Biomedical subjects

A E Pearson

Publications and source records attributed to A E Pearson.

11 recordsLinked to original sources

PubMed2000

Antimutagenic effects of wheat bran diet through modification of xenobiotic metabolising enzymes.

Diets containing wheat bran (WB) protect against cancers of the colon or breast in rats, and may be beneficial in humans. In a previous study of rats treated with the carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), inclusion of 10% wheat bran in the diet led to an apparent reduction in IQ metabolites but not of intact IQ in plasma. In the present study, male Wistar rats were fed diets containing 0, 10 or 20% wheat bran, and effects on xenobiotic metabolising enzymes compared. Wheat bran-supplementation showed differential effects on phase I enzymes, significantly increasing the activity of hepatic cytochrome P450 isozyme CYP3A2, but slightly reducing the activity of CYP1A1/2. The activities of both hepatic phase II detoxification enzymes glutathione-S-transferase and glucuronosyl transferase were also reduced. Western blotting revealed similar effects on expression of the proteins. Interestingly, the expression of xenobiotic metabolising enzymes (XME) in the colon appeared to be modulated independently of hepatic XME. Although the wheat bran-supplemented diet still led to an increased expression of CYP3A, it now slightly increased CYP1A in the colon. However, 20% wheat bran significantly increased the expression of both glutathione transferase isozymes, GST A1 & A2, in the colon. Natures Gold (NG) is a commercial wheat bran derivative which is lower than wheat bran in dietary fibre, but enriched in vitamins, minerals and various phytochemicals. Dietary supplementation with 20% Natures Gold led to similar trends as seen in wheat bran-fed rats, but more potent effects in both hepatic and colonic enzymes. The significance of these changes for activation of carcinogens to mutagenic metabolites was investigated using the Salmonella/mammalian microsome mutagenicity test. The activation of IQ and benzo[a]pyrene, but not cyclophosphamide, to a mutagen by hepatic S9 from wheat bran-fed or Natures Gold-fed rats was significantly reduced compared with S9 from animals on a diet lacking wheat bran. We suggest that modulation of xenobiotic metabolising enzymes may be an important component of cancer protection by wheat bran, and this effect may relate to micronutrients or cancer-protective non-nutrient phytochemicals rather more than to dietary fibre.

Animals↗

PubMed1997

In vivo effects of chlorophyllin on the antitumour agent cyclophosphamide.

Cyclophosphamide (CP) is a potent antitumour agent used against many forms of cancer and against certain other diseases. Chlorophyllin (CHL), which is obtained by hydrolysis of chlorophyll to remove phytyl alcohol, is an efficient antimutagenic agent and has been used as a dietary supplement or to diminish the intensity of the discomforting side effects of CP therapy. We undertook to determine the antimutagenic effectiveness of CHL against CP in a mouse model and to determine whether the antitumour efficacy of CP was compromised in vivo by CHL treatment. Experiments utilised CHL administered either in drinking water (1%) for 2 days before treatment, or by gavage (200 mg/kg) 2 hr before treatment with CP (220 mg/kg). Urinary mutagenicity following CP treatment, as determined by the Salmonella/microsome assay, was decreased by both regimes of CHL co-treatment. Similarly, the increase in micronuclei in bone marrow polychromatic erythrocytes in response to CP was reduced by concomitant CHL treatment. In contrast, antitumour efficacy, as determined by growth delay of Colon 38 adenocarcinomas, was not diminished by CHL treatment. We conclude that CHL may have beneficial effects when used in combination with CP therapy.

Animals↗

PubMed1996

The clinical use of mutagenic anticancer drugs.

Cytotoxic chemotherapy is routinely used in the treatment of cancer, and has been an important factor in increasing 5-year survival rates for some types of this disease. A range of drugs are currently available, with differing modes of action. As well as causing some direct toxic effects, most if not all of these drugs are both mutagenic and carcinogenic. Although comparative information on these properties is generally available for anticancer drugs which alkylate DNA, it has been less readily accessible for other drug classes. This special issue contains seven reviews on the mutagenic properties of the major classes of cytotoxic drugs in clinical use, as well as one on a class of drugs that is under development. Some carcinogenicity data are also summarised, where available. Additionally, there are four more general papers, including one on the use of genetic activity profiles for comparing mutagenicity of the drugs, two on germ-cell effects, and one on biomonitoring for exposure to genotoxic anticancer drugs.

Adolescent↗

PubMed1994

Regulation of interleukin-8 expression in porcine alveolar macrophages by bacterial lipopolysaccharide.

