Different vaccine strategies used to protect against Theileria annulata.

SPAG-1, a sporozoite surface antigen of T. annulata, has previously been shown to elicit partial protection when used, as an hepatitis B core antigen fusion, to immunize cattle. The objective of this study was to try and improve the protective capacity of this antigen by enlisting different vaccine strategies. Cattle were immunized with SPAG-1, as a fusion protein with a His6 tag, either incorporated into ISCOMs, with or without the merozoite antigens TAMS 1-1 and 1-2, or with RWL as adjuvant three times at monthly intervals. Another group of cattle were immunized with p67, the T. parva sporozoite antigen, in RWL to assess whether any cross-protection could be induced. The animals were then challenged with an estimated LD50 of T. annulata sporozoites, and their ability to resist the infection was investigated. Serum responses and T-cell proliferative responses were analyzed throughout the trial. Post-challenge analyses included lymph node biopsies and blood smears to check for the presence of parasites, routine hematological parameters, and observation for clinical manifestations of the disease. The results of this trial will be discussed.

Correlating students' undergraduate science GPAs, their MCAT scores, and the academic caliber of their undergraduate colleges with their first-year academic performances across five classes at Dartmouth Medical School.

Reviewing the predictive validity of admission criteria to improve the selection process is important to a school in maintaining quality in the entering class. For this reason, the authors studied how the academic criteria used to select the 420 students who entered Dartmouth Medical School from 1982 to 1986 compared with the students' first-year academic performances. The criteria used were Medical College Admission Test scores, undergraduate science grade-point averages, and college selectivity (i.e., the academic caliber of the students' undergraduate colleges). Results showed that a combination of these criteria were useful in identifying the students who were successful in their first year. The authors suggest that their findings also demonstrate the ability to an admission committee to subjectively weigh these academic criteria with consistent results in student performance.

Relationship of medical students' admission interview scores to their dean's letter ratings.

The authors examined the relationship between the admission interview scores for 62 students in the 1986 entering class at Dartmouth Medical School and the students' dean's letter ratings given four years later; they found the relationship to be significant (V = .372, p = .014) and the interview scores to be better independent predictors of the ratings than were total Medical College Admission Test scores or science grade-point averages. Among the 17 students receiving "strong" admission interview scores, 53% received dean's letter ratings in the top one-third and 47% received ratings in the lower two-thirds. Of those 34 who received "medium" interview scores, 68% received ratings in the lower two-thirds; all 11 students who received "weak" interview scores received ratings in the lower two-thirds. The authors suggest (1) that admission interview scores help schools to identify more clearly those applicants most likely to become strong, competitive performers in residency and (2) that the significant relationship between interview scores and dean's letter ratings indicates a need to discover what qualities the interview actually measures and to consider the methods by which interviewers are trained, rather than to forsake the interview.

Longitudinal trends in the applicant pool for U.S. medical schools, 1974--1999.

PURPOSE: To examine the pool of applicants to U.S. medical schools from 1974--1999 for changes in size and demographics and to identify factors that may be associated with such changes. METHOD: Data on characteristics of the total applicant pools to U.S. medical schools for 1974--1999 were collected from the Association of American Medical Colleges' Data Warehouse. Data on undergraduates' receiving bachelor's degrees and unemployment rates were obtained from the National Center for Education Statistics and the U.S. Bureau of Labor Statistics, respectively. Variables such as race/ethnicity, gender, age, and first time or reapplicant status were compared across the study period. RESULTS: The percentage of women applicants increased from 20% of the pool in 1974 to 45% of the pool in 1999, while the percentage of men dropped from 80% to 55%. The number of underrepresented minority (URM) applicants increased 45% during the period, from 2,890 to 4,181, but URM applicants represented only 11% of the total applicant pool in 1999. Between 1974 and 1999, the number of URM men applying to medical school dropped by 18%, from 1,984 to 1,629, while the number of URM women nearly tripled, from 906 to 2,552. The number of Asian/Pacific Islander applicants increased dramatically, from 986 in 1974 to 7,622 in 1999, and they now represent a fifth of all applicants. The proportion of reapplicants grew when the applicant pool grew and it shrank when the applicant pool shrank. No relationship was found between the size of the applicant pool and economic indicators, age, or geographic origin. CONCLUSION: Changes in the proportions of women and Asian/Pacific Islander applicants were the driving force in the expansion of the applicant pool between 1974 and 1999.

