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Biomedical subjects

J Cairns

Publications and source records attributed to J Cairns.

At least 91 records · Page 5Linked to original sources

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

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↗

Antibody responses of adults, adolescents, and children to a plasma-derived hepatitis B vaccine in a rural African setting.

A field trial of a plasma-derived hepatitis B vaccine in five rural villages in Zambia was analyzed to determine if adults in a rural African setting respond to this vaccine as well as adults in Western countries and to determine the immunogenicity of fewer than the recommended three doses; 255 residents, including 171 who were susceptible to hepatitis B, were vaccinated. Among those who received three vaccine doses, protective levels of antibody to hepatitis B surface antigen (anti-HBs) developed in 67% of adults (ages 21 to 70 years), 87% of adolescents (ages 12 to 19 years), and 100% of children (ages 0 to 11 years). The 67% of vaccinated adults who developed anti-HBs at the protective level was lower than the 96% reported among adults receiving the same vaccine at the same dose and dosage schedule in studies in Western countries. No difference was seen in the response of those receiving two doses compared with those receiving three doses among adults and adolescents, suggesting that a two-dose regimen may be acceptable in these age groups in developing countries to reduce costs and improve compliance. Use of hepatitis B vaccine in a region where prevaccination hepatitis B serologic screening was not available did not appear to increase the number of severity of adverse reactions.

Adolescent↗

Effects of ammonia on periphytic communities.

Laboratory tests were conducted to evaluate the chronic effects of ammonia on periphytic communities. Species richness of the protozoan component of these communities was affected at un-ionized ammonia concentrations of </= 0.01 mg NH3 litre(-1). A biologically important concentration was defined as the concentration of ammonia affecting 20% of species and was estimated from a concentration-response regression as 0.011 mg litre(-1). A comparable value based on literature reports of chronic toxicity to fish and invertebrates was 0.0126 mg litre(-1). Other non-taxonomic responses were equally sensitive to ammonia. Biomass (ash-free dry weight) and algal biomass (in vivo fluorescence) were significantly reduced even at the lowest tested ammonia treatment, 0.01 mg litre(-1), but the abundance of bacteria was reduced only in the highest treatment group, 0.43 mg litre(-1). Net community metabolism was reduced in all ammonia treatments. Periphyton communities were affected at levels below the USEPA chronic criterion of 0.027 mg litre(-1) (temperature = 8.8 degrees C and pH = 8.1). Successional maturity or age of the periphytic community affected the amount of biomass and algal biomass, but did not modify sensitivity to ammonia.

Journal Article↗

Enumerating low densities of genetically engineered Erwinia carotovora in soil.

An inexpensive, quantitative, and sensitive technique was developed for detection of genetically engineered Erwinia carotovora in soil samples. Enrichment media, antibiotic resistance, and most probable number (MPN) analysis were used to enumerate as few as 1 to 10 target cells/10 g soil. The MPN technique recovered significantly higher cell densities than plating; however, densities estimated by the two techniques were strongly correlated. After inoculation of soil microcosms with genetically engineered E. carotovora, a decline rate of 1.2 log units/g soil/10 days and then subsequent disappearance was observed using the MPN technique.

Colony Count, Microbial↗

Genetically Engineered Erwinia carotovora: Survival, Intraspecific Competition, and Effects upon Selected Bacterial Genera.

Environmental use of genetically engineered microorganisms has raised concerns about potential ecological impact. This research evaluated the survival, competitiveness, and effects upon selected bacterial genera of wild-type and genetically engineered Erwinia carotovora subsp. carotovora to ascertain if differences between the wild-type and genetically engineered strains exist in soil microcosms. The engineered strain contained a chromosomally inserted gene for kanamycin resistance. No significant differences in survival in nonsterile soil over 2 months or in the competitiveness of either strain were observed when the strains were added concurrently to microcosms. For reasons that remain unclear, the engineered strain did survive longer in sterilized soil. The effects of both strains on total bacteria, Pseudomonas and Staphylococcus strains, and actinomycetes were observed. While some apparent differences were observed, they were not statistically significant. A better understanding of the microbial ecology of engineered bacteria, especially pathogens genetically altered for use as biological control agents, is essential before commercial applications can be accomplished.

Journal Article↗

The cost-effectiveness of routine post myocardial infarction exercise stress testing.

The cost-effectiveness of the strategy of a routine pre-discharge exercise test (followed by coronary angiography and coronary artery bypass surgery if indicated) in patients with an uncomplicated myocardial infarction was compared with a policy of no routine exercise testing. Using data from the literature, a decision tree was developed to estimate the number of lives saved by the routine exercise test strategy (12 lives saved per 1000 tests), as well as the number of angiograms and coronary artery bypass procedures that would be performed. It was assumed that surgery decreases one year mortality by 25%. The resources consumed by bypass surgery were obtained from a chart review and the costs were estimated using a method of fully allocated costing. Both direct and indirect costs were included. The average cost of coronary artery bypass surgery was $14,958 (1985 Canadian dollars). The cost of routine exercise testing was $255,726 per life saved. With sensitivity analyses this varied from $139,487 (coronary bypass surgery 50% effective) to $1,022,904 (bypass surgery 7.5% effective). A routine post myocardial infarction stress test is an example of how a relatively inexpensive technology, by leading to other expensive clinical actions, can consume a significant amount of resources.

Angiography↗