A prepared mind--Ernest Edward Tyzzer's legacy of research into avian diseases.

Ernest Edward Tyzzer (1875-1965) was a physician, specializing at first (1902-1916) in cancer research and then from 1916 as a parasitologist. He was born of English parents in Wakefield, Massachusetts, where he lived all his life. Educated in Wakefield public schools, Brown University (Ph.B., A.M., Hon. Sc.D.), and Harvard University (M.D.), he established during his 40-yr career (1902-1942) an international reputation in oncology, pathology, virology, bacteriology, parasitology, and taxonomic zoology in relation to human and veterinary medicine. His contributions to knowledge of avian diseases were outstanding and wide-ranging. Seminal work included: new descriptions of tumors in chickens; the first record of Cryptosporidium in birds; studies on the biology, morphology, in vitro culture, and epizootiology of the blackhead (histomonosis) parasite and its reclassification under a new genus Histomonas; descriptions of eight new taxa of amebae and flagellates in chickens, turkeys, and ruffed grouse; descriptions of seven new species of Eimeria in chickens, turkeys, pheasants, and quail as well as studies on their biology, immunogenicity, virulence, and epizootiology; a description of the trematode Collyriclum in English sparrows; the first record of mycosis in ruffed grouse; the recognition of birds as a source of equine encephalomyelitis infections of humans; the first American record of infectious sinusitis in turkeys and discovery of a curative treatment; and studies of Newcastle disease and avian influenza during the war research program of the 1940s. Application of Tyzzer's histomonosis research to farm practice saved the Massachusetts turkey industry from extinction in the 1920s and significantly influenced the recovery of turkey farming nationally.

Forty years of monensin for the control of coccidiosis in poultry.

In July 1971, the polyether ionophorous antibiotic monensin was introduced in the United States for the control of coccidiosis in poultry. At that time, prospects for new anticoccidial agents were not good. Amprolium had enjoyed several years of use, but many other compounds had been abandoned as resistance to them developed. After the introduction of monensin, most commercial broilers were medicated with the drug and it is still widely used for this purpose today. Apart from in poultry, monensin is also used to control coccidiosis in game birds, sheep, and cattle. Indeed, more animals have been medicated with ionophores, such as monensin, for control of disease than any other medicinal agents in the history of veterinary medicine. In this review, we discuss the discovery, mode of action, and efficacy of monensin, together with matters of importance to the poultry industry such as commercial use, drug resistance, toxicity, pharmacology and residues, host immunity to coccidiosis, and effects in other avian species.

The correct date of the original description and availability of the coccidian name Eimeria meleagridis Tyzzer (Apicomplexa: Eimeriorina: Eimeriidae).

The coccidian Eimeria meleagridis Tyzzer, an apicomplexan parasite of the turkey, was long believed to be innocuous, but recent research suggests that it may be of greater economic importance than previously realised. Hitherto, the date of publication of both the name and the original species description has invariably been wrongly cited as 1927, an error first committed by the describer himself and perpetuated ever since. In fact, the name as published in 1927 was a nomen nudum, being unaccompanied by any indication or description. Tyzzer's first valid publication of the name with a description was two years later. Hence the correct formal authorship attribution is Eimeria meleagridis Tyzzer, 1929.

Coccidian oöcysts as type-specimens: long-term storage in aqueous potassium dichromate solution preserves DNA.

