Tyrosinase family proteins are antigens specific to Vogt-Koyanagi-Harada disease

Vogt-Koyanagi-Harada (VKH) disease (and sympathetic ophthalmia) is an ocular inflammatory disease that is considered to be a cell-mediated autoimmune disease against melanocytes. The purpose of this study was to determine the Ags specific to VKH disease and to develop an animal model of VKH disease. We found that exposure of lymphocytes from patients with VKH disease to peptides (30-mer) derived from the tyrosinase family proteins led to significant proliferation of the lymphocytes. Immunization of these peptides into pigmented rats induced ocular and extraocular changes that highly resembled human VKH disease, and we suggest that an experimental VKH disease was induced in these rats. We conclude that VKH disease is an autoimmune disease against the tyrosinase family proteins.     

A similarity-based method for genome-wide prediction of disease-relevant human genes

MOTIVATION: A method for prediction of disease relevant human genes from the phenotypic appearance of a query disease is presented. Diseases of known genetic origin are clustered according to their phenotypic similarity. Each cluster entry consists of a disease and its underlying disease gene. Potential disease genes from the human genome are scored by their functional similarity to known disease genes in these clusters, which are phenotypically similar to the query disease. RESULTS: For assessment of the approach, a leave-one-out cross-validation of 878 diseases from the OMIM database, using 10672 candidate genes from the human genome, is performed. Depending on the applied parameters, in roughly one-third of cases the true solution is contained within the top scoring 3% of predictions and in two-third of cases the true solution is contained within the top scoring 15% of predictions. The prediction results can either be used to identify target genes, when searching for a mutation in monogenic diseases or for selection of loci in genotyping experiments in genetically complex diseases.     

Epizootiology of tropical canine pancytopenia

Tropical canine pancytopenia (TCP) is a newly recognized infectious disease of dogs in diverse tropical and subtropical areas. The disease is characterized by hemorrhage, pancytopenia, severe emaciation and persistent infection. Dogs with TCP are often presented with epistaxis, which is the most dramatic sign of the disease; however, a large number of affected dogs develop severe pancytopenia and die without manifesting clinical signs of hemorrhage. The disease has been reported most frequently in the German Shepherd. Pathological findings consist of petechial and ecchymotic hemorrhages on serosal and mucosal surfaces of numerous organs. The most prominent histological finding is a perivascular plasma cell infiltrate in most organs. Disease, indistinguishable from the natural disease, has been produced in laboratory dogs inoculated with whole blood from affected dogs. Ehrlichia canis has been consistently recovered from all experimentally infected dogs. Attempts to transmit the disease to other laboratory animals and to propagate the agent in cell cultures and embryonating eggs have been unsuccessful. The tick is the probable vector of the disease.     

The association between periodontal disease and periosteal lesions in the St. Mary Graces cemetery, London, England A.D. 1350-1538

Numerous studies have demonstrated significant associations between periodontal disease and many other diseases in living populations, and some studies have shown that individuals with periodontal disease are at elevated risks of mortality. Recent analysis of a medieval skeletal sample from London has also shown that periodontal disease was associated with increased risks of mortality in the past. This study examines whether periodontal disease is associated with periosteal lesions in a skeletal sample from the urban St. Mary Graces cemetery (n = 265) from medieval London. The results reveal a significant association between periodontal disease and periosteal lesions in the St. Mary Graces sample (i.e., individuals with periodontal disease were also likely to have periosteal lesions), and the association between the two is independent of age. The association between the two pathological conditions might reflect underlying reduced immune competence and thus heightened susceptibility to pathogens that cause periodontal disease or periosteal lesions, exposure to an environmental factor, or underlying heightened inflammatory responses.     

The incidence and distribution of some diseases of the adult honeybee (Apis mellifera L.) in England and Wales

Although epidemics of bee disease have been repoited in Europe for hundreds of years it was not until recent times that detailed notes on the incidence and distribution of one of these epidemics, the so-called 'Isle of Wight disease' epidemic, were made.
Since 1918 four complaints of the adult honeybee, acarine disease, Nosema disease, Amoeba disease and bee paralysis, have been recognized in this country.
Surveys in England and Wales to determine the incidence and distribution of acarine disease, Nosema disease and Amoeba disease were carried out during the winters of 1941-2 and 1943-4. These surveys showed that none of these diseases is clearly confined to any definite areas of England and Wales. Acarine disease is, however, apparently more abundant in the west and south-west; and Nosema disease appears to be most prevalent in Buckinghamshire, Hertfordshire, Middlesex and Surrey, and also has other areas of heavy infection in Leicestershire and Cumberland, Lancashire and Yorkshire.
Sufficient cases of Amoeba disease have not yet been recorded for it to be possible to conclude that any one area is more heavily infected than another. It is estimated that approximately one out of every five or six of the colonies of bees in England and Wales is suffering from acarine disease. Less than 1% are likely to be suffering from Nosema or Amoeba disease. Bee paralysis is both common and widespread, but probably does little serious harm.     

