PubMed Health⌕ Search

Biomedical subjects

G R Russ

Publications and source records attributed to G R Russ.

At least 19 recordsLinked to original sources
PubMed2005

Prospective, multicenter, randomized trial to compare incidence of new-onset diabetes mellitus and glucose metabolism in patients receiving cyclosporine microemulsion versus tacrolimus after de novo kidney transplantation.

New-onset diabetes mellitus (NODM) is associated with increased risk of graft failure and death in renal transplant recipients. Some clinical studies have indicated that NODM risk is higher with tacrolimus than cyclosporine, but no comparative trial has used American Diabetic Association (ADA)/World Health Organization (WHO) criteria for diagnosis of diabetes mellitus. The Diabetes Incidence After Renal Transplantation, Neoral C2 Monitoring Versus Tacrolimus (DIRECT) study is a 6-month open-label, multicenter trial comparing the impact of tacrolimus and Neoral (cyclosporine microemulsion) on glucose metabolism in 700 de novo kidney transplant recipients, based on ADA/WHO criteria. Patients are randomized to tacrolimus (C0 monitoring) or Neoral (C2 monitoring), stratified by baseline diabetic status and ethnicity. All patients receive basiliximab, corticosteroids, and mycophenolate mofetil or enteric-coated mycophenolate acid (myfortic). Pooled interim 3-month results from a subset of 115 patients receiving either tacrolimus or Neoral showed that the primary efficacy end-point (biopsy-proven acute rejection [BPAR], graft loss or death) occurred in 11 patients (10%). There were four graft losses and only one death, which occurred after graft loss. Eight patients experienced BPAR (7.3%). Among 99 patients who were nondiabetic at baseline, 14 developed NODM by month 3, 17 developed impaired fasting glucose or impaired glucose tolerance, and another 5 patients received hypoglycemic treatment for at least 14 consecutive days or at the month 3 visit, resulting in a 36% incidence of impaired glucose metabolism. At 3 months, median GFR (Nankivell) was 63.7 mL/min; median serum creatinine was 137 micromol/L. Full complete results are expected in December 2005.

Adrenal Cortex Hormones↗
PubMed2003

Reduced and standard target concentration tacrolimus with sirolimus in renal allograft recipients.

We report 6-month results of renal allograft recipients enrolled in seven Australian centers as part of a worldwide, multicenter, randomized, open-label, concentration-controlled trial comparing standard tacrolimus (sTAC) with reduced tacrolimus (rTAC) both with sirolimus (SRL) and steroids. Patients were randomized 1:1 to either rTAC (n = 33) with a target maintenance concentration of SRL of 8 to 15 ng/mL and TAC of 3 to 7 ng/mL, or sTAC (n = 31) with SRL target of 5 to 10 ng/mL and TAC of 8 to 12 ng/mL. Antibody induction was prohibited. Adult recipients of a first or second cadaveric or non-HLA-identical living donor renal graft were eligible for enrollment. Recipients with a panel-reactive antibody level of >50% and recipients of regrafts who had lost their first graft from rejection within the first 6 months were ineligible. The groups were compared for graft function, incidence of rejection, and patient and graft survival at 6 months. There were no differences in demographics. There were 30% and 29% discontinuations in the rTAC and sTAC groups mainly due to adverse events in the first month. The 6-month patient and graft survival by intention-to-treat analysis was 94% and 91% for rTAC and 100% and 97% for sTAC (P = NS), respectively. Incidence and severity of biopsy-proven acute rejection was not different between the two groups, being 21% for rTAC and 19% for sTAC. The mean serum creatinine was 121 micromol/L and 148 micromol/L for rTAC and sTAC groups (P =.09), respectively. Glomerular filtration rate (GFR) was 68 mL/min and 62 mL/min (P =.23), respectively. Adverse events, infections, and antihypertensive and antilipidemic agent usage were similar. Of interest is that the overall incidence of thrombotic microangiopathy was 14%. These results support the safety and efficacy of SRL + TAC. Reduced TAC is associated with a trend toward improved renal function.

