A full-length cDNA infectious clone of North American type 1 porcine reproductive and respiratory syndrome virus: expression of green fluorescent protein in the Nsp2 region

The recent emergence of a unique group of North American type 1 porcine reproductive and respiratory syndrome virus (PRRSV) in the United States presents new disease control problems for a swine industry that has already been impacted seriously by North American type 2 PRRSV. In this study, a full-length cDNA infectious clone was generated from a low-virulence North American type 1 PRRSV isolate, SD01-08. In vitro studies demonstrated that the cloned virus maintained growth properties similar to those of the parental virus. Virological, pathological, and immunological observations from animals challenged with cloned viruses were similar to those from animals challenged with the parental virus and a modified live virus vaccine. To further explore the potential use as a viral backbone for expressing foreign genes, the green fluorescent protein (GFP) was inserted into a unique deletion site located at amino acid positions 348 and 349 of the predicted Nsp2 region in the virus, and expression of the Nsp2-GFP fusion protein was visualized by fluorescent microscopy. The availability of this North American type 1 infectious clone provides an important research tool for further study of the basic viral biology and pathogenic mechanisms of this group of type 1 PRRSV in the United States.     

猪繁殖与呼吸综合征病毒分子生物学研究进展

猪繁殖与呼吸综合征是由猪繁殖与呼吸综合征病毒(PRRSV)诱发的一种接触性传染病,其症状主要表现为怀孕母猪流产、早产、产死胎、木乃伊胎及成年猪的呼吸道症状。本病自1987年在美国爆发后,给世界养猪业造成巨大损失。近年来,由于其危害性大而引起专家学者的关注,PRRS在分子生物学方面研究者较多。就其病原特性,基因结构,病毒蛋白,分子生物学诊断以及PRRS基因工程疫苗的研究等方面进行论述。     

Wegener's Granulomatosis: A Review of Three Cases

Clinical and autopsy features in three cases of Wegener''s granulomatosis are presented. The disease is characterized by the triad of necrotizing granulomatous lesions of the respiratory tract, segmental necrotizing angiitis of arteries and veins, and necrotizing glomerulitis commonly terminating in uremia. Correct antemortem diagnosis was made in two of the three cases-in one by recognition of the characteristic triad and in the other by a biopsy from the antrum. Pathological lesions were chiefly in respiratory tract, spleen, kidneys and blood vessels. Necrotizing granulomatous lesions were present in the lungs. Glomerular lesions were particularly severe and wide-spread in two of the three patients, leading to uremia. Trabeculitis of the spleen, an unusual lesion, was a noticeable feature in all three. Fibrinoid necrosis, with little or no inflammatory infiltration, was the prevailing type of vascular necrosis. The characteristics of the disease process suggest a hypersensitivity mechanism. Similarities to, but significant differences from, polyarteritis nodosa are recognized.     

Wegener's granulomatosis: clinico-radiological finding at initial presentation

Diagnosis of Wegener's granulomatosis at the early stage is difficult because of the nonspecific symptoms which mimic other disorders. The aim of this paper is to describe clinical and radiological features of Wegener's granulomatosis (WG) in a Serbian population at initial presentation. A retrospective review of 37 patient's case records was carried out. All those patients were diagnosed with WG and they attended the Institute for lung diseases in Belgrade over the period of 15 years. There were 20 males and 17 females, ranging in age from 18 to 73 years (mean age 46.2 years). The mean period from the onset of the first symptoms to diagnosis of WG was 4.59 +/- 6.15 months. The criteria of American College of Rheumatology were fulfilled in all patients. Twenty-five of 37 patients had systemic, generalized form of WG and while 12 of them had a limited involvement of upper and lower respiratory system. The frequency of different system involvement was: upper respiratory tract 64.8%, lower respiratory tract 100%, kidneys 67.5%, musculoskeletal system 40.5%, skin 27.2%, eyes 8.1%, and nervous system two patients. ANCA (antineutrophil cytoplasmic antibodies) test was positive in 32 ((86.5%) patients, and negative in 5 (13.5%). All patients were ANA negative. Histological evidence of granulomatous vasculitis was obtained in 34 (91.9%), whereas in three patients the diagnosis was based on clinical manifestations and positive c-ANCA test. There are minor variations in our data when compared with those reported in literature.     

