Science.gov

Sample records for acute human disease

  1. A previously unknown reovirus of bat origin is associated with an acute respiratory disease in humans

    PubMed Central

    Chua, Kaw Bing; Crameri, Gary; Hyatt, Alex; Yu, Meng; Tompang, Mohd Rosli; Rosli, Juliana; McEachern, Jennifer; Crameri, Sandra; Kumarasamy, Verasingam; Eaton, Bryan T.; Wang, Lin-Fa

    2007-01-01

    Respiratory infections constitute the most widespread human infectious disease, and a substantial proportion of them are caused by unknown etiological agents. Reoviruses (respiratory enteric orphan viruses) were first isolated from humans in the early 1950s and so named because they were not associated with any known disease. Here, we report a previously unknown reovirus (named “Melaka virus”) isolated from a 39-year-old male patient in Melaka, Malaysia, who was suffering from high fever and acute respiratory disease at the time of virus isolation. Two of his family members developed similar symptoms ≈1 week later and had serological evidence of infection with the same virus. Epidemiological tracing revealed that the family was exposed to a bat in the house ≈1 week before the onset of the father's clinical symptoms. Genome sequence analysis indicated a close genetic relationship between Melaka virus and Pulau virus, a reovirus isolated in 1999 from fruit bats in Tioman Island, Malaysia. Screening of sera collected from human volunteers on the island revealed that 14 of 109 (13%) were positive for both Pulau and Melaka viruses. This is the first report of an orthoreovirus in association with acute human respiratory diseases. Melaka virus is serologically not related to the different types of mammalian reoviruses that were known to infect humans asymptomatically. These data indicate that bat-borne reoviruses can be transmitted to and cause clinical diseases in humans. PMID:17592121

  2. NPMc+ cooperates with Flt3/ITD mutations to cause acute leukemia recapitulating human disease

    PubMed Central

    Rau, Rachel; Magoon, Daniel; Greenblatt, Sarah; Li, Li; Annesley, Colleen; Duffield, Amy S.; Huso, David; McIntyre, Emily; Clohessy, John G.; Reschke, Markus; Pandolfi, Pier Paolo; Small, Donald; Brown, Patrick

    2013-01-01

    Cytoplasmic nucleophosmin (NPMc+) mutations and FMS-like tyrosine kinase 3 (FLT3) internal tandem duplication (ITD) mutations are two of the most common known molecular alterations in acute myeloid leukemia (AML), and they frequently occur together suggesting cooperative leukemogenesis. To explore the specific relationship between NPMc+ and FLT3/ITD in vivo, we crossed Flt3/ITD knock-in mice with transgenic NPMc+ mice. Mice with both mutations develop a transplantable leukemia of either myeloid or lymphoid lineage, definitively demonstrating cooperation between Flt3/ITD and NPMc+. In mice with myeloid leukemia, functionally significant loss of heterozygosity of the wild-type Flt3 allele is common, similar to what is observed in human FLT3/ITD+ AML, providing further in vivo evidence of the importance of loss of wild-type FLT3 in leukemic initiation and progression. Additionally, in vitro clonogenic assays reveal that the combination of Flt3/ITD and NPMc+ mutations causes a profound monocytic expansion, in excess of that seen with either mutation alone consistent with the predominance of myelomonocytic phenotype in human FLT3/ITD+/NPMc+ AML. This in vivo model of Flt3/ITD+/NPMc+ leukemia closely recapitulates human disease and will therefore serve as a tool for the investigation of the biology of this common disease entity. PMID:24184354

  3. Five genome sequences of subspecies B1 human adenoviruses associated with acute respiratory disease.

    PubMed

    Dehghan, Shoaleh; Liu, Elizabeth B; Seto, Jason; Torres, Sarah F; Hudson, Nolan R; Kajon, Adriana E; Metzgar, David; Dyer, David W; Chodosh, James; Jones, Morris S; Seto, Donald

    2012-01-01

    Five genomes of human subspecies B1 adenoviruses isolated from cases of acute respiratory disease have been sequenced and archived for reference. These include representatives of two prevalent genomic variants of HAdV-7, i.e., HAdV-7h and HAdV-7d2. The other three are HAdV-3/16, HAdV-16 strain E26, and HAdV-3+7 strain Takeuchi. All are recombinant genomes. Genomics and bioinformatics provide detailed views into the genetic makeup of these pathogens and insight into their molecular evolution. Retrospective characterization of particularly problematic older pathogens such as HAdV-7h (1987) and intriguing isolates such as HAdV-3+7 strain Takeuchi (1958) may provide clues to their phenotypes and serology and may suggest protocols for prevention and treatment. PMID:22158846

  4. Mouse models and methods for studying human disease, acute kidney injury (AKI).

    PubMed

    Ramesh, Ganesan; Ranganathan, Punithavathi

    2014-01-01

    Acute kidney injury (AKI) is serious complication in hospitalized patients with high level of mortality. There is not much progress made for the past 50 years in reducing the mortality rate despite advances in understanding disease pathology. Using variety of animal models of acute kidney injury, scientist studies the pathogenic mechanism of AKI and to test therapeutic drugs, which may reduce renal injury. Among them, renal pedicle clamping and cisplatin induced nephrotoxicity in mice are most prominently used, mainly due to the availability of gene knockouts to study specific gene functions, inexpensive and availability of the inbred strain with less genetic variability. However, ischemic mouse model is highly variable and require excellent surgical skills to reduce variation in the observation. In this chapter, we describe a detailed protocol of the mouse model of bilateral renal ischemia-reperfusion and cisplatin induced nephrotoxicity. We also discuss the protocol for the isolation and analysis of infiltrated inflammatory cell into the kidney by flow cytometry. Information provided in this chapter will help scientist who wants to start research on AKI and want to establish the mouse model for ischemic and toxic kidney injury. PMID:25064118

  5. Bridging translation for acute kidney injury with better preclinical modeling of human disease.

    PubMed

    Skrypnyk, Nataliya I; Siskind, Leah J; Faubel, Sarah; de Caestecker, Mark P

    2016-05-15

    The current lack of effective therapeutics for patients with acute kidney injury (AKI) represents an important and unmet medical need. Given the importance of the clinical problem, it is time for us to take a few steps back and reexamine current practices. The focus of this review is to explore the extent to which failure of therapeutic translation from animal studies to human studies stems from deficiencies in the preclinical models of AKI. We will evaluate whether the preclinical models of AKI that are commonly used recapitulate the known pathophysiologies of AKI that are being modeled in humans, focusing on four common scenarios that are studied in clinical therapeutic intervention trials: cardiac surgery-induced AKI; contrast-induced AKI; cisplatin-induced AKI; and sepsis associated AKI. Based on our observations, we have identified a number of common limitations in current preclinical modeling of AKI that could be addressed. In the long term, we suggest that progress in developing better preclinical models of AKI will depend on developing a better understanding of human AKI. To this this end, we suggest that there is a need to develop greater in-depth molecular analyses of kidney biopsy tissues coupled with improved clinical and molecular classification of patients with AKI. PMID:26962107

  6. Molecular determinants of severe acute respiratory syndrome coronavirus pathogenesis and virulence in young and aged mouse models of human disease.

    PubMed

    Frieman, Matthew; Yount, Boyd; Agnihothram, Sudhakar; Page, Carly; Donaldson, Eric; Roberts, Anjeanette; Vogel, Leatrice; Woodruff, Becky; Scorpio, Diana; Subbarao, Kanta; Baric, Ralph S

    2012-01-01

    SARS coronavirus (SARS-CoV) causes severe acute respiratory tract disease characterized by diffuse alveolar damage and hyaline membrane formation. This pathology often progresses to acute respiratory distress (such as acute respiratory distress syndrome [ARDS]) and atypical pneumonia in humans, with characteristic age-related mortality rates approaching 50% or more in immunosenescent populations. The molecular basis for the extreme virulence of SARS-CoV remains elusive. Since young and aged (1-year-old) mice do not develop severe clinical disease following infection with wild-type SARS-CoV, a mouse-adapted strain of SARS-CoV (called MA15) was developed and was shown to cause lethal infection in these animals. To understand the genetic contributions to the increased pathogenesis of MA15 in rodents, we used reverse genetics and evaluated the virulence of panels of derivative viruses encoding various combinations of mouse-adapted mutations. We found that mutations in the viral spike (S) glycoprotein and, to a much less rigorous extent, in the nsp9 nonstructural protein, were primarily associated with the acquisition of virulence in young animals. The mutations in S likely increase recognition of the mouse angiotensin-converting enzyme 2 (ACE2) receptor not only in MA15 but also in two additional, independently isolated mouse-adapted SARS-CoVs. In contrast to the findings for young animals, mutations to revert to the wild-type sequence in nsp9 and the S glycoprotein were not sufficient to significantly attenuate the virus compared to other combinations of mouse-adapted mutations in 12-month-old mice. This panel of SARS-CoVs provides novel reagents that we have used to further our understanding of differential, age-related pathogenic mechanisms in mouse models of human disease. PMID:22072787

  7. Molecular Determinants of Severe Acute Respiratory Syndrome Coronavirus Pathogenesis and Virulence in Young and Aged Mouse Models of Human Disease

    PubMed Central

    Yount, Boyd; Agnihothram, Sudhakar; Page, Carly; Donaldson, Eric; Roberts, Anjeanette; Vogel, Leatrice; Woodruff, Becky; Scorpio, Diana; Subbarao, Kanta; Baric, Ralph S.

    2012-01-01

    SARS coronavirus (SARS-CoV) causes severe acute respiratory tract disease characterized by diffuse alveolar damage and hyaline membrane formation. This pathology often progresses to acute respiratory distress (such as acute respiratory distress syndrome [ARDS]) and atypical pneumonia in humans, with characteristic age-related mortality rates approaching 50% or more in immunosenescent populations. The molecular basis for the extreme virulence of SARS-CoV remains elusive. Since young and aged (1-year-old) mice do not develop severe clinical disease following infection with wild-type SARS-CoV, a mouse-adapted strain of SARS-CoV (called MA15) was developed and was shown to cause lethal infection in these animals. To understand the genetic contributions to the increased pathogenesis of MA15 in rodents, we used reverse genetics and evaluated the virulence of panels of derivative viruses encoding various combinations of mouse-adapted mutations. We found that mutations in the viral spike (S) glycoprotein and, to a much less rigorous extent, in the nsp9 nonstructural protein, were primarily associated with the acquisition of virulence in young animals. The mutations in S likely increase recognition of the mouse angiotensin-converting enzyme 2 (ACE2) receptor not only in MA15 but also in two additional, independently isolated mouse-adapted SARS-CoVs. In contrast to the findings for young animals, mutations to revert to the wild-type sequence in nsp9 and the S glycoprotein were not sufficient to significantly attenuate the virus compared to other combinations of mouse-adapted mutations in 12-month-old mice. This panel of SARS-CoVs provides novel reagents that we have used to further our understanding of differential, age-related pathogenic mechanisms in mouse models of human disease. PMID:22072787

  8. Murine Models of Acute Alcoholic Hepatitis and Their Relevance to Human Disease.

    PubMed

    Wilkin, Richard J W; Lalor, Patricia F; Parker, Richard; Newsome, Philip N

    2016-04-01

    Alcohol-induced liver damage is a major burden for most societies, and murine studies can provide a means to better understand its pathogenesis and test new therapies. However, there are many models reported with widely differing phenotypes, not all of which fully regenerate the spectrum of human disease. Thus, it is important to understand the implications of these variations to efficiently model human disease. This review critically appraises key articles in the field, detailing the spectrum of liver damage seen in different models, and how they relate to the phenotype of disease seen in patients. A range of different methods of alcohol administration have been studied, ranging from ad libitum consumption of alcohol and water to modified diets (eg, Lieber deCarli liquid diet). Other feeding regimens have taken more invasive routes using intragastric feeding tubes to infuse alcohol directly into the stomach. Notably, models using wild-type mice generally produce a milder phenotype of liver damage than those using genetically modified mice, with the exception of the chronic binge-feeding model. We recommend panels of tests for consideration to standardize end points for the evaluation of the severity of liver damage-key for comparison of models of injury, testing of new therapies, and subsequent translation of findings into clinical practice. PMID:26835538

  9. Human hematopoietic cell lines: a model system for study of minimal residual disease detection technique in acute leukemia.

    PubMed

    Koníková, E; Kusenda, J; Babusíková, O; Glasová, M

    1995-01-01

    these surface and cytoplasmic marker combinations minor neoplastic cell populations could be detected. Human hematopoietic cell lines could serve as a reliable model system for monitoring minimal residual disease in acute leukemia patients. PMID:8552200

  10. The role of human adenoviruses type 41 in acute diarrheal disease in Minas Gerais after rotavirus vaccination

    PubMed Central

    Reis, Thaís Aparecida Vieira; Assis, Andrêssa Silvino Ferreira; do Valle, Daniel Almeida; Barletta, Vívian Honorato; de Carvalho, Iná Pires; Rose, Tatiana Lundgren; Portes, Silvana Augusta Rodrigues; Leite, José Paulo Gagliardi; da Rosa e Silva, Maria Luzia

    2016-01-01

    Human adenovirus species F (HAdV-F) type 40 and 41 are commonly associated with acute diarrheal disease (ADD) across the world. Despite being the largest state in southeastern Brazil and having the second largest number of inhabitants, there is no information in the State of Minas Gerais regarding the role of HAdV-F in the etiology of ADD. This study was performed to determine the prevalence, to verify the epidemiological aspects of infection, and to characterize the strains of human adenoviruses (HAdV) detected. A total of 377 diarrheal fecal samples were obtained between January 2007 and August 2011 from inpatient and outpatient children of age ranging from 0 to 12 years. All samples were previously tested for rotavirus, norovirus, and astrovirus, and 314 of 377 were negative. The viral DNA was extracted, amplified using the polymerase chain reaction and the HAdV-positive samples were sequenced and phylogenetically analyzed. Statistical analyses were performed using the Chi-square test (p < 0.05), considering two conditions: the total of samples tested (377) and the total of negative samples for the remaining viruses tested (314). The overall prevalence of HAdV was 12.47% (47/377); and in 76.60% (36/47) of the positive samples, this virus was the only infectious agent detected. The phylogenetic analysis of partial sequences of 32 positive samples revealed that they all clustered with the HAdV-F type 41. The statistical analysis showed that there was no correlation between the onset of the HAdV infection and the origin of the samples (inpatients or outpatients) in the two conditions tested: the total of samples tested (p = 0.598) and the total of negative samples for the remaining viruses tested (p = 0.614). There was a significant association in the occurrence of infection in children aged 0–12 months for the condition 1 (p = 0.030) as well as condition 2 (p = 0.019). The occurrence of infections due to HAdV did not coincide with a pattern of seasonal

  11. Microcirculation in Acute and Chronic Kidney Diseases.

    PubMed

    Zafrani, Lara; Ince, Can

    2015-12-01

    The renal microvasculature is emerging as a key player in acute and chronic kidney diseases. Renal microvascular disease involves alterations in endothelial barrier permeability, exaggerated inflammation, impairment of endothelium-dependent vasorelaxation involving the nitric oxide system, increased oxidative stress, and loss of angiogenic factors. Moreover, evidence suggests that there is a microvascular component to the pathogenesis of renal scarring. New technology is being developed to explore renal microcirculation in vivo in experimental models and humans. This technology will provide a better understanding of the pathogenesis of kidney diseases and will help guide specific therapeutic strategies aimed at restoring the renal microcirculation. This article reviews the cellular and molecular mechanisms of renal microvascular dysfunction in acute and chronic kidney diseases and the potential diagnostic and therapeutic implications of these findings. Recent developments in the monitoring of renal microcirculation are described with respect to their advantages and limitations, and future directions are outlined. PMID:26231789

  12. Risk Factors for Acute Graft-Versus-Host Disease After Human Leukocyte Antigen–Identical Sibling Transplants for Adults With Leukemia

    PubMed Central

    Hahn, Theresa; McCarthy, Philip L.; Zhang, Mei-Jie; Wang, Dan; Arora, Mukta; Frangoul, Haydar; Gale, Robert Peter; Hale, Gregory A.; Horan, John; Isola, Luis; Maziarz, Richard T.; van Rood, Jon J.; Gupta, Vikas; Halter, Joerg; Reddy, Vijay; Tiberghien, Pierre; Litzow, Mark; Anasetti, Claudio; Pavletic, Stephen; Ringdén, Olle

    2008-01-01

    Purpose Acute graft-versus-host disease (GVHD) causes substantial morbidity and mortality after human leukocyte antigen (HLA)-identical sibling transplants. No large registry studies of acute GVHD risk factors have been reported in two decades. Risk factors may have changed in this interval as transplant-related techniques have evolved. Patients and Methods Acute GVHD risk factors were analyzed in 1,960 adults after HLA-identical sibling myeloablative transplant for acute myeloid leukemia (AML), acute lymphocytic leukemia (ALL), or chronic myeloid leukemia (CML) reported by 226 centers worldwide to the Center for International Blood and Marrow Transplant Research from 1995 to 2002. Outcome was measured as time from transplant to onset of grade 2 to 4 acute GVHD, with death without acute GVHD as a competing risk. Results Cumulative incidence of grade 2 to 4 acute GVHD was 35% (95% CI, 33% to 37%). In multivariable analyses, factors significantly associated with grade 2 to 4 acute GVHD were cyclophosphamide + total-body irradiation versus busulfan + cyclophosphamide (relative risk [RR] = 1.4; P < .0001), blood cell versus bone marrow grafts in patients age 18 to 39 years (RR = 1.43; P = .0023), recipient age 40 and older versus age 18 to 39 years receiving bone marrow grafts (RR = 1.44; P = .0005), CML versus AML/ALL (RR = 1.35; P = .0003), white/Black versus Asian/Hispanic race (RR = 1.54; P = .0003), Karnofsky performance score less than 90 versus 90 to 100 (RR = 1.27; P = .014), and recipient/donor cytomegalovirus-seronegative versus either positive (RR = 1.20; P = .04). Stratification by disease showed the same significant predictors of grade 2 to 4 acute GVHD for CML; however, KPS and cytomegalovirus serostatus were not significant predictors for AML/ALL. Conclusion This analysis confirmed several previously reported risk factors for grade 2 to 4 acute GVHD. However, several new factors were identified whereas others are no longer significant. These new data may

  13. Acute Werdnig-Hoffmann disease

    PubMed Central

    Pearn, J. H.; Wilson, J.

    1973-01-01

    76 cases of acute Werdnig-Hoffmann disease (acute infantile spinal muscular atrophy) have been reviewed. The cases comprise an unselected consecutive series in which rigid diagnostic criteria have been applied. The natural history of the disease has been investigated. In at least one-third of cases the disease is manifest before or at delivery. All cases have shown delayed milestones by 5 months of age: 95% are dead by 18 months. Cumulative frequency curves for age at onset and age at death figures are presented for use both as prognostic guidelines and as aids in the management of sibs of index cases. Diagnosis, management, and genetic implications are discussed. ImagesFIG. 1 PMID:4712772

  14. A Neutralizing Human Monoclonal Antibody Protects against Lethal Disease in a New Ferret Model of Acute Nipah Virus Infection

    PubMed Central

    Bossart, Katharine N.; Zhu, Zhongyu; Middleton, Deborah; Klippel, Jessica; Crameri, Gary; Bingham, John; McEachern, Jennifer A.; Green, Diane; Hancock, Timothy J.; Chan, Yee-Peng; Hickey, Andrew C.; Dimitrov, Dimiter S.; Wang, Lin-Fa; Broder, Christopher C.

    2009-01-01

    Nipah virus is a broadly tropic and highly pathogenic zoonotic paramyxovirus in the genus Henipavirus whose natural reservoirs are several species of Pteropus fruit bats. Nipah virus has repeatedly caused outbreaks over the past decade associated with a severe and often fatal disease in humans and animals. Here, a new ferret model of Nipah virus pathogenesis is described where both respiratory and neurological disease are present in infected animals. Severe disease occurs with viral doses as low as 500 TCID50 within 6 to 10 days following infection. The underlying pathology seen in the ferret closely resembles that seen in Nipah virus infected humans, characterized as a widespread multisystemic vasculitis, with virus replicating in highly vascular tissues including lung, spleen and brain, with recoverable virus from a variety of tissues. Using this ferret model a cross-reactive neutralizing human monoclonal antibody, m102.4, targeting the henipavirus G glycoprotein was evaluated in vivo as a potential therapeutic agent. All ferrets that received m102.4 ten hours following a high dose oral-nasal Nipah virus challenge were protected from disease while all controls died. This study is the first successful post-exposure passive antibody therapy for Nipah virus using a human monoclonal antibody. PMID:19888339

  15. Morbilliviruses and human disease.

    PubMed

    Rima, Bertus K; Duprex, W Paul

    2006-01-01

    Morbilliviruses are a group of viruses that belong to the family Paramyxoviridae. The most instantly recognizable member is measles virus (MV) and individuals acutely infected with the virus exhibit a wide range of clinical symptoms ranging from a characteristic mild self-limiting infection to death. Canine distemper virus (CDV) and rinderpest virus (RPV) cause a similar but distinctive pathology in dogs and cattle, respectively, and these, alongside experimental MV infection of primates, have been useful models for MV pathogenesis. Traditionally, viruses were identified because a distinctive disease was observed in man or animals; an infectious agent was subsequently isolated, cultured, and this could be used to recapitulate the disease in an experimentally infected host. Thus, satisfying Koch's postulates has been the norm. More recently, particularly due to the advent of exceedingly sensitive molecular biological assays, many researchers have looked for infectious agents in disease conditions for which a viral aetiology has not been previously established. For these cases, the modified Koch's postulates of Bradford Hill have been developed as criteria to link a virus to a specific disease. Only in a few cases have these conditions been fulfilled. Therefore, many viruses have over the years been definitely and tentatively linked to human diseases and in this respect the morbilliviruses are no different. In this review, human diseases associated with morbillivirus infection have been grouped into three broad categories: (1) those which are definitely caused by the infection; (2) those which may be exacerbated or facilitated by an infection; and (3) those which currently have limited, weak, unsubstantiated or no credible scientific evidence to support any link to a morbillivirus. Thus, an attempt has been made to clarify the published data and separate human diseases actually linked to morbilliviruses from those that are merely anecdotally associated. PMID:16362981

  16. Ultrasound in Acute Kidney Disease.

    PubMed

    Meola, Mario; Nalesso, Federico; Petrucci, Ilaria; Samoni, Sara; Ronco, Claudio

    2016-01-01

    Kidneys' imaging provides useful information in acute kidney injury (AKI) diagnosis and management. Today, several imaging techniques give information on kidneys anatomy, urinary obstruction, differential diagnosis between AKI and chronic kidney disease (CKD), renal blood flow and glomerular filtration rate. Ultrasound is a safe, non-invasive and repeatable imaging technique so it is widely used in the first level work-up of AKI. The utility of contrast-enhanced computed tomography and magnetic resonance imaging in AKI or in AKI during CKD is limited because of renal toxicity associated with contrast agents used. PMID:27169556

  17. Acute Chagas Disease in a Returning Traveler

    PubMed Central

    Carter, Yvonne L.; Juliano, Jonathan J.; Montgomery, Susan P.; Qvarnstrom, Yvonne

    2012-01-01

    Acute Chagas disease is rarely recognized, and the risk for acquiring the disease is undefined in travelers to Central America. We describe a case of acute Chagas disease in a traveler to Costa Rica and highlight the need for increased awareness of this infection in travelers to Chagas-endemic areas. PMID:23091192

  18. [Acute respiratory failure in neuromuscular disease].