Adult↗
PubMed2001

Early peri-operative glycaemic control and allograft rejection in patients with diabetes mellitus: a pilot study.

BACKGROUND: Hyperglycemia alters the inflammatory response to infection and ischemia. We hypothesize that perioperative glycemic control could also influence the risk for allograft rejection. METHODS: Consecutive patients with established diabetes undergoing their first cadaveric renal transplantation and receiving steroid-sparing immunosuppression were identified (n=50). Records of capillary glucose observations over the first 100 hr following surgery and transplantation variables pertaining to graft function, acute rejection, and postoperative infection were identified and entered into multivariate analysis. RESULTS: Perioperative glycemic control was associated with an increased incidence of infection and acute rejection. Only 3 of 27 patients (11%) with optimal glycemic control during the 100 hr following surgery (mean<11.2 mmol/L) had rejection episodes compared with 58% of patients with poor control (>11.2 mmol/L). All patients with poor glycemic control experienced postoperative infection. CONCLUSIONS: This pilot study suggests that hyperglycemia may be associated with an increased risk of both allograft rejection and postoperative infection in patients with diabetes.

Adult↗
PubMed2001

Four cases of CMV ureteritis: emergence of a new pattern of disease?

Although cytomegalovirus (CMV) infection is common in renal transplant recipients, urinary tract involvement has been rare. Only six cases of symptomatic ureteritis have been reported in renal transplant recipients and all within the last five years. We describe an additional four cases of CMV ureteritis. The presentation of CMV ureteritis is obstructive nephropathy often in the absence of systemic illness. Presentation may also mimic allograft rejection with minimal obstructive symptoms. We hypothesize that CMV ureteritis is an emerging complication of CMV disease, possibly due to changes in transplant practice.

Adult↗
PubMed2001

Human myeloid dendritic cells transduced with an adenoviral interleukin-10 gene construct inhibit human skin graft rejection in humanized NOD-scid chimeric mice.

Human myeloid DC were generated from peripheral blood mononuclear cells by monocyte adhesion and subsequent culture with rhGM-CSF and rhIL-4. We transduced immature (day 5 of culture) myeloid DC with an E1-deleted replication-deficient adenoviral vector encoding the cytokine IL-10 (AdV IL-10) and a control adenovirus MX-17 (AdV MX 17). Human DC transduced with AdV IL-10 showed inhibition of the mixed leukocyte culture, reduced cell surface expression of co-stimulatory molecules (CD80/CD86) and were unable to produce the potent allo-stimulatory cytokine, interleukin-12. In order to test the in vivo properties of these cells a humanized immunodeficient mouse skin transplantation model was developed. Immunodeficient NOD-scid mice were engrafted with human skin, reconstituted via intraperitoneal injection with allogeneic mononuclear cells (MNC) mixed with 1 x 10(6) DC that were autologous to the skin donor and that had been transduced with either AdV IL-10 or AdV MX-17. Skin grafts were removed at day 7 and 14 after reconstitution and studied histologically for evidence of rejection. In animals that received DC modified with AdV IL-10 there was reduced skin graft rejection as characterized by reduced mononuclear cell infiltration and less dermo-epidermal junction destruction compared with those animals that received DC modified with the control virus alone. Injection of equivalent numbers of donor-derived fibroblasts transduced with AdV IL-10 were ineffective at modifying rejection of skin grafts. Immunosuppressive cytokine gene therapy targeting human DC is a novel means of inhibition of the alloimmune response.

Adenoviridae↗
PubMed2000

Early peri-operative hyperglycaemia and renal allograft rejection in patients without diabetes.