Medical malpractice in perspective. I--The American experience.

Concern over the possibility of an American style medical malpractice "crisis" in the United Kingdom has recently been voiced by members of both medical and legal professions. The validity of such fears is examined by reviewing the conditions that have given rise to the current American difficulties. It is argued that the rise in malpractice insurance premiums and associated restrictions in availability should be seen against the background of underwriting problems specific to medical liability in conjunction with a general decline in reinsurance cover. The evidence in relation to the clinical and resource implications of malpractice is analysed. In particular, arguments that increased litigation has influenced the practice of "defensive" medicine and the choice of specialty are critically examined. Medical malpractice claims and insurance are only part of a professional environment which is undergoing dramatic social and economic changes, many of which seem more plausible candidates to be treated as important influences on the nature and organisation of health care in the United States.     

Britton Chance (1913-2010)--from sailing to biophysics and biochemistry and back

A short CV of Britton Chance, an outstanding American biophysicist and biochemists, who has passed away in November 2010, is presented. Chance invented and applied in biochemical research fast recording of difference spectra during chemical reactions. Due to this technique he discovered and studied formation of enzyme-substrate complexes as exemplified by the peroxidase reaction. He also described spectral changes of electron carriers of mitochondrial respiratory chain that accompany transition from the resting to the active (phosphorylating) states. Applying vibrating platinum electrode, he recorded changes in the rate of oxygen uptake by isolated mitochondria in resting and phosphorylating states and defined the so-called respiratory states, called after his name. He was the first to describe formation of reactive oxygen species by mitochondria. Britton Chance was a devoted yachtsman and won a gold medal for the United States in sailing at the 1952 Olympic Games in Helsinki.     

Focus: Allergic Diseases and Type II Immunity: Amlexanox: A Novel Therapeutic for Atopic,Metabolic, and Inflammatory Disease

Amlexanox, a small molecule targeted therapy which has been used in the treatment of atopic conditions was previously but is not currently available in the United States. Amlexanox has also been legally utilized and administered in Japan as a treatment for asthma, a chronic pulmonary disease characterized by inflammation of the lower respiratory tract. Amlexanox’s immune modulatory effects have been the subject of studies which have repurposed the drug for potential therapeutic applications in metabolic and inflammatory disease. Because amlexanox inhibits TANK-binding kinase1 (TBK1) and nuclear factor kB kinase epsilon (IKKε), several studies have demonstrated its usefulness through its evidence downregulation of the immune system and attenuation of downstream TBK1 signaling. Novel therapies, such as amlexanox, for inflammatory conditions such as asthma will continue to be of value in clinical management. This report summarizes key applications of the drug based on animal and human studies and explores its potential in treatment of metabolic and inflammatory diseases.     

Experimental Sendai virus infection in laboratory rats. II. Pathology and immunohistochemistry

Intranasal inoculation of 5 to 8 week old specific pathogen-free Sprague-Dawley rats with 5 X 10(3) egg infectious doses of Sendai virus resulted in severe rhinitis, bronchiolitis and alveolitis. The most severe rhinitis occurred on postinoculation (PI) days 4-6, and pneumonia on day 4. Rhinitis and pneumonia persisted to PI day 21, with peribronchial lymphoid infiltration detectable at PI day 42. Immunohistochemical studies showed that Sendai virus antigens were present primarily in columnar epithelial cells of the respiratory mucosa of the nasal cavity and in bronchiolar and alveolar epithelium. Antigen was first detectable at PI day 1, was most prominent at days 3-4 and was undetectable after day 7. More antigen could be seen in the nasal mucosa than in the lung at any stage in the infection. These studies show that Sendai virus by itself is capable of evoking severe, although transient, rhinitis and pneumonia in laboratory rats free of other significant pathogens.     

Evidence of probable scurvy in subadults from archeological sites in North America

The authors surveyed subadult human skeletons from Native American archeological sites in the United States for evidence of skeletal lesions associated with scurvy. Geographic regions surveyed include the Midatlantic area, the Southeast (Florida), the Southwest, and the Plains. The prevalence of probable subadult scurvy ranged from zero in the Plains samples to 38% in a small sample from Florida. These data indicate the likelihood that scurvy was a significant childhood disease in many Native American groups. Reasons for variation in prevalence remain speculative but include regional and seasonal variation in food types and abundance, cultural patterns of storage and utilization, periodic food shortages, and the relative importance of corn in the diet. These factors are part of a nutritional complex that is related to disease prevalence which can be studied through evidence seen in archeological human remains.     

