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Biomedical subjects

J Cairns

Publications and source records attributed to J Cairns.

At least 109 records · Page 6Linked to original sources

Expression of c-erbB-2 oncoprotein: a prognostic indicator in human breast cancer.

Sections of formalin-fixed, paraffin-embedded tissue from 185 primary breast carcinomas were stained immunohistochemically using a polyclonal antibody against the c-erbB-2 oncoprotein. Positive staining, which is known to correlate with gene amplification, was associated with earlier relapse, shorter postrelapse survival, and shorter overall survival. Lymph node, epidermal growth factor receptor, and estrogen receptor status, tumor size, and histological grade also had prognostic significance but, applying multivariate analysis, only lymph node status was a more important predictor of relapse-free and overall survival than staining for the oncoprotein. Positive staining was correlated with negative estrogen receptor status and high histological grade, but there was no association with either lymph node or epidermal growth factor receptor status or tumor size. Expression of the c-erbB-2 oncoprotein appears to be an important independent indicator of prognosis in human breast cancer.

Analysis of Variance↗

Genetically Engineered Erwinia carotovora in Aquatic Microcosms: Survival and Effects on Functional Groups of Indigenous Bacteria.

The survival of genetically engineered Erwinia carotovora L-864, with a kanamycin resistance gene inserted in its chromosome, was monitored in the water and sediment of aquatic microcosms. The density of genetically engineered and wild-type E. carotovora strains declined at the same rate, falling in 32 days below the level of detection by viable counts. We examined the impact of the addition of genetically engineered and wild-type strains on indigenous bacteria belonging to specific functional groups important in nutrient cycling. For up to 16 days, the densities of total and proteolytic bacteria were significantly higher (P < 0.05) in microcosms inoculated with genetically engineered or wild-type E. carotovora, but by 32 days after inoculation, they had decreased to densities similar to those in control microcosms. Inoculation of genetically engineered or wild-type E. carotovora had no apparent effect on the density of amylolytic and pectolytic bacteria in water and sediment. Genetically engineered and wild-type E. carotovora did not have significantly different effects on the densities of specific functional groups of indigenous bacteria (P > 0.05).

Journal Article↗

The evolution of cancer research.

The modern War against Cancer began in the United States in 1970 with the publication of the Yarborough Report, which set forth recommendations and delineated the "means and measures necessary to facilitate success in the treatment, cure and elimination of cancer--at the earliest possible date." If the architects of the Report had known more about the history of the conquest of diseases, we might by now have made a greater impact on the death rate from cancer. As many people have pointed out, the exercise was not that of mobilizing a vast amount of money and resources in order to apply an existing technology to a very limited goal--some special bombs for one or two airplanes and the support for a few astronauts. Quite the opposite, the problem required the development of a level of understanding and a technological base which would allow solutions to the cancer problem that are so inexpensive that they can be offered to 200 million people.

Communicable Diseases↗

The origin of mutants.

Nucleic acids are replicated with conspicuous fidelity. Infrequently, however, they undergo changes in sequence, and this process of change (mutation) generates the variability that allows evolution. As the result of studies of bacterial variation, it is now widely believed that mutations arise continuously and without any consideration for their utility. In this paper, we briefly review the source of this idea and then describe some experiments suggesting that cells may have mechanisms for choosing which mutations will occur.

Arabinose↗

Soluble CD23 is released by B lymphocytes cycling in response to interleukin 4 and anti-Bp50 (CDw40).

An enzyme-linked immunoassay was developed to quantitate the production of soluble CD23 from cycling B lymphocytes. This molecule has identity both with B cell-derived B cell growth factor and with an IgE-binding factor. B lymphocytes, which had been stimulated for 3 days with phorbol dibutyrate and calcium ionophore, washed and recultured, failed to produce detectable levels of CD23 over the following 3 days. Soluble CD23 was found, however, in the supernatant of cultures where recombinant interleukin 4 had been included. The level of CD23 rose dramatically when anti-Bp50 had also been added. By contrast, anti-Bp50, alone or together with low molecular weight T cell-derived B cell growth factor, failed to promote the release of CD23 in detectable amounts. There was a strong correlation between the appearance of soluble CD23 in culture supernatants and the expression of CD23 on the surface of restimulated cells. The level of CD23 release appeared to relate more to the continued cycling of cells than to their differentiation to immunoglobulin secretion. These findings are discussed with particular emphasis on the role of CD23 as an important multi-functional lymphokine in B lymphocyte physiology.

