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B C Jaques

Publications and source records attributed to B C Jaques.

14 recordsLinked to original sources
PubMed2006

Ischemia-reperfusion injury in cadaveric nonheart beating, cadaveric heart beating and live donor renal transplants.

PURPOSE: Ischemia-reperfusion injury is gaining importance in transplantation as being responsible for allograft dysfunction. Ischemia occurs during kidney procurement, which is shortest in LDs, and prolonged in cadaveric HBDs and NHBDs. MATERIALS AND METHODS: Renal transplants from 17 LDs, 15 HBDs and 19 NHBDs were assessed during reperfusion for biochemical markers of ischemia-reperfusion injury and assessed clinically. Central venous blood sampling was assayed for free radicals using electron spin resonance and tissue injury biomarkers, namely lactate dehydrogenase, fatty acid binding protein, alanine aminopeptidase, lactate and total antioxidants. RESULTS: The return to stable renal function was more rapid in LD renal transplants, while recovery continued from 3 months after hospital discharge in NHBD renal transplants. Injury markers, such as lactate dehydrogenase, fatty acid binding protein, alanine aminopeptidase and lactate, were raised at the time of reperfusion, especially in NHBD renal transplants. Free radical release measured by electron spin resonance showed 2 phase release, that is early (0 to 10-minute) and late (20 to 40-minute) release. In NHBD, HBD and LD renal transplants the index of free radical release in the early phase was 1.43, 1.36 and 1.20, and in the late phase it was 1.43, 1.38 and 0.97, respectively (each ANOVA p <0.05). CONCLUSIONS: NHBD renal transplants were accompanied by a greater release of free radicals at reperfusion (NHBD > HBD > LD), which was associated with an increase in tissue injury markers at reperfusion. This was reflected in a slower return to stable renal function in NHBD compared to HBD and LD renal transplants.

Adult↗
PubMed2005

Management of hilar cholangiocarcinoma in the North of England: pathology, treatment, and outcome.

AIM: To assess the management and outcome of hilar cholangiocarcinoma (Klatskin tumor) in a single tertiary referral center. METHODS: The notes of all patients with a diagnosis of hilar cholangiocarcinoma referred to our unit for over an 8-year period were identified and retrospectively reviewed. Presentation, management and outcome were assessed. RESULTS: Seventy-five patients were identified. The median age was 64 years (range 34-84 years). Male to female ratio was 1:1. Eighty-nine percent of patients presented with jaundice. Most patients referred were under Bismuth classification 3a, 3b or 4. Seventy patients required biliary drainage, 65 patients required 152 percutaneous drainage procedures, and 25 had other complications. Forty-one patients had 51 endoscopic drainage procedures performed (15 failed). Of these, 36 subsequently required percutaneous drainage. The median number of drainage procedures for all patients was three, 18 patients underwent resection (24%), nine had major complications and three died post-operatively. The 5-year survival rate was 4.2% for all patients, 21% for resected patients and 0% for those who did not undergo resection (P = 0.0021). The median number of admissions after diagnosis in resected patients was two and three in non-resected patients (P<0.05). Twelve patients had external-beam radiotherapy, seven brachytherapy, and eight chemotherapy. There was no significant benefit in terms of survival (P = 0.46) or hospital admissions. CONCLUSION: Resection increases survival but carries the risk of significant morbidity and mortality. Percutaneous biliary drainage is almost always necessary and endoscopic drainage should be avoided if possible.

Adult↗
PubMed2005

Do recipients of kidneys from donors treated with streptokinase develop anti-streptokinase antibodies?

Streptokinase is used for preflush for non-heart-beating donors (NHBDs) in our center. The aim of this study was to evaluate whether the use of thrombolytic streptokinase results in the production of anti-streptokinase antibodies in the recipients after renal transplantation. Recipient sera taken prior to and at 1 and 6 months posttransplant were tested for the presence of antibodies to streptokinase using an enzyme-linked immunosorbent assay assay. No differences were detected between a group of 18 recipients who had kidneys from thrombolytic-treated NHBDs and a further group of 18 who received NHBD kidneys without such treatment.

Antibodies↗
PubMed2004

Reperfusion injury in renal transplantation: comparison of LD, HBD and NHBD renal transplants.