Interleukin (IL)-8 is a macrophage-derived neutrophil chemotactic factor that plays an important role in the recruitment of neutrophils to inflammatory loci. Hence, expression of IL-8 by alveolar macrophages may be a significant factor in host defense in the lung and in the pathogenesis of pneumonia in swine. To initiate molecular studies of IL-8 regulation in pigs, we cloned IL-8 cDNA and examined the regulation of its mRNA in alveolar macrophages. The porcine IL-8 cDNA consists of 1491 base pairs including a coding region of 309 base pairs. The deduced amino acid sequence was 75 and 81% similar to human and rabbit IL-8, respectively. Resting macrophages contained low levels of IL-8 mRNA, which increased markedly after exposure to bacterial lipopolysaccharide (LPS). LPS induction of IL-8 was direct, not mediated through elevation of tumor necrosis factor or interleukin-1. The effect of LPS on IL-8 expression was dose dependent, and induction was observed at a concentration of 10 pg/ml. IL-8 mRNA expression was detectable within 0.5 h after stimulation with LPS, peaked at 3-6 h at about 30-fold higher levels than in resting cells, and was maintained for 24 h. Secreted IL-8, measured by neutrophil chemotaxis, was induced within 4 h by LPS, and accumulated in the media throughout the 24-h period. The mechanism of induction of IL-8 mRNA appeared to involve transcription and RNA processing. Nuclear run-on analysis showed that the IL-8 gene was actively transcribed in noninduced cells; upon stimulation with LPS, the rate of IL-8 transcription was increased about 4-fold. A single mature mRNA species was detected by primer extension analysis. The half-life of IL-8 mRNA transcripts in aveolar macrophages was approximately 2 h and did not change after LPS stimulation. The ability of LPS to induce IL-8 expression was suppressed by recombinant human IL-4 and dexamethasone in a concentration-dependent manner. These observations indicate that the expression of IL-8 is an early event in the sequelae to bacterial infection in the lung.

Amino Acid Sequence↗

PubMed1984

Chemotherapy in combination with pelvic irradiation: a time-dependence study in mice.

The importance of timing of drug administration in combination with pelvic irradiation on animal lethality was investigated in male CBA mice. The chemotherapeutic agents cyclophosphamide, cytosine arabinoside, 5-fluorouracil, methotrexate, cis-dichlorodiammine platinum (II), adriamycin, CCNU, VP-16 and bleomycin were administered at various times up to 2 weeks before and 2 weeks after pelvic irradiation (4 weeks before and after in the case of cyclophosphamide) of unanaesthetised mice and the LD50/30 days and dose enhancement factors determined. The results indicate a potentiation of radiation-induced damage when drugs are given near to the time of irradiation, particularly at about 3 days post-irradiation.

Animals↗

PubMed1983

The relationship between 'early' and 'late' radiation-induced skin reactions as seen in two strains of mice that differ in radiosensitivity.

The acute skin reaction and time-course of skin contraction following graded single doses of X-rays were studied in CBA and C57B1 mice, in order to elucidate the relationship between 'early' and 'late' skin damage in strains that are known to differ in radiosensitivity. A dose-dependent acute reaction and rapid skin contraction was noted 0-50 days after irradiation in both strains, and both parameters of response were greatest in the C57B1 mice. Following this initial shrinkage there was a slight relaxation, which was again more evident in the C57s. A gradual, continuous, dose-independent contraction from 50-466 days was evident in CBA mice, whereas in C57s there was no evidence of late shrinkage. Histological examination at 466 days post-irradiation revealed a greater epidermal hyperplasia in CBA than in C57 mice. Comparison of these results with data on acute intestinal damage and early and late lung damage shows no general relationship between the incidence of early and late radiation damage in these two strains of mice.

Acute Disease↗

PubMed1983

Bleomycin and radiation-induced lung damage in mice.

Bleomycin-induced lung damage was assessed using both a functional end-point and mortality. The extent of lung damage was found to depend on the schedule, mode of administration and dose of the drug. Greater damage occurred following twice-weekly administration than when the same dose was given as a single injection. Intravenous administration resulted in greater damage than intraperitoneal administration. When bleomycin was given with thoracic irradiation lung damage occurred earlier and at lower radiation doses than with radiation alone. Similar responses were obtained whether bleomycin was given four weeks before, with or four weeks after irradiation. Thus although there was enhanced damage from the combined treatment, there was no evidence of a time-dependent interaction.

