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J Cairns

Publications and source records attributed to J Cairns.

At least 19 recordsLinked to original sources
PubMed1992

Discounting and health benefits: another perspective.

This paper reviews the argument advanced by Parsonage and Neuburger that the non-monetary benefits of health programmes should be discounted at a lower rate than that used for financial flows. The conceptual issues raised in that paper are discussed and others, such as the tradability of non-monetary benefits and the link between individual and social discount rates, are introduced. The collection and assessment of more evidence is needed before Parsonage and Neuburger's proposition can be supported.

Forecasting↗
PubMed1992

Immunohistochemical demonstration of glutathione S-transferases in primary human breast carcinomas.

The expression of cytosolic glutathione S-transferase (GST) isoenzymes has been assessed in a series of 74 primary human breast carcinomas using an immunohistochemical method. GST pi was detected in sections from all 74 tumours; it was expressed by non-epithelial (stromal and inflammatory) cells in 62 tumours (84 per cent), but by tumour epithelium in only 35 (47 per cent). Non-neoplastic mammary epithelium was uniformly positive for GST pi. Expression of GST alpha and mu was observed in 19 and 42 per cent of the tumours, respectively, and was largely confined to the neoplastic component. Lack of staining of tumour epithelium for GST pi was significantly associated with poorer tumour differentiation (higher grade). There was no association between expression of any of the three isoenzymes and either menopausal status or expression of c-erbB-2 oncogene protein product. Immunohistochemistry is a useful method for the investigation of expression and cellular localization of GSTs within tumours; such data are needed to improve our understanding of the role of these enzymes in neoplasia and in resistance to cytotoxic drug therapy.

Adult↗
PubMed1992

Relationship between c-erbB-2 protein product expression and response to endocrine therapy in advanced breast cancer.

Of 221 patients with breast cancer of known epidermal growth factor receptor (EGFR) and oestrogen receptor (ER) status, 99 had developed recurrences during the period of follow-up (range 3-60 months, median 24 months). Of these, 72 received endocrine therapy as first-line treatment for relapse. Immunohistochemical assessment of c-erbB-2 protein product expression was made using paraffin-embedded tumour tissue from 65 of these 72 patients. Including patients whose disease remained stable for more than 6 months with those showing an objective response (CR or PR for more than 3 months), only one (7%) of 14 c-erbB-2 positive tumours responded to endocrine manipulation compared with 19 (37%) of 51 c-erbB-2 negative tumours (P less than 0.05). Coexpression of c-erbB-2 reduced the response rate of ER positive patients from 48% to 20% and of ER negative cases from 27% to 0% (P less than 0.01). EGFR and c-erbB-2 protein appeared to have additive effects in reducing the likelihood of response, and none of eight patients with EGFR positive, c-erbB-2 positive tumours derived benefit from endocrine therapy. The results of this study suggest that c-erbB-2 protein overexpression, a marker of poor prognosis in breast cancer, is associated with a lack of response to endocrine therapy on relapse, and particularly in combination with EGFR may be useful in directing therapeutic choices.

Adult↗
PubMed1992

Response to mitoxantrone in advanced breast cancer: correlation with expression of c-erbB-2 protein and glutathione S-transferases.

Sixty-eight patients with advanced breast cancer were treated with mitoxantrone and clinical responses assessed. Expression of c-erbB-2 protein and cytosolic glutathione S-transferase (GST) isoenzymes pi, alpha and mu by the primary tumours of these patients was determined immunohistochemically, and correlated with treatment response. Tumours overexpressing c-erbB-2 (n = 16, 23%) showed a lower response rate (50% vs 58%) and shorter duration of response to treatment, compared with c-erbB-2 negative tumours. These associations were not statistically significant but survival following start of treatment was significantly shorter in the c-erbB-2 positive group. For each GST isoenzyme, the response rate and duration of response of the group showing enzyme expression did not differ significantly from those with negatively staining tumours. These data do not support a role for expression of GSTs alone in resistance to mitoxantrone monotherapy in advanced breast cancer. The poorer post treatment survival of patients with c-erbB-2 positive tumours suggests they could be selected for more intensive treatment regimens.

Adult↗
PubMed1992

Mechanisms of directed mutation.