    PubMed

    Damak, H; Décosterd, D

    2015-09-30

    Neuromuscular diseases can affect all respiratory muscles, leading to acute respiratory failure, which is the most common cause of morbidity and mortality in those patients. Two situations must be distinguished. 1) Acute respiratory failure as part of a neuromuscular disorder of acute onset and possibly reversible (Guillain-Barre syndrome, myasthenic crisis...). 2) Acute respiratory failure occurring in a patient with an already advanced neuromuscular disease (amyotrophic lateral sclerosis, Duchenne muscular dystrophy...). This article describes the neuromuscular acute respiratory failure in these different aspects, discusses its initial management in the emergency department and identifies the parameters that have to be monitored. PMID:26619704

  19. Focus on acute diarrhoeal disease

    PubMed Central

    Baldi, Fabio; Bianco, Maria Antonia; Nardone, Gerardo; Pilotto, Alberto; Zamparo, Emanuela

    2009-01-01

    Diarrhoea is an alteration of normal bowel movement characterized by an increase in the water content, volume, or frequency of stools. Diarrhoea needs to be classified according to the trends over time (acute or chronic) and to the characteristics of the stools (watery, fatty, inflammatory). Secretory diarrhoeas, mostly acute and of viral aetiology in more than 70% of cases, are by far the most important subtype of diarrhoeas in terms of frequency, incidence and mortality (over 2.5 million deaths/year in developing countries). Natural and synthetic opiates such as morphine, codeine, and loperamide which react with endogenous opiates (enkephalins, beta-endorphins, dynorphins) mainly act on intestinal motility and slow down transit. An antidiarrhoeal drug developed in recent years, racecadotril, acts as an enkephalinase inhibitor. Clinical studies have shown that it is just as effective as loperamide in resolving acute diarrhoea but with greater reduction in pain and abdominal distension. Some studies have explored the prevalence of diarrhoea in old age. An epidemiological study carried out in Italy by 133 General Practitioners on 5515 elderly outpatients reported a prevalence of diarrhoea, defined according to the Rome criteria, of 9.1%. Infectious diseases (19%) and drug use (16%) were the most common causes of diarrhoea in old age. Regardless of the cause, the treatment of elderly patients with diarrhoea must include rehydration and nutritional support. Every year, more than 50 million tourists travel from industrialized countries to places where hygiene levels are poor. At least 75% of those travelling for short periods mention health problems, and in particular traveller’s diarrhoea. PMID:19610134

  20. Genomic and Bioinformatics Analysis of HAdV-4, a Human Adenovirus Causing Acute Respiratory Disease: Implications for Gene Therapy and Vaccine Vector Development

    PubMed Central

    Purkayastha, Anjan; Ditty, Susan E.; Su, Jing; McGraw, John; Hadfield, Ted L.; Tibbetts, Clark; Seto, Donald

    2005-01-01

    Human adenovirus serotype 4 (HAdV-4) is a reemerging viral pathogenic agent implicated in epidemic outbreaks of acute respiratory disease (ARD). This report presents a genomic and bioinformatics analysis of the prototype 35,990-nucleotide genome (GenBank accession no. AY594253). Intriguingly, the genome analysis suggests a closer phylogenetic relationship with the chimpanzee adenoviruses (simian adenoviruses) rather than with other human adenoviruses, suggesting a recent origin of HAdV-4, and therefore species E, through a zoonotic event from chimpanzees to humans. Bioinformatics analysis also suggests a pre-zoonotic recombination event, as well, between species B-like and species C-like simian adenoviruses. These observations may have implications for the current interest in using chimpanzee adenoviruses in the development of vectors for human gene therapy and for DNA-based vaccines. Also, the reemergence, surveillance, and treatment of HAdV-4 as an ARD pathogen is an opportunity to demonstrate the use of genome determination as a tool for viral infectious disease characterization and epidemic outbreak surveillance: for example, rapid and accurate low-pass sequencing and analysis of the genome. In particular, this approach allows the rapid identification and development of unique probes for the differentiation of family, species, serotype, and strain (e.g., pathogen genome signatures) for monitoring epidemic outbreaks of ARD. PMID:15681456

  1. Genomic and bioinformatics analysis of HAdV-4, a human adenovirus causing acute respiratory disease: implications for gene therapy and vaccine vector development.

    PubMed

    Purkayastha, Anjan; Ditty, Susan E; Su, Jing; McGraw, John; Hadfield, Ted L; Tibbetts, Clark; Seto, Donald

    2005-02-01

    Human adenovirus serotype 4 (HAdV-4) is a reemerging viral pathogenic agent implicated in epidemic outbreaks of acute respiratory disease (ARD). This report presents a genomic and bioinformatics analysis of the prototype 35,990-nucleotide genome (GenBank accession no. AY594253). Intriguingly, the genome analysis suggests a closer phylogenetic relationship with the chimpanzee adenoviruses (simian adenoviruses) rather than with other human adenoviruses, suggesting a recent origin of HAdV-4, and therefore species E, through a zoonotic event from chimpanzees to humans. Bioinformatics analysis also suggests a pre-zoonotic recombination event, as well, between species B-like and species C-like simian adenoviruses. These observations may have implications for the current interest in using chimpanzee adenoviruses in the development of vectors for human gene therapy and for DNA-based vaccines. Also, the reemergence, surveillance, and treatment of HAdV-4 as an ARD pathogen is an opportunity to demonstrate the use of genome determination as a tool for viral infectious disease characterization and epidemic outbreak surveillance: for example, rapid and accurate low-pass sequencing and analysis of the genome. In particular, this approach allows the rapid identification and development of unique probes for the differentiation of family, species, serotype, and strain (e.g., pathogen genome signatures) for monitoring epidemic outbreaks of ARD. PMID:15681456

  2. Diurnal and twenty-four hour patterning of human diseases: acute and chronic common and uncommon medical conditions.

    PubMed

    Smolensky, Michael H; Portaluppi, Francesco; Manfredini, Roberto; Hermida, Ramon C; Tiseo, Ruana; Sackett-Lundeen, Linda L; Haus, Erhard L

    2015-06-01

    The symptom intensity and mortality of human diseases, conditions, and syndromes exhibit diurnal or 24 h patterning, e.g., skin: atopic dermatitis, urticaria, psoriasis, and palmar hyperhidrosis; gastrointestinal: esophageal reflux, peptic ulcer (including perforation and hemorrhage), cyclic vomiting syndrome, biliary colic, hepatic variceal hemorrhage, and proctalgia fugax; infection: susceptibility, fever, and mortality; neural: frontal, parietal, temporal, and occipital lobe seizures, Parkinson's and Alzheimer's disease, hereditary progressive dystonia, and pain (cancer, post-surgical, diabetic neuropathic and foot ulcer, tooth caries, burning mouth and temporomandibular syndromes, fibromyalgia, sciatica, intervertebral vacuum phenomenon, multiple sclerosis muscle spasm, and migraine, tension, cluster, hypnic, and paroxysmal hemicranial headache); renal: colic and nocturnal enuresis and polyuria; ocular: bulbar conjunctival redness, keratoconjunctivitis sicca, intraocular pressure and anterior ischemic optic neuropathy, and recurrent corneal erosion syndrome; psychiatric/behavioral: major and seasonal affective depressive disorders, bipolar disorder, parasuicide and suicide, dementia-associated agitation, and addictive alcohol, tobacco, and heroin cravings and withdrawal phenomena; plus autoimmune and musculoskeletal: rheumatoid arthritis, osteoarthritis, axial spondylarthritis, gout, Sjögren's syndrome, and systemic lupus erythematosus. Knowledge of these and other 24 h patterns of human pathophysiology informs research of their underlying circadian and other endogenous mechanisms, external temporal triggers, and more effective patient care entailing clinical chronopreventive and chronotherapeutic strategies. PMID:25129839

  3. An association between human leucocyte antigen alleles and acute and chronic graft-versus-host disease after allogeneic haematopoietic stem cell transplantation.

    PubMed

    Remberger, Mats; Persson, Ulla; Hauzenberger, Dan; Ringdén, Olle

    2002-12-01

    The association between various human leucocyte antigen (HLA) alleles and the occurrence of acute and chronic graft-versus-host disease (GVHD) was evaluated in 493 haematopoietic stem-cell transplant (HSCT) patients with HLA identical sibling donors. There were 307 men and 186 women with a median age of 30 years (0.2-77). Most of the patients had a haematological malignancy and received total body irradiation or busulphan combined with cyclophosphamide as conditioning before transplantation. GVHD prophylaxis consisted of monotherapy with methotrexate (MTX) or cyclosporin (CsA) in 118 patients, MTX + CsA in 323, T-cell depletion in 28 and other combinations in 24. In total, 84 patients (17%) received a peripheral blood stem-cell graft, whereas the rest received bone marrow. The cumulative incidence of acute GVHD grades II-IV was 20%, and chronic GVHD 46%. In the multivariate analysis, HLA-A10 (OR 2.14, CI 1.04-4.41, P = 0.03) and HLA-B7 (OR 1.80, CI 1.04-3.12, P = 0.03) correlated with an increased risk of acute GVHD grades II-IV. We also found an association between HLA-B27 (RR 0.60, CI 0.37-0.95, P = 0.04) and a lower incidence of chronic GVHD. These HLA alleles were independent of other known risk factors for acute or chronic GVHD, as shown by multivariate analysis. These results show that major histocompatibility comlex (MHC) alleles may influence the incidence of GVHD in HSCT with HLA identical sibling donors. PMID:12437654

  4. Sex-specific Differences in Hyperoxic Lung Injury in Mice: Implications for Acute and Chronic Lung Disease in Humans

    PubMed Central

    Lingappan, Krithika; Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I.; Barrios, Roberto; Moorthy, Bhagavatula

    2014-01-01

    Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO2>0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F2 alpha (8-iso-PGF 2α) (LC-MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. CytochromeP450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2α levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F>M) and VEGF (M>F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. PMID:23792423

  5. Sex-specific differences in hyperoxic lung injury in mice: Implications for acute and chronic lung disease in humans

    SciTech Connect

    Lingappan, Krithika; Jiang, Weiwu; Wang, Lihua; Couroucli, Xanthi I.; Barrios, Roberto; Moorthy, Bhagavatula

    2013-10-15

    Sex-specific differences in pulmonary morbidity in humans are well documented. Hyperoxia contributes to lung injury in experimental animals and humans. The mechanisms responsible for sex differences in the susceptibility towards hyperoxic lung injury remain largely unknown. In this investigation, we tested the hypothesis that mice will display sex-specific differences in hyperoxic lung injury. Eight week-old male and female mice (C57BL/6J) were exposed to 72 h of hyperoxia (FiO{sub 2} > 0.95). After exposure to hyperoxia, lung injury, levels of 8-iso-prostaglandin F{sub 2} alpha (8-iso-PGF 2α) (LC–MS/MS), apoptosis (TUNEL) and inflammatory markers (suspension bead array) were determined. Cytochrome P450 (CYP)1A expression in the lung was assessed using immunohistochemistry and western blotting. After exposure to hyperoxia, males showed greater lung injury, neutrophil infiltration and apoptosis, compared to air-breathing controls than females. Pulmonary 8-iso-PGF 2α levels were higher in males than females after hyperoxia exposure. Sexually dimorphic increases in levels of IL-6 (F > M) and VEGF (M > F) in the lungs were also observed. CYP1A1 expression in the lung was higher in female mice compared to males under hyperoxic conditions. Overall, our results support the hypothesis that male mice are more susceptible than females to hyperoxic lung injury and that differences in inflammatory and oxidative stress markers contribute to these sex-specific dimorphic effects. In conclusion, this paper describes the establishment of an animal model that shows sex differences in hyperoxic lung injury in a temporal manner and thus has important implications for lung diseases mediated by hyperoxia in humans. - Highlights: • Male mice were more susceptible to hyperoxic lung injury than females. • Sex differences in inflammatory markers were observed. • CYP1A expression was higher in females after hyperoxia exposure.

  6. Epidemiology and transmission characteristics of human adenovirus type 7 caused acute respiratory disease outbreak in military trainees in East China

    PubMed Central

    Cheng, Jun; Qi, Xiaoping; Chen, Dawei; Xu, Xujian; Wang, Guozheng; Dai, Yuzhu; Cui, Dawei; Chen, Qingyong; Fan, Ping; Ni, Liuda; Liu, Miao; Zhu, Feiyan; Yang, Mei; Wang, Changjun; Li, Yuexi; Sun, Changgui; Wang, Zhongyong

    2016-01-01

    Background: Human adenovirus type 7 (HAdV7) is globally attracting great concern as its high morbidity and severity in respiratory diseases, especially in Asia. Objective: To investigate the clinical and epidemiologic characteristics of HAdV7 infection outbreak in East China. Methods: The clinical samples were collected from the patients of an ARD outbreak in East Chinafor the detection of causative pathogens by multiplex PCR. The molecular type of human adenovirus isolates were identified by sequencing and homologous comparison based on their hexon genes. The spatiotemporal dynamics of global HAdV7 was investigated using the phylogenetic and phylogeographic analyses. Total 67 referenced HAdV7 hexon sequences (>800 bp) from GenBank were selected for constructing the maximum likelihood tree by MEGA 5.1.0, grouped according to the tree topology for the further migration analysis by PAUP* 4.0 and MigraPhyla 1.0 b to understand the transmission patterns of HAdV7 in global epidemics. Results: The results showed HAdV7 as the causative pathogen in this outbreak, and the outbreak strains had the hexon sequences highly identical with the isolates in Shaanxi (2012). The origin of HAdV7 was inferred as California, meanwhile a total of 21 migration routes were acquired. HAdV7 in this outbreak was statistically proven dispersed from Shaanxi province (2012). Conclusions: The analyses of epidemiology and transmission pattern of HAdV7 would not only enrich the molecular biological basic database but also provide theoretical basis for HAdV7 prevention and control strategy. PMID:27347341

  7. Human models of acute lung injury

    PubMed Central

    Proudfoot, Alastair G.; McAuley, Danny F.; Griffiths, Mark J. D.; Hind, Matthew

    2011-01-01

    Acute lung injury (ALI) is a syndrome that is characterised by acute inflammation and tissue injury that affects normal gas exchange in the lungs. Hallmarks of ALI include dysfunction of the alveolar-capillary membrane resulting in increased vascular permeability, an influx of inflammatory cells into the lung and a local pro-coagulant state. Patients with ALI present with severe hypoxaemia and radiological evidence of bilateral pulmonary oedema. The syndrome has a mortality rate of approximately 35% and usually requires invasive mechanical ventilation. ALI can follow direct pulmonary insults, such as pneumonia, or occur indirectly as a result of blood-borne insults, commonly severe bacterial sepsis. Although animal models of ALI have been developed, none of them fully recapitulate the human disease. The differences between the human syndrome and the phenotype observed in animal models might, in part, explain why interventions that are successful in models have failed to translate into novel therapies. Improved animal models and the development of human in vivo and ex vivo models are therefore required. In this article, we consider the clinical features of ALI, discuss the limitations of current animal models and highlight how emerging human models of ALI might help to answer outstanding questions about this syndrome. PMID:21357760

  8. Acute Chagas Disease: New Global Challenges for an Old Neglected Disease

    PubMed Central

    Andrade, Daniela V.; Gollob, Kenneth J.; Dutra, Walderez O.

    2014-01-01

    Chagas disease is caused by infection with the protozoan Trypanosoma cruzi, and although over 100 years have passed since the discovery of Chagas disease, it still presents an increasing problem for global public health. A plethora of information concerning the chronic phase of human Chagas disease, particularly the severe cardiac form, is available in the literature. However, information concerning events during the acute phase of the disease is scarce. In this review, we will discuss (1) the current status of acute Chagas disease cases globally, (2) the immunological findings related to the acute phase and their possible influence in disease outcome, and (3) reactivation of Chagas disease in immunocompromised individuals, a key point for transplantation and HIV infection management. PMID:25077613

  9. Re-emergent human adenovirus genome type 7d caused an acute respiratory disease outbreak in Southern China after a twenty-one year absence.

    PubMed

    Zhao, Suhui; Wan, Chengsong; Ke, Changwen; Seto, Jason; Dehghan, Shoaleh; Zou, Lirong; Zhou, Jie; Cheng, Zetao; Jing, Shuping; Zeng, Zhiwei; Zhang, Jing; Wan, Xuan; Wu, Xianbo; Zhao, Wei; Zhu, Li; Seto, Donald; Zhang, Qiwei

    2014-01-01

    Human adenoviruses (HAdVs) are highly contagious pathogens causing acute respiratory disease (ARD), among other illnesses. Of the ARD genotypes, HAdV-7 presents with more severe morbidity and higher mortality than the others. We report the isolation and identification of a genome type HAdV-7d (DG01_2011) from a recent outbreak in Southern China. Genome sequencing, phylogenetic analysis, and restriction endonuclease analysis (REA) comparisons with past pathogens indicate HAdV-7d has re-emerged in Southern China after an absence of twenty-one years. Recombination analysis reveals this genome differs from the 1950s-era prototype and vaccine strains by a lateral gene transfer, substituting the coding region for the L1 52/55 kDa DNA packaging protein from HAdV-16. DG01_2011 descends from both a strain circulating in Southwestern China (2010) and a strain from Shaanxi causing a fatality and outbreak (Northwestern China; 2009). Due to the higher morbidity and mortality rates associated with HAdV-7, the surveillance, identification, and characterization of these strains in population-dense China by REA and/or whole genome sequencing are strongly indicated. With these accurate identifications of specific HAdV types and an epidemiological database of regional HAdV pathogens, along with the HAdV genome stability noted across time and space, the development, availability, and deployment of appropriate vaccines are needed. PMID:25482188

  10. Re-emergent Human Adenovirus Genome Type 7d Caused an Acute Respiratory Disease Outbreak in Southern China After a Twenty-one Year Absence

    PubMed Central

    Zhao, Suhui; Wan, Chengsong; Ke, Changwen; Seto, Jason; Dehghan, Shoaleh; Zou, Lirong; Zhou, Jie; Cheng, Zetao; Jing, Shuping; Zeng, Zhiwei; Zhang, Jing; Wan, Xuan; Wu, Xianbo; Zhao, Wei; Zhu, Li; Seto, Donald; Zhang, Qiwei

    2014-01-01

    Human adenoviruses (HAdVs) are highly contagious pathogens causing acute respiratory disease (ARD), among other illnesses. Of the ARD genotypes, HAdV-7 presents with more severe morbidity and higher mortality than the others. We report the isolation and identification of a genome type HAdV-7d (DG01_2011) from a recent outbreak in Southern China. Genome sequencing, phylogenetic analysis, and restriction endonuclease analysis (REA) comparisons with past pathogens indicate HAdV-7d has re-emerged in Southern China after an absence of twenty-one years. Recombination analysis reveals this genome differs from the 1950s-era prototype and vaccine strains by a lateral gene transfer, substituting the coding region for the L1 52/55 kDa DNA packaging protein from HAdV-16. DG01_2011 descends from both a strain circulating in Southwestern China (2010) and a strain from Shaanxi causing a fatality and outbreak (Northwestern China; 2009). Due to the higher morbidity and mortality rates associated with HAdV-7, the surveillance, identification, and characterization of these strains in population-dense China by REA and/or whole genome sequencing are strongly indicated. With these accurate identifications of specific HAdV types and an epidemiological database of regional HAdV pathogens, along with the HAdV genome stability noted across time and space, the development, availability, and deployment of appropriate vaccines are needed. PMID:25482188

  11. Genomic and bioinformatics analysis of HAdV-7, a human adenovirus of species B1 that causes acute respiratory disease: implications for vector development in human gene therapy.

    PubMed

    Purkayastha, Anjan; Su, Jing; Carlisle, Steve; Tibbetts, Clark; Seto, Donald

    2005-02-01

    Human adenovirus serotype 7 (HAdV-7) is a reemerging pathogen identified in acute respiratory disease (ARD), particularly in epidemics affecting basic military trainee populations of otherwise healthy young adults. The genome has been sequenced and annotated (GenBank accession no. ). Comparative genomics and bioinformatics analyses of the HAdV-7 genome sequence provide insight into its natural history and phylogenetic relationships. A putative origin of HAdV-7 from a chimpanzee host is observed. This has implications within the current biotechnological interest of using chimpanzee adenoviruses as vectors for human gene therapy and DNA vaccine delivery. Rapid genome sequencing and analyses of this species B1 member provide an example of exploiting accurate low-pass DNA sequencing technology in pathogen characterization and epidemic outbreak surveillance through the identification, validation, and application of unique pathogen genome signatures. PMID:15661145

  12. Nicotinamide Phosphoribosyltransferase in Human Diseases

    PubMed Central

    Zhang, Li Qin; Heruth, Daniel P.; Ye, Shui Qing

    2011-01-01

    Nicotinamide phosphoribosyltransferase (NAMPT) was first reported as a pre-B-cell colony enhancing factor in 1994 with little notice, but it has received increasing attention in recent years due to accumulating evidence indicating that NAMPT is a pleiotropic protein such as a growth factor, a cytokine, an enzyme and a visfatin. Now, NAMPT has been accepted as an official name of this protein. Because of NAMPT’s multiple functions in a variety of physiological processes, their dysregulations have been implicated in the pathogenesis of a number of human diseases or conditions such as acute lung injury, aging, atherosclerosis, cancer, diabetes, rheumatoid arthritis and sepsis. This review will cover the current understanding of NAMPT’s structure and functions with an emphasis on recent progress of nicotinamide phosphoribosyltransferase’s pathological roles in various human diseases and conditions. Future directions on exploring its Terra incognita will be offered in the end. PMID:22140607

  13. Autophagy and human diseases

    PubMed Central

    Jiang, Peidu; Mizushima, Noboru

    2014-01-01

    Autophagy is a major intracellular degradative process that delivers cytoplasmic materials to the lysosome for degradation. Since the discovery of autophagy-related (Atg) genes in the 1990s, there has been a proliferation of studies on the physiological and pathological roles of autophagy in a variety of autophagy knockout models. However, direct evidence of the connections between ATG gene dysfunction and human diseases has emerged only recently. There are an increasing number of reports showing that mutations in the ATG genes were identified in various human diseases such as neurodegenerative diseases, infectious diseases, and cancers. Here, we review the major advances in identification of mutations or polymorphisms of the ATG genes in human diseases. Current autophagy-modulating compounds in clinical trials are also summarized. PMID:24323045

  14. VNI Cures Acute and Chronic Experimental Chagas Disease

    PubMed Central

    Villalta, Fernando; Dobish, Mark C.; Nde, Pius N.; Kleshchenko, Yulia Y.; Hargrove, Tatiana Y.; Johnson, Candice A.; Waterman, Michael R.; Johnston, Jeffrey N.; Lepesheva, Galina I.

    2013-01-01

    Chagas disease is a deadly infection caused by the protozoan parasite Trypanosoma cruzi. Afflicting approximately 8 million people in Latin America, Chagas disease is now becoming a serious global health problem proliferating beyond the traditional geographical borders, mainly because of human and vector migration. Because the disease is endemic in low-resource areas, industrial drug development has been lethargic. The chronic form remains incurable, there are no vaccines, and 2 existing drugs for the acute form are toxic and have low efficacy. Here we report the efficacy of a small molecule, VNI, including evidence of its effectiveness against chronic Chagas disease. VNI is a potent experimental inhibitor of T. cruzi sterol 14α-demethylase. Nontoxic and highly selective, VNI displays promising pharmacokinetics and administered orally to mice at 25 mg/kg for 30 days cures, with 100% cure rate and 100% survival, the acute and chronic T. cruzi infection. PMID:23372180

  15. Cryoglobulins in acute and chronic liver diseases

    PubMed Central

    Florin-Christensen, A.; Roux, María E. B.; Arana, R. M.