Contribution of aerosols generated during mixing and loading of pesticides to operator inhalation exposure.

The occupational exposure resulting from the application of crop protection agents continues to be of great interest for the purposes of identifying hazards or determining safer chemical handling methods. The purpose of the present study was to identify the potential respirator exposure of a mixer/loader to chlorothalonil, with the mixing and loading operation as the only source of aerosols (particles <13 microm diameter). Three worst-case mixing/loading scenarios were simulated in the lab: (1) a spill of undiluted chlorothalonil formulation onto a dry, horizontal metal surface; (2) a spill of undiluted chlorothalonil formulation onto a rapidly rotating shaft; and (3) pouring undiluted chlorothalonil formulation into a container of water. Aerosol generation from these scenarios was compared to that resulting from atomizing dilute chlorothalonil through hydraulic nozzles. Aerosols were captured with a cascade impactor, and quantified by gas chromatography. Results indicated that simulated spill scenarios generated aerosol concentrations between 2.1 and 5.3 ng/l, which were in the same order of magnitude as, and only marginally higher than, the detection threshold (1.7 ng/l) and background levels (2.2 ng/l). In comparison, atomization of dilute chlorothalonil through a hollow cone and flat fan nozzles resulted in airborne concentrations of 354 and 96 ng/l, respectively, related to the atomization characteristics of these nozzles. Measurement of the dimensions of the aerosol cloud indicated that aerosols resulting from a spill amounted to approximately 10(-5)% of the spilled chlorothalonil. It was estimated that a male worker respiring 29 l/min would inhale approximately 0.32-0.78 ng of chlorothalonil during a typical 30 s spill, assuming a 1% transfer efficiency between the spill site and the mixer/loader. These estimates were between 10000 and 480000 times less than literature data for respiratory exposure of chlorothalonil by applicators and harvesters, suggesting that inhalation of aerosols from mixing and loading represents a minor component of overall exposure.

Tissue damage in cattle infected with Theileria annulata accompanied by metastasis of cytokine-producing, schizont-infected mononuclear phagocytes.

The distribution of schizont-infected cells in six calves undergoing acute, lethal sporozoite-induced infections with Theileria annulata was examined, the calves being killed in the early, middle or late stages of disease. A combination of histological and immunocytochemical techniques showed that schizont-infected cells became disseminated rapidly through the lymphoid tissues from the prescapular lymph node draining the site of inoculation to distant lymph nodes (e.g., precrural, mesenteric and mediastinal) and to the spleen and thymus. The parasitized cells also spread rapidly into non-lymphoid organs, being found in the liver, kidney, lung, abomasum, adrenal glands and pituitary gland by day 7, in the brain by day 12 and in the heart by day 14 after infection. As infection progressed, the schizonts differentiated into merozoites. By the late stages of disease, the cells containing merozoites greatly out-numbered schizont-infected cells. The parasitized mononuclear cells were labelled by antibodies to bovine interferon-alpha1 and tumour necrosis factor-alpha and, during the later stages of the disease, contained erythrocytes parasitized by piroplasms. The results suggested that the parasitized mononuclear cells themselves played a role in the development of clinical disease and in tissue damage. These findings provide new evidence that tropical theileriosis can no longer be viewed as a lymphoproliferative disease resulting from the uncontrolled multiplication and metastasis of lymphoid cells infected with T. annulata schizonts, but is caused by a parasite that lives in, and is disseminated by, cytokine-secreting, proliferating mononuclear phagocytes.

Theileria annulata: control measures, diagnosis and the potential use of subunit vaccines.