B-Lymphocytes↗

Putting the eco in ecotoxicology.

Testing of pesticides and often other persistent chemicals increasingly involves aquatic mesocosms. Since our intention is to protect natural systems, predictions of their response based on surrogate systems are desirable. Toxicity tests at a variety of levels of biological organization are now available, ranging from single-species laboratory tests to those carried out in field enclosures of portions of natural systems. Validation is essential to determine accuracy of the predictions that will almost certainly not be identical for the wide variety of testing systems now available. Some important scientific considerations in the development of protocols are discussed.

Animals↗

Changes in epilithic communities due to individual and combined treatments of zinc and snail grazing in stream mesocosms.

Effects of 0.5 mg/liter zinc (Zn) and snail grazing (400 snails/m2) on density of dominant algal and protozoan taxa, epilithic glucose respiration, and ash-free dry weight (AFDW) were examined using established (12-day colonization) periphyton communities in flow-through stream mesocosms with four treatments (Zn, snails, Zn and snails, control) for 30 days. Grazing and Zn similarly reduced the abundance of 5 of 10 dominant algal taxa and AFDW during the first 10 days of treatment. Abundance of these taxa and AFDW in grazed (ambient Zn) treatments approached control levels after 10 days as the effect due to snails decreased. Decreasing temperatures may have reduced snail activity. Snails, Zn, and the combination of these treatments contributed to higher rates of glucose respiration per unit AFDW. Protozoan species abundance was reduced to less than half by Zn but was unaffected by snails. Although Zn and snails individually altered structural and functional aspects of this microbial community, the effects when both treatments were combined could not always be inferred from the individual effects. Testing individual and combined variables that affect periphyton with a corresponding assessment of population dynamics, biomass, and community functional attributes will enhance understanding of the overall effects of pollutants on periphyton communities.

Animals↗

The marmoset B-lymphoblastoid cell line (B95-8) produces and responds to B-cell growth and differentiation factors: role of shed CD23 (sCD23).

The EBV-producing marmoset B-cell line (B95-8), commonly used as a source of EBV for stimulation and transformation of human B cells, was shown to proliferate in response to supernatants containing human B-cell growth factors (BCGF) derived from PHA-activated T cells or the KG-la cell line, and to a commercial low molecular weight BCGF (BCGFlow), but not to recombinant human IL-4 (rhIL-4). In this respect, B95-8 responded in much the same way as human EBV-transformed lymphoblastoid cell lines (LCL). In contrast, B95-8 did not secrete immunoglobulin in response to B-cell differentiation factor (BCDF) containing supernatants from the KG-la cell line, nor to BCGFlow, or IL-6 obtained from the T24 bladder carcinoma cell line, whereas significant responses were obtained with human EBV-transformed LCL. Both B95-8 and control EBV-transformed human LCL secreted BCGF and BCDF detected with the indicator B-cell lines CESS, L4, and HFB1, but only the human LCL secreted BCGF detectable in co-stimulation assays with TPA-activated tonsillar B cells. Unlike EBV-transformed LCL, B95-8 did not express detectable surface CD23, and did not release into the culture medium soluble CD23 (sCD23) recognized by an EIA for the human molecule. Although not releasing detectable sCD23, B95-8 cells did proliferate in response to purified human sCD23, and were found to be 1000 times more sensitive in this assay than EBV-transformed LCL. This may provide a basis for a sensitive bioassay for sCD23. Unlike EBV-transformed LCL, it seems that in vitro proliferation of B95-8 may involve an autocrine loop which does not depend on CD23.

Animals↗

Biochemistry of protein-isocyanate interactions: a comparison of the effects of aryl vs. alkyl isocyanates.