    1974-01-01

    Cryoglobulins were detected in the sera of thirteen patients with acute viral hepatitis and of twelve with chronic hepatic diseases (active chronic hepatitis, primary biliary cirrhosis and cryptogenic cirrhosis). Their nature and antibody activity was studied. In both groups, most of them consisted of mixed cryoimmunoglobulins (IgM, IgG and/or IgA), but some were single-class immunoglobulins with one or both types of light chains. Unusual components were also found. α1-fetoprotein was present in four cryoprecipitates: in two as the single constituent and in two associated to immunoglobulins; hepatitis-associated antigen co-existed in one of the latter. Some cryoglobulins showed antibody activity against human IgG, smooth muscle and mitochondrial antigens. In one case, the IgM-kappa of the cryoprecipitate had antibody activity against α1-fetoprotein; this antigen was also present in the cryoprecipitate, suggesting immune-complex formation. Autoantibodies were also looked for in the sera of the twenty-five patients; apart from the most common ones, antibodies to α1-fetoprotein were found in two patients. PMID:4143195

  16. Autophagosomes and human diseases.

    PubMed

    Beau, Isabelle; Mehrpour, Maryam; Codogno, Patrice

    2011-04-01

    The autophagosome is a double-membrane bound compartment that initiates macroautophagy, a degradative pathway for cytoplasmic material terminating in the lysosomal compartment. The discovery of ATG genes involved in the formation of autophagosomes has greatly increased our understanding of the molecular basis of macroautophagy, and its role in cell function. Macroautophagy plays a pivotal role in cell fitness by removing obsolete organelles and protein aggregates. Its stimulation is an adaptive response to stressful situations, such as nutrient deprivation, intended to maintain a level of ATP compatible with cell survival. Macroautophagy is central for organ homeostasis, embryonic development, and longevity. Malfunctioning autophagy is observed in many human diseases including cancer, neurodegenerative diseases, cardiac and muscular diseases, infectious and inflammatory diseases, diabetes, and obesity. Discovering potential drug therapies that can be used to modulate macroautophagy is a major challenge, and likely to enhance the therapeutic arsenal against many human diseases. PMID:21256243

  17. Zygomycetes in Human Disease

    PubMed Central

    Ribes, Julie A.; Vanover-Sams, Carolyn L.; Baker, Doris J.

    2000-01-01

    The Zygomycetes represent relatively uncommon isolates in the clinical laboratory, reflecting either environmental contaminants or, less commonly, a clinical disease called zygomycosis. There are two orders of Zygomycetes containing organisms that cause human disease, the Mucorales and the Entomophthorales. The majority of human illness is caused by the Mucorales. While disease is most commonly linked to Rhizopus spp., other organisms are also associated with human infection, including Mucor, Rhizomucor, Absidia, Apophysomyces, Saksenaea, Cunninghamella, Cokeromyces, and Syncephalastrum spp. Although Mortierella spp. do cause disease in animals, there is no longer sufficient evidence to suggest that they are true human pathogens. The spores from these molds are transmitted by inhalation, via a variety of percutaneous routes, or by ingestion of spores. Human zygomycosis caused by the Mucorales generally occurs in immunocompromised hosts as opportunistic infections. Host risk factors include diabetes mellitus, neutropenia, sustained immunosuppressive therapy, chronic prednisone use, iron chelation therapy, broad-spectrum antibiotic use, severe malnutrition, and primary breakdown in the integrity of the cutaneous barrier such as trauma, surgical wounds, needle sticks, or burns. Zygomycosis occurs only rarely in immunocompetent hosts. The disease manifestations reflect the mode of transmission, with rhinocerebral and pulmonary diseases being the most common manifestations. Cutaneous, gastrointestinal, and allergic diseases are also seen. The Mucorales are associated with angioinvasive disease, often leading to thrombosis, infarction of involved tissues, and tissue destruction mediated by a number of fungal proteases, lipases, and mycotoxins. If the diagnosis is not made early, dissemination often occurs. Therapy, if it is to be effective, must be started early and requires combinations of antifungal drugs, surgical intervention, and reversal of the underlying risk

  18. Adenosine Signaling During Acute and Chronic Disease States

    PubMed Central

    Karmouty-Quintana, Harry; Xia, Yang; Blackburn, Michael R.

    2013-01-01

    Adenosine is a signaling nucleoside that is produced following tissue injury, particularly injury involving ischemia and hypoxia. The production of extracellular adenosine and its subsequent signaling through adenosine receptors plays an important role in orchestrating injury responses in multiple organs. There are four adenosine receptors that are widely distributed on immune, epithelial, endothelial, neuronal and stromal cells throughout the body. Interestingly, these receptors are subject to altered regulation following injury. Studies in mouse models and human cells and tissues have identified that the production of adenosine and its subsequent signaling through its receptors plays largely beneficial roles in acute disease states, with the exception of brain injury. In contrast, if elevated adenosine levels are sustained beyond the acute injury phase, adenosine responses can become detrimental by activating pathways that promote tissue injury and fibrosis. Understanding when during the course of disease adenosine signaling is beneficial as opposed to detrimental and defining the mechanisms involved will be critical for the advancement of adenosine based therapies for acute and chronic diseases. The purpose of this review is to discuss key observations that define the beneficial and detrimental aspects of adenosine signaling during acute and chronic disease states with an emphasis on cellular processes such as inflammatory cell regulation, vascular barrier function and tissue fibrosis. PMID:23340998

  19. Oxidants in Acute and Chronic Lung Disease

    PubMed Central

    Mannam, Praveen; Srivastava, Anup; Sugunaraj, Jaya Prakash; Lee, Patty J; Sauler, Maor

    2015-01-01

    Oxidants play an important role in homeostatic function, but excessive oxidant generation has an adverse effect on health. The manipulation of Reactive Oxygen Species (ROS) can have a beneficial effect on various lung pathologies. However indiscriminate uses of anti-oxidant strategies have not demonstrated any consistent benefit and may be harmful. Here we propose that nuanced strategies are needed to modulate the oxidant system to obtain a beneficial result in the lung diseases such as Acute Lung Injury (ALI) and Chronic Obstructive Pulmonary Disease (COPD). We identify novel areas of lung oxidant responses that may yield fruitful therapies in the future. PMID:25705575

  20. Abdominal Mondor disease mimicking acute appendicitis

    PubMed Central

    Schuppisser, Myriam; Khallouf, Joe; Abbassi, Ziad; Erne, Michel; Vettorel, Denise; Paroz, Alexandre; Naiken, Surennaidoo P.

    2016-01-01

    Introduction Mondor disease (MD), a superficial thrombophlebitis of the thoraco-epigastric veins and their confluents is rarely reported in the literature. The superior epigastric vein is the most affected vessel but involvement of the inferior epigastric vessels or their branches have also been described. There is no universal consensus on treatment in the literature but most authors suggest symptomatic treatment with non-steroid anti-inflammatory drugs (NSAIDs). Case report We report the case of a marathon runner who presented with right iliac fossa pain mimicking the clinical symptomatology of an acute appendicitis. The history and the calculated Alvarado score were not in favor of an acute appendicitis. This situation motivated multiple investigations and we finally arrived at the diagnosis of MD. Discussion Acute appendicitis (AA) is the most common cause of surgical emergencies and one of the most frequent indications for an urgent abdominal surgical procedure around the world. In some cases, right lower quadrant pain remains unclear in spite of US, CT scan, and exclusion of urological and gynecological causes, thus we need to think of some rare pathologies like MD. Conclusion MD is often mentioned in the differential diagnosis of breast pathologies but rarely in abdominal pain assessment. It should be mentioned in the differential diagnosis of the right lower quadrant pain when the clinical presentation is unclear and when acute appendicitis has been excluded. Awareness of MD can avoid misdiagnosis and decrease extra costs by sparing unnecessary imaging. PMID:26803533

  1. Allogeneic human mesenchymal stem cell therapy (remestemcel-L, Prochymal) as a rescue agent for severe refractory acute graft-versus-host disease in pediatric patients.

    PubMed

    Kurtzberg, Joanne; Prockop, Susan; Teira, Pierre; Bittencourt, Henrique; Lewis, Victor; Chan, Ka Wah; Horn, Biljana; Yu, Lolie; Talano, Julie-An; Nemecek, Eneida; Mills, Charles R; Chaudhury, Sonali

    2014-02-01

    Severe steroid-refractory acute graft-versus-host disease (aGVHD) is related to significant mortality and morbidity after allogeneic stem cell transplantation. Early clinical trials of therapy with human mesenchymal stem cells (hMSCs) in pediatric patients with severe aGVHD resistant to multiple immunosuppressive agents showed promising results. In this study, we evaluated the risk/benefit profile of remestemcel-L (Prochymal), a third-party, off-the-shelf source of hMSCs, as a rescue agent for treatment-resistant aGVHD in pediatric patients. Children with grade B-D aGVHD failing steroids and, in most cases, other immunosuppressive agents were eligible for enrollment. Patients received 8 biweekly i.v. infusions of 2 × 10(6) hMSCs/kg for 4 weeks, with an additional 4 weekly infusions after day +28 for patients who achieved either a partial or mixed response. The enrolled patients compose a very challenging population with severe disease that was nonresponsive to the standard of care, with 88% of the patients experiencing severe aGVHD (grade C or D). Seventy-five patients (median age, 8 yr; 58.7% male; and 61.3% Caucasian) were treated in this study. Sixty-four patients (85.3%) had received an unrelated hematopoietic stem cell graft, and 28 patients (37.3%) had received a cord blood graft. At baseline, the distribution of aGVHD grades B, C, and D was 12.0%, 28.0%, and 60.0%, respectively. The median duration of aGVHD before enrollment was 30 d (range, 2 to 1639 d), and patients failed a median of 3 immunosuppressive agents. Organ involvement at baseline was 86.7% gastrointestinal, 54.7% skin, and 36.0% liver. Thirty-six patients (48.0%) had 2 organs involved, and 11 patients (14.7%) had all 3 organs involved. When stratified by aGVHD grade at baseline, the rate of overall response (complete and partial response) at day +28 was 66.7% for aGVHD grade B, 76.2% for grade C, and 53.3% for grade D. Overall response for individual organs at day +28 was 58.5% for

  2. Recent developments in epigenetics of acute and chronic kidney diseases.

    PubMed

    Reddy, Marpadga A; Natarajan, Rama

    2015-08-01

    The growing epidemic of obesity and diabetes, the aging population as well as prevalence of drug abuse has led to significant increases in the rates of the closely associated acute and chronic kidney diseases, including diabetic nephropathy. Furthermore, evidence shows that parental behavior and diet can affect the phenotype of subsequent generations via epigenetic transmission mechanisms. These data suggest a strong influence of the environment on disease susceptibility and that, apart from genetic susceptibility, epigenetic mechanisms need to be evaluated to gain critical new information about kidney diseases. Epigenetics is the study of processes that control gene expression and phenotype without alterations in the underlying DNA sequence. Epigenetic modifications, including cytosine DNA methylation and covalent post-translational modifications of histones in chromatin, are part of the epigenome, the interface between the stable genome and the variable environment. This dynamic epigenetic layer responds to external environmental cues to influence the expression of genes associated with disease states. The field of epigenetics has seen remarkable growth in the past few years with significant advances in basic biology, contributions to human disease, as well as epigenomics technologies. Further understanding of how the renal cell epigenome is altered by metabolic and other stimuli can yield novel new insights into the pathogenesis of kidney diseases. In this review, we have discussed the current knowledge on the role of epigenetic mechanisms (primarily DNAme and histone modifications) in acute and chronic kidney diseases, and their translational potential to identify much needed new therapies. PMID:25993323

  3. Recent Developments in Epigenetics of Acute and Chronic Kidney Diseases

    PubMed Central

    Reddy, Marpadga A.; Natarajan, Rama

    2015-01-01

    The growing epidemic of obesity and diabetes, the aging population as well as prevalence of drug abuse has led to significant increases in the rates of the closely associated acute and chronic kidney diseases, including diabetic nephropathy. Furthermore, evidence shows that parental behavior and diet can affect the phenotype of subsequent generations via epigenetic transmission mechanisms. These data suggest a strong influence of the environment on disease susceptibility and that, apart from genetic susceptibility, epigenetic mechanisms need to be evaluated to gain critical new information about kidney diseases. Epigenetics is the study of processes that control gene expression and phenotype without alterations in the underlying DNA sequence. Epigenetic modifications, including cytosine DNA methylation and covalent post translational modifications of histones in chromatin are part of the epigenome, the interface between the stable genome and the variable environment. This dynamic epigenetic layer responds to external environmental cues to influence the expression of genes associated with disease states. The field of epigenetics has seen remarkable growth in the past few years with significant advances in basic biology, contributions to human disease, as well as epigenomics technologies. Further understanding of how the renal cell epigenome is altered by metabolic and other stimuli can yield novel new insights into the pathogenesis of kidney diseases. In this review, we have discussed the current knowledge on the role of epigenetic mechanisms (primarily DNA me and histone modifications) in acute and chronic kidney diseases, and their translational potential to identify much needed new therapies. PMID:25993323

  4. Nongenital human papillomavirus disease.

    PubMed

    Mayeaux, E J; Khan, Michelle J

    2013-06-01

    Human papillomavirus (HPV) is the most common viral cause of cancer, and is responsible for 5% of cancers worldwide. Following demonstration of the causative link between HPV and cervical cancer, HPV has been shown to be associated with several anogenital malignancies and with oral pharyngeal cancers. HPV-related anal and oral pharyngeal disease is rising in incidence and includes anal warts and neoplasia, recurrent respiratory papillomatosis, and oral pharyngeal neoplasia. This article presents an overview of the epidemiology, clinical manifestations, diagnosis, and treatment of nongenital HPV-related disease. PMID:23732034

  5. Acute Myopericarditis caused by Human Metapneumovirus

    PubMed Central

    Choi, Min Joo; Yang, Tae Un; Jeon, Ji Ho; Noh, Ji Yun; Hong, Kyung Wook; Cheong, Hee Jin; Kim, Woo Joo

    2016-01-01

    Human metapneumovirus is known to be similar to respiratory syncytial virus. Because of an incomplete protective immune response to new genotypes, re-infection occurs frequently, especially in the elderly. However, the clinical manifestations of human metapneumovirus need to be further characterized in adults. A 73-year-old woman presented to the emergency room with acute dyspnea, chest discomfort and influenza-like illness. The patient was diagnosed with human metapneumovirus infection, complicated by pneumonia and myopericarditis. With supportive care including oxygen supplementation, the patient recovered completely without any serious sequelae. Human metapneumovirus infection may contribute to the development of cardiovascular manifestations, particularly in the elderly population. PMID:27104014

  6. Zebrafish Models for Human Acute Organophosphorus Poisoning

    PubMed Central

    Faria, Melissa; Garcia-Reyero, Natàlia; Padrós, Francesc; Babin, Patrick J.; Sebastián, David; Cachot, Jérôme; Prats, Eva; Arick II, Mark; Rial, Eduardo; Knoll-Gellida, Anja; Mathieu, Guilaine; Le Bihanic, Florane; Escalon, B. Lynn; Zorzano, Antonio; Soares, Amadeu M.V.M; Raldúa, Demetrio

    2015-01-01

    Terrorist use of organophosphorus-based nerve agents and toxic industrial chemicals against civilian populations constitutes a real threat, as demonstrated by the terrorist attacks in Japan in the 1990 s or, even more recently, in the Syrian civil war. Thus, development of more effective countermeasures against acute organophosphorus poisoning is urgently needed. Here, we have generated and validated zebrafish models for mild, moderate and severe acute organophosphorus poisoning by exposing zebrafish larvae to different concentrations of the prototypic organophosphorus compound chlorpyrifos-oxon. Our results show that zebrafish models mimic most of the pathophysiological mechanisms behind this toxidrome in humans, including acetylcholinesterase inhibition, N-methyl-D-aspartate receptor activation, and calcium dysregulation as well as inflammatory and immune responses. The suitability of the zebrafish larvae to in vivo high-throughput screenings of small molecule libraries makes these models a valuable tool for identifying new drugs for multifunctional drug therapy against acute organophosphorus poisoning. PMID:26489395

  7. Zebrafish Models for Human Acute Organophosphorus Poisoning.

    PubMed

    Faria, Melissa; Garcia-Reyero, Natàlia; Padrós, Francesc; Babin, Patrick J; Sebastián, David; Cachot, Jérôme; Prats, Eva; Arick Ii, Mark; Rial, Eduardo; Knoll-Gellida, Anja; Mathieu, Guilaine; Le Bihanic, Florane; Escalon, B Lynn; Zorzano, Antonio; Soares, Amadeu M V M; Raldúa, Demetrio

    2015-01-01

    Terrorist use of organophosphorus-based nerve agents and toxic industrial chemicals against civilian populations constitutes a real threat, as demonstrated by the terrorist attacks in Japan in the 1990 s or, even more recently, in the Syrian civil war. Thus, development of more effective countermeasures against acute organophosphorus poisoning is urgently needed. Here, we have generated and validated zebrafish models for mild, moderate and severe acute organophosphorus poisoning by exposing zebrafish larvae to different concentrations of the prototypic organophosphorus compound chlorpyrifos-oxon. Our results show that zebrafish models mimic most of the pathophysiological mechanisms behind this toxidrome in humans, including acetylcholinesterase inhibition, N-methyl-D-aspartate receptor activation, and calcium dysregulation as well as inflammatory and immune responses. The suitability of the zebrafish larvae to in vivo high-throughput screenings of small molecule libraries makes these models a valuable tool for identifying new drugs for multifunctional drug therapy against acute organophosphorus poisoning. PMID:26489395

  8. Elevation of Serum Acid Sphingomyelinase Activity in Acute Kawasaki Disease.

    PubMed

    Konno, Yuuki; Takahashi, Ikuko; Narita, Ayuko; Takeda, Osamu; Koizumi, Hiromi; Tamura, Masamichi; Kikuchi, Wataru; Komatsu, Akira; Tamura, Hiroaki; Tsuchida, Satoko; Noguchi, Atsuko; Takahashi, Tsutomu

    2015-01-01

    Kawasaki disease (KD) is an acute systemic vasculitis that affects both small and medium-sized vessels including the coronary arteries in infants and children. Acid sphingomyelinase (ASM) is a lysosomal glycoprotein that hydrolyzes sphingomyelin to ceramide, a lipid, that functions as a second messenger in the regulation of cell functions. ASM activation has been implicated in numerous cellular stress responses and is associated with cellular ASM secretion, either through alternative trafficking of the ASM precursor protein or by means of an unidentified mechanism. Elevation of serum ASM activity has been described in several human diseases, suggesting that patients with diseases involving vascular endothelial cells may exhibit a preferential elevation of serum ASM activity. As acute KD is characterized by systemic vasculitis that could affect vascular endothelial cells, the elevation of serum ASM activity should be considered in these patients. In the present study, serum ASM activity in the sera of 15 patients with acute KD was determined both before and after treatment with infusion of high-dose intravenous immunoglobulin (IVIG), a first-line treatment for acute KD. Serum ASM activity before IVIG was significantly elevated in KD patients when compared to the control group (3.85 ± 1.46 nmol/0.1 ml/6 h vs. 1.15 ± 0.10 nmol/0.1 ml/6 h, p < 0.001), suggesting that ASM activation may be involved in the pathophysiology of this condition. Serum ASM activity before IVIG was significantly correlated with levels of C-reactive protein (p < 0.05). These results suggest the involvement of sphingolipid metabolism in the pathophysiology of KD. PMID:26447086

  9. Acute rheumatic fever and rheumatic heart disease.

    PubMed

    Carapetis, Jonathan R; Beaton, Andrea; Cunningham, Madeleine W; Guilherme, Luiza; Karthikeyan, Ganesan; Mayosi, Bongani M; Sable, Craig; Steer, Andrew; Wilson, Nigel; Wyber, Rosemary; Zühlke, Liesl

    2016-01-01

    Acute rheumatic fever (ARF) is the result of an autoimmune response to pharyngitis caused by infection with group A Streptococcus. The long-term damage to cardiac valves caused by ARF, which can result from a single severe episode or from multiple recurrent episodes of the illness, is known as rheumatic heart disease (RHD) and is a notable cause of morbidity and mortality in resource-poor settings around the world. Although our understanding of disease pathogenesis has advanced in recent years, this has not led to dramatic improvements in diagnostic approaches, which are still reliant on clinical features using the Jones Criteria, or treatment practices. Indeed, penicillin has been the mainstay of treatment for decades and there is no other treatment that has been proven to alter the likelihood or the severity of RHD after an episode of ARF. Recent advances - including the use of echocardiographic diagnosis in those with ARF and in screening for early detection of RHD, progress in developing group A streptococcal vaccines and an increased focus on the lived experience of those with RHD and the need to improve quality of life - give cause for optimism that progress will be made in coming years against this neglected disease that affects populations around the world, but is a particular issue for those living in poverty. PMID:27188830

  10. Genetic Mapping in Human Disease

    PubMed Central

    Altshuler, David; Daly, Mark J.; Lander, Eric S.

    2009-01-01

    Genetic mapping provides a powerful approach to identify genes and biological processes underlying any trait influenced by inheritance, including human diseases. We discuss the intellectual foundations of genetic mapping of Mendelian and complex traits in humans, examine lessons emerging from linkage analysis of Mendelian diseases and genome-wide association studies of common diseases, and discuss questions and challenges that lie ahead. PMID:18988837

  11. Acute myeloid leukaemia as a cause of acute ischaemic heart disease

    PubMed Central

    van Haelst, P.L.; Schot, B.; Hoendermis, E.S.; van den Berg, M.P.

    2006-01-01

    Ischaemic heart disease is almost invariably the result of atherosclerotic degeneration of the coronary arteries. However, other causes of ischaemic heart disease should always be considered. Here we describe two patients with a classic presentation of ischaemic heart disease resulting from acute leukaemia. The pathophysiological mechanisms of acute leukaemia leading to ischaemic heart disease are discussed. ImagesFigure 1AFigure 1BFigure 2 PMID:25696595

  12. Acute Human Inkoo and Chatanga Virus Infections, Finland

    PubMed Central

    Kantele, Anu; Levanov, Lev; Kivistö, Ilkka; Brummer-Korvenkontio, Markus; Vaheri, Antti; Vapalahti, Olli

    2016-01-01

    Inkoo virus (INKV) and Chatanga virus (CHATV), which are circulating in Finland, are mosquitoborne California serogroup orthobunyaviruses that have a high seroprevalence among humans. Worldwide, INKV infection has been poorly described, and CHATV infection has been unknown. Using serum samples collected in Finland from 7,961 patients suspected of having viral neurologic disease or Puumala virus infection during the summers of 2001–2013, we analyzed the samples to detect California serogroup infections. IgM seropositivity revealed 17 acute infections, and cross-neutralization tests confirmed presence of INKV or CHATV infections. All children (<16 years of age) with INKV infection were hospitalized; adults were outpatients with mild disease, except for 1 who was hospitalized with CHATV infection. Symptoms included fever, influenza-like illness, nausea or vomiting, disorientation, nuchal rigidity, headache, drowsiness, and seizures. Although many INKV and CHATV infections appear to be subclinical, these viruses can cause more severe disease, especially in children. PMID:27088268

  13. A rare cause of acute flaccid paralysis: Human coronaviruses.

    PubMed

    Turgay, Cokyaman; Emine, Tekin; Ozlem, Koken; Muhammet, S Paksu; Haydar, A Tasdemir

    2015-01-01

    Acute flaccid paralysis (AFP) is a life-threatening clinical entity characterized by weakness in the whole body muscles often accompanied by respiratory and bulbar paralysis. The most common cause is Gullian-Barre syndrome, but infections, spinal cord diseases, neuromuscular diseases such as myasthenia gravis, drugs and toxins, periodic hypokalemic paralysis, electrolyte disturbances, and botulism should be considered as in the differential diagnosis. Human coronaviruses (HCoVs) cause common cold, upper and lower respiratory tract disease, but in the literature presentation with the lower respiratory tract infection and AFP has not been reported previously. In this study, pediatric case admitted with lower respiratory tract infection and AFP, who detected for HCoV 229E and OC43 co-infection by the real-time polymerase chain reaction, has been reported for the first time. PMID:26557177

  14. A rare cause of acute flaccid paralysis: Human coronaviruses

    PubMed Central

    Turgay, Cokyaman; Emine, Tekin; Ozlem, Koken; Muhammet, S. Paksu; Haydar, A. Tasdemir

    2015-01-01

    Acute flaccid paralysis (AFP) is a life-threatening clinical entity characterized by weakness in the whole body muscles often accompanied by respiratory and bulbar paralysis. The most common cause is Gullian–Barre syndrome, but infections, spinal cord diseases, neuromuscular diseases such as myasthenia gravis, drugs and toxins, periodic hypokalemic paralysis, electrolyte disturbances, and botulism should be considered as in the differential diagnosis. Human coronaviruses (HCoVs) cause common cold, upper and lower respiratory tract disease, but in the literature presentation with the lower respiratory tract infection and AFP has not been reported previously. In this study, pediatric case admitted with lower respiratory tract infection and AFP, who detected for HCoV 229E and OC43 co-infection by the real-time polymerase chain reaction, has been reported for the first time. PMID:26557177

  15. Modeling human gastrointestinal inflammatory diseases using microphysiological culture systems.

    PubMed

    Hartman, Kira G; Bortner, James D; Falk, Gary W; Ginsberg, Gregory G; Jhala, Nirag; Yu, Jian; Martín, Martín G; Rustgi, Anil K; Lynch, John P

    2014-09-01

    Gastrointestinal illnesses are a significant health burden for the US population, with 40 million office visits each year for gastrointestinal complaints and nearly 250,000 deaths. Acute and chronic inflammations are a common element of many gastrointestinal diseases. Inflammatory processes may be initiated by a chemical injury (acid reflux in the esophagus), an infectious agent (Helicobacter pylori infection in the stomach), autoimmune processes (graft versus host disease after bone marrow transplantation), or idiopathic (as in the case of inflammatory bowel diseases). Inflammation in these settings can contribute to acute complaints (pain, bleeding, obstruction, and diarrhea) as well as chronic sequelae including strictures and cancer. Research into the pathophysiology of these conditions has been limited by the availability of primary human tissues or appropriate animal models that attempt to physiologically model the human disease. With the many recent advances in tissue engineering and primary human cell culture systems, it is conceivable that these approaches can be adapted to develop novel human ex vivo systems that incorporate many human cell types to recapitulate in vivo growth and differentiation in inflammatory microphysiological environments. Such an advance in technology would improve our understanding of human disease progression and enhance our ability to test for disease prevention strategies and novel therapeutics. We will review current models for the inflammatory and immunological aspects of Barrett's esophagus, acute graft versus host disease, and inflammatory bowel disease and explore recent advances in culture methodologies that make these novel microphysiological research systems possible. PMID:24781339

  16. Modeling human gastrointestinal inflammatory diseases using microphysiological culture systems

    PubMed Central

    Hartman, Kira G.; Bortner, James D.; Falk, Gary W.; Ginsberg, Gregory G.; Jhala, Nirag; Yu, Jian; Martín, Martín G.; Rustgi, Anil K.; Lynch, John P.