Theileria annulata is an important pathogen of domestic Bovidae across a broad region of the world with some 250 million cattle at risk. Our basic knowledge of the incidence and mortality is reviewed together with an outline of current control measures, including the use of acaricides, chemotherapy and attenuated cell line vaccines. The limitations and potential problems of these control measures are discussed and considered in relation to the use of a subunit vaccine. Research over the last ten years on the protective immune response to the disease in both laboratory and field studies suggests that a humoral immune response to the sporozoite could be protective although the primary protective response appears to be mediated by cytotoxic T-cells recognising the macroschizont-infected lymphocyte stage. Recent work on the study of protective antigens using recombinant DNA and hybridoma technologies is discussed together with the potential advantages and problems of such approaches. Possible future developments in our understanding of the immune response and the identification of the relevant antigens are considered in addition to the use of new techniques for diagnosis and the analysis of parasite diversity.

Windbreaks as a pesticide drift mitigation strategy: a review.

The use of natural and artificial barriers to mitigate pesticide drift from agricultural and forest applications is discussed. This technique has been considered as an alternative to current methods at a time when environmental concerns are under great public scrutiny. There has been a variety of research experiments on this subject from New Zealand to The Netherlands which have documented reductions in spray drift of up to 80-90%. However, there are still enormous data gaps to utilize this method accurately. The aerodynamic factors of wind barriers and shelter effects on crop growth and yield have been well investigated. In contrast, some of the important aspects of drift mitigation, e.g. porosity and turbulence, have been difficult to obtain and no standard methodologies are currently available to evaluate and classify windbreaks and shelterbelts or to determine their efficiency in reducing drift. Thus there is a significant opportunity to incorporate windbreaks into the tool set of drift mitigation tactics. Government policies, initiatives, legislation, etc, which currently address water quality, BMP, stewardship, buffers, etc, are issues which so far have not included windbreaks as a valuable drift mitigation strategy.

Antigens and immunity in Theileria annulata.

About 200 million cattle are believed to be at risk from the debilitating and often fatal effects of tropical theileriosis, caused by Theileria annulata. Currently, there is no very cheap effective drug for treatment of T. annulata infections, although the hydroxynophthoquinones parvaquone and buparvaquone are reported to give good results(1-4). Control of the parasite principally involves vector control against the ixodid tick vectors - mainly by cattle dipping and spraying with acaricides - and vaccination using attenuated macroschizont-infected leucocytes (1-17) (see Box I). In this article, Roger Hall discusses the nature of immunity that can be achieved against T. annulata, and progress in identifying the main antigens involved in this immunity.

Financial aid for medical students: a review and a proposal.

By making it possible for all students admitted to medical school to finance their education, the federal government has been a dominant variable in medical education for over two decades. Financial aid programs during the 1960s were directed at increasing the number of applicants, medical school places, and, ultimately, the number of physicians. With these goals largely achieved, a trimming of the federal systems of financial aid seems probable. Unless accommodations can be made, such changes will have broad financial implications for both students and medical schools and could threaten the diversity, stability, and quality of the applicant pool. The authors in this article review the history of medical school financial aid and describe the development of an institutionally based, privately financed loan program. The authors propose that such programs can help preserve adequate financial aid for medical students as federal programs decline.

Matrix metalloproteinases mediate the metastatic phenotype of Theileria annulata-transformed cells.

Theileria annulata infects and reversibly transforms bovine leucocytes. The parasite-transformed cells are immortalized, metastatic and express a number of metalloproteinases including matrix metalloproteinase 9 which they secrete. All the metalloproteinases observed on substrate gels are inhibited by tissue inhibitor of metalloproteinase 1 and 4 synthetic inhibitors BB94, GM6001, BRL29808AI and Ro31-4724. We have adapted an in vitro assay for metastatic behaviour that measures the ability of parasitized cells to cross reconstituted basement membrane, Matrigel. Using this we demonstrated that macroschizont-infected cells are invasive in vitro and that their invasive properties can be almost eliminated by the same specific inhibitors of metalloproteinases as used in the substrate gels. This demonstrates that the metastatic behaviour of the infected cells is due in part to metalloproteinase activity and strongly suggests a role for the metalloproteinases we observed on gels. This is further supported by the fact that an attenuated vaccine line which shows much reduced metalloproteinase activity also exhibits a marked reduction in metastatic behaviour. We suggest that these metalloproteinases are virulence factors mediating some pathological features of the disease and their loss in the vaccine line could provide an explanation for attenuation.