Impact of rhinitis on airway inflammation: biological and therapeutic implications

There is increasing evidence for a close link between the upper and the lower respiratory tracts and the fact that rhinitis has an important impact on asthma. Several clinical and experimental observations suggest a similar immunopathology between the upper and lower airways in allergic subjects. The common inflammatory process that develops in the respiratory tract explains some of the complex interactions among different clinical diseases such as rhinitis, sinusitis, asthma, bronchial hyperresponsiveness and viral infections. There are also non-inflammatory mechanisms that may contribute to the link between rhinitis and asthma. Moreover, the outcomes of various pharmacological treatments of rhinitis have recently provided further support for the hypothesis of the united airways. We discuss some of the recent observations on the nose-lung interaction and some of the novel therapeutic approaches used to treat rhinitis and asthma that arise from this.     

Detection of Borrelia burgdorferi Sensu Stricto ospC Alleles Associated with Human Lyme Borreliosis Worldwide in Non-Human-Biting Tick Ixodes affinis and Rodent Hosts in Southeastern United States

Comparative analysis of ospC genes from 127 Borrelia burgdorferi sensu stricto strains collected in European and North American regions where Lyme disease is endemic and where it is not endemic revealed a close relatedness of geographically distinct populations. ospC alleles A, B, and L were detected on both continents in vectors and hosts, including humans. Six ospC alleles, A, B, L, Q, R, and V, were prevalent in Europe; 4 of them were detected in samples of human origin. Ten ospC alleles, A, B, D, E3, F, G, H, H3, I3, and M, were identified in the far-western United States. Four ospC alleles, B, G, H, and L, were abundant in the southeastern United States. Here we present the first expanded analysis of ospC alleles of B. burgdorferi strains from the southeastern United States with respect to their relatedness to strains from other North American and European localities. We demonstrate that ospC genotypes commonly associated with human Lyme disease in European and North American regions where the disease is endemic were detected in B. burgdorferi strains isolated from the non-human-biting tick Ixodes affinis and rodent hosts in the southeastern United States. We discovered that some ospC alleles previously known only from Europe are widely distributed in the southeastern United States, a finding that confirms the hypothesis of transoceanic migration of Borrelia species.     

Pathogenesis of avian influenza (H7) virus infection in mice and ferrets: enhanced virulence of Eurasian H7N7 viruses isolated from humans

Before 2003, only occasional case reports of human H7 influenza virus infections occurred as a result of direct animal-to-human transmission or laboratory accidents; most of these infections resulted in conjunctivitis. An increase in isolation of avian influenza A H7 viruses from poultry outbreaks and humans has raised concerns that additional zoonotic transmissions of influenza viruses from poultry to humans may occur. To better understand the pathogenesis of H7 viruses, we have investigated their ability to cause disease in mouse and ferret models. Mice were infected intranasally with H7 viruses of high and low pathogenicity isolated from The Netherlands in 2003 (Netherlands/03), the northeastern United States in 2002-2003, and Canada in 2004 and were monitored for morbidity, mortality, viral replication, and proinflammatory cytokine production in respiratory organs. All H7 viruses replicated efficiently in the respiratory tracts of mice, but only Netherlands/03 isolates replicated in systemic organs, including the brain. Only A/NL/219/03 (NL/219), an H7N7 virus isolated from a single fatal human case, was highly lethal for mice and caused severe disease in ferrets. Supporting the apparent ocular tropism observed in humans following infection with viruses of the H7 subtype, both Eurasian and North American lineage H7 viruses were detected in the mouse eye following ocular inoculation, whereas an H7N2 virus isolated from the human respiratory tract was not. Therefore, in general, the relative virulence and cell tropism of the H7 viruses in these animal models correlated with the observed virulence in humans.     

