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E Cole

Publications and source records attributed to E Cole.

At least 37 records · Page 2Linked to original sources
PubMed1997

Serum-dependent and cell cycle-dependent expression from a cytomegalovirus-based mammalian expression vector.

Cytomegalovirus-based mammalian expression vectors are widely used to drive the expression of transfected genes in cultured cells. Immunofluorescent staining of the WT1 protein in 3T3 and 293 cell clones, stably transfected with a cyomegalovirus (CMV) expression vector carrying a cDNA coding for the tumour suppressor protein WT1, showed extreme cell to cell variation in the amount of recombinant protein expressed, indicative of cell cycle dependence. This was investigated further by Western blot and FACS analysis which showed that WT1 protein expression was highest in S phase and almost absent in G0/G1. Northern blot analysis of cell clones expressing sense or antisense WT1 cDNAs regulated by the CMV promoter/enhancer showed that RNA expression was also cell cycle-dependent. Western blotting of cells expressing a luciferase reporter gene driven by the CMV promoter/enhancer also showed apparent cell cycle-dependent expression. We further demonstrated that the expression of these gene constructs was serum responsive with a 10-fold increase in expression occurring 2 h after the addition of serum. These results show that the CMV promoter/enhancer system varied in its response to serum and the cell cycle state. Therefore, care must be taken when interpreting any phenotypic alterations (or lack of them) produced in cells transfected with CMV-based expression vectors.

3T3 Cells↗
PubMed1997

Transplantation in the elderly: a review.

PURPOSE: 1. To review current knowledge about patient and graft survival, complication rates, patient selection and management protocols in patients aged 60 years or more with a renal transplant. 2. To review the advantages and disadvantages of cadaveric organ retrieval from older donors. DATA SOURCES: Evidence was obtained from published articles identified using a MEDLINE search from 1976 to 1996; expert opinion and citations from previous review articles. RESULTS: Survival rates have improved with time and now range from 54 to 75% 5-year patient survival and 52-74% 5-year graft survival. The most common reason for graft loss is patient death as both acute and chronic rejection is less commonly seen in older patients. Censored graft survival (if death with a functioning graft is treated as censored data) is higher in elderly patients compared to younger ESRD patients. Based on cohort data from an administrative database a survival advantage is seen in older dialysis patients accepted for transplantation even after matching for comorbidity. Post-transplant morbidity is mainly attributable to infectious complications and an increased prevalence of malignancy. There is insufficient data about the most optimal immunosuppression regime and further research is required in this direction. The evidence currently supports the use of kidneys from older donors because of a relative lack of cadaveric organs from younger donors although a worse patient and graft outcome is recognized in the long term. Insufficient evidence exists to support a firm conclusion regarding age matching or targeting of older organs to special groups.

Age Factors↗
PubMed1997

Germline and somatic transformation of mating Tetrahymena thermophila by particle bombardment.

Mating Tetrahymena thermophila were bombarded with ribosomal DNA-coated particles at various times in development. Both macronuclear and micronuclear transformants were recovered. Optimal developmental stages for transformation occurred during meiosis for the micronucleus and during anlagen formation for the macronucleus. Evidence is given for transient retention of the introduced plasmid. Genetic and molecular tests confirmed that sexually heritable transformation was associated with integration at the homologous site in the recipient micronuclear chromosome.

Animals↗
PubMed1997

First-onset psychotic illness: patients' and relatives' satisfaction with services.