Preservation of the exogenous oöcyst stage of coccidian parasites (phylum Apicomplexa N.D. Levine, 1970) as type-specimens of newly described species has long been problematical. Conventional fixatives have proved unsatisfactory, and compromises such as embedding oöcysts in resin or photographing them are not entirely appropriate for various reasons. As an alternative, chilled potassium dichromate solution (normally used in the laboratory to prevent putrefaction of temporary preparations of live oöcysts) has been tested as a long-term preservative of sporulated oöcysts of Eimeria brunetti P.P. Levine, 1942, E. maxima Tyzzer, 1929, E. mitis Tyzzer, 1929, E. necatrix Johnson, 1930, E. praecox Johnson, 1930 and E. tenella (Railliet & Lucet, 1891) (suborder Eimeriorina Léger, 1911; family Eimeriidae Minchin, 1903). Oöcysts from faeces of chickens Gallus gallus (Linnaeus) were placed in 2.5% w/v aqueous potassium dichromate solution (PDS) and stored in the dark at 4 +/- 2 degrees C. After 23 years in storage, oöcysts of each species were administered orally to chickens and failed to initiate infections, indicating that the oöcysts were dead. Nevertheless, after about 24 years, DNA was still recoverable from the oöcysts, and the original species identifications made by classic parasitological methods were confirmed by polymerase chain reaction assays. Furthermore, after almost 25 years, microscopical examination revealed that the walls and internal structures remained well preserved in 83-98% of the oöcysts of the six species investigated. Hence, PDS is potentially suitable for the long-term preservation of sporulated coccidian oöcysts as type-specimens for taxonomic purposes. The samples used in this study are now in the care of the Natural History Museum, London, UK. It is recommended that they be monitored in like manner, by suitably qualified scientists, at intervals of about 5 years to assess their state of preservation and the recoverability of DNA. Enough material is available to monitor it until it is at least 100 years old.

Social setting: influence on the physiological response to electric shock in the rat.

A significant fall in tail blood pressure occurs in paired rats after shock-induced aggression. Pressure returns to baseline levels within 4 hours after fighting. Conversely, single rats subjected to jump threshold measurements or to shocks identical to those used in the aggression paradigm show significant elevations in tail blood pressure. The size of the pressure increase in rats shocked alone appears dependent on the intensity of the shocks, while the pressure fall in rats shocked in pairs occurs over a broad range of shock intensities.

Delta 9 -tetrahydrocannabinol and ethanol: differential effects on sympathetic activity in differing environmental setting.

Serum dopamine beta-hydroxylase activity, a useful biochemical index of peripheral sympathetic nervous activity, was measured in rats treated with Delta(9)-tetrahydrocannabinol or ethanol or both substances. After 7 days of treatment with either substance, serum dopamine beta-hydroxylase activity decreased significantly. Combined treatment with both agents enhanced the effects of each given alone. In rats subjected to immobilization stress, treatment with Delta(9)- tetrahydrocannabinol appeared to potentiate the stress-induced increase in serum enzyme activity. Treatment with ethanol, with or without Delta(9)-tetrahydrocannabinol, effectively blocked this increase in enzyme activity. These results show that both substances have significant effects on the sympathetic nervous system which are critically influenced by environmental setting.

Rat fighting behavior: serum dopamine- -hydroxylase and hypothalamic tyrosine hydroxylase.

Male Sprague-Dawley rats were subjected to 4 weeks of daily periods of immobilization stress. One of two experimental groups was allowed 1 month of recovery. After 4 weeks of stress, there was a significant increase in shockinduced fighting, in the activity of serum dopamine-beta-hydroxylase, and in the activity of hypothalamic tyrosine hydroxylase. The concentration of hypothalamic norepinephrine was not decreased. After 4 weeks of recovery, only serum dopamine-betahydroxylase activity returned to normal; it therefore appears that longterm stress may increase central catecholamine synthesis. possibly resulting in a persistent increase in aggressive behavior.

Type A behavior and elevated physiological and neuroendocrine responses to cognitive tasks.

Qualitatively distinct patterns of cardiovascular and neuroendocrine responses were observed in male college students during mental work and during sensory intake task performance. During mental work, Type A (coronary-prone) subjects showed greater muscle vasodilatation and more enhanced secretion of norepinephrine, epinephrine, and cortisol than Type B subjects. During sensory intake, Type A hyperresponsivity was found for testosterone and, among those subjects with a positive family history of hypertension, for cortisol. As a demonstration of combined cardiovascular, sympathetic nervous system, and neuroendocrine hyperresponsivity to specific cognitive tasks in Type A subjects, this study breaks ground in the search for mechanisms mediating the increased coronary disease risk among Type A persons.