In addition to their use in the polyurethane and pesticide industries, isocyanates have proven to be useful probes for the exploration of protein structure. This paper focuses on three aspects of isocyanates: their broad reactivity, their reversible interaction with cholinesterases, and the relative hydrolysis rates of alkyl and aryl isocyanates. The broad reactivity of isocyanates as well as the demonstrated affinity labeling of serine and sulfhydryl esterases are discussed. Extension of the affinity labeling studies to include the analysis of the inhibition of cholinesterases by methyl isocyanate shows that methyl isocyanate is not an effective inhibitor of any of the cholinesterases. The inhibition of cholinesterases by alkyl isocyanates shows a pattern of decreased specificity with decreased alkyl chain length. The inhibition of cholinesterases by isocyanates is shown to be reversible, with a maximum rate of reversal seen at physiological pH. This reversal is characteristic of the reaction of an isocyanate with a sulfhydryl group. Finally, the affinity labeling of proteins must compete successfully with the hydrolysis of isocyanates in aqueous solution. The hydrolysis of alkyl isocyanates is shown to be significantly slower than that of the aryl isocyanates.

Affinity Labels↗

Role of antithrombotic therapy in unstable angina, myocardial infarction and sudden death.

The role of platelets and the clotting system in the initiation and progression of atherosclerosis has received significant attention. Most importantly, platelets and thrombosis play a pivotal role in the pathogenesis of the acute coronary syndromes of unstable angina, myocardial infarction and sudden death. In each stage of the development of coronary artery disease, from the early symptomatic stage through the growing lesion and finally to the complicated plaque that results in the precipitation of the acute coronary syndromes, platelets and the clotting system serve as a common link among them. Antithrombotic therapy aimed at halting the progression of these syndromes, preventing their occurrence or even reversing them (such as in the early stages of acute myocardial infarction), has provided exciting new modalities to treat these disorders. The use of aspirin in unstable angina in two well designed studies has clearly shown a reduction in fatal as well as nonfatal cardiac events compared with control groups not treated with aspirin. Although demonstration of a benefit of anticoagulant and antiplatelet therapy is difficult owing to a low event rate of thrombotic events (low sensitivity) and other nonthrombotic fatal events (low specificity) after myocardial infarction, pooled results have shown a favorable effect with their use. The usefulness of thrombolytic therapy in the early stages of acute myocardial infarction depends on the timing of initiation of therapy, the severity of the residual stenosis and possible use of agents that protect the ischemic myocardium. Other potential therapies for the acute coronary syndromes are also suggested. Further studies are in progress to establish the clinical benefits of antithrombotic agents in acute coronary syndromes.

Anticoagulants↗

The sleep of remitted bipolar depressives: comparison with sex and age-matched controls.

The sleep of 10 bipolar patients was recorded for five consecutive nights following their recovery from a depressive episode. In all respects except the number of arousals, their sleep did not differ reliably from that of 10 sex and age-matched control subjects. We conclude that sleep measures are unlikely to be useful as trait markers of a depressive diathesis in bipolar disorder.

Adult↗

Horizontal transmission of hepatitis B virus among children and adults in five rural villages in Zambia.

To determine whether horizontal transmission of the hepatitis B virus contributes to the high prevalence of infection with this virus in an endemic region, residents of five villages in Zambia were tested for hepatitis B serologic markers. The prevalence of hepatitis B was determined by testing samples from 620 residents. By examining paired serum samples from 79 children and 80 adults, it was determined that new infections occurred during the five years of this study in at least 14 children (18%) (aged 4-17 years) and ten adults (12%) (aged 23-65 years). These 24 new infections were distributed among 20 households and were not associated with active HBV infections in the mother or, in most cases, other family members. Intervention to prevent hepatitis B in regions such as rural Zambia will require vaccination of susceptible children and adults as well as newborn infants.

Adolescent↗

Pulmonary edema associated with isoxsuprine therapy.

A 0.5% incidence of pulmonary edema was observed when the records of 1,407 patients treated with parenteral isoxsuprine over a 7-year interval were reviewed. Drug infusion rates were within the normal range in the seven affected patients. Discontinuation of therapy, oxygenation, and the administration of diuretics with or without digoxin were successful in reversing the process in all cases. Anemia, multiple gestation, and excessive intravenous fluids were identified as possible risk factors.

Adult↗