BACKGROUND: Despite the growth in patient satisfaction studies, scant attention has been paid to the satisfaction of patients with a first episode of psychotic illness soon after presentation to services. We were particularly interested in any ethnic differences in satisfaction at this seminal stage in patient care. METHOD: Using multi-item questionnaire, face-to-face interviews were conducted with patients and relatives 12 months after first contact with psychiatric services. Relatives were also questioned on support and advice issues related to after-care. RESULTS: Most patients and relatives were generally satisfied with the treatment, and with the 'humane' qualities of psychiatric staff, but were less satisfied with the 'hotel' aspects of hospital care. Patients, and particularly relatives, were most concerned about levels of information and advice received. Relatives were dissatisfied with after-care. There were no significant differences between Black and other patients, but some differences between their relatives. Patients born abroad were significantly more satisfied than those born in Britain, irrespective of ethnicity. Compulsory detention under the Mental Health Act was also significant in determining low satisfaction for patients and especially for their relatives. CONCLUSIONS: For improved care in the community patients and their relatives need to be seen as partners in care rather than as passive recipients. The issue of information-giving by psychiatric services demands serious attention. Black patients and their relatives were not especially likely to be dissatisfied.

Black or African American↗
PubMed1997

Treatment of Kaposi's sarcoma after solid organ transplantation.

PURPOSE: This retrospective review of all patients who developed Kaposi's sarcoma (KS) after solid organ transplantation at a single institution was undertaken to define the clinical presentation of this malignancy in the setting of iatrogenic immunodeficiency, and to determine the most appropriate treatment for patients in this clinical setting. MATERIALS AND METHODS: The records of 2,099 patients who underwent heart, lung, liver, or kidney transplantation at The Toronto Hospital between January 1, 1981 and June 30, 1995, were reviewed. Twelve patients were identified who developed biopsy-proven KS in the posttransplantation period. Five patients who had disseminated KS who had not responded to either reduction or withdrawal of immunosuppression or to local radiotherapy were treated with combination chemotherapy consisting of doxorubicin 20 to 30 mg/m2, bleomycin 10 mg/m2, and vincristine 2 mg (ABV) administered intravenously every 3 weeks. RESULTS: Eight of 12 patients were male and nine were of Italian origin. KS was limited to a localized area of the skin for only six patients, all after kidney transplantation. Visceral KS was present in three patients. Four of five patients responded to ABV chemotherapy (two complete and two partial remissions). The fifth patient responded to second-line etoposide and cisplatin. The median duration of response was in excess of 13 months (range, 8+ to 45+ months). Toxicity was limited to grade 1 neurotoxicity and grade 1 skin toxicity. CONCLUSION: KS is an uncommon but recognized complication of solid organ transplantation. Combination chemotherapy is a safe and effective treatment for patients with disseminated or visceral KS that fails to respond to changes in immunosuppression.

Adult↗
PubMed1997

Thrombotic microangiopathy in renal transplant recipients treated with cyclosporin A.

Thrombotic microangiopathy is an uncommon but well described complication of renal transplantation. This study is a review of the case records of 18 patients with biopsy proven post transplant thrombotic microangiopathy, without cellular rejection. There was no single characteristic underlying cause of renal failure in native kidneys. Although only two (11%) patients had undergone previous transplantation, 16 (89%) had panel reactive antibodies (PRA). All patients received prophylactic antilymphocyte globulin, a single patient had cyclosporin A (CSA) at the time of transplant and in 16 patients CSA was introduced when graft function was established. On this protocol 16 (89%) patients had early graft function. All patients developed acute renal failure and 16 (89%) required dialysis. Nine (50%) patients developed hematological abnormalities. All patients were treated aggressively with anti-rejection therapy, CSA was temporarily withdrawn, and 2 (11%) patients received plasmapheresis. Seven (39%) patients lost their grafts. Renal function in the remaining patients recovered to serum creatinine levels ranging from 104 mumol/l to 430 mumol/l (1.2 mg% to 4.8 mg%). All patients with surviving grafts had CSA successfully reintroduced. This study indicates that there is an association between patients who develop posttransplant thrombotic microangiopathy after CSA administration and high PRA levels. The condition appears to respond to anti-rejection therapy and stopping CSA in the majority of cases. The safe reintroduction of CSA suggests that endothelial cell damage in the posttransplant period may be multifactorial and not solely due to CSA therapy.

Adolescent↗
PubMed1996

A randomized, prospective multicenter pharmacoepidemiologic study of cyclosporine microemulsion in stable renal graft recipients. Report of the Canadian Neoral Renal Transplantation Study Group.