BACKGROUND: Patients with diabetes have an increased risk for allograft rejection, possibly related to peri-operative hyperglycaemia. Hyperglycaemia is also common following transplantation in patients without diabetes. We hypothesise that exposure of allograft tissue to hyperglycaemia could influence the risk for rejection in any patient with high sugars. To investigate the relationship of peri-operative glucose control to acute rejection in renal transplant patients without diabetes, all patients receiving their first cadaveric graft in a single center were surveyed and patients without diabetes receiving cyclosporin-based immunosuppression were reviewed (n = 230). Records of the plasma blood glucose concentration following surgery and transplant variables pertaining to allograft rejection were obtained. All variables suggestive of association were entered into multivariate logistic regression analysis, their significance analysed and modeled. RESULTS: Hyperglycaemia (>8.0 mmol/L) occurs in over 73% of non-diabetic patients following surgery. Glycaemic control immediately following renal transplantation independently predicted acute rejection (Odds ratio=1.08). 42% of patients with a glucose < 8.0 mmol/L following surgery developed rejection compared to 71% of patients who had a serum glucose above this level. Hyperglycaemia was not associated with any delay of graft function. CONCLUSION: Hyperglycaemia is associated with an increased risk for allograft rejection. This is consistent with similar findings in patients with diabetes. We hypothesise a causal link concordant with epidemiological and in vitro evidence and propose further clinical research.

Acute Disease↗
PubMed2000

Ovine interleukin 12 has biological activity on ovine and human activated peripheral blood mononuclear cells.

Interleukin 12 (IL-12) is a heterodimeric cytokine composed of two subunits that form the biologically active p70 molecule, and is a potent inducer of the pro-inflammatory cytokine IFN-gamma. In this study the coding sequence for ovine interleukin 12 p35 and p40 subunits was derived by RT-PCR cloning. Ovine p35 and p40 cDNA sequences show a high level of similarity at the nucleic acid and protein levels when compared to corresponding bovine and human sequences. In particular, cysteine residues and N-linked glycosylation sites are conserved between species. Secretion of the IL-12 heterodimer from CHO cells co-transfected with ovine p35 and p40 cDNA was shown by immunoprecipitation of a 60 and 66 kDa protein from transfectant supernatant. In addition, the supernatant from co-transfected cells augmented the proliferation of Con A-activated ovine peripheral blood mononuclear cells (PBMNC). Cross-species activity was shown by the enhancement of proliferation of human phytohaemagglutinin (PHA)-activated PBMNC. Supernatants from co-transfectants of hu p35/ov p40 and ov p35/hu p40, to generate chimeric heterodimers, also demonstrated stimulatory activity. Human and chimeric IL-12-induced proliferation of activated PBMNC was inhibited using an anti-human IL-12 polyclonal antibody, however this antibody showed minimal inhibition of ovine IL-12. This study suggests that ovine IL-12 has biological properties similar to its human counterpart.

Amino Acid Sequence↗
PubMed2000

Excellent long-term graft survival in low risk, primary renal allografts treated with prednisolone-avoidance immunosuppression.

Primary avoidance of oral corticosteroids for renal transplant recipients is uncommon. The South Australian renal transplant service used a double therapy (DT) regimen of cyclosporin and azathioprine from August 1986 to July 1996 for low risk (first graft, PRA < 50%) allografts. Oral corticosteroid, prednisolone (P), was reserved for severe rejection or two mild rejection episodes, but could be later withdrawn at the physician's discretion. This regimen is associated with more early acute rejection (Russ et al., Clin Transplant 1990: 4: 26). We have now analysed long-term patient survival (PS) and graft survival (GS) for this group. Of 448 transplants in South Australia between August 1986 and July 1996, 295 commenced DT regimen. Ninety-four (31.8%) never received P at any stage post-transplantation (group 1), 96 (32.5%) were placed on P and later weaned (group 2), and 97 (33%) remained on long-term P (group 3). Technical losses, eight (2.7%), within 30 d of transplantation, were excluded from sub-group analysis. PS for the total DT cohort at 1, 5 and 9 yr post-transplantation was 97, 88 and 74%, respectively. GS over the same time period was 88, 75 and 55%, respectively. There was no statistically significant difference in survival compared to other 'low risk' grafts in the rest of Australia during the same time period. Mean serum creatinine concentration (CrC) for the DT group at 3 and 6 months and 1, 3, 5 and 10 yr was not significantly different to the rest of the Australian 'low risk' grafts. In the DT cohort, there were 334 acute rejections ( < 90 d) in 206 patients (70%), but only 42 (12.5%) required anti-lymphocyte antibody therapy (OKT3 or ATG) for rejection. PS at 9 yr was not statistically significantly different between groups 1 and 2, but both groups survived better than group 3 (p < 0.0043). GS for group 1 at 1, 5 and 9 yr post-transplantation was 90, 81 and 73%, respectively; for group 2, 98, 87 and 66%, respectively; and for group 3, 84, 63 and 29%, respectively. Statistical significance was reached in group 1 versus 3 (p < 0.001) and group 2 versus 3 (p < 0.001). In summary, a DT regimen in low risk, first renal allografts gives excellent long-term patient and GS and minimises long-term P, despite a high rate of early acute rejection.