Pathogenesis of Eimeria praecox in chickens: virulence of field strains compared with laboratory strains of E. praecox and Eimeria acervulina.

The pathogenesis in chickens of the apicomplexan Eimeria praecox was compared with that of Eimeria acervulina, using intestinal lesions, mucosal integrity, body weight gain (BWG) and the feed conversion ratio (FCR) as criteria. Characteristics of each species were described by combinations of polymerase chain reaction assays and classic parasitological signs. There were considerable overlaps in lengths, breadths, shape indices and volumes of the oocysts of each species. Both species caused statistically significant reductions in BWG at the lowest inocula tested (500,000 sporulated oocysts per bird of E. praecox and 250,000 of E. acervulina). E. praecox was observed for the first time to cause actual body weight loss and marked increases in FCR, as did E. acervulina. E. acervulina caused gross, white pathognomonic lesions, but E. praecox caused micro-lesions, visible in fresh tissue only with a dissecting microscope. Occasionally, lesions of the Houghton strain of E. acervulina were observed to be rounded, rather than typically "ladder-like". Both species caused villous erosion and atrophy. No mortality occurred in birds receiving up to 1 million sporulated oocysts of either species. Using BWG and FCR as criteria, the virulence of recent field strains of E. praecox from Wales (Tynygongl) and the USA (Raleigh) was compared with English laboratory strains of E. praecox (Houghton) and E. acervulina (Houghton). E. praecox (Tynygongl) was markedly more virulent than E. acervulina (Houghton), which was more virulent than E. praecox (Raleigh) and E. praecox (Houghton).

Effect of phthiocerol dimycocerosate deficiency on the transcriptional response of human macrophages to Mycobacterium tuberculosis.

The control of mycobacterial infections is dependent on the finely tuned synergism between the innate and adaptive immune responses. The macrophage is the major host cell for Mycobacterium tuberculosis and the degree of virulence of mycobacteria may influence the initial macrophage response to infection. The cell wall molecule, phthiocerol dimycocerosate (DIM), is an important virulence factor that influences the early growth of M. tuberculosis in the lungs. To explore the basis for this effect we have compared the early gene response of human THP-1 macrophages to infection with virulent M. tuberculosis and the DIM-deficient DeltafadD26 M. tuberculosis strain using microarrays. Detailed analysis revealed a common core of macrophage genes, which were rapidly induced following infection with both strains, and deficiency of DIM had no significant effect on this initial macrophage transcriptional responses. In addition to chemokines and pro-inflammatory cytokines, the early response genes included components of the Toll-like receptor signalling, antigen presentation and apoptotic pathways, interferon response genes, cell surface receptors and their ligands, including TNF-related apoptosis inducing ligand (TRAIL) and CD40, and other novel genes. Therefore, although fadD26 deficiency is responsible for the early attenuation of the growth of M. tuberculosis in vivo, this effect is not associated with differences in the initial macrophage transcriptional response.

Tracing the emergence of drug-resistance in coccidia (Eimeria spp.) of commercial broiler flocks medicated with decoquinate for the first time in the United Kingdom.