Spontaneous mutants arise among nondividing populations of Escherichia coli in apparent response to selective conditions. In this report we investigate several hypotheses to account for the role of selection in the production of these "directed" or "adaptive" mutations. We found that the Lac+ phenotypes of some mutants that arise late after lactose selection are due to suppressor mutations that are unlinked to the mutant lacZ allele; thus the production of these Lac+ mutants does not require an information flow from successful proteins back to the DNA that encodes them. Transcriptional induction of the lac operon, even in the presence of another, utilizable carbon source, did not stimulate the occurrence of Lac+ mutants in the absence of lactose, indicating that the role of the selective agent is not merely to induce transcription. The absence of two DNA repair pathways-methyl-directed mismatch repair and alkylation repair-also did not result in an accumulation of Lac+ mutants in the absence of lactose, suggesting that these repair pathways are not normally responsible for correcting transient variants that might arise in the absence of selection. However, in one case the Lac+ mutation is likely to be due to a miscoding lesion occurring on the nontranscribed DNA strand, indicating that, at least in this instance, DNA replication is required before directed mutations can arise.

DNA Repair↗
PubMed1991

How should results from completed studies influence ongoing clinical trials? The CAFA Study experience.

Seven randomized studies during the past 5 years have evaluated or are evaluating the efficacy of warfarin or aspirin or both in decreasing the risk of embolic events in patients with nonrheumatic atrial fibrillation. By March 1990, two of the studies had been published, both of which showed a statistically significant decrease in embolic events in patients treated with warfarin and a low rate of major bleeding events. The investigators associated with the other ongoing studies were forced to consider how these results should affect the decision to recruit and continue follow-up of patients in their own studies. The Steering Committee of the Canadian Atrial Fibrillation Anticoagulation (CAFA) study thought the newly published results from other studies were valid, clinically important, and generalizable. The committee considered the following options for the CAFA study: continue patient recruitment as planned, provide the data available in CAFA to its External Safety and Efficacy Monitoring Committee for analysis to determine whether the CAFA data already showed a benefit of warfarin, stop patient recruitment but continue to follow patients in the group to which they were assigned, stop the trial immediately and perform a final analysis, and attempt to perform a meta-analysis of all data available from all trials. The Steering Committee of CAFA decided that the evidence of benefit with warfarin, from the two published studies, was sufficiently compelling as to stop recruitment into CAFA without any preliminary examination of the CAFA data.

Aspirin↗
PubMed1991

Report of the Canadian Cardiovascular Society's consensus conference on the Management of the Postmyocardial Infarction Patient.

In October 1989, the Canadian Cardiovascular Society announced a program to achieve consensus on important issues in the care of patients with cardiovascular disease. This report on the management of the postmyocardial infarction patient represents the first in a series of these consensus conferences. The process for establishing consensus recommendations involved several steps. A primary panel of 11 experts from various fields was selected to review the available clinical evidence and to make a list of recommendations about management decisions in the postmyocardial infarction period. The initial report was distributed to a secondary panel of 16 reviewers* representing allied health care constituencies from across Canada. On the basis of the critical reviews and feedback from these reviewers, a revised report was distributed to all members (over 800) of the Canadian Cardiovascular Society for further review and feedback. This iterative approach resulted in a penultimate report that was presented at a plenary session of the annual scientific meeting of the Canadian Cardiovascular Society on Oct. 18, 1990, in Halifax, NS. On the basis of discussion and feedback from this symposium, the consensus review was completed.

Canada↗
PubMed1991

Issues in the early termination of the aspirin component of the Physicians' Health Study. Data Monitoring Board of the Physicians' Health Study.

The Physicians' Health Study is a randomized, double-blind, placebo-controlled prevention trial of 22,071 US physicians, using a factorial design to evaluate the role of aspirin in the prevention of cardiovascular mortality and beta carotene in the reduction of cancer incidence. After approximately 5 years of follow-up, the aspirin component was terminated, 3 years ahead of schedule. Several factors were considered in the decision to terminate, including a cardiovascular mortality rate markedly lower than expected in both aspirin and placebo subjects, precluding the evaluation of the primary aspirin hypothesis, and a highly significant (P < .00001) and impressive (44%) reduction in the risk of first myocardial infarction in the aspirin group. Issues in the decision to terminate are described in this report.

Adult↗
PubMed1991

Enhanced expression of glutathione S-transferases in colorectal carcinoma compared to non-neoplastic mucosa.