Histoplasmosis—A Review of Three Cases Studied in San Diego County

Three cases of histoplasmosis, a disease seldom reported in California, were diagnosed clinically by the authors in San Diego County. It is probable that there is a higher incidence of this disease in California than is at present recognized.Travel history, histoplasmin skin testing and serologic studies for mycotic infection are important in the diagnosis. Cultures of secretions and biopsy material are of great value if positive; but negative cultures (at least in non-endemic areas) do not rule out the disease. Travel and migration to and from endemic areas present opportunities for this disease to constitute a diagnostic problem far from the geographic area in which the disease was acquired.Although usually benign, histoplasmosis may be severe in the acute state, may disseminate or may be chronically active and progressive. Amphotericin B is the only effective chemotherapeutic agent and it is usually reserved for these forms of the disease.     

Bayesian modeling of incidence and progression of disease from cross-sectional data

In the absence of longitudinal data, the current presence and severity of disease can be measured for a sample of individuals to investigate factors related to disease incidence and progression. In this article, Bayesian discrete-time stochastic models are developed for inference from cross-sectional data consisting of the age at first diagnosis, the current presence of disease, and one or more surrogates of disease severity. Semiparametric models are used for the age-specific hazards of onset and diagnosis, and a normal underlying variable approach is proposed for modeling of changes with latency time in disease severity. The model accommodates multiple surrogates of disease severity having different measurement scales and heterogeneity among individuals in disease progression. A Markov chain Monte Carlo algorithm is described for posterior computation, and the methods are applied to data from a study of uterine leiomyoma.     

Using Qualitative Disease Risk Analysis for Herpetofauna Conservation Translocations Transgressing Ecological and Geographical Barriers

Through the exploration of disease risk analysis methods employed for four different UK herpetofauna translocations, we illustrate how disease hazards can be identified, and how the risk of disease can be analysed. Where ecological or geographical barriers between source and destination sites exist, parasite populations are likely to differ in identity or strain between the two sites, elevating the risk from disease and increasing the number and category of hazards requiring analysis. Simplification of the translocation pathway through the avoidance of these barriers reduces the risk from disease. The disease risk analysis tool is intended to aid conservation practitioners in decision making relating to disease hazards prior to implementation of a translocation.     

Uptake and metabolism of radioactively labeled sphingomyelin in cultured skin fibroblasts from controls and patients with Niemann-Pick disease and other lysosomal storage diseases

The metabolism of [stearoyl-1-14C]- and [choline-methyl-14C]sphingomyelin, [stearoyl-1-14C]ceramide-1-phospho-N,N-dimethylethanolamine (demethylsphingomyelin) and [choline-methyl-14C]phosphatidylcholine was measured 1, 3 and 5 days after uptake from the media of cultured skin fibroblasts. This was done to measure the relative contributions of lysosomal sphingomyelinase and plasma membrane phosphocholine transferase on the metabolism of sphingomyelin, a component of all cell membranes. By using cell lines from controls and from patients with Niemann-Pick disease and other lysosomal storage diseases, it was concluded that a significant portion (10-15%) of the observed degradation of sphingomyelin is due to exchange of the phosphocholine moiety producing phosphatidylcholine. Although cell lines from type A and B Niemann-Pick disease have only 0-2% of lysosomal sphingomyelinase activity measured in vitro, three cell lines from type B Niemann-Pick disease could metabolize 54.4% of the labeled sphingomyelin by day 3 while cell lines from type A Niemann-Pick disease could only metabolize 18.5% by day 3. This compares to 86.7% metabolized in control cells by day 3. Cells from one patient with juvenile Niemann-Pick disease and one with type D Niemann-Pick disease metabolized sphingomyelin normally while cells from two other patients with juvenile or type C Niemann-Pick disease could only metabolize 58.2% by day 3. Cells from patients with I-cell disease and 'lactosylceramidosis' also demonstrated decreased metabolism of sphingomyelin (55.1 and 54.9% by day 3, respectively). Cells from the patient with Farber disease accumulated [14C]stearic acid-labeled ceramide produced from [14C]sphingomyelin. Studies with choline-labeled sphingomyelin and phosphatidylcholine demonstrated that phosphocholine exchange takes place in either direction in the cells, and this is normal in Niemann-Pick disease. Studies in cells from patients with all clinical types of sphingomyelinase deficiency have led to new methods for diagnosis and prognosis and to a better understanding of sphingomyelin metabolism.     