Acute Disease↗
PubMed2000

Renal transplantation in Australia and New Zealand 1963 to 1999.

The main feature of transplantation in Australia and New Zealand over the last few years has been the increasing proportion of living donor transplants on the background of a cadaveric organ donation rate, which is very low by international standards. The increase in living donor transplants has occurred predominantly as a result of an increase in the number of unrelated grafts. The success rate in transplantation in Australia is excellent with a one-year primary cadaveric graft survival rate of around 90% for each year since 1994 to the present. The accumulated one-year graft survival for unrelated living-donor grafts performed between 1990-1999 was 91.6%, which compares favourably with graft survival for all cadaveric grafts over the same period of 86.5%.

Australia↗
PubMed1999

A new model of orthotopic penetrating corneal transplantation in the sheep: graft survival, phenotypes of graft-infiltrating cells and local cytokine production.

BACKGROUND: Orthotopic penetrating keratoplasty in the sheep was developed as an outbred preclinical model to allow correlation of the cellular infiltrate during graft rejection with local production of cytokine mRNA. METHODS: Penetrating corneal autografts and allografts were performed in Merino sheep. Graft outcome was followed at the slit-lamp. Corneal infiltrates were examined by immunoperoxidase staining on postmortem specimens. Cytokine mRNA was detected by polymerase chain reaction. RESULTS: Corneal autografts survived indefinitely. Allografts became vascularized and underwent rejection at a median of 20 days postgraft. Both endothelial and epithelial rejection lines were observed. Immunohistochemical staining of rejecting grafts showed up-regulation of major histocompatibility complex class I molecules on corneal graft epithelium, damaged or absent graft endothelium and a marked, predominantly mononuclear cell infiltrate. CD4-positive T cells were observed in the graft within 2 days of the onset of rejection, followed several days later by CD8-positive T cells. Messenger RNA transcripts for interleukin (IL)-2, tumour necrosis factor (TNF)-alpha and IL-10 (but not for interferon (IFN)-gamma or IL-4) were found in autografted corneas. Proportionately, more allografts than autografts contained transcripts for IL-2 and TNF-alpha, and IFN-gamma was detected in three of four allografts. CONCLUSIONS: Corneal graft rejection in the sheep is macroscopically and histologically similar to human corneal graft rejection. Allografts become infiltrated by both CD4- and CD8-positive T cells and local production of pro-inflammatory cytokines occurs during graft rejection.

Animals↗
PubMed1998

Combined anti-vascular cell adhesion molecule-1 and anti-leukocyte function-associated molecule-1 monoclonal antibody therapy does not prolong allograft survival in an ovine model of renal transplantation.