    2014-01-01

    Gastrointestinal (GI) illnesses are a significant health burden for the US population, with 40 million office visits each year for gastrointestinal complaints and nearly 250,000 deaths. Acute and chronic inflammation are a common element of many GI diseases. Inflammatory processes may be initiated by a chemical injury (acid reflux in the esophagus), an infectious agent (Helicobacter pylori infection in the stomach), autoimmune processes (graft versus host disease after bone marrow transplantation), or idiopathic (as in the case of inflammatory bowel diseases). Inflammation in these settings can contribute to acute complaints (pain, bleeding, obstruction, diarrhea) as well as chronic sequelae including strictures and cancer. Research into the pathophysiology of these conditions has been limited by the availability of primary human tissues or appropriate animal models that attempt to physiologically model the human disease. With the many recent advances in tissue engineering and primary human cell culture systems, it is conceivable that these approaches can be adapted to develop novel human ex vivo systems that incorporate many human cell types to recapitulate in vivo growth and differentiation in inflammatory microphysiological environments. Such an advance in technology would improve our understanding of human disease progression and enhance our ability to test for disease prevention strategies and novel therapeutics. We will review current models for the inflammatory and immunological aspects of Barrett’s esophagus, acute graft versus host disease, and inflammatory bowel disease and explore recent advances in culture methodologies that make these novel microphysiological research systems possible. PMID:24781339

  17. [Acute pancreatitis with hypertriglyceridemia--an underestimated disease?].

    PubMed

    Wild, Wolfgang; Tajjiou, Morad; Ferschke, Melanie; Bormann, Fabian; Dörr, Pius; Schwarzbach, Matthias

    2016-01-01

    Hypertriglyceridemia is a rare, but since a long time well known etiology for acute pancreatitis. It could occure alone or coactive with other triggers like alcohlic excess. Nevertheless it found no approach to the current classifications and parameters of prognosis of the acute pancreatitis. We refer about two patients with hypertriglyceridemia and acute pancreatitis, whose initial disease was limited on the tail of the pancreas with just a circumscripted or--in the other case--no necrosis. However, in both cases and although a consequent treatment started immediately, a serious process developed including a life-threatening acute respiratory distress syndrome in one case, which necessitated an extracorporal membrane oxygenation. PMID:26710203

  18. Acute Demyelinating Disease after Oral Therapy with Herbal Extracts

    PubMed Central

    Kostianovsky, Alex; Maskin, Patricio; Noriega, María M.; Soler, Cristina; Bonelli, Ignacio; Riley, Claire S.; O'Connor, Kevin C.; Saubidet, Cristi´n López; Alvarez, Paulino A.

    2011-01-01

    Central nervous system demyelinating processes such as multiple sclerosis and acute disseminated encephalomyelitis constitute a group of diseases not completely understood in their physiopathology. Environmental and toxic insults are thought to play a role in priming autoimmunity. The aim of the present report is to describe a case of acute demyelinating disease with fatal outcome occurring 15 days after oral exposure to herbal extracts. PMID:21738505

  19. [Acute pulmonary histoplasmosis as an imported disease].

    PubMed

    van Crevel, R; van der Ven, A J; Meis, J F; Kullberg, B J

    1997-06-21

    A previously healthy 44-year-old male traveller presented with a dry cough, fever and an abnormal chest X-ray after a stay in Guatemala, where he had explored bat caves. Acute pulmonary histoplasmosis was diagnosed after culture of Histoplasma capsulatum from bronchial washings. A favourable response was seen upon treatment with itraconazole for six weeks. Acute pulmonary histoplasmosis should be considered in a healthy traveller returning with fever from the USA or subtropical areas. PMID:9380167

  20. Acquired Cell-Mediated Immunodepression in Acute Chagas' Disease

    PubMed Central

    Teixeira, Antonio R. L.; Teixeira, Glória; Macêdo, Vanize; Prata, Aluizio

    1978-01-01

    In this study two groups of patients with acute Chagas' disease were identified. Group one consisted of five patients with apparent acute Chagas' disease. These patients showed symptoms and signals of an acute illness, such as high fever and enlarged spleen. One of these patients developed severe myocarditis and heart failure. Group two consisted of seven patients with inapparent acute Chagas' disease. This was a nonclinical entity, not perceived by the patient who did not seek medical care. The diagnosis was made by the shift of a serologic test which indicates the presence of immunoglobulin M antibodies to Trypanosoma cruzi. The patients with apparent acute Chagas' disease showed positive delayed-type skin response to T. cruzi antigen. Also, their leukocytes showed significant inhibition of migration in the presence of this antigen. By contrast, the patients with the inapparent acute Chagas' disease did not show positive delayed-type skin response to T. cruzi antigen and no significant inhibition was observed when their cells migrated in the presence of this antigen. Of interest, none of these patients was capable of developing contact sensitivity to 2,4-dinitrochlorobenzene. However, three out of five patients with the apparent acute disease and all the normal control subjects showed positive contact reaction after sensitization to this drug. The results of these experiments would suggest that the thymus-derived (T)-lymphocyte function is depressed in patients with the clinically inapparent acute Chagas' disease. This immunodepression seems to be acquired in the course of the T. cruzi infection because all patients showed positive delayed-type skin response to at least one ubiquitous microbial extract, thus indicating previously normal T-cell function. We hypothesize that T. cruzi antigens may directly stimulate T cells with the concomitant release of factors that might become supressive for T-cell responses. Furthermore, the suppressive effect might interfere

  1. Human bocavirus in children with acute respiratory infections in Vietnam.

    PubMed

    Tran, Dinh Nguyen; Nguyen, Tran Quynh Nhu; Nguyen, Tuan Anh; Hayakawa, Satoshi; Mizuguchi, Masashi; Ushijima, Hiroshi

    2014-06-01

    Acute respiratory infections are the major cause of morbidity and mortality globally. Human bocavirus (HBoV), a novel virus, is recognized to increasingly associate with previously unknown etiology respiratory infections in young children. In this study, the epidemiological, clinical, and molecular characteristics of HBoV infections were described in hospitalized Vietnamese pediatric patients. From April 2010 to May 2011, 1,082 nasopharyngeal swab samples were obtained from patients with acute respiratory infections at the Children's Hospital 2, Ho Chi Minh City, Vietnam. Samples were screened for HBoV by PCR and further molecularly characterized by sequencing. HBoV was found in 78 (7.2%) children. Co-infection with other viruses was observed in 66.7% of patients infected with HBoV. Children 12-24 months old were the most affected age group. Infections with HBoV were found year-round, though most cases occurred in the dry season (December-April). HBoV was possible to cause severe diseases as determined by higher rates of hypoxia, pneumonia, and longer hospitalization duration in patients with HBoV infection than in those without (P-value <0.05). Co-infection with HBoV did not affect the disease severity. The phylogenetic analysis of partial VP1 gene showed minor variations and all HBoV sequences belonged to species 1 (HBoV1). In conclusion, HBoV1 was circulating in Vietnam and detected frequently in young children during dry season. Acute respiratory infections caused by HBoV1 were severe enough for hospitalization, which implied that HBoV1 may have an important role in acute respiratory infections among children. PMID:24123072

  2. [Demyelinating diseases in children with acute neurological symptoms].

    PubMed

    Olofsson, Isa Amalie; Skov, Liselotte; Miranda, Maria Jose

    2015-12-01

    Demyelinating diseases in children is a broad group of illnesses, which affect the central nervous system. Demyelinating diseases can be monophasic or chronic and comprise acute disseminated encephalomyelitis, optic neuritis, transverse myelitis, multiple sclerosis and neuromyelitis optica. Demyelinating diseases are rare, but it is important for the physician to recognize these diseases, as well as to understand the differential diagnoses. This review summarizes the current knowledge of demyelinating disorders in children, focusing on an approach to diagnosis and management. PMID:26651911

  3. Acute myeloid leukemia developing in patients with autoimmune diseases

    PubMed Central

    Ramadan, Safaa M.; Fouad, Tamer M; Summa, Valentina; Hasan, Syed KH; Lo-Coco, Francesco

    2012-01-01

    Therapy-related acute myeloid leukemia is an unfortunate complication of cancer treatment, particularly for patients with highly curable primary malignancies and favorable life expectancy. The risk of developing therapy-related acute myeloid leukemia also applies to patients with non-malignant conditions, such as autoimmune diseases treated with cytotoxic and/or immunosuppressive agents. There is considerable evidence to suggest that there is an increased occurrence of hematologic malignancies in patients with autoimmune diseases compared to the general population, with a further increase in risk after exposure to cytotoxic therapies. Unfortunately, studies have failed to reveal a clear correlation between leukemia development and exposure to individual agents used for the treatment of autoimmune diseases. Given the dismal outcome of secondary acute myeloid leukemia and the wide range of available agents for treatment of autoimmune diseases, an increased awareness of this risk and further investigation into the pathogenetic mechanisms of acute leukemia in autoimmune disease patients are warranted. This article will review the data available on the development of acute myeloid leukemia in patients with autoimmune diseases. Possible leukemogeneic mechanisms in these patients, as well as evidence supporting the association of their primary immunosuppressive status and their exposure to specific therapies, will also be reviewed. This review also supports the idea that it may be misleading to label leukemias that develop in patients with autoimmune diseases who are exposed to cytotoxic agents as ‘therapy-related leukemias’. A better understanding of the molecular defects in autoimmune disease patients who develop acute leukemia will lead to a better understanding of the association between these two diseases entities. PMID:22180424

  4. Cerebrospinal Fluid Proteome of Patients with Acute Lyme Disease

    SciTech Connect

    Angel, Thomas E.; Jacobs, Jon M.; Smith, Robert P.; Pasternack, Mark S.; Elias, Susan; Gritsenko, Marina A.; Shukla, Anil K.; Gilmore, Edward C.; McCarthy, Carol; Camp, David G.; Smith, Richard D.

    2012-10-05

    Acute Lyme disease results from transmission of and infection by the bacterium Borrelia burgdorferi following a tick bite. During acute infection, bacteria can disseminate to the central nervous system (CNS) leading to the development of Lyme meningitis. Here we have analyzed pooled cerebrospinal fluid (CSF) allowing for a deep view into the proteome for a cohort of patients with early-disseminated Lyme disease and CSF inflammation leading to the identification of proteins that reflect host responses, which are distinct for subjects with acute Lyme disease. Additionally, we analyzed individual patient samples and quantified changes in protein abundance employing label-free quantitative mass spectrometry based methods. The measured changes in protein abundances reflect the impact of acute Lyme disease on the CNS as presented in CSF. We have identified 89 proteins that differ significantly in abundance in patients with acute Lyme disease. A number of the differentially abundant proteins have been found to be localized to brain synapse and thus constitute important leads for better understanding of the neurological consequence of disseminated Lyme disease.

  5. Relationship between haze and acute cardiovascular, cerebrovascular, and respiratory diseases in Beijing.

    PubMed

    Zhang, Jin-Jun; Cui, Meng-Meng; Fan, Da; Zhang, De-Shan; Lian, Hui-Xin; Yin, Zhao-Yin; Li, Jin

    2015-03-01

    Haze is an atmospheric phenomenon in which dry particulate pollutants obscure the sky. Haze has been associated with chronic diseases, but its relationship with acute diseases is less clear. We aimed to determine the association between haze and acute cardiovascular, cerebrovascular, and respiratory diseases, in order to determine the influence of haze on human health. We compared the number of cases of acute cardiovascular, cerebrovascular, and respiratory diseases in Beijing Emergency Center between 2006 and 2013, with haze data from Beijing Observatory. The relationship between the number of hazy days and the number of cases of the above types of diseases was analyzed using univariate analyses. Both the number of cases and the number of hazy days showed a rising trend. The average number of cases per day for all three diseases was higher on hazy days than on non-hazy days. There was a positive correlation between the number of hazy days and the number of cases, and this correlation showed a hysteretic quality. Haze has an influence on acute cardiovascular (CVDs), cerebrovascular (CBDs), and respiratory system (RSDs) diseases. Haze seems to have an additive effect, since the associations between haze and number of cases were stronger in the following month than in the preceding month. The increasing trend in the number of hazy days might worsen the problem of haze-related diseases. PMID:25292298

  6. Mouse models of human disease

    PubMed Central

    Perlman, Robert L.

    2016-01-01

    The use of mice as model organisms to study human biology is predicated on the genetic and physiological similarities between the species. Nonetheless, mice and humans have evolved in and become adapted to different environments and so, despite their phylogenetic relatedness, they have become very different organisms. Mice often respond to experimental interventions in ways that differ strikingly from humans. Mice are invaluable for studying biological processes that have been conserved during the evolution of the rodent and primate lineages and for investigating the developmental mechanisms by which the conserved mammalian genome gives rise to a variety of different species. Mice are less reliable as models of human disease, however, because the networks linking genes to disease are likely to differ between the two species. The use of mice in biomedical research needs to take account of the evolved differences as well as the similarities between mice and humans. PMID:27121451

  7. Acute Phase Reactants as Novel Predictors of Cardiovascular Disease

    PubMed Central

    Ahmed, M. S.; Jadhav, A. B.; Hassan, A.; Meng, Qing H.

    2012-01-01

    Acute phase reaction is a systemic response which usually follows a physiological condition that takes place in the beginning of an inflammatory process. This physiological change usually lasts 1-2 days. However, the systemic acute phase response usually lasts longer. The aim of this systemic response is to restore homeostasis. These events are accompanied by upregulation of some proteins (positive acute phase reactants) and downregulation of others (negative acute phase reactants) during inflammatory reactions. Cardiovascular diseases are accompanied by the elevation of several positive acute phase reactants such as C-reactive protein (CRP), serum amyloid A (SAA), fibrinogen, white blood cell count, secretory nonpancreatic phospholipase 2-II (sPLA2-II), ferritin, and ceruloplasmin. Cardiovascular disease is also accompanied by the reduction of negative acute phase reactants such as albumin, transferrin, transthyretin, retinol-binding protein, antithrombin, and transcortin. In this paper, we will be discussing the biological activity and diagnostic and prognostic values of acute phase reactants with cardiovascular importance. The potential therapeutic targets of these reactants will be also discussed. PMID:24049653

  8. Cohesin and Human Disease

    PubMed Central

    Liu, Jinglan; Krantz, Ian D.

    2016-01-01

    Cornelia de Lange syndrome (CdLS) is a dominant multisystem disorder caused by a disruption of cohesin function. The cohesin ring complex is composed of four protein subunits and more than 25 additional proteins involved in its regulation. The discovery that this complex also has a fundamental role in long-range regulation of transcription in Drosophila has shed light on the mechanism likely responsible for its role in development. In addition to the three cohesin proteins involved in CdLS, a second multisystem, recessively inherited, developmental disorder, Roberts-SC phocomelia, is caused by mutations in another regulator of the cohesin complex, ESCO2. Here we review the phenotypes of these disorders, collectively termed cohesinopathies, as well as the mechanism by which cohesin disruption likely causes these diseases. PMID:18767966

  9. Antigenuria in infants with acute and congenital Chagas' disease.

    PubMed Central

    Freilij, H L; Corral, R S; Katzin, A M; Grinstein, S

    1987-01-01

    Detection and partial characterization of Trypanosoma cruzi soluble antigens (SAg) in urine, as well as demonstration of parasite circulating antigens (CAg) in serum from pediatric patients with acute (10 patients) and congenital (10 patients) Chagas' disease, are reported. Classical techniques for parasite detection and antibody serology were also conducted in both groups. Samples collected before the onset of parasiticidal drug treatment were tested by an enzyme-linked immunosorbent assay for SAg and CAg demonstration. The control population consisted of 6 children with acute toxoplasmosis, 6 with cutaneous leishmaniasis, and 20 healthy individuals. Patients with acute cases were 100% positive for both SAg and CAg, whereas patients with congenital disease were 80% CAg positive and 100% SAg positive. Controls yielded negative results in all cases. Partial characterization of SAg from two patients with acute disease was performed by iodination, affinity chromatography, immunoprecipitation, and two-dimensional gel electrophoresis. Two different antigenic glycoproteins (80 kilodaltons, pI 6 to 6.5 and 55 kilodaltons, pI 6.5 to 7) were identified by these methods. Traditional serology and classical parasitologic tests failed, each in a different way, to provide an accurate diagnosis in the total of our patients. The enzyme-linked immunosorbent assay for SAg detection proved to be the most effective procedure for achieving early and precise proof of infection in acute and congenital cases of Chagas' disease. Images PMID:3098778

  10. Novel human astroviruses: Novel human diseases?

    PubMed

    Vu, Diem-Lan; Cordey, Samuel; Brito, Francisco; Kaiser, Laurent

    2016-09-01

    Astroviruses are small, non-enveloped, single-stranded positive RNA viruses that belong to the Astroviridae family. While classical human astroviruses (HAstV) are a well-recognized cause of acute non-bacterial diarrhea among young children worldwide, novel astroviruses, named HAstV-MLB and HAstV-VA/HMO, have been identified recently in humans by molecular assays. They are phylogenetically more related to animal astroviruses than to classical human astroviruses, thus suggesting cross-species transmission. Serological studies demonstrated a surprisingly high seroprevalence in certain populations and highlighted a high infection rate in the early years of life. Although their pathogenic role has not yet been clearly determined, novel astrovirus RNA sequences have been identified in different biological specimens of symptomatic patients, including the feces, plasma, cerebrospinal fluid, and brain biopsies. Thus, there is evidence that they could contribute not only to digestive tract infection, but also to unexpected clinical syndromes, notably encephalitis and meningitis. Severe infections affect mainly immunocompromised patients. These findings indicate that novel astroviruses should be considered in the differential diagnosis of immunocompromised patients with meningitis or encephalitis of unknown origin. PMID:27434149

  11. Respiratory symptoms and acute painful episodes in sickle cell disease.

    PubMed

    Jacob, Eufemia; Sockrider, Marianna M; Dinu, Marlen; Acosta, Monica; Mueller, Brigitta U

    2010-01-01

    The authors examined the prevalence of respiratory symptoms and determined whether respiratory symptoms were associated with prevalence of chest pain and number of acute painful episodes in children and adolescents with sickle cell disease. Participants (N = 93; 44 females, 49 males; mean age 9.8 +/- 4.3 years) reported coughing in the morning (21.5%), at night (31.2%), and during exercise (30.1%). Wheezing occurred both when they had a cold or infection (29.0%) and when they did not have (23.7%) a cold or infection. Sleep was disturbed by wheezing in 20.4%. Among the 76 patients who were school-age (>5 years), 19.7% of patients missed more than 4 days of school because of respiratory symptoms. The majority of patients reported having acute painful episodes (82.8%), and most (66.7%) reported having chest pain during acute painful episodes in the previous 12 months. Participants with acute pain episodes greater than 3 during the previous 12 months had significantly higher reports of breathing difficulties (P = .01) and chest pain (P = .002). The high number of respiratory symptoms (cough and wheeze) among patients with sickle cell disease may trigger acute painful episodes. Early screening and recognition, ongoing monitoring, and proactive management of respiratory symptoms may minimize the number of acute painful episodes. PMID:20038672

  12. Review of Elephant Endotheliotropic Herpesviruses and Acute Hemorrhagic Disease.

    PubMed

    Long, Simon Y; Latimer, Erin M; Hayward, Gary S

    2016-01-01

    More than 100 young captive and wild Asian elephants are known to have died from a rapid-onset, acute hemorrhagic disease caused primarily by multiple distinct strains of two closely related chimeric variants of a novel herpesvirus species designated elephant endotheliotropic herpesvirus (EEHV1A and EEHV1B). These and two other species of Probosciviruses (EEHV4 and EEHV5) are evidently ancient and likely nearly ubiquitous asymptomatic infections of adult Asian elephants worldwide that are occasionally shed in trunk wash secretions. Although only a handful of similar cases have been observed in African elephants, they also have proved to harbor their own multiple and distinct species of Probosciviruses-EEHV2, EEHV3, EEHV6, and EEHV7-found in lung and skin nodules or saliva. For reasons that are not yet understood, approximately 20% of Asian elephant calves appear to be susceptible to the disease when primary infections are not controlled by normal innate cellular and humoral immune responses. Sensitive specific polymerase chain reaction (PCR) DNA blood tests have been developed, routine monitoring has been established, the complete large DNA genomes of each of the four Asian EEHV species have now been sequenced, and PCR gene subtyping has provided unambiguous evidence that this is a sporadic rather than epidemic disease that it is not being spread among zoos or other elephant housing facilities. Nevertheless, researchers have not yet been able to propagate EEHV in cell culture, determine whether or not human antiherpesvirus drugs are effective inhibitors, or develop serology assays that can distinguish between antibodies against the multiple different EEHV species. PMID:26912715

  13. Acute hemodynamic responses to weightlessness in humans

    NASA Technical Reports Server (NTRS)

    Lathers, C. M.; Charles, J. B.; Elton, K. F.; Holt, T. A.; Mukai, C.; Bennett, B. S.; Bungo, M. W.