BACKGROUND: The safety, tolerability, and pharmacokinetics of conventional cyclosporine (ConCsA) and cyclosporine microemulsion (MeCsA) were compared under conditions of normal clinical practice in a prospective, randomized, concentration-controlled, pharmacoepidemiologic study. METHODS: Between September 1994 and March 1995, 1097 stable renal transplant recipients in 14 Canadian centers were randomized 2:1 to treatment with MeCsA or ConCsA. Patients were commenced on each study drug at a dose equal to their previous therapy with ConCsA, and the dose was adjusted to maintain predose whole blood cyclosporine concentrations within the therapeutic range established for each center. Prednisone and azathioprine were continued unless dose adjustment was required for clinical reasons. RESULTS: The mean cyclosporine concentration was comparable in both treatment groups at all time points throughout the 6 months of follow-up. The mean dose of cyclosporine was 3.6 mg/kg/day in both treatment groups at entry to the study, and declined by 0.3% and by 2.8% in patients receiving ConCsA and MeCsA, respectively. The nature and severity of adverse events were similar in both treatment groups, but there was a transient increase in neurological and gastrointestinal complications in the group receiving MeCsA within the first month after conversion (P<0.05). Serum creatinine and creatinine clearance did not change in either treatment group throughout the study. Biopsy-proven acute rejection occurred in three patients (0.8%) receiving ConCsA and in seven patients (0.9%) receiving MeCsA, with non-histologically proven acute rejection in an additional three patients (0.8%) receiving ConCsA and five patients (0.6%) receiving MeCsA (P=NS). Serum creatinine rose transiently in 35 patients (9.8%) receiving ConCsA and 138 patients (18.7%) receiving MeCsA (P<0.05) and resolved either spontaneously or after a reduction in the cyclosporine dose. One graft was lost in the MeCsA group due to irreversible rejection, and seven patients died, three in the group receiving ConCsA and four of those receiving MeCsA (P=NS). Absorption of cyclosporine was more rapid and complete from MeCsA than from ConCsA during the first 4 hr of the dosing interval, resulting in almost 40% greater exposure to the drug (P<0.001). There was close correlation between area under the time-concentration curve (AUC) over the first 4 hr of the 12-hr dosage interval and AUC over the entire 12-hr dosage interval for both formulations, making AUC over the first 4 hr a good predictor of total cyclosporine exposure. Using this parameter, patients with low absorption randomized to receive MeCsA showed a marked increase in drug exposure by months 3 and 6, whereas there was no change in those who continued on ConCsA. A limited sampling strategy utilizing samples at the predose and postdose trough levels provided an excellent correlation with drug exposure, particularly for patients receiving MeCsA (r2=0.94 MeCsA vs. r2=0.89 ConCsA). CONCLUSIONS: MeCsA appears to be a safe and effective therapy in stable renal transplant patients and provides superior and more consistent absorption of cyclosporine when compared with ConCsA. Transient toxicity after conversion to MeCsA occurs in some patients, and may reflect the increased exposure to cyclosporine. Use of a limited sampling approach combining trough and 2-hr postdose concentrations may provide an effective way to monitor this exposure.

Adolescent↗
PubMed1995

Pattern of disease after murine hepatitis virus strain 3 infection correlates with macrophage activation and not viral replication.

