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Biomedical subjects

A Draper

Publications and source records attributed to A Draper.

13 recordsLinked to original sources

Determination of the T cell epitopes of the lipocalin allergen, Rat n 1.

BACKGROUND: Laboratory animal allergy (LAA) is an important cause of occupational sensitization and asthma. Rats are a frequent cause of LAA and the major rat allergen, Rat n 1, is a member of the lipocalin protein family, which includes several other animal allergens such as the cow allergen, Bos d 2. To date, Bos d 2 is the only mammalian lipocalin allergen to have been studied in detail. OBJECTIVE: We undertook a cross-sectional study of a large population of individuals exposed to laboratory rats to determine the proliferative responses of peripheral blood mononuclear cells (PBMCs) to the major rat allergen, Rat n 1. METHODS: Eighty-three cases (defined by a positive skin prick test (SPT) > or =3 mm and/or a positive RAST > or =2% binding) and 274 referents without specific IgE to rats were tested for their proliferative responses of PBMCs to rat allergen. Cytokine release to rat urinary protein was examined in 28 sensitized and 42 non-sensitized exposed individuals. RESULTS: Proliferation to rat urinary protein was weak in all individuals. Four regions within Rat n 1 were identified as containing potential immunodominant T cell epitopes and three of these co-localized within the conserved regions of the lipocalin molecule. All four regions within Rat n 1 overlapped considerably with the characterized epitopes of the lipocalin allergen, Bos d 2. IL-5 and ratios of IL-5/IFN-gamma were significantly increased in cases. CONCLUSION: The response to Rat n 1 is remarkably similar to the cow lipocalin allergen Bos d 2. T cell epitopes within lipocalins appear to co-localize with the conserved regions of the molecule. LAA is characterized by an increased production of IL-5. Investigation of other lipocalin allergens will provide further information about the allergenicity of this group of proteins.

Allergens↗

Occupational asthma from fungicides fluazinam and chlorothalonil.

We report two cases of occupational asthma caused by sensitisation to powdered fungicides fluazinam and chlorothalonil, from the same fungicide formulation plant. Both developed work related lower respiratory symptoms after a latent interval of asymptomatic exposure. The diagnosis in each case was confirmed with a serial peak flow record in the workplace followed by specific inhalation tests. These fungicides are known to cause dermatitis; this report indicates that these compounds can induce specific immunological reactions in the airways as well as skin.

Aminopyridines↗

Estimating the incidence of occupational asthma and rhinitis from laboratory animal allergens in the UK, 1999-2000.

We report a survey of the number of persons handling laboratory animals in the UK in 1999-2000. This estimate has allowed us to calculate annual incidence rates of allergic asthma and rhinitis attributable to laboratory animals, insects, and birds using numerators derived from cases reported to a national surveillance scheme (SWORD). The number of exposed employees has almost halved since the early 1980s. From these data, the estimated annual incidence rate of occupational asthma among persons working with small mammals is 1.56/1000 employees. Although reported cases are rare, estimated incidence rates of asthma attributable to birds (23.9/1000/year) and insects (2.35/1000/year) are high.

Allergens↗

Strategic planning: going beyond the basics.

Boards are discovering that many of the strategies of the '90s that took their organizations far afield from their core mission did not pan out as intended. Now they need to take a new strategic approach--combining the basics with a view toward a dynamic health care environment.

Delivery of Health Care, Integrated↗

Consumer focus can spur group practice turnaround.

Many healthcare organizations have lost money on their employed group practices. The solution to this dilemma is not necessarily divestment of the group practices. Instead, some healthcare organizations should view their physicians as an asset. Healthcare organizations and physicians need to develop a new framework for their relationship to optimize their competitive advantage. Three guiding principles that will help accomplish this objective are to recast the healthcare organization-physician relationship to focus on the consumer, reconfigure the economic model to exceed consumer demands, and restructure the group practice to encourage fiscal and service excellence. In developing a new relationship framework, the stakeholders need to define the group practice's mission, strategic direction, composition, infrastructure, compensation model, and structure.

Delivery of Health Care, Integrated↗

Seven unique food consumption patterns identified among women in the UK Women's Cohort Study.

OBJECTIVE: [corrected] To identify groups of subjects with similar food consumption patterns so that complex disease-diet relationships can be investigated at the level of the whole diet, rather than just in terms of nutrient intake. SUBJECTS: 33,971 women in the UK Women's Cohort Study. 60,000 women on the World Cancer Research Fund mailing list were initially invited to take part. Subjects were selected to include a high proportion of vegetarians. DESIGN: The cohort completed a 217 item food frequency questionnaire. Cluster analysis was used to identify groups of women with similar food consumption patterns. Clusters were compared on socio-demographic characteristics, indicators of health and diet, and nutrient intakes. RESULTS: Seven clusters were identified including two vegetarian clusters. Groups appeared to be differentiated by differences in food types and in diversity of diet. Socio-demographic, health and diet characteristics and nutrient intakes all differed significantly between groups. CONCLUSION: Classifying diets in more pragmatic terms than just nutrient intake should provide valuable insight into understanding complex diet-disease relationships. Dietary advice, whilst based on nutrient content of meals, needs to take account of the combinations of different food types that people naturally choose to use together. SPONSORSHIP: World Cancer Research Fund.

Adult↗

Occupational asthma caused by bacillary amylase used in the detergent industry.