Efficacy of the APimicos-B to control and prevent chalkbrood disease in honey bees

Chalkbrood disease in Apis mellifera is a fungal disease affecting developing brood, infested larvae become mummified. As it is a factorial disease, studies on this pathology are obstructed by the need of some predisposing conditions which must occur for such disease to develop. Thus, many questions are yet to be answered about which treatments to apply. The aim of this work is to evaluate the efficacy of the Apimicos-B, a treatment against chalk brood. To induce the disease, some pieces of combs containing susceptible worker brood both from infected and treated colonies and from infected and untreated colonies were cooled. No significant differences were registered (53.12% and 59.58% of mummification respectively).     

Case Fatality Proportion

A precise definition of case fatality proportion for compartmental disease transmission models with disease induced mortality rate is given. This is applied in classical epidemic modeling frameworks to models with multiple infectious stages, with multi-groups, with spatial patches, and with age of infection. It is shown that the case fatality proportion is the sum over all stages of the product of the probability of dying from the disease at a given stage and the probability of surviving to that stage. The derived expressions for case fatality can be used to estimate the disease induced death rates from more readily available data.     

Apollo, sudden death, and Homer's "Odyssey": a warning from the past that we may be unable to eradicate coronary artery disease

Over recent years there has been a gratifying decrease in the incidence of recorded deaths from coronary artery disease in the Western world. The common view is that coronary artery disease is a recent phenomenon, that we have been subject to an epidemic in the mid-20th century that is now tailing off, and that with appropriate risk modification we may eradicate this disease or make it very rare. However, this article examines the cases of sudden, nontraumatic death described in Homer's Odyssey, which dates from c. 800 BCE. The results suggest that a high incidence of death from coronary artery disease may not be a recent phenomenon. Together with other described evidence, this study casts doubt on the view that coronary artery disease is a modern epidemic that can be eradicated.     

Immunology and immunotherapy of Alzheimer's disease

Although Alzheimer's disease is considered to be a degenerative brain disease, it is clear that the immune system has an important role in the disease process. As discussed in this Review, immune-based therapies that are designed to remove amyloid-beta peptide from the brain have produced positive results in animal models of the disease and are being tested in humans with Alzheimer's disease. Although immunotherapy holds great promise for the treatment of Alzheimer's disease, clinical trials of active amyloid-beta vaccination of patients with Alzheimer's disease were discontinued after some patients developed meningoencephalitis. New immunotherapies using humoral and cell-based approaches are currently being investigated for the treatment and prevention of Alzheimer's disease.     

Inhibition of nitric oxide synthase initiates relapsing remitting experimental autoimmune encephalomyelitis in rats, yet nitric oxide appears to be essential for clinical expression of disease.

Myelin basic protein-CFA-induced experimental autoimmune encephalomyelitis (EAE) in Lewis rats is an acute monophasic disease from which animals recover. In this model, spontaneous relapses do not occur and rats develop a resistance to further active reinduction of disease. Previously, we reported that oral administration of the NO synthase inhibitor N-methyl-L-arginine acetate (L-NMA) to recovered rats precipitated a second episode of disease in 100% of animals. Further studies now show that this second clinical episode is actually a chronic relapsing disease that persists for months. This occurs only in rats that have recovered from actively induced EAE and not in rats recovered from passively induced EAE, suggesting the need for a peripheral Ag depot to induce secondary disease. We have also determined that clinical signs of EAE in L-NMA-treated recovered rats do not appear until L-NMA treatment has stopped. This is despite the fact that, at the same time point, CNS inflammatory lesions in symptomless animals receiving L-NMA are qualitatively and quantitatively similar to those with severe disease symptoms from whom L-NMA treatment has been withdrawn. The latter animals have significantly higher levels of reactive nitrogen intermediates in the cerebrospinal fluid than the former group. This study examines the mechanism of reinduction of disease by L-NMA treatment, and the findings suggest a dual role for NO in regulation of pathology in EAE that is dependent on site and timing of NO production.     