Restoration of threatened species: a noble cause for transgenic trees

Some of the first applications of transgenic trees in North America may be for the conservation or restoration of threatened forest trees that have been devastated by fungal pathogens or insect pests. In some cases, where resistance has yet to be found in the natural population of a tree species, incorporating genes from other organisms may offer the only hope for restoration. In others, transgenics may play a role as part of an integrated approach, along with conventional breeding or biocontrol agents. American chestnut (Castanea dentata) was wiped out as a canopy species by a fungal disease accidentally introduced into the United States around 1900. Similarly, American elm (Ulmus americana) virtually disappeared as a favored street tree from Northeastern U.S. cities after the introduction of the Dutch elm disease fungus in the 1940s. In both cases, progress has been made toward restoration via conventional techniques such as selection and propagation of tolerant cultivars (American elm) or breeding with a related resistant species (American chestnut). Recently, progress has also been made with development of systems for engineering antifungal candidate genes into these “heritage trees.” An Agrobacterium-leaf disk system has been used to produce transgenic American elm trees engineered with an antimicrobial peptide gene that may enhance resistance to Dutch elm disease. Two gene transfer systems have been developed for American chestnut using Agrobacterium-mediated transformation of embryogenic cultures, setting the stage for the first tests of potential antifungal genes for their ability to confer resistance to the chestnut blight fungus. Despite the promise of transgenic approaches for restoration of these heritage trees, a number of technical, environmental, economic, and ethical questions remain to be addressed before such trees can be deployed, and the debate around these questions may be quite different from that associated with transgenic trees developed for other purposes.     

Epidemic 2014 Enterovirus D68 Cross-Reacts with Human Rhinovirus on a Respiratory Molecular Diagnostic Platform

Enterovirus D68 (EV-D68) is an emerging virus known to cause sporadic disease and occasional epidemics of severe lower respiratory tract infection. However, the true prevalence of infection with EV-D68 is unknown, due in part to the lack of a rapid and specific nucleic acid amplification test as well as the infrequency with which respiratory samples are analyzed by enterovirus surveillance programs. During the 2014 EV-D68 epidemic in the United States, we noted an increased frequency of “low-positive” results for human rhinovirus (HRV) detected in respiratory tract samples using the GenMark Diagnostics eSensor respiratory viral panel, a multiplex PCR assay able to detect 14 known respiratory viruses but not enteroviruses. We simultaneously noted markedly increased admissions to our Pediatric Intensive Care Unit for severe lower respiratory tract infections in patients both with and without a history of reactive airway disease. Accordingly, we hypothesized that these “low-positive” RVP results were due to EV-D68 rather than rhinovirus infection. Sequencing of the picornavirus 5’ untranslated region (5’-UTR) of 49 samples positive for HRV by the GenMark RVP revealed that 33 (67.3%) were in fact EV-D68. Notably, the mean intensity of the HRV RVP result was significantly lower in the sequence-identified EV-D68 samples (20.3 nA) compared to HRV (129.7 nA). Using a cut-off of 40 nA for the differentiation of EV-D68 from HRV resulted in 94% sensitivity and 88% specificity. The robust diagnostic characteristics of our data suggest that the cross-reactivity of EV-D68 and HRV on the GenMark Diagnostics eSensor RVP platform may be an important factor to consider in making accurate molecular diagnosis of EV-D68 at institutions utilizing this system or other molecular respiratory platforms that may also cross-react.     

Perspective on the host response to human metapneumovirus infection: what can we learn from respiratory syncytial virus infections?

Human metapneumovirus (HMPV) is a recently discovered pathogen first identified in respiratory specimens from young children suffering from clinical respiratory syndromes ranging from mild to severe lower respiratory tract illness. HMPV has worldwide prevalence, and is a leading cause of respiratory tract infection in the first years of life, with a spectrum of disease similar to respiratory syncytial virus (RSV). The disease burden associated with HMPV infection has not been fully elucidated; however, studies indicate that HMPV may cause upper or lower respiratory tract illness in patients between ages 2 months and 87 years, may co-circulate with RSV, and HMPV infection may be associated with asthma exacerbation. The mechanisms and effector pathways contributing to immunity or disease pathogenesis following infection are not fully understood; however, given the clinical significance of HMPV, there is a need for a fundamental understanding of the immune and pathophysiological processes that occur following infection to provide the foundation necessary for the development of effective vaccine or therapeutic intervention strategies. This review provides a current perspective on the processes associated with HMPV infection, immunity, and disease pathogenesis.     