Comparison of reperfusion injury in kidneys transplanted from LD, HBD or NHBD donors is presented in the paper. Central venous blood samples (taken during perioperative period) was assessed for free radicals, total antioxidant activity and various markers of tissue injury. There was demonstrable ischemia reperfusion injury occurring at the time of revascularization, which was particularly notable in kidneys transplanted from NHBD donors.

Adult↗
PubMed2001

Influence of diabetes mellitus on patient and graft survival in recipients of kidney transplantation.

AIMS: To investigate the outcomes in patients who have pre-existing diabetes and those who develop post-transplant diabetes mellitus (PTDM). METHODS: We retrospectively reviewed the charts of 939 patients who received a first functioning renal transplant in the cyclosporine (CyA) era between 1984 and 1999. RESULTS: Sixty-six (7%) patients had renal failure due to insulin-dependent diabetes mellitus (IDDM) and 7 (0.8%) patients due to non-insulin-dependent diabetes mellitus (NIDDM). Ten (1.1%) patients had coexistent diabetes and 48 (5.1%) recipients developed PTDM. The mean graft survival for the patients with PTDM was 9.7 yr versus 11.3 yr for the non-diabetic patients, while mean graft survival was 10.1 yr for patients with IDDM and 2.9 yr with NIDDM and 8.3 yr for those with coexistent diabetes (p=ns). However, there was a statistically significant difference in patient survival between patients who developed PTDM and in those who did not develop this complication. The mean survivals of patients with IDDM, NIDDM, coexistent diabetics and PTDM were 8.4, 3.7, 8.6 and 10.3 yr, respectively. The mean survival of the patients without pre-existing diabetes or PTDM was 12.8 yr (p<0.001). The survival of patients older than 55 yr with PTDM was no different to the control group. However, in those younger than 55 yr, PTDM was associated with a higher risk of death (relative risk of 2.54, p<0.001). Fifty percent of patients with IDDM developed acute rejection episodes, whereas rejection rate was 57.1% in NIDDM group, 50.0% in the PTDM group, 20.0% in the coexistent diabetes group and 44.3% in the control group (p=ns). CONCLUSION: Patient survival, but not graft survival, was adversely affected by both pre-existing diabetes and by PTDM, particularly in those with an age less than 55 yr.

Acute Disease↗
PubMed2001

The impact of late acute rejection after cadaveric kidney transplantation.

BACKGROUND: Acute graft rejection (AR) following renal transplantation results in reduced graft survival. However, there is uncertainty regarding the definition, aetiology and long-term graft and patient outcome of AR occurring late in the post-transplant period. AIM: To determine if rejection episodes can be classified by time from transplantation by their impact on graft survival into early acute rejection (EAR) and late acute rejection (LAR). MATERIALS AND METHODS: 687 consecutive adult renal transplant recipients who received their first cadaveric renal transplant at a single centre. All received cyclosporine (CyA)-based immunosuppression, from 1984 to 1996, with a median follow-up of 6.9 yr. Details were abstracted from clinical records, with emphasis on age, sex, co-morbid conditions, HLA matching, rejection episodes, patient and graft survival. ANALYSIS: Patients were classified by the presence and time to AR from the date of transplantation. Using those patients who had no AR (NAR) as a baseline, we determined the relative risk of graft failure by time to rejection. The characteristics of patients who had no rejection, EAR and LAR were compared. RESULTS: Compared with NAR, the risk of graft failure was higher for those patients who suffered a rejection episode. A much higher risk of graft failure was seen when the first rejection episode occurred after 90 d. Thus, a period of 90 d was taken to separate EAR and LAR (relative risk of 3.06 and 5.27 compared with NAR as baseline, p<0.001). Seventy-eight patients (11.4%) had LAR, 271 (39.4%) had EAR and 338 (49.2%) had NAR. The mean age for each of these groups differed (LAR 39.6 yr, EAR 40.8 yr compared with NAR 44 yr, p<0.003). The 5-yr graft survival for those who had LAR was 45% and 10-yr survival was 28%. HLA mismatches were more frequent in those with EAR vs. NAR (zero mismatches in HLA-A: 36 vs. 24%, HLA-B: 35 vs. 23% and HLA-DR: 63 vs. 41%, p<0.003). There was no difference in mismatching frequency between NAR and LAR. CONCLUSIONS: AR had a deleterious impact on graft survival, particularly if occurring after 90 d. AR episodes should therefore be divided into early and late phases. In view of the very poor graft survival associated with LAR, it is important to gain further insight into the main aetiological factors. Those such as suboptimal CyA blood levels and non-compliance with medication should be further investigated with the aim of developing more effective immunosuppressive regimens in order to reduce the incidence of LAR.