Murine hepatitis virus strain (MHV-3) produces a strain-dependent pattern of disease which has been used as a model for fulminant viral hepatitis. This study was undertaken to examine whether there was a correlation between macrophage activation and susceptibility or resistance to MHV-3 infection. Peritoneal macrophages were isolated from resistant A/J and susceptible BALB/cJ mice and, following stimulation with MHV-3 or lipopolysaccharide (LPS), analyzed for transcription of mRNA and production of interleukin-1 (IL-1), tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), mouse fibrinogen-like protein (musfiblp), tissue factor (TF), leukotriene B4, and prostaglandin E2 (PGE2). Macrophages from BALB/cJ mice produced greater amounts of IL-1, TNF-alpha, TGF-beta, leukotriene B4, and musfiblp following MHV-3 infection than macrophages from resistant A/J mice, whereas in response to LPS, equivalent amounts of IL-1, TNF-alpha, TGF-beta, and TF were produced by macrophages from both strains of mice. Levels of mRNA of IL-1, TNF-alpha, and musfiblp were greater and more persistent in BALB/cJ than in A/J macrophages, whereas the levels and kinetics of IL-1, TNF-alpha, and TF mRNA following LPS stimulation were identical in macrophages from both strains of mice. Levels of production of PGE2 by MHV-3-stimulated macrophages from resistant and susceptible mice were equivalent; however, the time course for induction of PGE2, differed, but the total quantity of PGE2 produced was insufficient to inhibit induction of musfiblp, a procoagulant known to correlate with development of fulminant hepatic necrosis in susceptible mice. These results demonstrate marked differences in production of inflammatory mediators to MHV-3 infection in macrophages from resistant A/J and susceptible BALB/cJ mice, which may explain the marked hepatic necrosis and fibrin deposition and account for the lethality of MHV-3 in susceptible mice.

Animals↗
PubMed1995

Pathways to care for patients with a first episode of psychosis. A comparison of ethnic groups.

BACKGROUND: It is reported that patients from ethnic minority groups, in particular Afro-Caribbeans, are more likely to enter less desirable pathways to psychiatric care. We aimed to determine whether ethnicity significantly affected time to presentation, type of first contact, rates of compulsory admission and police and primary care involvement, in patients with their first episode of psychosis. METHOD: As part of a prospective epidemiological study, patients and their carers were interviewed using a semi-structured questionnaire to trace the various persons and agencies seen en route to their first contact with psychiatric services. RESULTS: While compulsory admission was more likely for Black patients, the excess was less striking than in previous studies. Black patients were no more likely than other patients to have police involvement. The most important factors in avoiding an adverse pathway were having a supportive family member or friend and the presence of a general practitioner to assist in gaining access to psychiatric services. CONCLUSIONS: The routes to psychiatric services for first onset patients are different to those for chronic patients. Variables associated with social support were more important than ethnicity in determining pathways to care. Police involvement and compulsory admissions were strongly associated with the absence of GP involvement and the absence of help-seeking by a friend or relative. It may be that ethnicity becomes an important variable after the patient has come into contact with psychiatric services.

Adolescent↗
PubMed1995

An analysis of predictors of long-term cadaveric renal allograft survival.

To determine factors predictive of long-term graft function in patients treated prophylactically with an antilymphocyte antibody, 670 first cadaveric adult renal transplant procedures performed between 1985 and 1991 were reviewed. The actuarial 1- and 5-year patient survival in this group was 95% and 87% respectively, and graft survival was 84% and 70% respectively. The final analysis was based on a study group of 635 patients which excluded 28 patients who lost grafts to early technical failures and 8 patients who were not induced with an antilymphocyte preparation. Multivariate analysis showed that 5-year graft survival was lower in patients with delayed graft function (p = 0.0001), in those who had an acute rejection episode in the first 6 months post-transplant (p = 0.0001), recipients greater than 55 years of age at the time of transplant (p = 0.0001), in patients who were highly sensitized at the time of transplant (p = 0.0331) and, finally, in those who received a graft from an older donor (p = 0.044). The 209 patients with delayed graft function had a 16% lower long-term graft survival than 425 patients with early graft function (62% vs. 78% respectively at 5 years). One or more rejection episodes in the first 6 months post-transplant (329 patients) reduced long-term graft survival by 13% compared to those who did not have a rejection episode (67% vs. 80% respectively at 5 years).(ABSTRACT TRUNCATED AT 250 WORDS)

Actuarial Analysis↗
PubMed1994

Sera from habitual aborters induce monocyte procoagulant activity: a lymphocyte-dependent event.