Cysticercosis Update

Already the most common brain parasite disease, cysticercosis has been increasingly seen throughout the American Southwest. Symptoms arise from infection with larvae of Taenia solium, the pork tapeworm. Seizures, hydrocephalus, focal deficits and chronic meningitis most commonly result. Cerebrospinal fluid eosinophilia, serology by indirect hemagglutination and computed tomography are helpful adjuncts to diagnosis. New evidence suggests that selective immunosuppression is important for the parasites'' survival and that cyst death permits renewed host immunity, which may actually precipitate an acute neurologic presentation. New larvicides, including praziquantel, are being tested in humans; caution is indicated in assessing these drugs because of the acute worsening associated with cyst death. Conventional therapy includes anticonvulsants, steroids or ventricular drainage as needed. Prevention remains the best management. Person-to-person transmission within the United States has recently been documented and merits public health scrutiny.     

North American blastomycosis in Central Canada: A review of 36 cases

Experience with 36 cases of North American blastomycosis in Central Canada is reported. Symptoms referable to the respiratory tract predominated, but no uniform clinical pattern for the disease process was evident. Cutaneous and genitourinary tract involvement was present in only a small proportion of patients. The majority of the patients resided in rural areas or were associated with some form of outdoor occupation or activity. No characteristic radiologic appearance could be identified in this series. Amphotericin B administered intravenously is the treatment of choice for this condition. North American blastomycosis is more widespread on this continent than has been previously demonstrated.     

Invasion by the marine gastropod Ocinebrellus inornatus in France: I. Scenario for the source of introduction

The rate of introduction of exotic marine species has dramatically increased during the 19th and 20th centuries. Exemplifying this trend, the marine gastropod Ocinebrellus inornatus was first detected outside its native range in 1924 on the American Pacific coast, then in 1995 on the French Atlantic coast. To determine the origin of the French populations of this invasive species, we compared a French population with populations collected in Asia—the native range—and with a population collected in the United States. Analyses of mitochondrial DNA and allozyme polymorphism revealed that the French and American populations were closely related and substantially differentiated from the Asian populations. According to our results, the most likely scenario is that the source population of the French Atlantic coast populations was located in the United States. Indeed, taken altogether, the genetic structure of Asian populations, the time lag separating the introduction on the American Pacific coast from the introduction on the French Atlantic coast and the high level of genetic diversity in the two introduced areas (indicating an absence of major founder events) are hardly compatible with a scenario in which French population resulting only from primary introduction events from the native area. Finally, although similar, the French and American populations were not identical. Thus, even if the main source population of the French populations was located in the United States, the genetic structure of French populations may have been modified by cryptic and recurrent introduction events directly from Asia.     

婴儿肉毒杆菌中毒的临床研究进展

婴儿肉毒杆菌中毒(infant botulism,IB)于1976年在美国首次被发现,常发生在12月以下婴儿中。迄今为止,在有人居住的大陆几乎都报告了IB病例。IB是肉毒杆菌孢子产生神经毒素(BONT)所导致的进行性运动神经麻痹性疾病。由于婴儿肠道菌群还未完全建立,肠道功能还未发育成熟,孢子更容易在肠道定植导致,使婴儿出现以便秘、吞咽困难、烦躁、自主神经功能障碍、肌无力和弛缓性麻痹等为主的症候群,严重影响了婴儿健康,甚至死亡。因此本文就IB的病因、发病机制、流行病学、临床表现、诊断依据和治疗进行总结归纳,以期为防治该病提供参考。     

The eugenics movement and its impact on art education in the United States

This article argues that the eugenics movement has had three major influences on education in the United States, and reveals how these influences have had an impact on visual arts education in particular. The first influence began with a debate between John Dewey and David Snedden that resulted in a two-tiered tracking system that separated college bound and vocational students. The second is the influence of eugenics on the establishment of the hierarchical framework for the public school curriculum. The third influence of eugenics discussed in this article is its impact on standardized testing. These influences have justified American imperialism in schools, and have led to the marginalization of visual arts education in the United States.