Ten paired samples of primary human colorectal carcinoma and adjacent non-neoplastic mucosa were analysed for total glutathione S-transferase (GST) activities as determined by 1-chloro-2,4-dinitrobenzene assays. These tissues were also investigated for the expression of acidic (pi), basic (alpha) and neutral (mu) GSTs using Western blotting procedures and immunohistochemical staining. For each of the paired samples examined the total GST activity was higher in tumour than in adjacent non-neoplastic mucosa. Western blotting, using an antibody against acidic GST also showed strong immunoreactivity in all the samples with more intense reactions in tumour compared to mucosa in nine out of the ten paired samples. Low levels of basic GST were also expressed in all samples of tumour and mucosa. Neutral GST was not detectable in two samples of tumour and corresponding mucosa, but low levels of expression were demonstrated in the remaining eight. Immunohistochemical staining for acidic GST showed a dark brown reaction in all tumour cells; in non-neoplastic mucosa there was positive immunoreactivity for epithelial cells situated deep within the crypts and a negative reaction for surface epithelial cells. Immunohistochemical staining for basic GST was negative except for one sample of tumour and two of mucosa. Neutral GST was expressed only in two samples of tumour and two samples of mucosa. We therefore conclude that there is enhanced expression of GSTs, acidic GST being the predominant form, in tumour compared to normal mucosa, in keeping with a role for GSTs in colonic carcinogenesis and acquired or innate drug resistance.

Blotting, Western↗
PubMed1991

Adaptive reversion of a frameshift mutation in Escherichia coli.

Mutation rates are generally thought not to be influenced by selective forces. This doctrine rests on the results of certain classical studies of the mutations that make bacteria resistant to phages and antibiotics. We have studied a strain of Escherichia coli which constitutively expresses a lacI-lacZ fusion containing a frameshift mutation that renders it Lac-. Reversion to Lac+ is a rare event during exponential growth but occurs in stationary cultures when lactose is the only source of energy. No revertants accumulate in the absence of lactose, or in the presence of lactose if there is another, unfulfilled requirement for growth. The mechanism for such mutation in stationary phase is not known, but it requires some function of RecA which is apparently not required for mutation during exponential growth.

Adaptation, Biological↗
PubMed1991

Beta-2-adrenoceptor agonists up-regulate the in vitro Fc epsilon receptor II/CD23 expression on, and release from, the promonocytic cell line U937 and human blood monocytes.

The possible regulatory role of beta 2-adrenoceptor agonists in the modulation of CD23 on the human promonocytic cell line U937 and on human monocytes was investigated. Incubation for 48 h in the presence of interleukin-4 (IL-4; 30 U/ml) induced optimal expression and release of CD23 on both U937 cells and human monocytes. When a beta 2-adrenoceptor agonist, either salbutamol or fenoterol, was added to U937 cells or monocytes both the IL-4-induced CD23 expression and release were markedly up-regulated. This effect was dose-dependent, starting at 10 nM and reaching a maximum at 1 microM final concentration of either salbutamol or fenoterol. The potentiating effect of salbutamol and fenoterol on CD23 expression and release was not observed when a beta-adrenoceptor antagonist, either D,L-propranolol (1 microM) or butoxamine (1 microM), was added to the incubation medium. The alpha-adrenoceptor agonist norepinephrine (1 microM) was ineffective in enhancing the IL-4-induced expression and release of CD23 from U937 cells or human monocytes, demonstrating the specificity of the beta 2-adrenoceptor-mediated effect. In the absence of IL-4, a moderate but significant increase in the CD23 expression on U937 cells and human monocytes by these drugs was observed, as compared to the basal values. These results indicate that, besides their bronchodilator effect, beta 2-adrenoceptor agonists may regulate IgE-dependent processes.

Adrenergic beta-Agonists↗
PubMed1991

Sleep disturbance in depression reconsidered.

The well documented observation of a characteristic sleep disturbance in depression has been accorded a good deal of significance. Several current hypotheses regarding the etiology of depression, are based on these findings. However, a review of the descriptive studies shows that care has not generally been taken either to restrict or objectively measure daytime sleep. Evidence is presented suggesting that daytime sleep may occur in depressed patients more frequently than commonly thought and that, in normal subjects, daytime napping can result in nocturnal sleep changes similar to those seen in depressed patients. A model is proposed in which the nocturnal sleep disturbance in depression reflects the occurrence, during the daytime, of frank slow wave sleep or periods of large amplitude, slow wave EEG activity as a consequence of a dampening of the circadian rhythm of sleep propensity.