Four cases are reported of occupational asthma due to amylase derived from Bacillus licheniformis, used in detergent washing powders. It is thought that these are the first reported cases of asthma due to this enzyme in the detergent industry. All four employees (men) were from the same factory and none had a history of asthma or atopy. All developed symptoms of wheeze at work after an initial symptom free period. Symptoms improved during periods away from work. All undertook serial peak flow recordings (not diagnostic) and underwent skin prick tests, radio allergosorbent test (RAST) measurement, and specific bronchial provocation testing. The bronchial provocation testing was performed by a dust tipping method in a single blind manner, with lactose as an inert control and powdered amylase, provided by the employer, as an active agent. Serial measurements of forced expiratory volume in 1 second (FEV(1)) were recorded and histamine provocative concentration causing a 20% fall in FEV(1) (PC(20)) tests were determined before and 24 hours after each challenge. Patient 1 developed an isolated early reaction, patient 2 an isolated late reaction, and patients 3 and 4 developed dual reactions. All showed an increased non-specific bronchial responsiveness after active challenge. The introduction of encapsulated enzymes in the detergent industry was followed by a reduction in the incidence of respiratory sensitisation. These patients developed occupational asthma despite working only with encapsulated enzymes. This highlights the importance of careful surveillance after the introduction of new agents in the workplace.

Adult↗

Induction of liver microsomal cytochrome P450 in cynomolgus monkeys.

The aim of this study was to determine whether treatment of cynomolgus monkeys (Macaca fasicularis) with phenobarbital, beta-naphthoflavone, or dexamethasone causes an induction of microsomal crytochrome P450 (CYP) enzymes that are structurally and functionally related to rat enzymes belonging to the CYP1A, CYP2B, and CYP3A gene families. Oral treatment of male and female monkeys with phenobarbital resulted in a marked induction of a protein recognized by antibody against rat CYP2B1, as determined by Western immunoblotting. This protein, presumably a CYP2B enzyme, was not detectable in untreated monkeys, and was modestly inducible by dexamethasone but not beta-naphthoflavone. Induction of this CYP2B enzyme by phenobarbital was associated with a relatively large increase (up to 5-fold) in the rate of testosterone 16 beta-hydroxylation. Antibody, against rat CYP2B1 markedly inhibited this reaction in liver microsomes from phenobarbital-treated monkeys, but not from control monkeys. Consequently, the antibody-inhibitable rate of testosterone 16 beta-hydroxylation increased 17-fold after treatment of monkeys with phenobarbital, which is comparable with the situation in rats. In contrast to the rat CYP2B enzymes, the monkey CYP2B enzyme had little or no capacity to convert testosterone to 16 alpha-hydroxytestosterone or androstenedione, and had negligible capacity to O-dealkylate 7-pentoxyresorufin and 7-benzyloxyresorufin. Oral treatment of male and female monkeys with beta-naphthoflavone resulted in a marked induction of a protein recognized by polyclonal and monoclonal antibodies against rat CYP1A1 or against both CYP1A1 and CYP1A2. This protein was apparently a mixture of CYP1A1 and CYP1A2, neither of which was readily detectable in liver microsomes from control monkeys or monkeys treated with phenobarbital or dexamethasone. Induction of monkey CYP1A1/2 was associated with a marked increase in the O-dealkylation of 7-methoxyresorufin (up to 65-fold), the O-dealkylation of 7-ethoxyresorufin (up to 30-fold), and the N3-demethylation of caffeine (up to 17-fold), but only a 2-fold increase in benzo[a]pyrene 3-hydroxylation. Polyclonal antibodies against CYP1A1 markedly inhibited the N3-demethylation of caffeine and the O-dealkylation of 7-methoxy- and 7-ethoxyresorufin by liver microsomes from beta-naphthoflavone-treated monkeys, and partially inhibited the 3-hydroxylation of benzo[a]pyrene, indicating that monkey CYP1A1 and/or CYP1A2, like the corresponding rat enzymes, can catalyze all four reactions. Treatment of monkeys with phenobarbital resulted in a 2- to 3-fold induction of a protein recognized by antibody against rat CYP3A1. This protein (CYP3A8 or an immunochemically related enzyme) was constitutively expressed in untreated monkeys of both sexes.(ABSTRACT TRUNCATED AT 400 WORDS)

Alkylation↗

The energy and nutrient intakes of different types of vegetarian: a case for supplements?

Vegetarians of three types were studied in Greater London: thirty-four meat-avoiders, fifty-two lacto-ovo-vegetarians, and thirty-eight vegans. Weighed dietary intake measures were made over 3 d. Cereals were the mainstay of the diet, supplemented by dairy products (demi-vegetarians and lacto-ovo-vegetarians), vegetables and fruit, and soya-bean products (vegans). Many vegans progressed by stages to complete avoidance of animal foods; some had retreated, but most were highly committed. Demi-vegetarians were the least involved in a 'vegetarian lifestyle'. All groups had mean energy intakes close to the current dietary reference values (DRV), with adequate protein intakes. Only vegans had fat intakes close to current recommendations; all groups had high dietary polyunsaturated:saturated fatty acid ratios. Mean intakes of all micronutrients studied for demi- and lacto-ovo-vegetarians met the UK DRV. Intakes of iodine, riboflavin, and vitamin B12 for vegans were below DRV; more than half considered their diets supplied all necessary vitamins. About 25% took some type of dietary supplement during the survey. The impact of low I intakes should be further studied, and it is recommended that 'new' vegetarians and vegans should use appropriate dietary supplements.

Adult↗