A Comparison of Disease Risk Analysis Tools for Conservation Translocations

Conservation translocations are increasingly used to manage threatened species and restore ecosystems. Translocations increase the risk of disease outbreaks in the translocated and recipient populations. Qualitative disease risk analyses have been used as a means of assessing the magnitude of any effect of disease and the probability of the disease occurring associated with a translocation. Currently multiple alternative qualitative disease risk analysis packages are available to practitioners. Here we compare the ease of use, expertise required, transparency, and results from, three different qualitative disease risk analyses using a translocation of the endangered New Zealand passerine, the hihi (Notiomystis cincta), as a model. We show that the three methods use fundamentally different approaches to define hazards. Different methods are used to produce estimations of the risk from disease, and the estimations are different for the same hazards. Transparency of the process varies between methods from no referencing, or explanations of evidence to justify decisions, through to full documentation of resources, decisions and assumptions made. Evidence to support decisions on estimation of risk from disease is important, to enable knowledge acquired in the future, for example, from translocation outcome, to be used to improve the risk estimation for future translocations. Information documenting each disease risk analysis differs along with variation in emphasis of the questions asked within each package. The expertise required to commence a disease risk analysis varies and an action flow chart tailored for the non-wildlife health specialist are included in one method but completion of the disease risk analysis requires wildlife health specialists with epidemiological and pathological knowledge in all three methods. We show that disease risk analysis package choice may play a greater role in the overall risk estimation of the effect of disease on animal populations involved in a translocation than might previously have been realised.     

A stochastic compartment model representation of chronic disease dependence: Techniques for evaluating parameters of partially unobserved age inhomogeneous stochastic processes

Human disease states are commonly viewed in one of two ways. First, there is the clinical definition of disease as the presence or absence of a pathological condition. Second, there is the biologist's representation of disease as a point in a multivariate space of continuous physiological variables associated with suboptimal performance and survival. We present a model to represent dependency between multiple disease processes. The model is consistent with both concepts of disease and is designed to be estimated in the usual context of chronic disease information, i.e., a general lack of information about the time of disease incidence and progression. Consideration is made of the effects of individuals' differential susceptibility to disease and how these effects distinguish the disease incidence functions estimated at the individual level from those estimated for a population.     

Unchanged prevalence of shell disease in the edible crab Cancer pagurus four years after decommissioning of a sewage outfall at Langland Bay, UK

Shell disease is a bacteria-associated degradative disease of the crustacean exoskeleton that leads to formation of extensive lesions in the cuticle with ultimate involvement of haemocoelic septicaemia. Field surveys of edible crabs Cancer pagurus from Langland Bay, Gower, UK, from February 1997 to March 1998 had revealed unusually high prevalence (ca. 55%) of this disease amongst the population, and it was suggested that one of the predisposing factors might have been the presence of raw sewage in this area. Since February 1999, a local raw sewage outfall affecting this area has been decommissioned, raising the possibility that the prevalence and severity of this disease could have become reduced as a result of the cessation of sewage exposure. Therefore, the aim of this study was to compare the prevalence and severity of shell disease in edible crabs from Langland Bay pre- and post-sewage discharge. The overall prevalence of shell disease from February 2003 to March 2004 was 59.2%, and in only 1 size class (80-99 mm carapace width, males) was the prevalence higher in 2003-04 than in 1997-98. In terms of severity, only smaller crabs (60-199 mm width) showed a significant reduction in 2003-04 compared with 1997-98. No changes were found in the severity of the disease in different regions of the exoskeleton of infected crabs between the 1997-98 survey and the present work. Overall, it is concluded that no significant changes in the occurrence of shell disease have resulted from the improvement in water quality (in terms of faecal pollution) at this site, suggesting that sewage pollution is probably not a major contributory factor to this disease.     

Using Qualitative Disease Risk Analysis for Herpetofauna Conservation Translocations Transgressing Ecological and Geographical Barriers

Through the exploration of disease risk analysis methods employed for four different UK herpetofauna translocations, we illustrate how disease hazards can be identified, and how the risk of disease can be analysed. Where ecological or geographical barriers between source and destination sites exist, parasite populations are likely to differ in identity or strain between the two sites, elevating the risk from disease and increasing the number and category of hazards requiring analysis. Simplification of the translocation pathway through the avoidance of these barriers reduces the risk from disease. The disease risk analysis tool is intended to aid conservation practitioners in decision making relating to disease hazards prior to implementation of a translocation.

     

Oxidative and non-oxidative DNA damage and cardiovascular disease

Evidence for the association of DNA damage with cardiovascular disease has been obtained from in vitro cell culture models, experimental cardiovascular disease and analysis of samples obtained from humans with disease. There is general acceptance that several factors associated with the risk of developing cardiovascular disease cause oxidative damage to DNA in cell culture models with both nuclear and mitochondrial DNA as targets. Moreover, evidence obtained over the past 10 years points to a possible mechanistic role for DNA damage in experimental atherosclerosis culminating in recent studies challenging the assumption that DNA damage is merely a biomarker of the disease process. This kind of mechanistic insight provides a renewed impetus for further studies in this area.