    1989-01-01

    As NASA designs space flights requiring prolonged periods of weightlessness for a broader segment of the population, it will be important to know the acute and sustained effects of weightlessness on the cardiovascular system since this information will contribute to understanding of the clinical pharmacology of drugs administered in space. Due to operational constraints on space flights, earliest effects of weightlessness have not been documented. We examined hemodynamic responses of humans to transitions from acceleration to weightlessness during parabolic flight on NASA's KC-135 aircraft. Impedance cardiography data were collected over four sets of 8-10 parabolas, with a brief rest period between sets. Each parabola included a period of 1.8 Gz, then approximately 20 seconds of weightlessness, and finally a period of 1.6 Gz; the cycle repeated almost immediately for the remainder of the set. Subjects were semi-supine (Shuttle launch posture) for the first set, then randomly supine, sitting and standing for each subsequent set. Transition to weightlessness while standing produced decreased heart rate, increased thoracic fluid content, and increased stroke index. Surprisingly, the onset of weightlessness in the semi-supine posture produced little evidence of a headward fluid shift. Heart rate, stroke index, and cardiac index are virtually unchanged after 20 seconds of weightlessness, and thoracic fluid content is slightly decreased. Semi-supine responses run counter to Shuttle crewmember reports of noticeable fluid shift after minutes to hours in orbit. Apparently, the headward fluid shift commences in the semi-supine posture before launch. is augmented by launch acceleration, but briefly interrupted immediately in orbit, then resumes and is completed over the next hours.

  14. Acute hemodynamic responses to weightlessness in humans.

    PubMed

    Lathers, C M; Charles, J B; Elton, K F; Holt, T A; Mukai, C; Bennett, B S; Bungo, M W

    1989-07-01

    As NASA designs space flights requiring prolonged periods of weightlessness for a broader segment of the population, it will be important to know the acute and sustained effects of weightlessness on the cardiovascular system since this information will contribute to understanding of the clinical pharmacology of drugs administered in space. Due to operational constraints on space flights, earliest effects of weightlessness have not been documented. We examined hemodynamic responses of humans to transitions from acceleration to weightlessness during parabolic flight on NASA's KC-135 aircraft. Impedance cardiography data were collected over four sets of 8-10 parabolas, with a brief rest period between sets. Each parabola included a period of 1.8 Gz, then approximately 20 seconds of weightlessness, and finally a period of 1.6 Gz; the cycle repeated almost immediately for the remainder of the set. Subjects were semi-supine (Shuttle launch posture) for the first set, then randomly supine, sitting and standing for each subsequent set. Transition to weightlessness while standing produced decreased heart rate, increased thoracic fluid content, and increased stroke index. Surprisingly, the onset of weightlessness in the semi-supine posture produced little evidence of a headward fluid shift. Heart rate, stroke index, and cardiac index are virtually unchanged after 20 seconds of weightlessness, and thoracic fluid content is slightly decreased. Semi-supine responses run counter to Shuttle crewmember reports of noticeable fluid shift after minutes to hours in orbit. Apparently, the headward fluid shift commences in the semi-supine posture before launch. is augmented by launch acceleration, but briefly interrupted immediately in orbit, then resumes and is completed over the next hours. PMID:2760255

  15. Animal models for human diseases.

    PubMed

    Rust, J H

    1982-01-01

    The use of animal models for the study of human disease is, for the most part, a recent development. This discussion of the use of animal models for human diseases directs attention to the sterile period, early advances, some personal experiences, the human as the model, biological oddities among common laboratory animals, malignancies in laboratory animals, problems created by federal regulations, cancer tests with animals, and what the future holds in terms of the use of animal models as an aid to understanding human disease. In terms of early use of animal models, there was a school of rabbis, some of whom were also physicians, in Babylon who studied and wrote extensively on ritual slaughter and the suitability of birds and beasts for food. Considerable detailed information on animal pathology, physiology, anatomy, and medicine in general can be found in the Soncino Babylonian Talmudic Translations. The 1906 edition of the "Jewish Encyclopedia," has been a rich resource. Although it has not been possible to establish what diseases of animals were studied and their relationship to the diseases of humans, there are fascinating clues to pursue, despite the fact that these were sterile years for research in medicine. The quotation from the Talmud is of interest: "The medical knowledge of the Talmudist was based upon tradition, the dissection of human bodies, observation of disease and experiments upon animals." A bright light in the lackluster years of medical research was provided by Galen, considered the originator of research in physiology and anatomy. His dissection of animals and work on apes and other lower animals were models for human anatomy and physiology and the bases for many treatises. Yet, Galen never seemed to suggest that animals could serve as models for human diseases. Most early physicians who can be considered to have been students of disease developed their medical knowledge by observing the sick under their care. 1 early medical investigator

  16. Is Progressive Chronic Kidney Disease a Slow Acute Kidney Injury?

    PubMed

    Cowgill, Larry D; Polzin, David J; Elliott, Jonathan; Nabity, Mary B; Segev, Gilad; Grauer, Gregory F; Brown, Scott; Langston, Cathy; van Dongen, Astrid M

    2016-11-01

    International Renal Interest Society chronic kidney disease Stage 1 and acute kidney injury Grade I categorizations of kidney disease are often confused or ignored because patients are nonazotemic and generally asymptomatic. Recent evidence suggests these seemingly disparate conditions may be mechanistically linked and interrelated. Active kidney injury biomarkers have the potential to establish a new understanding for traditional views of chronic kidney disease, including its early identification and possible mediators of its progression, which, if validated, would establish a new and sophisticated paradigm for the understanding and approach to the diagnostic evaluation, and treatment of urinary disease in dogs and cats. PMID:27593574

  17. Tocilizumab for steroid refractory acute graft-versus-host disease

    PubMed Central

    Roddy, Julianna V. F.; Haverkos, Bradley M.; McBride, Ali; Leininger, Kathryn M.; Jaglowski, Samantha; Penza, Sam; Klisovic, Rebecca; Blum, William; Vasu, Sumithira; Hofmeister, Craig C.; Benson, Don M.; Andritsos, Leslie A.; Devine, Steven M.; Efebera, Yvonne A.

    2015-01-01

    Acute graft-versus-host-disease (aGVHD) is a frequent and often lethal complication of allogeneic hematopoietic stem cell transplant despite prophylaxis. Tocilizumab is a humanized anti-IL-6 receptor monoclonal antibody that has evidence of activity in patients with steroid refractory (SR) GVHD. We retrospectively report on nine patients with grade 3 or 4 SR aGVHD who received tocilizumab. Eight mg/kg of tocilizumab was administered intravenously every 3–4 weeks. aGVHD grading and responses were based on consensus criteria. Median age at transplant was 48 years. Five patients had alternate donor sources. Median time from aGVHD onset to tocilizumab administration was 44 days. Two patients had complete responses and two had partial responses. Median survival from start of tocilizumab was 26 days (range 13–1054). Our limited experience demonstrated an overall response rate of 44% (CR + PR); however, this response was not durable. Further studies are needed to determine the optimal time for tocilizumab initiation. PMID:26140610

  18. Gut Microbial Succession Follows Acute Secretory Diarrhea in Humans

    PubMed Central

    David, Lawrence A.; Weil, Ana; Ryan, Edward T.; Calderwood, Stephen B.; Harris, Jason B.; Chowdhury, Fahima; Begum, Yasmin; Qadri, Firdausi

    2015-01-01

    ABSTRACT Disability after childhood diarrhea is an important burden on global productivity. Recent studies suggest that gut bacterial communities influence how humans recover from infectious diarrhea, but we still lack extensive data and mechanistic hypotheses for how these bacterial communities respond to diarrheal disease and its treatment. Here, we report that after Vibrio cholerae infection, the human gut microbiota undergoes an orderly and reproducible succession that features transient reversals in relative levels of enteric Bacteroides and Prevotella. Elements of this succession may be a common feature in microbiota recovery from acute secretory diarrhea, as we observed similar successional dynamics after enterotoxigenic Escherichia coli (ETEC) infection. Our metagenomic analyses suggest that multiple mechanisms drive microbial succession after cholera, including bacterial dispersal properties, changing enteric oxygen and carbohydrate levels, and phage dynamics. Thus, gut microbiota recovery after cholera may be predictable at the level of community structure but is driven by a complex set of temporally varying ecological processes. Our findings suggest opportunities for diagnostics and therapies targeting the gut microbiota in humans recovering from infectious diarrhea. PMID:25991682

  19. Proteins aggregation and human diseases

    NASA Astrophysics Data System (ADS)

    Hu, Chin-Kun

    2015-04-01

    Many human diseases and the death of most supercentenarians are related to protein aggregation. Neurodegenerative diseases include Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), frontotemporallobar degeneration, etc. Such diseases are due to progressive loss of structure or function of neurons caused by protein aggregation. For example, AD is considered to be related to aggregation of Aβ40 (peptide with 40 amino acids) and Aβ42 (peptide with 42 amino acids) and HD is considered to be related to aggregation of polyQ (polyglutamine) peptides. In this paper, we briefly review our recent discovery of key factors for protein aggregation. We used a lattice model to study the aggregation rates of proteins and found that the probability for a protein sequence to appear in the conformation of the aggregated state can be used to determine the temperature at which proteins can aggregate most quickly. We used molecular dynamics and simple models of polymer chains to study relaxation and aggregation of proteins under various conditions and found that when the bending-angle dependent and torsion-angle dependent interactions are zero or very small, then protein chains tend to aggregate at lower temperatures. All atom models were used to identify a key peptide chain for the aggregation of insulin chains and to find that two polyQ chains prefer anti-parallel conformation. It is pointed out that in many cases, protein aggregation does not result from protein mis-folding. A potential drug from Chinese medicine was found for Alzheimer's disease.

  20. Acute graft-vs-host disease: pathobiology and management.

    PubMed

    Goker, H; Haznedaroglu, I C; Chao, N J

    2001-03-01

    Acute graft-vs-host disease (GVHD) is a major obstacle to safe allogeneic hematopoietic stem cell transplantation (HSCT), leading to a significant morbidity and mortality. GVHD occurs when transplanted donor T lymphocytes react to foreign host cells. It causes a wide variety of host tissue injuries. This review focuses on the pathobiological basis, clinical aspects, and current management strategies of acute GVHD. Afferent phase of acute GVHD starts with myeloablative conditioning, i.e., before the infusion of the graft. Total-body irradiation (TBI) or high-dose chemotherapy regimens cause extensive damage and activation in host tissues, which release inflammatory cytokines and enhance recipient major histocompatibility complex (MHC) antigens. Recognition of the foreign host antigens by donor T cells and activation, stimulation, and proliferation of T cells is crucial in the afferent phase. Effector phase of acute GVHD results in direct and indirect damage to host cells. The skin, gastrointestinal tract, and liver are major target organs of acute GVHD. Combination drug prophylaxis in GVHD is essential in all patients undergoing allogeneic HSCT. Steroids have remained the standard for the treatment of acute GVHD. Several clinical trials have evaluated monoclonal antibodies or receptor antagonist therapy for steroid-resistant acute GVHD, with different successes in a variety of settings. There are some newer promising agents like mycophenolate mofetil, glutamic acid-lysine-alanine-tyrosine (GLAT), rapamycin, and trimetrexate currently entering in the clinical studies, and other agents are in development. Future experimental and clinical studies on GVHD will shed further light on the better understanding of the disease pathobiology and generate the tools to treat malignant disorders with allogeneic HSCT with specific graft-vs-tumor effects devoid of GVHD. PMID:11274753

  1. Cerebrospinal fluid proteome of patients with acute Lyme disease

    PubMed Central

    Angel, Thomas E.; Jacobs, Jon M.; Smith, Robert P.; Pasternack, Mark S.; Elias, Susan; Gritsenko, Marina A.; Shukla, Anil; Gilmore, Edward C.; McCarthy, Carol; Camp, David G.; Smith, Richard D.; Warren, H. Shaw

    2012-01-01

    During acute Lyme disease, bacteria can disseminate to the central nervous system (CNS) leading to the development of meningitis and other neurologic symptoms. Here we have analyzed pooled cerebrospinal fluid (CSF) allowing a deep view into the proteome for patients diagnosed with early-disseminated Lyme disease and CSF inflammation. Additionally, we analyzed individual patient samples and quantified differences in protein abundance employing label-free quantitative mass spectrometry based methods. We identified 108 proteins that differ significantly in abundance in patients with acute Lyme disease from controls. Comparison between infected patients and control subjects revealed differences in proteins in the CSF associated with cell death localized to brain synapses and others that likely originate from brain parenchyma. PMID:22900834

  2. Genomic responses in mouse models poorly mimic human inflammatory diseases

    PubMed Central

    Seok, Junhee; Warren, H. Shaw; Cuenca, Alex G.; Mindrinos, Michael N.; Baker, Henry V.; Xu, Weihong; Richards, Daniel R.; McDonald-Smith, Grace P.; Gao, Hong; Hennessy, Laura; Finnerty, Celeste C.; López, Cecilia M.; Honari, Shari; Moore, Ernest E.; Minei, Joseph P.; Cuschieri, Joseph; Bankey, Paul E.; Johnson, Jeffrey L.; Sperry, Jason; Nathens, Avery B.; Billiar, Timothy R.; West, Michael A.; Jeschke, Marc G.; Klein, Matthew B.; Gamelli, Richard L.; Gibran, Nicole S.; Brownstein, Bernard H.; Miller-Graziano, Carol; Calvano, Steve E.; Mason, Philip H.; Cobb, J. Perren; Rahme, Laurence G.; Lowry, Stephen F.; Maier, Ronald V.; Moldawer, Lyle L.; Herndon, David N.; Davis, Ronald W.; Xiao, Wenzhong; Tompkins, Ronald G.; Abouhamze, Amer; Balis, Ulysses G. J.; Camp, David G.; De, Asit K.; Harbrecht, Brian G.; Hayden, Douglas L.; Kaushal, Amit; O’Keefe, Grant E.; Kotz, Kenneth T.; Qian, Weijun; Schoenfeld, David A.; Shapiro, Michael B.; Silver, Geoffrey M.; Smith, Richard D.; Storey, John D.; Tibshirani, Robert; Toner, Mehmet; Wilhelmy, Julie; Wispelwey, Bram; Wong, Wing H

    2013-01-01

    A cornerstone of modern biomedical research is the use of mouse models to explore basic pathophysiological mechanisms, evaluate new therapeutic approaches, and make go or no-go decisions to carry new drug candidates forward into clinical trials. Systematic studies evaluating how well murine models mimic human inflammatory diseases are nonexistent. Here, we show that, although acute inflammatory stresses from different etiologies result in highly similar genomic responses in humans, the responses in corresponding mouse models correlate poorly with the human conditions and also, one another. Among genes changed significantly in humans, the murine orthologs are close to random in matching their human counterparts (e.g., R2 between 0.0 and 0.1). In addition to improvements in the current animal model systems, our study supports higher priority for translational medical research to focus on the more complex human conditions rather than relying on mouse models to study human inflammatory diseases. PMID:23401516

  3. Crohn's disease presenting as acute gastrointestinal hemorrhage

    PubMed Central

    Podugu, Amareshwar; Tandon, Kanwarpreet; Castro, Fernando J

    2016-01-01

    Severe gastrointestinal (GI) hemorrhage is a rare complication of Crohn’s disease (CD). Although several surgical and non-surgical approaches have been described over the last 2 decades this complication still poses significant diagnostic and therapeutic challenges. Given the relative infrequency of severe bleeding in CD, available medical literature on this topic is mostly in the form of retrospective case series and reports. In this article we review the risk factors, diagnostic modalities and treatment options for the management of CD presenting as GI hemorrhage. PMID:27122659

  4. Transfer RNA and human disease.

    PubMed

    Abbott, Jamie A; Francklyn, Christopher S; Robey-Bond, Susan M

    2014-01-01

    Pathological mutations in tRNA genes and tRNA processing enzymes are numerous and result in very complicated clinical phenotypes. Mitochondrial tRNA (mt-tRNA) genes are "hotspots" for pathological mutations and over 200 mt-tRNA mutations have been linked to various disease states. Often these mutations prevent tRNA aminoacylation. Disrupting this primary function affects protein synthesis and the expression, folding, and function of oxidative phosphorylation enzymes. Mitochondrial tRNA mutations manifest in a wide panoply of diseases related to cellular energetics, including COX deficiency (cytochrome C oxidase), mitochondrial myopathy, MERRF (Myoclonic Epilepsy with Ragged Red Fibers), and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). Diseases caused by mt-tRNA mutations can also affect very specific tissue types, as in the case of neurosensory non-syndromic hearing loss and pigmentary retinopathy, diabetes mellitus, and hypertrophic cardiomyopathy. Importantly, mitochondrial heteroplasmy plays a role in disease severity and age of onset as well. Not surprisingly, mutations in enzymes that modify cytoplasmic and mitochondrial tRNAs are also linked to a diverse range of clinical phenotypes. In addition to compromised aminoacylation of the tRNAs, mutated modifying enzymes can also impact tRNA expression and abundance, tRNA modifications, tRNA folding, and even tRNA maturation (e.g., splicing). Some of these pathological mutations in tRNAs and processing enzymes are likely to affect non-canonical tRNA functions, and contribute to the diseases without significantly impacting on translation. This chapter will review recent literature on the relation of mitochondrial and cytoplasmic tRNA, and enzymes that process tRNAs, to human disease. We explore the mechanisms involved in the clinical presentation of these various diseases with an emphasis on neurological disease. PMID:24917879

  5. Transfer RNA and human disease

    PubMed Central

    Abbott, Jamie A.; Francklyn, Christopher S.; Robey-Bond, Susan M.

    2014-01-01

    Pathological mutations in tRNA genes and tRNA processing enzymes are numerous and result in very complicated clinical phenotypes. Mitochondrial tRNA (mt-tRNA) genes are “hotspots” for pathological mutations and over 200 mt-tRNA mutations have been linked to various disease states. Often these mutations prevent tRNA aminoacylation. Disrupting this primary function affects protein synthesis and the expression, folding, and function of oxidative phosphorylation enzymes. Mitochondrial tRNA mutations manifest in a wide panoply of diseases related to cellular energetics, including COX deficiency (cytochrome C oxidase), mitochondrial myopathy, MERRF (Myoclonic Epilepsy with Ragged Red Fibers), and MELAS (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes). Diseases caused by mt-tRNA mutations can also affect very specific tissue types, as in the case of neurosensory non-syndromic hearing loss and pigmentary retinopathy, diabetes mellitus, and hypertrophic cardiomyopathy. Importantly, mitochondrial heteroplasmy plays a role in disease severity and age of onset as well. Not surprisingly, mutations in enzymes that modify cytoplasmic and mitochondrial tRNAs are also linked to a diverse range of clinical phenotypes. In addition to compromised aminoacylation of the tRNAs, mutated modifying enzymes can also impact tRNA expression and abundance, tRNA modifications, tRNA folding, and even tRNA maturation (e.g., splicing). Some of these pathological mutations in tRNAs and processing enzymes are likely to affect non-canonical tRNA functions, and contribute to the diseases without significantly impacting on translation. This chapter will review recent literature on the relation of mitochondrial and cytoplasmic tRNA, and enzymes that process tRNAs, to human disease. We explore the mechanisms involved in the clinical presentation of these various diseases with an emphasis on neurological disease. PMID:24917879

  6. Clinical disease registries in acute myocardial infarction

    PubMed Central

    Ashrafi, Reza; Hussain, Hussain; Brisk, Robert; Boardman, Leanne; Weston, Clive

    2014-01-01

    Disease registries, containing systematic records of cases, have for nearly 100 years been valuable in exploring and understanding various aspects of cardiology. This is particularly true for myocardial infarction, where such registries have provided both epidemiological and clinical information that was not readily available from randomised controlled trials in highly-selected populations. Registries, whether mandated or voluntary, prospective or retrospective in their analysis, have at their core a common study population and common data definitions. In this review we highlight how registries have diversified to offer information on epidemiology, risk modelling, quality assurance/improvement and original research-through data mining, transnational comparisons and the facilitation of enrolment in, and follow-up during registry-based randomised clinical trials. PMID:24976913

  7. [Acute cardiovascular disease and job retention].

    PubMed

    Fantoni-Quinton, Sophie; Tellart, Anne-Sophie; Cambier-Langrand, Evodie; Fassier, Jean Baptiste; Mounier-Vehier, Claire

    2016-05-01

    Since it allows a better quality of life, return to work must be considered ever since the early stages of the health care pathway following a cardiovascular disease. Seeing the occupational physician beforehand, so as to anticipate the return to work, is crucial. Dialogue between cardiologists, general practitioners and occupational physician, still observing medical confidentiality, must allow a better quality of return to work. Being recognized as a handicapped worker is a key element in the prevention of socio-professional exclusion. Even when dealing with long sick leave, permanent functional injuries or job loss, guiding the patients towards the appropriate person can improve return to work and job retention in the long term. PMID:27021479

  8. Pulmonary thromboembolic disease. Clinical management of acute and chronic disease.

    PubMed

    Torbicki, Adam

    2010-07-01

    Pulmonary thromboembolism falls between the areas of pulmonology and cardiology, internal medicine and intensive care, radiology and nuclear medicine, and hematology and cardiothoracic surgery. Depending on their clinical background, physicians faced with a patient with a pulmonary thromboembolism may speak different languages and adopt different treatment approaches. Now, however, there is an opportunity to end the Tower of Babel surrounding pulmonary thromboembolism. There is a growing acknowledgement that the key clinical problems in both acute pulmonary embolism and chronic thromboembolic pulmonary hypertension are linked to right ventricular pressure overload and right ventricular failure. As a result, cardiologists and cardiac intensive care specialists are taking an increasing interest in understanding and combating these conditions. The European Society of Cardiology was the first to elaborate comprehensive clinical practice guidelines for pulmonary thromboembolism and chronic thromboembolic pulmonary hypertension. The task forces involved in producing these guidelines included radiologists, pulmonologists, hematologists, intensive care physicians and surgeons, which ensured that the final document was universally acceptable. The aim of this article was to provide an overview of the epidemiology, risk factors, diagnosis, treatment, prognosis and prevention of acute pulmonary thromboembolism and chronic thromboembolic pulmonary hypertension, while taking into account European Society of Cardiology guidelines and incorporating new evidence where necessary. PMID:20609317

  9. Acute renal failure: outcomes and risk of chronic kidney disease.

    PubMed

    Block, C A; Schoolwerth, A C

    2007-09-01

    Acute renal failure (ARF) is a common condition, especially among the critically ill, and confers a high mortality. The incidence of ARF is increasing. Efforts such as the Acute Dialysis Quality Initiative (ADQI) are being undertaken to establish a consensus definition of ARF, and to distinguish between varying degrees of acute kidney injury that might confer a different prognosis. Data are emerging to allow comparison of the epidemiology of ARF across institutions internationally. There is ongoing recognition of the important interaction between ARF and chronic kidney disease and more information regarding recovery from ARF is available. Controversy exists regarding the optimal management of ARF. Recent publications emphasize the importance of timing and dose of renal replacement therapy rather than the modality of treatment (intermittent hemodialysis vs continuous therapies). These issues are explored in this review. PMID:17912228

  10. Managing acute and chronic renal stone disease.

    PubMed

    Moran, Conor P; Courtney, Aisling E

    2016-02-01

    Nephrolithiasis, or renal stone disease, is common and the incidence is increasing globally. In the UK the lifetime risk is estimated to be 8-10%. On a population level, the increase in stone incidence, erosion of gender disparity, and younger age of onset is likely to reflect increasing prevalence of obesity and a Western diet with a high intake of animal protein and salt. Stones can be detected by a variety of imaging techniques. The gold standard is a non-contrast CT of kidneys, ureters and bladder (CT KUB) which can identify > 99% of stones. CT KUB should be the primary mode of imaging for all patients with colic unless contraindicated. In such instances, or if a CT KUB is not available, an ultrasound KUB is an alternative. This has advantages in terms of radiation exposure and cost, but is limited in sensitivity, particularly for ureteric stones. Once diagnosed, a plain film KUB can be used for follow-up of radiopaque stones. For most patients diclofenac is a reasonable first choice of analgesia, e.g. 50-100 mg rectally, or 75 mg IM. Opioid medication can worsen nausea and be less effective, but should be used if there is a contraindication to NSAIDs. A combination of diclofenac, paracetamol, and/or codeine regularly can provide adequate pain control in many cases. Failure of this analgesic combination should prompt consideration of secondary care support. If a ureteric stone < 5 mm in diameter is identified, the expectation is that this will pass without intervention. Initially medical management is still useful for stones between 5 and 10mm in diameter, but urology input is more likely to be necessary as up to 50% of these may require intervention. Stones that are >10 mm in diameter should be discussed with the urology service as they are unlikely to pass spontaneously. PMID:27032222