Decoquinate is a quinolone coccidiostat introduced during 1967 as an in-feed prophylactic for broiler chickens. Despite early drug-resistance problems and its age, the drug is still used commercially worldwide. Decoquinate here serves as a valuable model in a field study that addresses the dynamics and economic impact of the development of coccidial resistance to potent synthetic anticoccidial drugs. The results of this unique, hitherto unpublished, study on the initial emergence of resistance of avian coccidia (Eimeria spp.) to a new drug in the field may be of strategic value in the continued use of decoquinate or the introduction of new drugs. The commercial performance of the first 3-5 crops of broilers to be medicated with decoquinate on each of six farms was monitored during 14 months in 1968-1969, supplemented by assessments of the species, population dynamics and decoquinate-resistance of coccidia isolated from each farm. During the rearing of each flock in a single shed on each farm, oocysts were counted in fresh faecal samples collected on three occasions, and the species were identified by their morphology if possible, supported if necessary by the biological characteristics of infections in chickens. E. acervulina was the most common species, followed by E. mitis, E. maxima, E. tenella and E. praecox. E. brunetti occurred rarely, and E. necatrix was not found. Decoquinate-resistance was evident in several species during the rearing of the first decoquinate-medicated crop on each farm, although clinical coccidiosis did not occur. It was concluded that inherently resistant mutants of E. acervulina, E. brunetti, E. maxima, E. tenella, and probably also E. mitis and E. praecox, were selected from field populations by 6 weeks during their first exposure to decoquinate. During up to four more subsequent crops, cycling of resistant parasites stimulated host immunity, which had no obvious adverse impact on commercial performance. There was no apparent seasonal effect. A hypothesis is proposed to explain the sudden and rapid emergence of quinolone-resistance in the coccidia, and why bird health was not thereby compromised in these circumstances.

Relative virulences of a drug-resistant and a drug-sensitive strain of Eimeria acervulina, a coccidium of chickens.

The virulence of a field strain of the chicken coccidian parasite Eimeria acervulina (Boreham I), dually resistant to the chemically unrelated anticoccidial agents decoquinate and clopidol, was compared with that of a drug-sensitive laboratory strain (Ongar) of the same species. Following a single heavy infection (prevented from recycling), both strains exhibited pathogenic effects typical of their species, viz., pathognomonic lesions, adverse effects on body weight gain and feed conversion ratio (FCR), but no mortality. One week after infection, chicks infected with either strain had a statistically significantly worse weight gain than the uninfected control; the Boreham I strain produced more oocysts, and caused slightly more severe duodenal lesions and poorer FCRs than the Ongar strain (all those effects being non-significant). After 3 weeks, there were no significant differences between any cumulative effects of either strain, nor any differences from the uninfected control. However, from 2 to 3 weeks after infection, chicks infected with either strain had a greater feed consumption and growth rate than uninfected chicks. When chicks reared on solid floors were given lighter infections of either strain, which were allowed subsequently to recycle naturally, there were no consistent reductions in weight gains, but feed consumption was higher than that of uninfected chicks. Whatever, the mode of infection, there were no significant differences between the weights of infected and uninfected chicks after 3 weeks, but the FCR of infected chicks was usually poorer than that of uninfected chicks. The difference between the virulences of the Boreham I and Ongar strains was not greater than that between various drug-resistant strains or between various sensitive strains of several Eimeria species recorded in the literature. It is therefore concluded that there was no difference between the virulences of the two strains of E. acervulina that could be attributed to the drug-resistance of one of them.

Counting coccidial oocysts in chicken faeces: a comparative study of a standard McMaster technique and a new rapid method.

For the assessment of coccidial oocyst production by chickens, some modified form of the McMaster counting method is commonly used. The objective of this study was to evaluate a standard method and to compare it to a new, faster method, in which all the preparative stages before counting are carried out in the same container into which the original faecal sample was collected. A stock suspension containing purified oocysts of all seven valid Eimeria species that parasitize chickens was prepared, from which seven concentrations of oocyst suspensions were made. Since the faecal material in a sample influences the ability of oocysts to float up in a McMaster chamber, the new method was tested to establish the optimal amount of faeces in the original sample. Control oocyst suspensions containing no faeces were also tested, and three series of counts using the new method were compared with the standard McMaster method. The results were statistically analysed by agreement analysis. Repeatability and between-operator variation of both methods were also tested by agreement analysis. Counting by the standard McMaster method underestimated the true number of oocysts. The new method gave counts in agreement with the true number of oocysts if using 1 g of faeces per sample. With 2 g of faeces, counts were obtained that agreed with counts by the standard McMaster method. Both methods showed agreement between repeated measurements. The new method used on a sample containing 2 g of faeces provides a convenient alternative to the standard modified McMaster method. A 1-g faecal sample increases agreement with the true numbers of oocysts. Processing of a sample with the new method is about nine times faster than with the standard method.