Acute Disease↗
PubMed1998

Thymus-dependent, anti-CD4-induced tolerance to rat cardiac allografts.

BACKGROUND: Treatment with anti-CD4 monoclonal antibodies (mAbs) leads to induction of transplant tolerance in rodent models, but the cellular mechanisms responsible are poorly defined. In this study, we used a rat model of cardiac transplantation to examine the contribution of the thymus gland to anti-CD4 mAb-induced tolerance. METHODS: Pretransplant administration of OX38 mAb partially depletes peripheral CD4 T cells and induces tolerance to fully allogeneic Lewis (RT1l) heterotopic cardiac allografts in DA (RT1a) recipients. Using this experimental model, the contribution of the adult thymus gland and of recent thymic emigrants to tolerance induction was assessed, and the cellular and humoral alloimmune responses accompanying tolerance defined. RESULTS: OX38 mAb selectively depleted mature CD4 T cells but spared CD4 T cells that had recently emerged from the thymus. Pretransplant thymectomy abrogated tolerance induction, but the data suggested a role for recent thymic emigrants rather than for the thymus gland per se. Both nonrejecting cardiac allografts in OX38-treated recipients and rejecting grafts in control animals were infiltrated to a similar extent by mononuclear cells, including activated T cells. Intragraft mRNA transcripts for interleukin (IL)-2, interferon-gamma, IL-4, IL-10, and IL-13 were similar in non-rejecting and rejecting allografts although, with the exception of IL-2, there was a trend towards reduced cytokine transcripts in tolerant grafts. CD4 T cells from long-term tolerant recipients proliferated normally to donor alloantigen in vitro, and produced IL-2, interferon-gamma, and IL-4 in amounts comparable to normal CD4 T cells. Tolerant recipients also developed a strong alloantibody response comprising both IgG1 (Th2-dependent) and IgG2b (Th1-dependent) subclasses. CONCLUSIONS: The results of this study suggest that the thymus, through the production of recent thymic emigrants, plays an important role in facilitating the induction of transplant tolerance after anti-CD4 mAb. Tolerant animals displayed strong cell-mediated and humoral alloimmune responses with no evidence of selective deviation from a Th1 to a Th2-like cytokine pattern.

Animals↗
PubMed1997

Reduction of alloantibody response to class I major histocompatibility complex by targeting synthetic allopeptides for presentation by B cells.

BACKGROUND: PVG.RT1(u) rats develop a strong CD4 T cell-dependent alloantibody response to class I major histocompatibility complex (MHC) A(a) antigen, during which CD4 T helper cells recognize and respond to A(a)-derived peptides presented by recipient class II MHC (indirect allorecognition). On the basis of evidence that CD4 T cells that encounter antigen presented by resting B cells become tolerant, we have targeted synthetic A(a)-derived allopeptides for in vivo presentation to class I MHC-disparate CD4 T cells by resting recipient B cells. METHODS: PVG.RT1(u) rats were treated with two peptides, P1 and P2, corresponding to the alpha-helical regions of A(a) (residues 57-80 and 143-163), which were conjugated via an N-terminal cysteine residue to monovalent Fab fragments of OX60 monoclonal antibody, which labels membrane IgD-positive B cells. RESULTS: RT1(u) rats primed with free (nonconjugated) P1 or P2 emulsified in complete Freund's adjuvant produced strong peptide-specific antibody responses and a heightened anti-A(a) antibody response to an A(a)-disparate PVG.R8 heart graft, confirming that each peptide encompasses one or more major T cell determinant for B cell help. Pretreatment of PVG.RT1(u) rats with a mixture of OX60-Fab-P1/P2 conjugates markedly reduced their ability to mount an A(a) antibody response when challenged with either A(a)-disparate blood transfusion or an A(a)-disparate heart graft, although PVG.R8 heart graft survival was not prolonged. CONCLUSIONS: In this report, we show that synthetic A(a)-derived allopeptides are able, when targeted for in vivo presentation to CD4 T cells by resting B cells, to impair the ability of RT1(u) rats to mount an antibody response to A(a) antigen. All subclasses of IgG anti-A(a) alloantibody were profoundly reduced, suggesting that the responsible mechanism is more likely to be CD4 T helper cell unresponsiveness rather than Th1/Th2 T cell polarization.