  11. Clinical Scenarios in Acute Kidney Injury: Parenchymal Acute Kidney Injury-Tubulo-Interstitial Diseases.

    PubMed

    Meola, Mario; Samoni, Sara; Petrucci, Ilaria; Ronco, Claudio

    2016-01-01

    Acute tubular necrosis (ATN) is the most common type of acute kidney injury (AKI) related to parenchymal damage (90% of cases). It may be due to a direct kidney injury, such as sepsis, drugs, toxins, contrast media, hemoglobinuria and myoglobinuria, or it may be the consequence of a prolonged systemic ischemic injury. Conventional ultrasound (US) shows enlarged kidneys with hypoechoic pyramids. Increased volume is largely sustained by the increase of anteroposterior diameter, while longitudinal axis usually maintains its normal length. Despite the role of color Doppler in AKI still being debated, many studies demonstrate that renal resistive indexes (RIs) vary on the basis of primary disease. Moreover, several studies assessed that higher RI values are predictive of persistent AKI. Nevertheless, due to the marked heterogeneity among the studies, further investigations focused on timing of RI measurement and test performances are needed. Acute interstitial nephritis is also a frequent cause of AKI, mainly due to non-steroidal anti-inflammatory drugs and antibiotics administration. The development of acute interstitial nephritis is due to an immunological reaction against nephritogenic exogenous antigens, processed by tubular cells. In acute interstitial nephritis, as well as in ATN, conventional US does not allow a definitive diagnosis. Kidneys appear enlarged and widely hyperechoic due to interstitial edema and inflammatory infiltration. Also, in this condition, hemodynamic changes are closely correlated to the severity and the progression of the anatomical damage. PMID:27169885

  12. Pulmonary hypertension during acute respiratory diseases in infants

    PubMed Central

    Bardi-Peti, Luiza; Ciofu, Eugen Pascal

    2010-01-01

    ABSTRACT Objectives:The study was undertaken to assess whether previously healthy infants with acute respiratory diseases develop elevated pulmonary artery pressures and to identify which type of disease is associated with pulmonary hypertension. Material and Methods:We performed 2D and Doppler echocardiography in 137 infants, aged between 1 and 12 month, from November 2007 to December 2009. 75 infants had acute respiratory diseases (49 bronchiolitis, 16 interstitial pneumonia, 3 bronchopneumonia, 6 episodic wheezing, 1 lobar pneumonia) and 62 were in the control group. We excluded children with congenital heart diseases and other conditions associated with pulmonary hypertension. The method of time to peak velocity corrected for heart rate was used to estimate pulmonary arterial pressure (PAP). We analysed 2 age-subgroups: 1-2 months and 2-12 months. A Student’s t-test for independent samples was used to compare the mean values of variables. Outcomes:Increased mean pulmonary pressures (>25mmHg) were measured in 18 infants with respiratory diseases, with the next distribution: 14 bronchiolitis, 2 bronchopneumonia, 1 episodic wheezing, 1 interstitial pneumonia. The values were categorized as mild-moderate pulmonary hypertension. Mean PAP were significantly increased in subjects with clinically bronchoobstructive disease (bronchiolitis, episodic wheezing, bronchopneumonia) vs. control (p=0.05 in first age-subgroup and<0.001 in second age-subgroup). In infants with bronchoobstructive disease hospitalization was significantly longer in patients with pulmonary hypertension vs. normal PAP (p= 0.04 in first age-subgroup and 0.005 in second age-subgroup). In patients with bronchoobstructive diseases, mean PAPm and PAPs were significantly increased in subjects with a moderate/severe episode of wheezing at admission vs. a mild episode (p=0.02). Mean PAPm and PAPs were increased in subjects with interstitial pneumonia vs. control, but without statistic significance

  13. Proteomics in human disease: cancer, heart and infectious diseases.

    PubMed

    Jungblut, P R; Zimny-Arndt, U; Zeindl-Eberhart, E; Stulik, J; Koupilova, K; Pleissner, K P; Otto, A; Müller, E C; Sokolowska-Köhler, W; Grabher, G; Stöffler, G

    1999-07-01

    In recent years, genomics has increased the understanding of many diseases. Proteomics is a rapidly growing research area that encompasses both genetic and environmental factors. The protein composition represents the functional status of a biological compartment. The five approaches presented here resulted in the detection of disease-associated proteins. Calgranulin B was upregulated in colorectal cancer, and hepatoma-derived aldose reductase-like protein was reexpressed in a rat model during hepatocarcinogenesis. In these two investigations, attention was focused on one protein, obviously differing in amount, directly after two-dimensional electrophoresis (2-DE). Additional methods, such as enzyme activity measurements and immunohistochemistry, confirmed the disease association of the two candidates resulting from 2-DE subtractive analysis. The following three investigations take advantage of the holistic potential of the 2-DE approach. The comparison of 2-DE patterns from dilated cardiomyopathy patients with those of controls revealed 25 statistically significant intensity differences, from which 12 were identified by amino acid analysis, Edman degradation or matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS). A human myocardial 2-DE database was constructed, containing 3300 protein spots and 150 identified protein species. The number of identified proteins was limited by the capacity of our group, rather than by the principle of feasibility. Another field where proteomics proves to be a valuable tool in identifying proteins of importance for diagnosis is proteome analysis of pathogenic microorganisms such as Borrelia burgdorferi (Lyme disease) and Toxoplasma gondii (toxoplasmosis). Sera from patients with early or late symptoms of Lyme borreliosis contained antibodies of various classes against about 80 antigens each, containing the already described antigens OspA, B and C, flagellin, p83/100, and p39. Similarly, antibody reactivity to

  14. Acute Hepatic Phenotype of Wilson Disease: Clinical Features of Acute Episodes and Chronic Lesions Remaining in Survivors

    PubMed Central

    Hayashi, Hisao; Tatsumi, Yasuaki; Yahata, Shinsuke; Hayashi, Hiroki; Momose, Kenji; Isaji, Ryohei; Sasaki, Youji; Hayashi, Kazuhiko; Wakusawa, Shinya; Goto, Hidemi

    2015-01-01

    Background and Aims: Wilson disease (WD) is an inherited disorder of copper metabolism, and an international group for the study of WD (IGSW) has proposed three phenotypes for its initial presentation: acute hepatic, chronic hepatic, and neurologic phenotypes. Characterization of the acute hepatic phenotype may improve our understanding of the disease. Methods: Clinical features of 10 WD patients with the acute hepatic phenotype and characteristics of chronic lesions remaining in survivors were assessed by the European Association for the Study of the Liver (EASL) guidelines. Results: All six patients younger than 30 years had survived an acute episode of hemolytic anemia with residual liver disease of cirrhosis or chronic hepatitis. The acute episode was self-limiting in two of the four patients over the age of 30 years and progressed to acute liver failure in the other two patients. One of the two survivors had residual liver disease of chronic hepatitis, while the other had chronic hepatitis and neurologic disease. Neurologic disease remained in a patient who successfully received a liver transplantation. During acute episodes, serum levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) changed rapidly along with anemia. Liver-specific ALT levels were age-dependently correlated with hemoglobin (Hb) concentrations. Enzyme reduction was milder for AST than ALT, which resulted in a high AST/ALT ratio in the anemic stage. The anemic stage in two patients transformed to acute liver failure. Conclusions: All survivors of an acute episode of the acute hepatic phenotype had residual liver disease or both liver and neurologic diseases. The rapid changes in liver enzymes during the acute episode and the liver and neurologic diseases remaining in survivors may provide a better understanding of WD. PMID:26807378

  15. Metabolomics and Its Application to Acute Lung Diseases

    PubMed Central

    Stringer, Kathleen A.; McKay, Ryan T.; Karnovsky, Alla; Quémerais, Bernadette; Lacy, Paige

    2016-01-01

    Metabolomics is a rapidly expanding field of systems biology that is gaining significant attention in many areas of biomedical research. Also known as metabonomics, it comprises the analysis of all small molecules or metabolites that are present within an organism or a specific compartment of the body. Metabolite detection and quantification provide a valuable addition to genomics and proteomics and give unique insights into metabolic changes that occur in tangent to alterations in gene and protein activity that are associated with disease. As a novel approach to understanding disease, metabolomics provides a “snapshot” in time of all metabolites present in a biological sample such as whole blood, plasma, serum, urine, and many other specimens that may be obtained from either patients or experimental models. In this article, we review the burgeoning field of metabolomics in its application to acute lung diseases, specifically pneumonia and acute respiratory disease syndrome (ARDS). We also discuss the potential applications of metabolomics for monitoring exposure to aerosolized environmental toxins. Recent reports have suggested that metabolomics analysis using nuclear magnetic resonance (NMR) and mass spectrometry (MS) approaches may provide clinicians with the opportunity to identify new biomarkers that may predict progression to more severe disease, such as sepsis, which kills many patients each year. In addition, metabolomics may provide more detailed phenotyping of patient heterogeneity, which is needed to achieve the goal of precision medicine. However, although several experimental and clinical metabolomics studies have been conducted assessing the application of the science to acute lung diseases, only incremental progress has been made. Specifically, little is known about the metabolic phenotypes of these illnesses. These data are needed to substantiate metabolomics biomarker credentials so that clinicians can employ them for clinical decision

  16. Metabolomics and Its Application to Acute Lung Diseases.

    PubMed

    Stringer, Kathleen A; McKay, Ryan T; Karnovsky, Alla; Quémerais, Bernadette; Lacy, Paige

    2016-01-01

    Metabolomics is a rapidly expanding field of systems biology that is gaining significant attention in many areas of biomedical research. Also known as metabonomics, it comprises the analysis of all small molecules or metabolites that are present within an organism or a specific compartment of the body. Metabolite detection and quantification provide a valuable addition to genomics and proteomics and give unique insights into metabolic changes that occur in tangent to alterations in gene and protein activity that are associated with disease. As a novel approach to understanding disease, metabolomics provides a "snapshot" in time of all metabolites present in a biological sample such as whole blood, plasma, serum, urine, and many other specimens that may be obtained from either patients or experimental models. In this article, we review the burgeoning field of metabolomics in its application to acute lung diseases, specifically pneumonia and acute respiratory disease syndrome (ARDS). We also discuss the potential applications of metabolomics for monitoring exposure to aerosolized environmental toxins. Recent reports have suggested that metabolomics analysis using nuclear magnetic resonance (NMR) and mass spectrometry (MS) approaches may provide clinicians with the opportunity to identify new biomarkers that may predict progression to more severe disease, such as sepsis, which kills many patients each year. In addition, metabolomics may provide more detailed phenotyping of patient heterogeneity, which is needed to achieve the goal of precision medicine. However, although several experimental and clinical metabolomics studies have been conducted assessing the application of the science to acute lung diseases, only incremental progress has been made. Specifically, little is known about the metabolic phenotypes of these illnesses. These data are needed to substantiate metabolomics biomarker credentials so that clinicians can employ them for clinical decision-making and

  17. Molybdenum cofactor and human disease.

    PubMed

    Schwarz, Guenter

    2016-04-01

    Four molybdenum-dependent enzymes are known in humans, each harboring a pterin-based molybdenum cofactor (Moco) in the active site. They catalyze redox reactions using water as oxygen acceptor or donator. Moco is synthesized by a conserved biosynthetic pathway. Moco deficiency results in a severe inborn error of metabolism causing often early childhood death. Disease-causing symptoms mainly go back to the lack of sulfite oxidase (SO) activity, an enzyme in cysteine catabolism. Besides their name-giving functions, Mo-enzymes have been recognized to catalyze novel reactions, including the reduction of nitrite to nitric oxide. In this review we cover the biosynthesis of Moco, key features of Moco-enzymes and focus on their deficiency. Underlying disease mechanisms as well as treatment options will be discussed. PMID:27055119

  18. Acute Cerebellitis in Children: A Many-Faceted Disease.

    PubMed

    Kornreich, Liora; Shkalim-Zemer, Vered; Levinsky, Yoel; Abdallah, Wafa; Ganelin-Cohen, Esther; Straussberg, Rachel

    2016-07-01

    Acute cerebellitis is a rare inflammatory condition. It may have a benign, self-limiting course or present as a fulminant disease resulting in severe cerebellar damage or even sudden death. We present the clinical, laboratory, and radiologic data in 9 children diagnosed with acute cerebellitis, who were identified by database search in our pediatric medical center from January 2000 to November 2014. The main presenting symptom was headache, and the main presenting sign was ataxia. Bilateral diffuse hemispheric involvement was the most common imaging finding at presentation. Mycoplasma pneumoniae was the most common infectious pathogen found. Treatment included steroids in all cases, antibiotics in 4, and intravenous immunoglobulins in 6. Six patients had a full recovery, and 3 had residual neurologic complications. Magnetic resonance imaging (MRI) is the modality of choice for diagnosis. The course of acute cerebellitis varies from a commonly benign and self-limiting disease to an occasionally fulminant disease, resulting in severe cerebellar damage or sudden death. PMID:26961264

  19. Coevolution, modularity and human disease.

    PubMed

    Fraser, Hunter B

    2006-12-01

    The concepts of coevolution and modularity have been studied separately for decades. Recent advances in genomics have led to the first systematic studies in each of these fields at the molecular level, resulting in several important discoveries. Both coevolution and modularity appear to be pervasive features of genomic data from all species studied to date, and their presence can be detected in many types of datasets, including genome sequences, gene expression data, and protein-protein interaction data. Moreover, the combination of these two ideas might have implications for our understanding of many aspects of biology, ranging from the general architecture of living systems to the causes of various human diseases. PMID:17005391

  20. CNVs, Aneuploidies and Human Disease

    PubMed Central

    Martin, Christa L.; Kirkpatrick, Brianne E.; Ledbetter, David H.

    2015-01-01

    In the perinatal setting, chromosome imbalances cause a wide range of clinically significant disorders and increase risk for other particular phenotypes. As technologies have improved to detect increasingly smaller deletions and duplications, collectively referred to as copy number variants (CNVs), we are learning the significant role that these types of genomic variants play in human disease and their relatively high frequency in ~1% of all pregnancies. In this overview, we will highlight key aspects of CNV detection and interpretation used during the course of clinical care in the prenatal and neonatal periods. Since CNVs are one of the most frequent causes of a broad spectrum of human disorders, early diagnosis and accurate interpretation is important to implement timely interventions and targeted clinical management. PMID:26042902

  1. Aluminium and human breast diseases.

    PubMed

    Darbre, P D; Pugazhendhi, D; Mannello, F

    2011-11-01

    The human breast is exposed to aluminium from many sources including diet and personal care products, but dermal application of aluminium-based antiperspirant salts provides a local long-term source of exposure. Recent measurements have shown that aluminium is present in both tissue and fat of the human breast but at levels which vary both between breasts and between tissue samples from the same breast. We have recently found increased levels of aluminium in noninvasively collected nipple aspirate fluids taken from breast cancer patients (mean 268 ± 28 μg/l) compared with control healthy subjects (mean 131 ± 10 μg/l) providing evidence of raised aluminium levels in the breast microenvironment when cancer is present. The measurement of higher levels of aluminium in type I human breast cyst fluids (median 150 μg/l) compared with human serum (median 6 μg/l) or human milk (median 25 μg/l) warrants further investigation into any possible role of aluminium in development of this benign breast disease. Emerging evidence for aluminium in several breast structures now requires biomarkers of aluminium action in order to ascertain whether the presence of aluminium has any biological impact. To this end, we report raised levels of proteins that modulate iron homeostasis (ferritin, transferrin) in parallel with raised aluminium in nipple aspirate fluids in vivo, and we report overexpression of mRNA for several S100 calcium binding proteins following long-term exposure of MCF-7 human breast cancer cells in vitro to aluminium chlorhydrate. PMID:22099158

  2. Expert consensus on acute exacerbation of chronic obstructive pulmonary disease in the People’s Republic of China

    PubMed Central

    Cai, Bai-qiang; Cai, Shao-xi; Chen, Rong-chang; Cui, Li-ying; Feng, Yu-lin; Gu, Yu-tong; Huang, Shao-guang; Liu, Rong-yu; Liu, Guang-nan; Shi, Huan-zhong; Shi, Yi; Song, Yuan-lin; Sun, Tie-ying; Wang, Chang-zheng; Wang, Jing-lan; Wen, Fu-qiang; Xiao, Wei; Xu, Yong-jian; Yan, Xi-xin; Yao, Wan-zhen; Yu, Qin; Zhang, Jing; Zheng, Jin-ping; Liu, Jie; Bai, Chun-xue

    2014-01-01

    Chronic obstructive pulmonary disease (COPD) is a common disease that severely threatens human health. Acute exacerbation of COPD (AECOPD) is a major cause of disease progression and death, and causes huge medical expenditures. This consensus statement represents a description of clinical features of AECOPD in the People’s Republic of China and a set of recommendations. It is intended to provide clinical guidelines for community physicians, pulmonologists and other health care providers for the prevention, diagnosis, and treatment of AECOPD. PMID:24812503

  3. Evolutionary Mutant Models for Human Disease

    PubMed Central

    Albertson, R. Craig; Cresko, William; Detrich, H. William; Postlethwait, John H.

    2010-01-01

    Although induced mutations in traditional laboratory animals have been valuable as models for human diseases, they have some important limitations. Here we propose a complementary approach to discover genes and mechanisms that might contribute to human disorders: the analysis of evolutionary mutant models whose adaptive phenotypes mimic maladaptive human diseases. If the type and mode of action of mutations favored by natural selection in wild populations are similar to those that contribute to human diseases, then studies in evolutionary mutant models have the potential to identify novel genetic factors and gene-by-environment interactions that affect human health and underlie human disease. PMID:19108930

  4. Acute paretic syndrome in juvenile White Leghorn chickens resembles late stages of acute inflammatory demyelinating polyneuropathies in humans

    PubMed Central

    2010-01-01

    Background Sudden limb paresis is a common problem in White Leghorn flocks, affecting about 1% of the chicken population before achievement of sexual maturity. Previously, a similar clinical syndrome has been reported as being caused by inflammatory demyelination of peripheral nerve fibres. Here, we investigated in detail the immunopathology of this paretic syndrome and its possible resemblance to human neuropathies. Methods Neurologically affected chickens and control animals from one single flock underwent clinical and neuropathological examination. Peripheral nervous system (PNS) alterations were characterised using standard morphological techniques, including nerve fibre teasing and transmission electron microscopy. Infiltrating cells were phenotyped immunohistologically and quantified by flow cytometry. The cytokine expression pattern was assessed by quantitative real-time PCR (qRT-PCR). These investigations were accomplished by MHC genotyping and a PCR screen for Marek's disease virus (MDV). Results Spontaneous paresis of White Leghorns is caused by cell-mediated, inflammatory demyelination affecting multiple cranial and spinal nerves and nerve roots with a proximodistal tapering. Clinical manifestation coincides with the employment of humoral immune mechanisms, enrolling plasma cell recruitment, deposition of myelin-bound IgG and antibody-dependent macrophageal myelin-stripping. Disease development was significantly linked to a 539 bp microsatellite in MHC locus LEI0258. An aetiological role for MDV was excluded. Conclusions The paretic phase of avian inflammatory demyelinating polyradiculoneuritis immunobiologically resembles the late-acute disease stages of human acute inflammatory demyelinating polyneuropathy, and is characterised by a Th1-to-Th2 shift. PMID:20109187

  5. Acute Chagas Disease Induces Cerebral Microvasculopathy in Mice

    PubMed Central

    Nisimura, Lindice Mitie; Estato, Vanessa; de Souza, Elen Mello; Reis, Patricia A.; Lessa, Marcos Adriano; Castro-Faria-Neto, Hugo Caire; Pereira, Mirian Claudia de Souza; Tibiriçá, Eduardo; Garzoni, Luciana Ribeiro

    2014-01-01

    Cardiomyopathy is the main clinical form of Chagas disease (CD); however, cerebral manifestations, such as meningoencephalitis, ischemic stroke and cognitive impairment, can also occur. The aim of the present study was to investigate functional microvascular alterations and oxidative stress in the brain of mice in acute CD. Acute CD was induced in Swiss Webster mice (SWM) with the Y strain of Trypanosoma cruzi (T. cruzi). Cerebral functional capillary density (the number of spontaneously perfused capillaries), leukocyte rolling and adhesion and the microvascular endothelial-dependent response were analyzed over a period of fifteen days using intravital video-microscopy. We also evaluated cerebral oxidative stress with the thiobarbituric acid reactive species TBARS method. Compared with the non-infected group, acute CD significantly induced cerebral functional microvascular alterations, including (i) functional capillary rarefaction, (ii) increased leukocyte rolling and adhesion, (iii) the formation of microvascular platelet-leukocyte aggregates, and (iv) alteration of the endothelial response to acetylcholine. Moreover, cerebral oxidative stress increased in infected animals. We concluded that acute CD in mice induced cerebral microvasculopathy, characterized by a reduced incidence of perfused capillaries, a high number of microvascular platelet-leukocyte aggregates, a marked increase in leukocyte-endothelium interactions and brain arteriolar endothelial dysfunction associated with oxidative stress. These results suggest the involvement of cerebral microcirculation alterations in the neurological manifestations of CD. PMID:25010691

  6. Acute Pelvic Inflammatory Disease and Clinical Response to Parenteral Doxycycline

    PubMed Central

    Chow, Anthony W.; Malkasian, Kay L.; Marshall, John R.; Guze, Lucien B.