Dimensional diagnosis and the medical student's grasp of psychiatry.

Two problems that interfere with the student's understanding and acceptance of psychiatric knowledge result largely from the use of a categorical model for psychiatric diagnosis. These two problems are: (1) the apparent inapplicability of the standard system of psychiatric diagnosis to real patients; and (2) the apparent irrelevance for general medical practice of psychiatric diagnosis and theory. Both problems may be avoided by presenting psychiatry in the framework of a multidimensional diagnostic schema that used familiar terms but treats them as dimensions with severe, moderate, and mild degrees of impairment rather than as categories of mutually exclusive psychiatric diseases. A teaching program is described in which detailed review of student interviews with psychiatric and especially nonpsychiatric patients is employed to demonstrate the usefulness of multidimensional psychiatric diagnosis.

Psychosocial correlates of job strain in a sample of working women.

BACKGROUND: This study identifies potential mediators of job strain effects on health by determining whether psychosocial factors known to predict an increased risk of cardiovascular disease and all-cause mortality are higher among women who report high levels of job strain. METHODS: Measures of job strain and other psychosocial risk factors were obtained in a sample of 152 female employees of a local corporation. Canonical correlation and analyses of covariance were used to assess relationships between job demands and decision latitude and other psychosocial risk factors. RESULTS: A significant (P = .002) solution to the canonical correlation analysis showed that high job demands and low decision latitude were correlated with a pattern of psychosocial factors consisting of (1) increased levels of negative emotions like anxiety, anger, depression, and hostility; (2) reduced levels of social support; and (3) a preponderance of negative compared with positive feelings in dealings with coworkers and supervisors. This pattern was confirmed by analyses of covariance that adjusted for demographic and specific job characteristics. CONCLUSIONS: The canonical correlation analysis results provide empirical support for the job strain construct. The most important finding is that health-damaging psychosocial factors like job strain, depression, hostility, anxiety, and social isolation tend to cluster in certain individuals.

Effects of oxidized LDL on mononuclear phagocytes: inhibition of induction of four inflammatory cytokine gene RNAs, release of NO, and cytolysis of tumor cells.

A critical step in development of atherosclerosis is the interaction of oxidized low-density lipoprotein (LDL) with mononuclear phagocytes. Oxidized LDL, as well as acetyl-LDL, is rapidly taken up into macrophages via a family of scavenger receptors. We report that macrophages treated with oxidized LDL have markedly lower levels of mRNA specific for the genes MCP-1, TNF-alpha, IL-1 alpha, and KC as measured by Northern blot analyses of lipopolysaccharide (LPS)-stimulated macrophages. By contrast, acetyl-LDL does not inhibit these genes at the doses at which oxidized-LDL is effective. Similar effects are observed whether the LDL is oxidized in the presence of Cu2+ or of Fe2+. Such inhibition also occurs when maleylated bovine serum albumin (BSA), which also clears by one or more scavenger receptors on macrophages, is used as the stimulant. Fe2+ or Cu2+ oxidized LDL inhibits release of nitric oxide when triggered by LPS and direct cytolysis of tumor cells when triggered by maleylated BSA or LPS. Taken together, the data presented indicate that oxidized LDL inhibits induction of several important gene RNAs as well as functional markers that characterize the development of inflammatory and fully activated macrophages.

The efficacy of a mixture of trimethoprim and sulphaquinoxaline against Plasmodium gallinaceum malaria in the domesticated fowl Gallus gallus.