This study investigates the therapeutic efficacy of an anti-vascular cell adhesion molecule (VCAM)-1 monoclonal antibody (mAb), alone or in combination with an anti-leukocyte function-associated-1 mAb, in prolonging allograft survival in an ovine model of renal transplantation. The kinetics of VCAM-1 induction and expression during renal allograft rejection have also been studied. Sheep receiving anti-ovine VCAM-1 antibody demonstrated graft failure at a mean of 8.4 (+/- SD; 0.7) days after transplantation compared with 9.3 (+/- 0.5) days after transplantation for the group given control antibody and 7.7 (+/- 0.3) days after transplantation in the animals given the combined anti-VCAM-1 and anti-leukocyte function-associated-1 mAb therapy. VCAM-1 expression was detected in the allografts at day 1 after transplantation, with peak expression detected by day 5. Tubular expression of VCAM-1 was minimal, with sparse focal staining at the basolateral surfaces. The degree of mononuclear cell infiltrate in the allografts paralleled the progressive increase in VCAM-1 expression after transplantation, and there was no difference in the level of mononuclear cell infiltrate compared with controls.

Animals↗
PubMed1998

Maintenance therapy with oral ganciclovir after treatment of cytomegalovirus infection.

While oral ganciclovir (OGCV) has been used as primary prophylaxis in patients at high risk for cytomegalovirus (CMV) infection after solid organ transplantation, its value in secondary prophylaxis is unknown. We have examined the use of OGCV as maintenance therapy following confirmed CMV infection on 16 occasions in 15 patients, in kidney (n = 4), kidney-pancreas (n = 3) lung (n = 6) and heart-lung (n = 1) recipients. OGCV was used in two distinct clinical situations. One group (n = 7) received OGCV as consolidation therapy (mean duration of 21 +/- 5 d) following i.v. ganciclovir induction therapy (mean duration of 16 +/- 5 d) for acute CMV infection, and sustained remission was achieved in 6/7 patients for a median follow-up of 300 d. In the second scenario, OGCV suppressed clinical disease in all patients with relapsing CMV infection (n = 9), with minimal or absent toxicity with a median follow-up of 152 d. OGCV reduced morbidity by allowing removal of central lines used for long-term i.v. therapy in patients with poor peripheral access. Hence, this study demonstrates the safe and effective use of OGCV as consolidation therapy after standard induction treatment with i.v. ganciclovir, and as long-term suppressive therapy in transplant recipients with recurrent CMV infection.

Administration, Oral↗
PubMed1997

Characterization of ovine umbilical vein endothelial cells and their expression of cell adhesion molecules: comparative study with human endothelial cells.

This paper reports the isolation and characterization of sheep umbilical vein endothelial cells (ShUVEC) and examines the kinetics of the expression of intercellular cell adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). In culture, the cells demonstrate the classical endothelial cell phenotype, including the expression of von Willebrand Factor (vWF), the metabolism of acetylated-low density lipoprotein (Ac-LDL) and the typical cobblestone monolayer appearance. Northern analysis of the expression of ICAM-1 and VCAM-1 mRNA by ShUVEC stimulated with either LPS or recombinant ovine (ro)-TNF-alpha or IL-1 beta demonstrated peak RNA expression for both molecules at between 2 and 6 h after stimulation. Maximum VCAM-1 protein expression occurred between 6 and 12 h after stimulation with ro-TNF-alpha, followed by a slight decrease to a plateau extending beyond 48 h. The levels and kinetics of expression of additional cell surface proteins on ShUVEC, including P-selectin (CD62P), beta 1 integrin (CD29) and ovine MHC classes I and II, were found to be almost identical to that observed on human endothelial cells (HUVEC) cultured under similar conditions. Based on the above results, we conclude that the ShUVEC represent the ovine equivalent of HUVEC, both phenotypically and functionally.

Animals↗
PubMed1997

Anti-ovine VCAM-1 monoclonal antibodies inhibit adhesion and proliferation between sheep endothelial and mononuclear cells in vitro.