    1975-01-01

    The bacteriology of acute pelvic inflammatory disease (PID) and clinical response to parenteral doxycycline were evaluated in 30 patients. Only 3 of 21 cul-de-sac cultures from PID patients were sterile, whereas all 8 normal control subjects yielded negative results (P< 0.005). Poor correlation was observed between cervical and cul-de-sac cultures. Neisseria gonorrhoeae, isolated from the cervix in 17 patients (57%), was recovered from the cul-de-sac only once. Streptococcus, Peptococcus, Peptostreptococcus, coliforms, and other organisms normally present in the vagina were the predominant isolates recovered from the cul-de-sac. Parenteral doxycycline resulted in rapid resolution of signs and symptoms (within 48 h) in 20 of 27 evaluable patients (74%). In five others, signs and symptoms of infection abated within 4 days. The remaining two patients failed to respond; in both cases, adnexal masses developed during doxycycline therapy. Gonococci were eradicated from the cervix in all but one patient who, nevertheless, had a rapid defervescence of symptoms. There was no clear-cut correlation between the clinical response and in vitro susceptibility of cul-de-sac isolates to doxycycline. These data confirm the usefulness of broad-spectrum antibiotics in acute PID. Culdocentesis is a reliable means of obtaining material for the bacteriological diagnosis of acute PID; however, the pathogenetic role and relative importance of gonococci and various other bacteria in acute PID need to be clarified further. PMID:1169908

  7. Therapies for human prion diseases

    PubMed Central

    Panegyres, Peter K; Armari, Elizabeth

    2013-01-01

    The pathological foundation of human prion diseases is a result of the conversion of the physiological form of prion protein (PrPc) to the pathological protease resistance form PrPres. Most patients with prion disease have unknown reasons for this conversion and the subsequent development of a devastating neurodegenerative disorder. The conversion of PrPc to PrPres, with resultant propagation and accumulation results in neuronal death and amyloidogenesis. However, with increasing understanding of neurodegenerative processes it appears that protein-misfolding and subsequent propagation of these rouge proteins, is a generic phenomenon shared with diseases caused by tau, α-synucleins and β-amyloid proteins. Consequently, effective anti-prion agents may have wider implications. A number of therapeutic approaches include polyanionic, polycyclic drugs such as pentosan polysulfate (PPS), which prevent the conversion of PrPc to PrPres and might also sequester and down-regulate PrPres. Polyanionic compounds might also help to clear PrPres. Treatments aimed at the laminin receptor, which is an important accessory molecule in the conversion of PrPc to PrPres – neuroprotection, immunotherapy, siRNA and antisense approaches have provided some experimental promise. PMID:24093082

  8. Biomarkers in the assessment of acute and chronic kidney diseases in the dog and cat.

    PubMed

    Cobrin, A R; Blois, S L; Kruth, S A; Abrams-Ogg, A C G; Dewey, C

    2013-12-01

    In both human and veterinary medicine, diagnosing and staging renal disease can be difficult. Measurement of glomerular filtration rate is considered the gold standard for assessing renal function but methods for its assessment can be technically challenging and impractical. The main parameters used to diagnose acute and chronic kidney disease include circulating creatinine and urea concentrations, and urine-specific gravity. However, these parameters can be insensitive. Therefore, there is a need for better methods to diagnose and monitor patients with renal disease. The use of renal biomarkers is increasing in human and veterinary medicine for the diagnosis and monitoring of acute and chronic kidney diseases. An ideal biomarker would identify site and severity of injury, and correlate with renal function, among other qualities. This article will review the advantages and limitations of renal biomarkers that have been used in dogs and cats, as well as some markers used in humans that may be adapted for veterinary use. In the future, measuring a combination of biomarkers will likely be a useful approach in the diagnosis of kidney disorders. PMID:24152019

  9. Acute Warfarin Toxicity as Initial Manifestation of Metastatic Liver Disease

    PubMed Central

    Jani, Nihar; Niazi, Masooma; Lvovsky, Dmitry

    2016-01-01

    Near complete infiltration of the liver secondary to metastasis from the head and neck cancer is a rare occurrence. The prognosis of liver failure associated with malignant infiltration is extremely poor; the survival time of patients is extremely low. We present a case of acute warfarin toxicity as initial manifestation of metastatic liver disease. Our patient is a 64-year-old woman presenting with epigastric pain and discomfort, found to have unrecordable International Normalized Ratio. She rapidly deteriorated with acute respiratory failure requiring mechanical ventilation, profound shock requiring high dose vasopressor infusion, severe coagulopathy, worsening liver enzymes with worsening of lactic acidosis and severe metabolic abnormalities, and refractory to aggressive supportive care and died in less than 48 hours. Autopsy revealed that >90% of the liver was replaced by tumor masses. PMID:27042361

  10. Postpartum Acute Pulmonary Oedema with Sub clinical Rheumatic Heart Disease.

    PubMed

    R, Padmaja; Gande, Sri Krishna Padma Challa Rao

    2015-02-01

    Acute dyspnea with pulmonary oedema in postpartum is uncommon but life-threatening event. Contributing factors for pulmonary oedema include, administration of tocolytics, underlying cardiac disease, iatrogenic fluid overload and preeclampsia acounting 0.08% of pregnancies. Pulmonary embolism, amniotic fluid embolism, pneumonia, aspiration and pulmonary oedema are some of the potentially devastating conditions that should be considered by the attending physician. Here, we report a case of postpartum acute pulmonary oedema referred to causality after an emergency caesarean section in a private hospital. No matter what the underlying pathology, prompt administration and appropriate resuscitation is always the first priority. Only after the patient has been stabilized attention must be turned to diagnosis and specific treatment. A diagnosis of severe Mitral Stenosis, probably of rheumatic origin was made after stabilizing the patient. PMID:25859501

  11. Acute Marchiafava-Bignami disease: clinical and serial MRI correlation

    PubMed Central

    Kakkar, Chandan; Prakashini, Koteshwara; Polnaya, Ashwin

    2014-01-01

    Marchiafava-Bignami disease (MBD) is a form of toxic demyelinating disease more often seen in chronic alcoholics. The disease process typically involves the corpus callosum and clinically often presents with altered sensorium, neurocognitive defects or seizures with acute cases often deteriorating to comatose state. The death rate is high. We report a rare case of MBD with complete clinical recovery. A 50-year-old male patient presented in an unconscious state and underwent MRI of the brain which showed significant lesions involving the corpus callosum. Following treatment with thiamine and supportive therapy, he improved clinically and a follow-up MRI revealed significant resolution of the earlier lesions. Diffusion-weighted MRI showed the changes more conspicuously as compared with conventional imaging. The clinical resolution corresponded well with the MRI pattern. The case highlights that diffusion-weighted MRI is an extremely useful tool in evaluation and prognostication of MBD. PMID:24850553

  12. Lithium-Induced Minimal Change Disease and Acute Kidney Injury

    PubMed Central

    Tandon, Parul; Wong, Natalie; Zaltzman, Jeffrey S

    2015-01-01

    Context: Lithium carbonate is a psychiatric medication commonly used in the treatment of bipolar disorder. It has been implicated in inducing nephrogenic diabetes inspidus, chronic tubulointerstitial nephropathy, and acute tubular necrosis. We describe a case of lithium-induced minimal change disease (MCD) and acute kidney injury (AKI). Case Report: A 32-year-old female with a medical history of bipolar disorder treated with chronic lithium therapy presented with anasarca, fatigue, and tremors. Work-up revealed supra-therapeutic lithium levels, hypoalbuminemia, and significant proteinuria. The patient was treated conservatively with fluids and discontinuation of lithium therapy. Subsequently, she developed significant AKI and persistent proteinuria. She underwent a renal biopsy that demonstrated effacement of podocyte foot processes consistent with lithium-induced MCD. This was treated with corticosteroids, which decreased the proteinuria and resolved all the patient's symptoms. Conclusion: Lithium-induced MCD is a rare disease that affects patients of all ages. It is often associated with therapeutic lithium and is typically resolved with discontinuation of lithium. In some cases, concurrent AKI may result due to vascular obstruction from hyperalbuminuria and associated renal interstitial edema. Corticosteroids may be needed to reduce the proteinuria and prevent progression to chronic kidney disease. As such, patients on lithium therapy may benefit from monitoring of glomerular function via urinalysis to prevent the onset of nephrotic syndrome. PMID:26258081

  13. Epidemiology of coronary heart disease and acute coronary syndrome

    PubMed Central

    Perez-Quilis, Carme; Leischik, Roman; Lucia, Alejandro

    2016-01-01

    The aim of this review is to summarize the incidence, prevalence, trend in mortality, and general prognosis of coronary heart disease (CHD) and a related condition, acute coronary syndrome (ACS). Although CHD mortality has gradually declined over the last decades in western countries, this condition still causes about one-third of all deaths in people older than 35 years. This evidence, along with the fact that mortality from CHD is expected to continue increasing in developing countries, illustrates the need for implementing effective primary prevention approaches worldwide and identifying risk groups and areas for possible improvement. PMID:27500157

  14. Epidemiology of coronary heart disease and acute coronary syndrome.

    PubMed

    Sanchis-Gomar, Fabian; Perez-Quilis, Carme; Leischik, Roman; Lucia, Alejandro

    2016-07-01

    The aim of this review is to summarize the incidence, prevalence, trend in mortality, and general prognosis of coronary heart disease (CHD) and a related condition, acute coronary syndrome (ACS). Although CHD mortality has gradually declined over the last decades in western countries, this condition still causes about one-third of all deaths in people older than 35 years. This evidence, along with the fact that mortality from CHD is expected to continue increasing in developing countries, illustrates the need for implementing effective primary prevention approaches worldwide and identifying risk groups and areas for possible improvement. PMID:27500157

  15. Role of anaerobes in acute pelvic inflammatory disease.

    PubMed

    Saini, S; Gupta, N; Batra, G; Arora, D R

    2003-01-01

    Pouch of Douglas aspirates were collected from 50 women with history and examination suggestive of acute pelvic inflammatory disease (PID) and 20 healthy women admitted for tubal ligation served as control. A total of 57 microorganisms were isolated from 37 patients out of 50 in study group. Of 37 positive cultures 21(56.7%) were monomicrobial and 16(43.2%) were polymicrobial. Most common symptom in study group was lower abdominal pain (90%), vaginal discharge (70%) and irregular bleeding (40%) and 30% patients had history of intrauterine contraceptive device (IUCD) implantation. The predominant aerobic isolates were Escherichia coli, Coagulase Negative Staphylococcus (CONS), Staphylococcus aureus, Klebsiella pneumoniae while common anaerobes were Bacteroides fragilis, Prevotella melaninogenica, Fusobacterium nucleatum and Peptostreptococcus spp. Our study shows that cefotaxime, cefuroxime and gentamicin may be used for gram negative aerobic bacilli; cloxacillin, cephaloridine and erythromycin for aerobic gram positive cocci and amikacin and ceftazidime for Pseudomonas aeruginosa. Thus for optimum therapy of acute PID it is beneficial to keep in mind major conceptual changes and therapeutic realities that have influenced current understanding of acute PID and have affected the choice of therapy. PMID:17643017

  16. Aspirin as Primary Prevention of Acute Coronary Heart Disease Events

    PubMed Central

    Glasser, Stephen P.; Hovater, Martha; Brown, Todd M.; Howard, George; Safford, Monika M.

    2015-01-01

    Background/Objective Aspirin for primary prophylaxis is controversial. This study evaluated associations between prophylactic aspirin use and incident acute coronary heart disease (CHD) events. Methods and Results The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study was accessed for aspirin use examining black and white hazards for incident CHD, for men and women, each adjusting incrementally for sampling, sociodemographics, and CHD risk factors. Stratified models examined risks across strata of the Framingham risk score, and all-cause mortality. 23,949 participants (mean 64 yo), had 503 incident events over a 3.5 year follow-up. Prophylactic aspirin use was not associated with incident acute CHD, HR 1.05 (95% CI 0.86, 1.29). Modeling had little impact on the HR (1.09 {95% CI 0.89, 1.33) nor did the addition of risk factors (HR 1.00 {95% CI 0.81, 1.23). Aspirin use was not associated with incident CHD for any Framingham risk level. Findings were similar when including all aspirin users (not just those taking aspirin prophylactically), and when examining associations with all-cause mortality. There was no excess hospitalized bleeding in the aspirin users. Conclusion Aspirin was not associated with lower risk for incident acute CHD overall, or within race, gender, or Framingham Risk Score. PMID:26413491

  17. [The deterministic concept of human diseases].

    PubMed

    Petlenko, V P; Strukov, A I; Khmel'nitskiĭ, O K

    1984-01-01

    Human disease is a complex systemic event, the theoretical analysis of which requires application of the methodological appratus of investigation. As such, the authors used the concept of Marxist-Leninist determinism. The latter is a system of universal interconnections and causative dependence of natural events, society, and human diseases in particular. Analysis of human diseases from the position of the Marxist-Leninist theory of determinism is one of the basic problems of the theory of pathology. A logical analysis of evolutionary, systemic, morphological and causative determinism is given which characterizes on the whole human diseases. PMID:6391430

  18. Advancing the Minimal Residual Disease Concept in Acute Myeloid Leukemia.

    PubMed

    Hokland, Peter; Ommen, Hans B; Mulé, Matthew P; Hourigan, Christopher S

    2015-07-01

    The criteria to evaluate response to treatment in acute myeloid leukemia (AML) have changed little in the past 60 years. It is now possible to use higher sensitivity tools to measure residual disease burden in AML. Such minimal or measurable residual disease (MRD) measurements provide a deeper understanding of current patient status and allow stratification for risk of subsequent clinical relapse. Despite these obvious advantages, and after over a decade of laboratory investigation and preclinical validation, MRD measurements are not currently routinely used for clinical decision-making or drug development in non-acute promyelocytic leukemia (non-APL) AML. We review here some potential constraints that may have delayed adoption, including a natural hesitancy of end users, economic impact concerns, misperceptions regarding the meaning of and need for assay sensitivity, the lack of one single MRD solution for all AML patients, and finally the need to involve patients in decision-making based on such correlates. It is our opinion that none of these issues represent insurmountable barriers and our hope is that by providing potential solutions we can help map a path forward to a future where our patients will be offered personalized treatment plans based on the amount of AML they have left remaining to treat. PMID:26111465

  19. Rabbit Models for Studying Human Infectious Diseases

    PubMed Central

    Peng, Xuwen; Knouse, John A; Hernon, Krista M

    2015-01-01

    Using an appropriate animal model is crucial for mimicking human disease conditions, and various facets including genetics, anatomy, and pathophysiology should be considered before selecting a model. Rabbits (Oryctolagus cuniculus) are well known for their wide use in production of antibodies, eye research, atherosclerosis and other cardiovascular diseases. However, a systematic description of the rabbit as primary experimental models for the study of various human infectious diseases is unavailable. This review focuses on the human infectious diseases for which rabbits are considered a classic or highly appropriate model, including AIDS (caused by HIV1), adult T-cell leukemia–lymphoma (human T-lymphotropic virus type 1), papilloma or carcinoma (human papillomavirus) , herpetic stromal keratitis (herpes simplex virus type 1), tuberculosis (Mycobacterium tuberculosis), and syphilis (Treponema pallidum). In addition, particular aspects of the husbandry and care of rabbits used in studies of human infectious diseases are described. PMID:26678367

  20. Rabbit Models for Studying Human Infectious Diseases.

    PubMed

    Peng, Xuwen; Knouse, John A; Hernon, Krista M

    2015-12-01

    Using an appropriate animal model is crucial for mimicking human disease conditions, and various facets including genetics, anatomy, and pathophysiology should be considered before selecting a model. Rabbits (Oryctolagus cuniculus) are well known for their wide use in production of antibodies, eye research, atherosclerosis and other cardiovascular diseases. However, a systematic description of the rabbit as primary experimental models for the study of various human infectious diseases is unavailable. This review focuses on the human infectious diseases for which rabbits are considered a classic or highly appropriate model, including AIDS (caused by HIV1), adult T-cell leukemia-lymphoma (human T-lymphotropic virus type 1), papilloma or carcinoma (human papillomavirus) , herpetic stromal keratitis (herpes simplex virus type 1), tuberculosis (Mycobacterium tuberculosis), and syphilis (Treponema pallidum). In addition, particular aspects of the husbandry and care of rabbits used in studies of human infectious diseases are described. PMID:26678367

  1. Major comorbid disease processes associated with increased incidence of acute kidney injury

    PubMed Central

    Farooqi, Salwa; Dickhout, Jeffrey G

    2016-01-01

    Acute kidney injury (AKI) is commonly seen amongst critically ill and hospitalized patients. Individuals with certain co-morbid diseases have an increased risk of developing AKI. Thus, recognizing the co-morbidities that predispose patients to AKI is important in AKI prevention and treatment. Some of the most common co-morbid disease processes that increase the risk of AKI are diabetes, cancer, cardiac surgery and human immunodeficiency virus (HIV) acquired immune deficiency syndrome (AIDS). This review article identifies the increased risk of acquiring AKI with given co-morbid diseases. Furthermore, the pathophysiological mechanisms underlying AKI in relation to co-morbid diseases are discussed to understand how the risk of acquiring AKI is increased. This paper reviews the effects of various co-morbid diseases including: Diabetes, cancer, cardiovascular disease and HIV AIDS, which all exhibit a significant increased risk of developing AKI. Amongst these co-morbid diseases, inflammation, the use of nephrotoxic agents, and hypoperfusion to the kidneys have been shown to be major pathological processes that predisposes individuals to AKI. The pathogenesis of kidney injury is complex, however, effective treatment of the co-morbid disease processes may reduce its risk. Therefore, improved management of co-morbid diseases may prevent some of the underlying pathology that contributes to the increased risk of developing AKI. PMID:26981437

  2. Crohnic Kidney Disease: Recurrent Acute Kidney Failure in a Patient With Crohn's Disease

    PubMed Central

    Demir, Mehmet Emin; Ercan, Zafer; Karakas, Emel Yigit; Ulas, Turgay; Buyukhatipoglu, Hakan

    2014-01-01

    Context: Short bowel syndrome is a rare and devastating complication in chronic inflammatory bowel disease following functional or anatomic loss of extensive segments of the intestine. Case Report: A 60-year-old male patient with Crohn's disease had undergone multiple resections of the intestine and developed short bowel syndrome. Despite up to 4-5 liters of orally fluid, sufficient calcium and magnesium intake, he suffered from recurrent acute kidney injury due to profound volume depletion and those electrolyte deficiencies. Administration of intravenous fluid and electrolyte repleacement treatment at regular intervals prevented further kidney injuries. Conclusion: We present a case of recurrent acute kidney failure in a patient with Crohn's disease, and aimed to remark importance of receiving sufficient parenteral fluid and electrolyte support in those with short bowel syndrome. PMID:25599054

  3. Risk Factors for Acute Toxoplasma gondii Diseases in Taiwan: A Population-Based Case-Control Study

    PubMed Central

    Chiang, Ting-Yi; Kuo, Ming-Chu; Chen, Chang-Hsun; Yang, Jyh-Yuan; Kao, Cheng-Feng; Ji, Dar-Der; Fang, Chi-Tai

    2014-01-01

    Although human toxoplasmosis is a notifiable disease in Taiwan since 2007, little is known about its risk factors. This study aimed to investigate the risk factors for acute Toxoplasma gondii diseases in Taiwan. We conducted a nationwide population-based case-control study. Cases of acute human toxoplasmosis notified to the Taiwan Centers for Diseases Control (Taipei, Taiwan) during 2008–2013 were compared with controls that were randomly selected from healthy T. gondii-seronegative blood donors who participated in a nationwide T. gondii seroepidemiologic study during 2009–2010. Cases and controls were matched according to age, gender and residency at an 1∶8 ratio. Structured questionnaires were used to gather information regarding risk factors. A total of 30 laboratory-confirmed acute T. gondii disease cases and 224 controls were enrolled. The most common clinical manifestation of the cases was flu-like symptoms (n = 20), followed by central nervous system disease (n = 4), ocular diseases (n = 3), abortion (n = 2), and congenital infection (n = 1). Multivariate conditional logistic regression showed that raw clam consumption (adjusted odds ratio [OR] = 3.7; 95% confidence interval [CI] = 1.4–9.9) and having a cat in the household (adjusted OR = 2.9; 95% CI = 1.1–7.9) were two independent risk factors for acute T. gondii disease. We conclude that raw shellfish consumption and domestic cat exposure were risk factors for acquiring acute T. gondii diseases in Taiwan. This finding may guide future research and control policies. PMID:24609112

  4. The Human Phenotypic Disease Network

    NASA Astrophysics Data System (ADS)

    Hidalgo, Cesar; Blumm, Nicholas; Barabasi, Albert-Laszlo; Christakis, Nicholas

    2008-03-01

    We study the evolution of patient illness using a network summarizing the disease associations extracted from 32 million Medicare claims recorded from 13 million elders using the ICD9-CM format. We find that the evolution of patients' illness is accurately described by a process in which once a patient develops a particular disease, subsequent disease are seen to occur among diseases lying close by in the network. In addition, we find that patients affected with diseases with high network connectivity are more likely to die during a follow-up period of eight years.

  5. Hooked! Modeling human disease in zebrafish.

    PubMed

    Santoriello, Cristina; Zon, Leonard I

    2012-07-01

    Zebrafish have been widely used as a model system for studying developmental processes, but in the last decade, they have also emerged as a valuable system for modeling human disease. The development and function of zebrafish organs are strikingly similar to those of humans, and the ease of creating mutant or transgenic fish has facilitated the generation of disease models. Here, we highlight the use of zebrafish for defining disease pathways and for discovering new therapies. PMID:22751109

  6. Functional engineered human cardiac patches prepared from nature's platform improve heart function after acute myocardial infarction.

    PubMed

    Wang, Qingjie; Yang, Hui; Bai, Aobing; Jiang, Wei; Li, Xiuya; Wang, Xinhong; Mao, Yishen; Lu, Chao; Qian, Ruizhe; Guo, Feng; Ding, Tianling; Chen, Haiyan; Chen, Sifeng; Zhang, Jianyi; Liu, Chen; Sun, Ning

    2016-10-01

    With the advent of induced pluripotent stem cells and directed differentiation techniques, it is now feasible to derive individual-specific cardiac cells for human heart tissue engineering. Here we report the generation of functional engineered human cardiac patches using human induced pluripotent stem cells-derived cardiac cells and decellularized natural heart ECM as scaffolds. The engineered human cardiac patches can be tailored to any desired size and shape and exhibited normal contractile and electrical physiology in vitro. Further, when patching on the infarct area, these patches improved heart function of rats with acute myocardial infarction in vivo. These engineered human cardiac patches can be of great value for normal and disease-specific heart tissue engineering, drug screening, and meet the demands for individual-specific heart tissues for personalized regenerative therapy of myocardial damages in the future. PMID:27509303

  7. Acute and non-acute effects of cannabis on human memory function: a critical review of neuroimaging studies.

    PubMed

    Bossong, Matthijs G; Jager, Gerry; Bhattacharyya, Sagnik; Allen, Paul

    2014-01-01

    Smoking cannabis produces a diverse range of effects, including impairments in learning and memory. These effects are exerted through action on the endocannabinoid system, which suggests involvement of this system in human cognition. Learning and memory deficits are core symptoms of psychiatric and neurological disorders such as schizophrenia and Alzheimer's disease, and may also be related to endocannabinoid dysfunction in these disorders. However, before new research can focus on potential treatments that work by manipulating the endocannabinoid system, it needs to be elucidated how this system is involved in symptoms of psychiatric disorders. Here we review neuroimaging studies that investigated acute and non-acute effects of cannabis on human learning and memory function, both in adults and in adolescents. Overall, results of these studies show that cannabis use is associated with a pattern of increased activity and a higher level of deactivation in different memory-related areas. This could reflect either increased neural effort ('neurophysiological inefficiency') or a change in strategy to maintain good task performance. However, the interpretation of these findings is significantly hampered by large differences between study populations in cannabis use in terms of frequency, age of onset, and time that subjects were abstinent from cannabis. Future neuroimaging studies should take these limitations into account, and should focus on the potential of cannabinoid compounds for treatment of cognitive symptoms in psychiatric disorders. PMID:23829369

  8. Managing the acutely ill adult with sickle cell disease.

    PubMed

    Brown, Marvelle

    Sickle cell disease (SCD) is an autosomal recessively inherited condition, affecting the structure of the haemoglobin. SCD is a long-term chronic condition which is manifested by periods of acute painful sickling crisis, known as vaso-occlusive crisis (VOC) and is the cause of 90% of sickle cell-related hospital admissions. SCD is one of the most common genetic conditions worldwide and in the UK there are approximately 12,500 people living with it (Streetly et al,1997; Howard et al, 2008), making it more common than cystic fibrosis, yet there still remains many challenges in managing these patients when they become acutely ill. Lack of awareness and understanding of the illness, concerns regarding addiction and limited attention to the psycho-social implications of the illness, leads to less than effective care for this patient group when they are hospitalized. The aims of this article are to outline the pathophysiology of SCD, identify the causes of VOC and discuss the key principles of nursing management for patients experiencing a VOC. PMID:22306637

  9. A randomized study of the prevention of acute graft-versus-host disease

    SciTech Connect

    Ramsay, N.K.C.; Kersey, J.H.; Robison, L.L.; McGlave, P.B.; Woods, W.G.; Krivit, W.; Kim, T.H.; Goldman, A.I.; Nesbit, M.E., Jr.

    1982-02-01

    Acute graft-versus-host disease is a major problem in allogeneic bone-marrow transplantation. We performed a randomized study to compare the effectiveness of two regimens in the prevention of acute graft-versus-host disease. Thirty-five patients received methotrexate alone, and 32 received methotrexate, antithymocyte globulin, and prednisone. Of the patients who received methotrexate alone, 48 percent had acute graft-versus-host disease, as compared with 21 per cent of those who received methotrexate, antithymocyte globulin, and prednisone (P = 0.01). The age of the recipient was a significant factor in the development of acute graft-versus-host disease: Older patients had a higher incidence of the disease (P = 0.001). We conclude that the combination of methotrexate, antithymocyte globulin, and prednisone significantly decreased the incidence of acute graft-versus-host disease and should be used to prevent this disorder in patients receiving allogeneic marrow transplants.