The apicomplexan parasite Plasmodium gallinaceum has not been much studied from the veterinary standpoint. Although it causes malaria in domesticated chickens, no effective drugs appear to be commercially available. A mixture of trimethoprim and sulphaquinoxaline (TMP/SQX, ratio 1:3), with a wide spectrum of activity against bacteria and coccidia, is here shown to be also efficacious against blood-induced P. gallinaceum malaria when administered therapeutically in the feed of chickens for 5-day periods, beginning on the day before infection, or on the day of infection, or up to four days after infection. Chickens were protected against mortality and reduction of weight gain. Three other criteria of efficacy, which showed good correlation with each other and also with the two commercial performance criteria, were the production of green diarrhoea (due to biliverdin), parasitaemia and reduced haematocrit values. When TMP/SQX treatments were initiated sooner than five days after infection, parasites were almost entirely eliminated from the blood, whereas treatments initiated later than four days after infection failed to protect birds against clinical disease. Birds protected by TMP/SQX against primary infection with P. gallinaceum were immune to clinical malaria when exposed to a severe blood-induced challenge of P. gallinaceum 28 days later.

Risk factors for epistaxis on British racecourses: evidence for locomotory impact-induced trauma contributing to the aetiology of exercise-induced pulmonary haemorrhage.

REASONS FOR PERFORMING STUDY: The proposed biological mechanisms for exercise-induced pulmonary haemorrhage (EIPH) are many and varied. Better knowledge of risk factors should lead to achievable measures to reduce the incidence. OBJECTIVES: To identify risk factors associated with epistaxis following racing in UK Thoroughbreds, to gain possible insights into the pathogenesis of the condition and to investigate the association between epistaxis and race finishing position. METHODS: The association of epistaxis occurring on UK racecourses between 1996 and 1998 with a wide range of race-, horse- and start-level variables was examined in multivariable mixed effect logistic regression analyses. Four multivariable analyses were conducted, one for all race types considered collectively and one each for flat, hurdle and steeplechase race types considered separately. RESULTS: Risk of epistaxis was significantly increased for hurdle and steeplechase race types compared to both flat and National Hunt flat races. In 3 of the 4 final models, there was a significant biological trend for increasing risk of epistaxis with increasing ground hardness ('going') and accumulated years spent racing. However, in flat races epistaxis was such a rare outcome (0.33 cases per 1000 starts) that this subset analysis had insufficient power to measure the detectable effect of 'going' as statistically significant. Horses with epistaxis were significantly more likely to have a poorer finishing position than those without blood at the nostrils. CONCLUSIONS: Findings were consistent with the theory that locomotory impact-induced trauma contributes to exercise-induced epistaxis. Further validation of this hypothesis through application of similar methods to endoscopically visible EIPH and through biomechanical studies is warranted. POTENTIAL RELEVANCE: Knowledge of significant risk factors should allow formulation of practical measures, such as track watering, to reduce the risks of EIPH and epistaxis in racehorses.

Changes in the collagen of rat heart in copper-deficiency-induced cardiac hypertrophy.

Groups of rats were maintained from weaning on copper-supplemented or copper-deficient diets. After 2, 4, 6, 8 or 12 weeks animals were killed, their hearts were removed and the solubility and phenotype composition of the collagen of the hearts was studied. In the hearts from the copper-supplemented animals 35 to 45% of the collagen could be extracted after two treatments with pepsin but up to 74% could be extracted from the hypertrophied copper-deficient hearts. Almost all of the increase in the soluble material was found in the first pepsin extract. Electrophoretic analysis of the extracts showed that in the copper-supplemented hearts the ratio of Type III/Type I collagen increased about threefold between 2 and 6 weeks after weaning but by 8 weeks it had returned to about the level found at 2 weeks and was maintained at this level to the end of the experimental period. In the copper-deficient hearts the ratio of Type III/Type I collagen had increased about fivefold by 6 weeks after weaning and from 8 weeks to the end of the experimental period it remained at two to three times the value found in the copper-supplemented hearts. There was an indication that the relative proportion of Type V collagen was reduced in the copper-deficient hearts. The possible significance of these results in relation to the known pathological effects of copper deficiency on the cardiovascular system is discussed.