Placental thrombosis is a prominent feature in patients with unexplained recurrent fetal loss. To determine whether induction of monocyte procoagulant activity might be a relevant mechanism for unexplained recurrent fetal loss, peripheral blood mononuclear cells isolated from normal healthy controls were cocultured with (a) sera from normal healthy controls (n = 16), (b) sera from habitual aborters (n = 41), and (c) lipopolysaccharide as a positive control. Sera from three patients were fractionated on Sephracryl S-300 and the inducing molecule(s) characterized. Sera from normal healthy controls failed to induce procoagulant activity above basal levels of 21 +/- 4.6 mU/10(5) peripheral blood mononuclear cells. Of the sera from 41 habitual aborters examined 26 (63%) induced procoagulant to a mean value of 410 +/- 48 mU/10(5) peripheral blood mononuclear cells (P < 0.01). Sera from 15 patients failed to augment procoagulant activity. The induction of procoagulant activity was maximal after 6 hr of incubation and was lymphocyte dependent. Fractionation of serum from the three patients on Sepharcryl S300 revealed the procoagulant activity (PCA)-inducing factor(s) to have a molecular weight of between 300,000 and 800,000 Da. The serum factor was found to be heat, alkaline, and acid sensitive. Both anti-IgM and anti-IgA immunoabsorbents reduced the PCA-inducing factor. We conclude that IgM and IgA from some patients with unexplained recurrent fetal loss are capable of inducing procoagulant activity and could contribute to the development of placental microthrombi and infarction, prominent features of this syndrome.

Abortion, Habitual↗
PubMed1994

Evaluation of new transport medium for detection of herpes simplex virus by culture and direct enzyme-linked immunosorbent assay.

The transport medium Multi-Microbe Media (M4) was evaluated prospectively by culture and direct enzyme-linked immunosorbent assay (ELISA) for detection of herpes simplex virus from 473 specimens. In addition, 377 specimens in Bartels Viral Transport Medium were evaluated. By using culture as a "gold standard," the ELISA sensitivity was approximately 85%, while the specificities exceeded 96% for both media.

Antigens, Viral↗
PubMed1992

Monoclonal antiprothrombinase (3D4.3) prevents mortality from murine hepatitis virus (MHV-3) infection.

The induction of monocyte/macrophage procoagulant activity (PCA) has been implicated in the pathogenesis of murine hepatitis virus strain 3 (MHV-3) infection and disease. Previously, we have shown that induction of PCA by MHV-3 correlated with resistance/susceptibility to infection in different mouse strains. In this study, all BALB/cJ mice that were infected with 10(3) plaque-forming units of MHV-3 developed severe liver disease and died within 96-120 h. Examination of the livers of these animals showed marked hepatic necrosis, deposition of fibrin, and cellular expression of PCA by direct immunofluorescence staining in areas of necrosis as well as in hepatic sinusoids. Splenic mononuclear cells recovered from these mice expressed high concentrations of PCA with time after infection. Infusion into mice of a high-titered monoclonal antibody that neutralized PCA (3D4.3) attenuated the development of hepatic necrosis and enhanced survival in a dose-dependent manner. All of the animals receiving 100 micrograms, and 44% and 22% of the animals that received 50 and 25 micrograms per day, respectively, survived for 10 d and made a full recovery. Administration of the antibody resulted in a dose-dependent reduction in fibrin deposition, PCA expression as detected by direct immunofluorescence staining and by a functional assay. In animals treated with high concentrations of antibody, titers of antibody to PCA fell from 87 +/- 15 micrograms/ml to 100 +/- 7 ng/ml during the active phase of the disease, consistent with sequestration due to binding of the immunoglobulin to cells expressing PCA. Surviving animals, when rechallenged with MHV-3, had a 40% mortality, consistent with the known rates of metabolism of immunoglobulin. This further suggested that protection was by a passive mechanism. The results reported here demonstrate that a neutralizing antibody to PCA protects animals from fulminant hepatitis and death associated with MHV-3 infection, and supports the notion that PCA is a potent inflammatory mediator that plays a pivotal role in the pathogenesis of liver injury resulting from MHV-3 infection.

Animals↗