective regulation of recipient complement by pig complement regulatory proteins (CRPs), and indeed transgenic expression of human CRPs in pigs can prevent hyperacute rejection. However, at least one pig CRP (CD59) efficiently regulates human complement in vitro, suggesting that it is the level of expression of a particular CRP(s) rather than cross-species incompatibility that explains the HAR of porcine xenografts. We investigated the relative effectiveness of transgenically expressed pig and human CD59 in providing protection of mouse hearts from human complement in an ex vivo setting. METHODS: Transgenic mice expressing pig CD59 or human CD59 under the control of the human ICAM-2 promoter, which restricts expression in tissues to vascular endothelium, were used. Hearts from mice expressing similar levels of pig CD59 or human CD59 were perfused ex vivo with 10% human plasma and heart function was monitored for 60 min. Sections of perfused hearts were examined for deposition of the membrane attack complex (MAC). RESULTS: Control nontransgenic hearts (n=5) were rapidly affected by the addition of human plasma, with mean function falling to less than 10% of the initial level within 15 min. In contrast, hearts expressing either pig CD59 (n=6) or human CD59 (n=8) were protected from plasma-induced injury, maintaining 31 and 35% function, respectively, after 60 min of perfusion. MAC deposition was markedly reduced in both pig CD59 and human CD59 transgenic hearts compared to nontransgenic control hearts. CONCLUSIONS: When highly expressed on endothelium in transgenic mice, pig CD59 provided equivalent protection to human CD59 in a model of human complement-mediated xenograft rejection. Thus supranormal expression of endogenous porcine CRPs may be a feasible alternative to the expression of human CRPs in preventing HAR of pig-to-primate xenografts.

Animals↗
PubMed1991

VLA-2 is a collagen receptor on endothelial cells.

In order to identify cell-substrate adhesion receptors on vascular endothelium, murine monoclonal antibodies (MoAb) were raised against human umbilical vein endothelial cells (HUVE). One anti-HUVE MoAb, RMAC11, identified the adhesion receptor VLA-2 as it immunoprecipitated a non-covalently linked heterodimer of 160 kD and 130 kD, which was identical to the heterodimer immunoprecipitated by the anti-VLA-2 MoAb, 12F1 and 5E8. Furthermore, proteolytic peptide maps of the VLA-2 alpha- and beta-chains were highly homologous with those of the RMAC11-recognized molecule. However, unlike other VLA-2 MoAb, RMAC11 also identified an 85 kD band which migrated to 90 kD under reducing conditions. This band was most likely a fragment of the 160 kD alpha-chain as a similar alpha-chain derived fragment has been demonstrated in the immunoprecipitates of some VLA-4 reactive monoclonals. However the possibility that this may be a novel molecule associated with VLA-2 has not been excluded. In vitro assays of HUVE adhesion to collagen types 1 and 4, laminin and fibronectin showed that RMAC11 blocked adhesion to collagen (types 1 and 4) and laminin, but had no effect on HUVE adhesion to fibronectin, confirming that VLA-2 is a collagen and laminin receptor for HUVE.

Antibodies, Monoclonal↗
PubMed1989

Human monoclonal antibodies to HIV-1: cross-reactions with gag and env products.

Human monoclonal antibodies were raised by in vitro immunization of normal human spleen cells with denatured HIV-1 and subsequent fusion to an Epstein-Barr virus (EBV) transformed cell line. Three monoclonals reacted with both gag-encoded p24 core protein and env-encoded gp41 transmembrane glycoprotein. The cross-reaction was confirmed by reactivity with p24- and gp41-derived recombinant peptides. The peptides share two amino acid sequences which may be the basis for the cross-reaction. Attempted epitope mapping using synthetic peptides was unsuccessful due to non-specific reactivity with the short linear peptides.

Antibodies, Monoclonal↗
PubMed1989

Low red cell arachidonic acid in cyclosporine-treated patients.