Animals↗

PubMed1981

Radiation effects on mouse incisor teeth following whole-body doses of up to 16 gray.

Experiments were performed to determine the threshold dose of radiation above which macroscopic tooth damage in C57BL mice occurs, the sequence of appearance of this damage, and the extent and rate of recovery in relation to radiation dose. Protection from the acute effects of radiation doses well in excess of the LD90 was obtained by the administration of non-absorbable antibiotics and bone marrow reconstitution, without the use of radioprotective drugs. However, gross effects on the incisors were observed at doses in excess of 10 gy. Body weight changes were to some extent linked with the incidence of tooth damage.

Animals↗

PubMedDate not supplied

Antimutagens in food plants eaten by Polynesians: micronutrients, phytochemicals and protection against bacterial mutagenicity of the heterocyclic amine 2-amino-3-methylimidazo[4,5-f]quinoline.

We have previously suggested that differences in cancer incidence between Polynesians (including Maoris and people from several Pacific islands) and Europeans in New Zealand may at least partially relate to differences in the species of food plants (fruits, vegetables and cereals) preferentially eaten by these groups. Twenty-five food plants that are typically eaten in different amounts by these two population groups were selected for detailed study. Antimutagenic properties of three extracts from each of the selected plants were investigated using a preincubation mutagenicity assay with Salmonella typhimurium strain TA1538 against the mutagenicity of the heterocyclic amine 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). The data revealed strong antimutagenic properties in several of the food plants commonly eaten by Polynesians, especially rice, watercress, pawpaw, taro leaves, green banana and mango. Using the New Zealand food database, a number of nutrients and micronutrients with antimutagenic and anticarcinogenic potential were identified from the selected food plants. Some of these were tested for antimutagenic potential in parallel experiments to those done with the food plant extracts. Although some of these micronutrients are antimutagens against IQ, their concentrations in the food plants failed to explain the protection against mutagenicity found in the experiments with extracts of the food plants. Thus, other types of chemical, not identified in the database, must be leading to antimutagenesis. Possible active molecules include chlorophylls, carotenoids, flavonoids and coumarins, many of which are also known to be anticarcinogens. If human cancer data are to be interpreted in terms of cancer protection, these components need urgently to be quantified in food plants in the New Zealand diet, especially in those food plants eaten in large amounts by Polynesians.

Animals↗

PubMedDate not supplied

Corporate redemption and the seven deadly sins.

Competitive purgatory is the sorry state of too many formerly proud U.S. corporations. They are languishing from the devastating effects of seven familiar sins: inconsistent product quality; slow response to the marketplace; lack of innovative, competitive products; uncompetitive cost structure; inadequate employee involvement; unresponsive customer service; and inefficient resource allocation. To make matters worse, the maladies are mostly management-induced, and the remedies most managers are employing-shifting strategy, reallocating resources, focusing on operations--are proving ineffective. The cures don't address the cause of the disease: negative, risk-averse, bureaucratic work environments that flourished in decades of easy growth but today are undermining competitive performance. What's needed is a total reinvention of the soft side of the organization to produce a work environment that stresses speed, Spartanism, innovation, and marketplace focus. First, top managers must decide what their company stands for and convince their employees of this uniqueness. Second, they must set standards that drive their business to worldclass levels and be tough about enforcing and raising them. Third, they must push constantly to ensure that enough innovations take place to change the company's future significantly. Three other factors are crucial: the right talent, an effective reward system, and CEOs who can drive the desired changes personally. Creating a dynamic work environment is not easy: it takes perseverance, flexibility, and commitment. But these efforts will pay off: how people tackle problems, work together, and think about their jobs are the activities that make a company great.

Administrative Personnel↗

PubMedDate not supplied

Six basics for general managers.

To sum up, outstanding GMs affect their companies in six important ways. They develop a distinctive work environment; spearhead innovative strategic thinking; manage company resources productively; direct the people development and deployment process; build a dynamic organization; and oversee day-to-day operations. Individually, none of these things is totally new or unique. But successful GMs are better at seeing the interrelationships among these six areas, setting priorities, and making the right things happen. As a result, their activities in these areas make a coherent and consistent pattern that moves the business forward. These six responsibilities don't tell the whole story, of course. Leadership skills and the GM's personal style and experience are important pieces of the whole. But focusing effort in these six areas will help any GM become more effective. And that should mean making the right things happen faster and more often--which is what all of us want to achieve as general managers.

Administrative Personnel↗