Arousal↗
PubMed1991

Expression of human recombinant CD23 in insect cells.

Human CD23 (low affinity receptor for IgE) has been expressed in insect cells (Sf9) using the baculovirus expression system and the baculovirus transfer vector pAc373. Insect cells infected with a recombinant baculovirus coding for CD23 synthesized a polypeptide not found in wild-type infected insect cells that had antigenic properties similar to natural CD23 produced in RPMI 8866 cells. Surface expression of recombinant CD23 was demonstrated by its ability to bind IgE. Recombinant CD23 expressed in insect cells had a slightly lower molecular weight (43 kDa) than that of natural CD23 (45 kDa) from RPMI 8866 cells as detected by SDS-PAGE followed by Western-blotting. Affinity-purified recombinant CD23 from infected insect cells showed B-cell growth promoting activitiy. These observations demonstrate for the first time that biologically active recombinant CD23 can be produced by the baculovirus expression system, thus providing a useful source of recombinant material to elucidate the biological functions of CD23.

Animals↗
PubMed1990

Sleep deprivation in depression: pattern of relapse and characteristics of preceding sleep.

The pattern of relapse following therapeutic response to 40-hr sleep deprivation (SD) was examined in nine depressed patients. On the night ending SD patients were awakened from polygraphically recorded sleep on one or more occasions, in order to assess the clinical state. All subjects were found to demonstrate a precipitous and full relapse over this night, the timing of the relapse varying considerably between individuals. No association was found between deterioration in the clinical state and characteristics of preceding sleep. These results are consistent with the notion that, in predisposed individuals, some process associated with sleep has a depressogenic effect. However, they necessitate revision of theories of SD and depression that emphasize the infrastructure of sleep.

Adult↗
PubMed1990

Leukotriene B4 potentiates the expression and release of Fc epsilon RII/CD23, and proliferation and differentiation of human B lymphocytes induced by IL-4.

This study documents the influence of leukotriene (LT) B4 on human B lymphocyte responses. Incubation of freshly isolated B lymphocytes with LTB4, but not LTC4, induced a slight but significant, time- and dose-dependent increase in the surface expression of Fc epsilon RII/CD23 and class II MHC Ag and in the release of soluble CD23. These changes were maximal at 10 nM LTB4 after an incubation period of 48 h. When B lymphocytes were preactivated in vitro with Staphylococcus aureus Cowan strain I (SAC), neither LTB4 nor LTC4 was able to promote proliferation and/or IgG and IgM secretion. In contrast, when resting B lymphocytes were stimulated with a suboptimal concentration (3 U/ml) of IL-4, LTB4, but not LTC4, potentiated both the Fc epsilon RII/CD23 and the class II MHC antigen expression, and the release of soluble CD23 in a dose-dependent manner, without affecting the kinetics of these responses. Furthermore, LTB4, but not LTC4, amplified both the proliferative response and the IgG and IgM secretion induced by addition of a suboptimal dose of IL-4 (3 U/ml) to SAC-preactivated B lymphocytes. Again, LTB4 did not modify the kinetics of the proliferative response promoted by IL-4. Although LTB4 potentiated IL-4-induced IgG and IgM secretion from SAC-activated B lymphocytes, no production of IgE was observed. These data indicate that LTB4 could play a regulatory role in the modulation of IL-4-induced signaling in human B lymphocytes.

Antigens, CD↗
PubMed1990

Prognostic significance of the estrogen-regulated protein, cathepsin D, in breast cancer. An immunohistochemical study.

Expression of the estrogen-regulated lysosomal protease, cathepsin D, was studied in a series of 94 breast cancers using an immunohistochemical technique. Granular staining of tumor cell cytoplasm was detected in 62 cases. Positive staining was associated with a significant increase in overall time to relapse and when survival was analyzed in terms of intensity of cathepsin D staining there was a significant trend for both increased time to relapse and increased length of survival. The presence of estrogen receptor was associated with positive cathepsin D immunostaining, and in the subgroup of estrogen receptor-positive tumors cathepsin D staining was associated with significantly prolonged survival; this was not the case for estrogen receptor-negative tumors. Positive cathepsin D immunostaining was associated with significant prognostic advantage in patients with confirmed lymph node metastasis but not in node-negative patients. It is suggested that cathepsin D expression reflects the functional integrity of the estrogen response pathway. Cathepsin D may prove a clinically useful adjunct to assessment of estrogen receptor status.

Adult↗