Animals↗
PubMed1995

Actinomycosis presenting as carcinoma.

Actinomycosis is rare compared to carcinoma, but the two conditions can present with very similar clinical pictures. Two cases of actinomycosis are reported, one thoracic and one pelvic-abdominal which presented as carcinoma and proceeded to surgery without a histological diagnosis having been established.

Actinomycosis↗
PubMed1995

Blood pressure in genetically hypertensive rats. Influence of the Y chromosome.

We used a cross between the stroke-prone spontaneously hypertensive rat (SHRSP) strain and the Wistar-Kyoto (WKY) normotensive strain to elucidate the genetic basis of hypertension. Previous studies have reported conflicting evidence for the contribution of the Y chromosome to hypertension in these models. To investigate further the role of the Y chromosome in hypertension, we performed two large reciprocal crosses: one with the SHRSP as a male progenitor of the cross, yielding 60 F2 rats, and another with the WKY as a male progenitor, yielding 83 F2 rats. The resulting F2 hybrids were phenotyped with the use of a radiotelemetry system (Data Sciences) for measurement of systolic, diastolic, and mean arterial pressures as well as heart rate and motor activity continuously for 96 hours at baseline and after 1% NaCl was added to the rats' drinking water for 12 days. Male F2 hybrids with the SHRSP grandfather had significantly higher average systolic, diastolic, and mean arterial pressures at baseline compared with male F2 hybrids with the WKY grandfather (188.7 +/- 18.1 versus 168.9 +/- 11.5, 130.3 +/- 14 versus 115.7 +/- 7.3, and 159.1 +/- 15.8 versus 141.5 +/- 9.4 mm Hg, respectively). These differences were also observed after salt loading (197.9 +/- 22.1 versus 176.8 +/- 11.7, 136.5 +/- 17.3 versus 120.7 +/- 7.6, and 166.7 +/- 19.5 versus 148 +/- 9.7 mm Hg, respectively; P < .0001 for each comparison). These results suggest that the SHRSP Y chromosome contains a locus or loci that contribute to hypertension in SHRSP/WKY F2 hybrids.

Animals↗
PubMed1982

The role of cell surface proteins in platelet stimulation by monosodium urate crystals.

To test whether urate crystal-membrane protein interactions mediate platelet stimulation, platelet membrane proteins were radiolabeled by lactoperoxidase, extracted with 1% Triton X-100, and incubated with urate crystals. The crystal-associated and supernate fractions were isolated and analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and by 2-dimensional isoelectric focusing followed by SDS-PAGE. Four of the lactoperoxidase-radiolabeled polypeptides that associated with urate crystals had reduced molecular weights and pIs of Mr = 105,000, pI 4.9; Mr = 123,000, pI = 4.9; Mr = 123,000, pI = 5.3; and Mr = 132,000, pI = 4.8-6.3, respectively. These proteins were characterized with regard to their labeling intensities, apparent isoelectric points, apparent molecular weights (reduced and nonreduced), lectin-binding properties, carbohydrate- and protein-staining characteristic, and presence or absence in Glanzmann's thrombasthenia. They have been identified as derived from glycoproteins Ib, IIb, and III (Phillips-Agin nomenclature) and an unidentified membrane protein. To test whether removal of these proteins would result in a diminution of platelet response to urate, intact platelets were digested with chymotrypsin, resulting in cleavage of more than 80% of these proteins and a 5-fold reduction in secretory responsiveness to urate crystals. Response to a second platelet stimulus, collagen, was unaffected, indicating an intact secretory mechanism. In addition, when platelets were preincubated with F(ab')2 fragments of an antibody directed against these proteins, platelet secretory response to urate was inhibited by 50%, whereas the responses to collagen and thrombin were unaffected. Thus, membrane proteins appear to mediate platelet stimulation by urate crystals.

Antibodies↗