This paper reports the production and characterization of three monoclonal antibodies (mAb) recognizing ovine vascular cell adhesion molecule-1 (VCAM-1). The mAb were raised against sheep umbilical vein endothelial cells (ShUVEC) and flow cytometric analysis demonstrated that one mAb, QE4G9, was cross-reactive with human VCAM-1 expressed on Chinese hamster ovary cell transfectants. Protein modulation studies on ShUVEC and immunoperoxidase staining of inflamed renal tissue further indicated the reactivity of the other two ovine mAb, QE1F3 and QE2G4, with ovine VCAM-1. The flow cytometric profile of the three mAb on stimulated ShUVEC was identical to that observed with the cross-reactive anti-human VCAM- mAb, HAE2-1. Peak expression occurred between 6-12 h after stimulation, followed by a slight decrease to a plateau extending beyond 48 h. In functional assays, all mAb inhibited adhesion of PMA-activated sheep PBMC to stimulated ShUVEC. In addition, QE4G9 inhibited proliferation of sheep PBMC in the mixed lymphocyte-endothelial cell reaction (MLER) by 56%. The results demonstrate that the three anti-ovine VCAM-1 mAb recognize functional epitopes on sheep vascular endothelial cells. These mAb will be valuable tools in the investigation of VCAM-1 expression in various pathophysiological conditions using sheep models, and in the study of VCAM-1-mediated leucocyte-endothelial cell interactions, both in vitro and in vivo.

Animals↗
PubMed1996

A novel activating anti-beta1 integrin monoclonal antibody binds to the cysteine-rich repeats in the beta1 chain.

The functional status of an integrin depends on the conformation of its extracellular domain, which is controlled by the cell expressing that receptor. The transmission of regulatory signals from within the cell is considered to be via propagated conformational changes from the receptor's cytoplasmic tails to the extracellular ligand binding "pocket." The end result is increased accessibility of the ligand binding pocket in the high affinity ("active") form of integrins. We report a novel monoclonal antibody (QE.2E5) that binds within the cysteine-rich repeats in the integrin beta1 chain and induces high affinity binding of fibronectin to the integrin alpha5beta1. The QE.2E5 epitope is located approximately 200 residues both from the predicted binding site for fibronectin and from the epitopes recognized by other activating anti-beta1 monoclonal antibodies. It is also expressed on beta1 integrins from a number of nonhuman species. Although they have the same functional effects, the binding of QE.2E5 and another activating antibody (8A2) to the receptor have contrasting effects on the expression of an activation-dependent epitope in the beta1 chain. We propose that the cysteine-rich repeats contain a regulatory region that is distinct from those previously described in the integrin beta1 chain.

Amino Acid Sequence↗
PubMed1995

Use of DNA polymorphisms and the polymerase chain reaction to examine the survival of a human limbal stem cell allograft.

PURPOSE: The extent to which limbal epithelial stem cell allografts will repopulate the human corneal ocular surface, and the time frame over which such cells survive, are uncertain. We investigated the survival of donor-derived epithelial cells after limbal stem cell allotransplantation in a patient with bilateral limbal stem cell failure by using short tandem-repeat DNA polymorphisms to distinguish donor and recipient cells. METHODS: Epithelial cells were harvested by impression cytology from the grafted eye before and at various times after transplantation. DNA was extracted and amplified by the polymerase chain reaction at an informative locus, D8S264. RESULTS: Cells of donor genotype were present over the grafted areas at the time of surgery but were not detected in the central cornea until 12 weeks postoperatively, indicating that repopulation of the epithelial surface from transplanted limbal stem cells took considerable time. However, by the 20th postoperative week, only recipient-type cells were detected in the grafted eye, despite systemic immunosuppression of the recipient with azathioprine and cyclosporine. CONCLUSIONS: Discrimination between donor and recipient cells on the ocular surface after limbal allotransplantation was possible using genotypic variation at DNA polymorphic sites (microsatellites). Long-term survival of donor cells after limbal transplantation did not occur in this patient. Detection of DNA polymorphisms amplified by the polymerase chain reaction is a simple, rapid, and noninvasive method of following the course of transplanted cells at the ocular surface.

Adult↗