Health policies and procedures for medical students at US medical schools: a progress report.

This paper presents the current status of school health policy at US medical schools and discusses implications for medical students with respect to physical health and occupational risks. The authors discuss the responsibility of schools to ensure that students are healthy and fit, both for their own benefit and to provide models of good health maintenance for their future patients. Schools have an obligation to monitor public safety issues, particularly in cases of chemical impairment, student mistreatment and infection control procedures.

Effects of soil water stress and twospotted spider mites on net photosynthesis and transpiration of apple leaves.

Soil water stress and twospotted spider mites (Tetranychus urticae Koch) were tested for their influence on the content and activity of leaves of greenhouse grown Delicious apple trees. Soil water stress caused reductions in net photosynthesis (Pn), transpiration (Tr), and shoot growth. Leaf water potential was decreased by both water stress and mite feeding. Feeding of 15 adult mites/leaf for 28 days resulted in a 16% reduction in Pn while an initial population of 10 mites leaf/left to develop for 20 days reduced Pn by 27%. Mite feeding reduced leaf nitrogen and non-structural carbohydrate levels when sampled 20 days after placement on the leaf. There was no interaction between the changed physiology of the leaf due to soil water stress and mite feeding.

Arrestment of male twospotted spider mite caused by female sex pheromone.

A glass slide bioassay was used to evaluate male twospotted spider mite,Tetranychus urticae Koch, arrestment caused by quiescent deutonymph extract. Males that were guarding quiescent deutonymphs prior to being tested were arrested by a 3-mm-diameter circle of quiescent deutonymph extract; nonguarding males and adult females were not arrested. Extracts of allT. urticae instars tested caused male arrestment, but mean arrestment duration was longest with quiescent deutonymph extract. Arrestment by volatile perception of pheromone and upwind orientation to point sources of extract were not observed. The mono- and sesquiterpene alcohols previously identified as components of the pheromone did not arrest males. HPLC separation of extract resulted in four active fractions; a subtractive bioassay showed that three were essential to elicit maximum male response.

Dislodgeable azinphosmethyl residues from air blast spraying of apple foliage in Ohio.

The distribution and decay rates of dislodgeable residues of azinphosmethyl applied by two types of air blast sprayers on apple foliage in Ohio were investigated. Leaf discs were taken from nine sites located on the periphery of Cortland apple trees at five dates after spraying. The sprayer delivering the higher airflow rate, but lower velocity, deposited the pesticide much more uniformly over the trees and applied more in the top of the tree. The other sprayer deposited the greatest proportion of pesticide on the site nearest the sprayer. The residue decreased at all sites and ranged from 42 to near 100% decrease at 14 days after spraying.

Quantitative and temporal analysis of effects of twospotted spider mite (acari: Tetranychidae) female sex pheromone on male guarding behavior.

Responses of male twospotted spider mite,Tetranychus urticae (Koch), to female sex pheromone were described by a glass slide bioassay and computerized pathway digitizer. Pheromone was extracted from quiescent deutonymphs and fractionated by HPLC, and responses of guarding males to each fraction, all fractions combined, unfractionated extract, and a hexane control were bioassayed for 6 min. Mean angular velocities, linear velocities, percent time stationary, and distance from the 3-mm-diameter treatment circle were calculated for each mite at 20-sec intervals and these behavioral parameters regressed on time. Analysis of variance of regression-equation intercepts showed that no differences in initial male angular velocities were observed among treatments, but initial linear velocities were greater in response to all fractions combined and to extract than to individual fractions, and greater in response to individual fractions than to the control. Angular velocities decreased and linear velocities increased more rapidly in response to individual fractions than to all fractions combined and extract, while males turned preferentially in one direction and were stationary (no displacement) more often in response to all-fraction combinations than to individual fractions and the control. Significant differences were observed among the parameter values elicited by individual fractions, suggesting that active fractions differed qualitatively. The described changes in movement parameters show that maleT. urticae response to presence of pheromone occurs almost immediately, and that multiple pheromonal components are necessary to elicit maximum male response. The overall effect of pheromonal components was to decrease the rate at which males moved away from the treatment cycle, thereby causing male arrestment.