Red blood cell phospholipid arachidonic acid concentration was determined in 38 renal transplant recipients on cyclosporine-azathioprine-prednisolone therapy and in a comparable group of 20 patients on azathioprine-prednisolone alone. Samples also were obtained from 18 normal controls and 30 patients with "classical" hemolytic uremic syndrome (HUS). The arachidonic acid content was estimated as the percentage relative to the five principal fatty acids in red blood cell phospholipids (C16:0, C18:0, C18:1 omega 9, C18:2 omega 6, C18:3 omega 6) and quoted as mean value +/- standard deviation. There was a highly significant difference between patients on cyclosporine (14.7 +/- 2.9) and non-cyclosporine-treated transplant recipients (17.1 +/- 2.5; p less than 0.002). This difference was even more significant when patients who had been on cyclosporine for less than 3 months were excluded (14.1 +/- 2.7; p less than 0.001). The mean arachidonic acid content in non-cyclosporine recipients also was significantly less than that in normal controls (19.2 +/- 1.5; p less than 0.005) whilst the HUS patients (11.2 +/- 3.6) had significantly reduced values when compared with all the other groups. Cyclosporine often causes nephrotoxicity and in some cases HUS may develop in cyclosporine-treated transplant recipients. We have found a significant negative correlation between serum creatinine levels and red blood cell phospholipid arachidonic acid levels (r = -0.45; p less than 0.01). We propose that the decreased concentration of arachidonic acid in the cyclosporine-treated group may be related to the development of nephrotoxicity in the long term and may be a useful marker in predicting the early development of nephrotoxicity in these patients.

Adolescent↗
PubMed1985

Blood transfusion and tumour growth: an experimental study.

An animal model using RIII mice, which have a high incidence of spontaneously occurring mammary tumours, was used to study the effects of blood transfusion on tumour growth. Virgin female mice were transfused with various dilutions of blood from C57b1 mice either before or both before and after inoculation of tumour cells from a tumour line. Allogeneic transfusion prior to inoculation did not affect survival compared with syngeneic transfusion. Both allogeneic and syngeneic blood given before and after tumour inoculation led to a prolonged survival compared with saline infusion. Survival was longest following syngeneic blood. The effect was attributed to the general beneficial effects of blood transfusion and not the result of immunological changes.

Animals↗
PubMed1981

Renal disease and sarcoidosis.

Renal involvement in sarcoidosis has recently been emphasized with increasing reports of associated glomerulonephritis. We report in detail a further case of mesangiocapillary glomerulonephritis in association with sarcoidosis. In addition, a review of 75 cases of sarcoidosis at Royal Melbourne Hospital over a 10-year period revealed one case of membranous glomerulonephritis and one case of granulomatous interstitial nephritis. Seven patients in the series had nephrocalcinosis, and eight further patients had abnormalities of urinary sediment of clinical symptoms of renal involvement. These findings suggest that, though renal failure is rare, renal involvement in sarcoidosis is more frequent than has previously been reported.

Adult↗
PubMed1981

Ureaplasma urealyticum in the upper urinary tracts of renal allograft recipients.

Urine samples from 123 renal transplant recipients were cultured for the presence of Ureaplasma urealyticum and other fastidious microorganisms. Ureaplasmas were recovered alone or in association with other microbial species from the bladder urine of 13 (11%) of the 123 patients, and evidence of involvement of the upper urinary tract was present in nine patients. Colonization of the upper urinary tract by U. urealyticum was not associated with a decline in function of the grafted kidney and was found only in patients with a primary diagnosis of reflux nephropathy (50% of such patients were positive for ureaplasmas) or glomerulonephritis (10% were positive) who had their own kidneys. The next most common isolate was Gardnerella vaginalis, recovered from 7% of patients, the majority of whom harbored the organism in the bladder only. The results confirm that U. urealyticum may colonize the upper urinary tracts of patients with proven renal disease.

Female↗
PubMed1980

Scleroderma crisis: response to therapy.

Renal failure in patients with systemic sclerosis is usually considered irreversible. Presented are two cases of patients with scleroderma and deterioration in renal function, one of whom has responded to therapy which included immunosuppressive agents, plasma exchange, and control of blood pressure.

Adult↗
PubMed1979

Transplant renal artery stenosis.

Renal artery stenosis occurred in 13.5% of 229 consecutive cadaver renal transplants performed at the Royal Melbourne Hospital over an eight and a half year period. Clinical and laboratory indices which suggested the diagnosis were examined. The presence and severity of hypertension were of little predictive value, while deterioration of renal function for which other causes had been excluded and the histological appearance of renal biopsy speciments were valuable in suggesting the diagnosis. A selective approach in both investigation and attempted surgical repair is recommended.

Adult↗
PubMed1978

Some uses of the continuous flow blood separator in the myeloproliferative syndrome.

A continuous flow blood separator was used for leucapheresis in two patients with chronic myeloid leukaemia, complicated by pregnancy and leukastasis respectively, and for thrombocytopheresis in a patient with megakaryocytic myelosis. The cases described, outline some of the clinical uses of this machine in the myeloproliferative syndrome.

Adult↗