  10. Mitochondrial dysfunction in inherited renal disease and acute kidney injury.

    PubMed

    Emma, Francesco; Montini, Giovanni; Parikh, Samir M; Salviati, Leonardo

    2016-05-01

    Mitochondria are increasingly recognized as key players in genetic and acquired renal diseases. Most mitochondrial cytopathies that cause renal symptoms are characterized by tubular defects, but glomerular, tubulointerstitial and cystic diseases have also been described. For example, defects in coenzyme Q10 (CoQ10) biosynthesis and the mitochondrial DNA 3243 A>G mutation are important causes of focal segmental glomerulosclerosis in children and in adults, respectively. Although they sometimes present with isolated renal findings, mitochondrial diseases are frequently associated with symptoms related to central nervous system and neuromuscular involvement. They can result from mutations in nuclear genes that are inherited according to classic Mendelian rules or from mutations in mitochondrial DNA, which are transmitted according to more complex rules of mitochondrial genetics. Diagnosis of mitochondrial disorders involves clinical characterization of patients in combination with biochemical and genetic analyses. In particular, prompt diagnosis of CoQ10 biosynthesis defects is imperative because of their potentially reversible nature. In acute kidney injury (AKI), mitochondrial dysfunction contributes to the physiopathology of tissue injury, whereas mitochondrial biogenesis has an important role in the recovery of renal function. Potential therapies that target mitochondrial dysfunction or promote mitochondrial regeneration are being developed to limit renal damage during AKI and promote repair of injured tissue. PMID:26804019

  11. Acute Psychosis as Major Clinical Presentation of Legionnaires' Disease

    PubMed Central

    Silva-dos-Santos, Amílcar; Talina, Miguel Cotrim

    2016-01-01

    We report a case of a 61-year-old woman who presented with acute psychosis as a major manifestation of Legionnaires' disease in the absence of other neuropsychiatric symptoms. Clinical history revealed dry cough and nausea. Observation showed fever and auscultation crackles in the lower lobe of the right lung. Laboratory testing demonstrated elevated C-reactive protein and lung chest radiograph showed patchy peribronchial and right lower lobe consolidation. Soon after admission, she started producing purulent sputum. Epidemiological data suggested Legionella pneumophila as possible cause of the clinical picture that was confirmed by urinary antigen detection and polymerase chain reaction of the sputum. She was treated with levofloxacin 750 mg/day for 10 days with complete remission of pulmonary and psychiatric symptoms. She has not had further psychotic symptoms. PMID:27547478

  12. Acute Psychosis as Major Clinical Presentation of Legionnaires' Disease.

    PubMed

    Coentre, Ricardo; Silva-Dos-Santos, Amílcar; Talina, Miguel Cotrim

    2016-01-01

    We report a case of a 61-year-old woman who presented with acute psychosis as a major manifestation of Legionnaires' disease in the absence of other neuropsychiatric symptoms. Clinical history revealed dry cough and nausea. Observation showed fever and auscultation crackles in the lower lobe of the right lung. Laboratory testing demonstrated elevated C-reactive protein and lung chest radiograph showed patchy peribronchial and right lower lobe consolidation. Soon after admission, she started producing purulent sputum. Epidemiological data suggested Legionella pneumophila as possible cause of the clinical picture that was confirmed by urinary antigen detection and polymerase chain reaction of the sputum. She was treated with levofloxacin 750 mg/day for 10 days with complete remission of pulmonary and psychiatric symptoms. She has not had further psychotic symptoms. PMID:27547478

  13. Invasive fungal diseases in patients with acute lymphoid leukemia.

    PubMed

    Nicolato, Andrea; Nouér, Simone A; Garnica, Marcia; Portugal, Rodrigo; Maiolino, Angelo; Nucci, Marcio

    2016-09-01

    Invasive fungal disease (IFD) represents an important complication in patients with acute lymphoid leukemia (ALL). The objectives of this study were to determine the prevalence of IFD in ALL patients with neutropenia, identify factors associated with IFD, and estimate the impact of IFD on the outcome. All patients with ALL who developed febrile neutropenia from 1987 to 2013 were evaluated. Cases of IFD were classified as proven or probable. Factors associated with IFD were evaluated by comparing episodes with and without a diagnosis of IFD. Among 350 episodes of febrile neutropenia, 31 IFDs were diagnosed (8.8%). Prolonged neutropenia was the only factor associated with IFD caused by yeasts. Factors associated with IFD caused by molds by multivariate analysis were the period after 2008, receipt of allogeneic transplant, relapsed ALL and prolonged neutropenia. Patients in relapse should receive induction chemotherapy in rooms with HEPA filter and receive antifungal prophylaxis. PMID:26949001

  14. Oxygen therapy in acute exacerbations of chronic obstructive pulmonary disease

    PubMed Central

    Brill, Simon E; Wedzicha, Jadwiga A

    2014-01-01

    Acute exacerbations of chronic obstructive pulmonary disease (COPD) are important events in the history of this debilitating lung condition. Associated health care utilization and morbidity are high, and many patients require supplemental oxygen or ventilatory support. The last 2 decades have seen a substantial increase in our understanding of the best way to manage the respiratory failure suffered by many patients during this high-risk period. This review article examines the evidence underlying supplemental oxygen therapy during exacerbations of COPD. We first discuss the epidemiology and pathophysiology of respiratory failure in COPD during exacerbations. The rationale and evidence underlying oxygen therapy, including the risks when administered inappropriately, are then discussed, along with further strategies for ventilatory support. We also review current recommendations for best practice, including methods for improving oxygen provision in the future. PMID:25404854

  15. CT appearance of acute inflammatory disease of the renal interstitium

    SciTech Connect

    Gold, R.P.; McClennan, B.L.; Rottenberg, R.R.

    1983-08-01

    Today, infection remains the most common disease of the urinary tract and constitutes almost 75% of patient problems requiring urologic evaluation. There have been several major factors responsible for our better understanding of the nature and pathophysiology of urinary tract infection. One has been quantitated urine bacteriology and another, the discovery that a significant part of the apparently healthy adult female population has asymptomatic bacteriuria. Abnormal conditions such as neurogenic bladder, bladder malignancy, prolonged catheter drainage and reflux, altered host resistance, diabetes mellitus, and urinary tract obstruction, as well as pregnancy, may either predispose to or be implicated in the pathogenesis of urinary tract infection. There is a wide range of conditions that result in acute renal inflammation and those under discussion affect primarily the interstitium. This term refers to the connective tissue elements separating the tubules in the cortex and medulla. Hence, the interstitial nephritides are to be distinguished from the glomerulonephritides and fall into two general etiologic categories: infectious and noninfectious.

  16. Genetically Engineered Pig Models for Human Diseases

    PubMed Central

    Prather, Randall S.; Lorson, Monique; Ross, Jason W.; Whyte, Jeffrey J.; Walters, Eric

    2015-01-01

    Although pigs are used widely as models of human disease, their utility as models has been enhanced by genetic engineering. Initially, transgenes were added randomly to the genome, but with the application of homologous recombination, zinc finger nucleases, and transcription activator-like effector nuclease (TALEN) technologies, now most any genetic change that can be envisioned can be completed. To date these genetic modifications have resulted in animals that have the potential to provide new insights into human diseases for which a good animal model did not exist previously. These new animal models should provide the preclinical data for treatments that are developed for diseases such as Alzheimer's disease, cystic fibrosis, retinitis pigmentosa, spinal muscular atrophy, diabetes, and organ failure. These new models will help to uncover aspects and treatments of these diseases that were otherwise unattainable. The focus of this review is to describe genetically engineered pigs that have resulted in models of human diseases. PMID:25387017

  17. Neurovascular changes in acute, sub-acute and chronic mouse models of Parkinson's disease.

    PubMed

    Sarkar, Sumit; Raymick, James; Mann, Dushyant; Bowyer, John F; Hanig, Joseph P; Schmued, Larry C; Paule, Merle G; Chigurupati, Srinivasulu

    2014-02-01

    Although selective neurodegeneration of nigro-striatal dopaminergic neurons is widely accepted as a cause of Parkinson's disease (PD), the role of vascular components in the brain in PD pathology is not well understood. However, the neurodegeneration seen in PD is known to be associated with neuroinflammatory-like changes that can affect or be associated with brain vascular function. Thus, dysfunction of the capillary endothelial cell component of neurovascular units present in the brain may contribute to the damage to dopaminergic neurons that occurs in PD. An animal model of PD employing acute, sub-acute and chronic exposures of mice to methyl-phenyl-tetrahydropyridine (MPTP) was used to determine the extent to which brain vasculature may be damaged in PD. Fluoro-Turquoise gelatin labeling of microvessels and endothelial cells was used to determine the extent of vascular damage produced by MPTP. In addition, tyrosine hydroxylase (TH) and NeuN were employed to detect and quantify dopaminergic neuron damage in the striatum (CPu) and substantia nigra (SNc). Gliosis was evaluated through GFAP immunohistochemistry. MPTP treatment drastically reduced TH immunoreactive neurons in the SNc (20.68 ± 2.83 in acute; 22.98 ± 2.14 in sub-acute; 10.20 ± 2.24 in chronic vs 34.88 ± 2.91 in controls; p<0.001). Similarly, TH immunoreactive terminals were dramatically reduced in the CPu of MPTP treated mice. Additionally, all three MPTP exposures resulted in a decrease in the intensity, length, and number of vessels in both CPu and SNc. Degenerative vascular changes such as endothelial cell 'clusters' were also observed after MPTP suggesting that vasculature damage may be modifying the availability of nutrients and exposing blood cells and/or toxic substances to neurons and glia. In summary, vascular damage and degeneration could be an additional exacerbating factor in the progression of PD, and therapeutics that protect and insure vascular integrity may be novel treatments for

  18. Blocking MHC class II on human endothelium mitigates acute rejection

    PubMed Central

    Abrahimi, Parwiz; Qin, Lingfeng; Chang, William G.; Bothwell, Alfred L.M.; Tellides, George; Saltzman, W. Mark; Pober, Jordan S.

    2016-01-01

    Acute allograft rejection is mediated by host CD8+ cytotoxic T lymphocytes (CTL) targeting graft class I major histocompatibility complex (MHC) molecules. In experimental rodent models, rejection requires differentiation of naive CD8+ T cells into alloreactive CTL within secondary lymphoid organs, whereas in humans, CTL may alternatively develop within the graft from circulating CD8+ effector memory T cells (TEM) that recognize class I MHC molecules on graft endothelial cells (EC). This latter pathway is poorly understood. Here, we show that host CD4+ TEM, activated by EC class II MHC molecules, provide critical help for this process. First, blocking HLA-DR on EC lining human artery grafts in immunodeficient mice reduces CD8+ CTL development within and acute rejection of the artery by adoptively transferred allogeneic human lymphocytes. Second, siRNA knockdown or CRISPR/Cas9 ablation of class II MHC molecules on EC prevents CD4+ TEM from helping CD8+ TEM to develop into CTL in vitro. Finally, implanted synthetic microvessels, formed from CRISPR/Cas9-modified EC lacking class II MHC molecules, are significantly protected from CD8+ T cell–mediated destruction in vivo. We conclude that human CD8+ TEM–mediated rejection targeting graft EC class I MHC molecules requires help from CD4+ TEM cells activated by recognition of class II MHC molecules. PMID:26900601

  19. Human Physiological Responses to Acute and Chronic Cold Exposure

    NASA Technical Reports Server (NTRS)

    Stocks, Jodie M.; Taylor, Nigel A. S.; Tipton, Michael J.; Greenleaf, John E.

    2001-01-01

    When inadequately protected humans are exposed to acute cold, excessive body heat is lost to the environment and unless heat production is increased and heat loss attenuated, body temperature will decrease. The primary physiological responses to counter the reduction in body temperature include marked cutaneous vasoconstriction and increased metabolism. These responses, and the hazards associated with such exposure, are mediated by a number of factors which contribute to heat production and loss. These include the severity and duration of the cold stimulus; exercise intensity; the magnitude of the metabolic response; and individual characteristics such as body composition, age, and gender. Chronic exposure to a cold environment, both natural and artificial, results in physiological alterations leading to adaptation. Three quite different, but not necessarily exclusive, patterns of human cold adaptation have been reported: metabolic, hypothermic, and insulative. Cold adaptation has also been associated with an habituation response, in which there is a desensitization, or damping, of the normal response to a cold stress. This review provides a comprehensive analysis of the human physiological and pathological responses to cold exposure. Particular attention is directed to the factors contributing to heat production and heat loss during acute cold stress, and the ability of humans to adapt to cold environments.

  20. Human bocavirus in acute gastroenteritis in children in Brazil.

    PubMed

    Campos, Gubio Soares; Silva Sampaio, Madina Lyve; Menezes, Aline Dorea Luz; Tigre, Dellane Martins; Moura Costa, Lilia Ferreira; Chinalia, Fabio Alexandre; Sardi, Silvia Ines

    2016-01-01

    Epidemiological surveillance for Human Bocavirus (HBoV) was conducted on 105 fecal specimens from children with acute gastroenteritis in Bahia, Brazil. Among of a total 105 stool samples, 44 samples were positive for HBoV as detected by nested-PCR. Of the 44 positive samples, co-infections with other enteric viruses (Norovirus, Adenovirus, and Rotavirus) were found in 12 pediatric patients. Mixed infections among HBoV with Norovirus were frequently observed in this population. The phylogenetic analysis identified the presence of HBoV-1, and HBoV 2A species. This study shows that HBoV is another viral pathogen in the etiology of acute gastroenteritis in children in Bahia, Brazil. PMID:26059266

  1. Chemopreventative effects of tetrahydrocurcumin on human diseases.

    PubMed

    Wu, Jia-Ching; Tsai, Mei-Ling; Lai, Ching-Shu; Wang, Ying-Jan; Ho, Chi-Tang; Pan, Min-Hsiung

    2014-01-01

    Chemoprevention is a relatively new and promising strategy to prevent human degenerative diseases, including cancer, and is defined as the use of natural dietary compounds and/or synthetic substances to block, inhibit, reverse, or retard the progress of human diseases. Tetrahydrocurcumin (THC) is a major metabolite of curcumin (extracted from the roots of the Curcuma longa Linn). THC has been demonstrated to prevent oxidative stress and inflammation, to act against neurodegeneration, and to possess anti-cancer activity. In this review, we summarize the current knowledge and underlying molecular mechanisms of the chemopreventative activities of THC and its potential effects on the development of various human diseases. PMID:24220621

  2. Human migration and infectious diseases.

    PubMed

    Soto, S M

    2009-01-01

    Emerging infectious diseases (EID) are defined as diseases that have appeared recently or that have recently increased in their frequency, geographical distribution or both. Commercial globalisation, population movements and environmental changes are the main factors favouring the international spread of microorganisms. Transport and communication development constitutes also a remarkable factor in the worldwide dispersion of microorganisms. The mass movement of large numbers of people creates new opportunities for the spread and establishment of common or novel infectious diseases. A surveillance system to detect emergent and re-emergent infections, a rapid responsiveness of healthcare systems and laboratories, vector control, and the provision of healthcare education programmes to inform the population of how to avoid infections are needed in order to stop the spread of infectious diseases. PMID:19220349

  3. Computer Models of Stress, Allostasis, and Acute and Chronic Diseases

    PubMed Central

    Goldstein, David S.

    2009-01-01

    The past century has seen a profound shift in diseases of humankind. Acute, unifactorial diseases are being replaced increasingly by multifactorial disorders that arise from complex interactions among genes, environment, concurrent morbidities and treatments, and time. According to the concept of allostasis, there is no single, ideal set of steady-state conditions in life. Allostasis reflects active, adaptive processes that maintain apparent steady states, via multiple, interacting effectors regulated by homeostatic comparators “homeostats.” Stress can be defined as a condition or state in which a sensed discrepancy between afferent information and a setpoint for response leads to activation of effectors, reducing the discrepancy. “Allostatic load” refers to the consequences of sustained or repeated activation of mediators of allostasis. From the analogy of a home temperature control system, the temperature can be maintained at any of a variety of levels (allostatic states) by multiple means (effectors), regulated by a comparator thermostat (homeostat). Stress might exert adverse health consequences via allostatic load. This presentation describes models of homeostatic systems that incorporate negative feedback regulation, multiple effectors, effector sharing, environmental influences, intrinsic obsolescence, and destabilizing positive feedback loops. These models can be used to predict effects of environmental and genetic alterations on allostatic load and therefore on the development of multi-system disorders and failures. PMID:19120114

  4. Experimental Models in Syrian Golden Hamster Replicate Human Acute Pancreatitis.

    PubMed

    Wang, Yunan; Kayoumu, Abudurexiti; Lu, Guotao; Xu, Pengfei; Qiu, Xu; Chen, Liye; Qi, Rong; Huang, Shouxiong; Li, Weiqin; Wang, Yuhui; Liu, George

    2016-01-01

    The hamster has been shown to share a variety of metabolic similarities with humans. To replicate human acute pancreatitis with hamsters, we comparatively studied the efficacy of common methods, such as the peritoneal injections of caerulein, L-arginine, the retrograde infusion of sodium taurocholate, and another novel model with concomitant administration of ethanol and fatty acid. The severity of pancreatitis was evaluated by serum amylase activity, pathological scores, myeloperoxidase activity, and the expression of inflammation factors in pancreas. The results support that the severity of pathological injury is consistent with the pancreatitis induced in mice and rat using the same methods. Specifically, caerulein induced mild edematous pancreatitis accompanied by minimal lung injury, while L-arginine induced extremely severe pancreatic injury including necrosis and neutrophil infiltration. Infusion of Na-taurocholate into the pancreatic duct induced necrotizing pancreatitis in the head of pancreas and lighter inflammation in the distal region. The severity of acute pancreatitis induced by combination of ethanol and fatty acids was between the extent of caerulein and L-arginine induction, with obvious inflammatory cells infiltration. In view of the advantages in lipid metabolism features, hamster models are ideally suited for the studies of pancreatitis associated with altered metabolism in humans. PMID:27302647

  5. Experimental Models in Syrian Golden Hamster Replicate Human Acute Pancreatitis

    PubMed Central

    Wang, Yunan; Kayoumu, Abudurexiti; Lu, Guotao; Xu, Pengfei; Qiu, Xu; Chen, Liye; Qi, Rong; Huang, Shouxiong; Li, Weiqin; Wang, Yuhui; Liu, George

    2016-01-01

    The hamster has been shown to share a variety of metabolic similarities with humans. To replicate human acute pancreatitis with hamsters, we comparatively studied the efficacy of common methods, such as the peritoneal injections of caerulein, L-arginine, the retrograde infusion of sodium taurocholate, and another novel model with concomitant administration of ethanol and fatty acid. The severity of pancreatitis was evaluated by serum amylase activity, pathological scores, myeloperoxidase activity, and the expression of inflammation factors in pancreas. The results support that the severity of pathological injury is consistent with the pancreatitis induced in mice and rat using the same methods. Specifically, caerulein induced mild edematous pancreatitis accompanied by minimal lung injury, while L-arginine induced extremely severe pancreatic injury including necrosis and neutrophil infiltration. Infusion of Na-taurocholate into the pancreatic duct induced necrotizing pancreatitis in the head of pancreas and lighter inflammation in the distal region. The severity of acute pancreatitis induced by combination of ethanol and fatty acids was between the extent of caerulein and L-arginine induction, with obvious inflammatory cells infiltration. In view of the advantages in lipid metabolism features, hamster models are ideally suited for the studies of pancreatitis associated with altered metabolism in humans. PMID:27302647

  6. Global change and human susceptibility to disease

    SciTech Connect

    Daily, G.C.; Ehrlich, P.R.

    1996-12-31

    Although the loss of good health is inherently unpredictable, human behavior at the individual and societal levels profoundly influences the incidence and evolution of disease. In this review, the authors define the human epidemiological environment and describe key biophysical, economic, sociocultural, and political factors that shape it. The potential impact upon the epidemiological environment of biophysical aspects of global change--changes in the size; mobility, and geographic distribution of the human population; land conversion; agricultural intensification; and climate change--is then examined. Human vulnerability to disease is strongly and deleteriously influenced by many of these ongoing, intensifying alterations. The authors then examine threats to human defenses against disease, including immune suppression, loss of biodiversity and indigenous knowledge, and the evolution of antibiotic resistance. Effective responses will require greatly enhanced attention by and collaboration among experts in diverse academic disciplines, in the private sector, and in government worldwide. 157 refs.

  7. Atypical prion diseases in humans and animals.

    PubMed

    Tranulis, Michael A; Benestad, Sylvie L; Baron, Thierry; Kretzschmar, Hans

    2011-01-01

    Although prion diseases, such as Creutzfeldt-Jakob disease (CJD) in humans and scrapie in sheep, have long been recognized, our understanding of their epidemiology and pathogenesis is still in its early stages. Progress is hampered by the lengthy incubation periods and the lack of effective ways of monitoring and characterizing these agents. Protease-resistant conformers of the prion protein (PrP), known as the "scrapie form" (PrP(Sc)), are used as disease markers, and for taxonomic purposes, in correlation with clinical, pathological, and genetic data. In humans, prion diseases can arise sporadically (sCJD) or genetically (gCJD and others), caused by mutations in the PrP-gene (PRNP), or as a foodborne infection, with the agent of bovine spongiform encephalopathy (BSE) causing variant CJD (vCJD). Person-to-person spread of human prion disease has only been known to occur following cannibalism (kuru disease in Papua New Guinea) or through medical or surgical treatment (iatrogenic CJD, iCJD). In contrast, scrapie in small ruminants and chronic wasting disease (CWD) in cervids behave as infectious diseases within these species. Recently, however, so-called atypical forms of prion diseases have been discovered in sheep (atypical/Nor98 scrapie) and in cattle, BSE-H and BSE-L. These maladies resemble sporadic or genetic human prion diseases and might be their animal equivalents. This hypothesis also raises the significant public health question of possible epidemiological links between these diseases and their counterparts in humans. PMID:21598097

  8. Physiochemical basis of human degenerative disease

    PubMed Central

    Lipinski, Boguslaw

    2015-01-01

    The onset of human degenerative diseases in humans, including type 2 diabetes, cardiovascular disease, neurological disorders, neurodevelopmental disease and neurodegenerative disease has been shown to be related to exposures to persistent organic pollutants, including polychlorinated biphenyls, chlorinated pesticides, polybrominated diphenyl ethers and others, as well as to polynuclear aromatic hydrocarbons, phthalates, bisphenol-A and other aromatic lipophilic species. The onset of these diseases has also been related to exposures to transition metal ions. A physiochemical mechanism for the onset of degenerative environmental disease dependent upon exposure to a combination of lipophilic aromatic hydrocarbons and transition metal ions is proposed here. The findings reported here also, for the first time, explain why aromatic hydrocarbons exhibit greater toxicity than aliphatic hydrocarbons of equal carbon numbers. PMID:27486355

  9. Epidemiological characteristics of human prion diseases.

    PubMed

    Chen, Cao; Dong, Xiao-Ping

    2016-01-01

    Human prion diseases are a group of transmissible, progressive, and invariably fatal neurodegenerative disorders, which include Kuru, Creutzfeldt-Jakob disease (CJD), Gerstmann-Sträussler-Scheinker syndrome, and fatal familial insomnia. Human prion diseases affect approximately 1-2 persons per million worldwide annually, occurring in sporadic, inherited, and acquired forms. These diseases have attracted both scientific and public attention not only because of their mysterious pathogen, but also due to their considerable threat to public health since the emergence of the variant CJD.There are still no specific therapeutic and prophylactic interventions available for prion diseases, thus active surveillance of human prion diseases is critical for disease control and prevention. Since 1993, CJD surveillance systems have been established in many countries and regions, and several long-term multinational cooperative projects have been conducted.In this paper, the epidemiological characteristics of various human prion diseases and the active surveillance systems pertaining to them in different countries and regions are summarized and reviewed. PMID:27251305

  10. Evolutionary Response to Human Infectious Diseases

    ERIC Educational Resources Information Center

    Armelagos, George J.; Dewey, John R.

    1970-01-01

    Gives an overview of human history, relating cultural changes with resulting changes in population density and in ecological balance to patterns of infectious diseases in man. Discusses mechanisms of evolution of resistance. Suggests that in populations where infectious diseases can be controlled, attention should shift to degenerative diseases…

  11. Melanized Fungi in Human Disease

    PubMed Central

    Revankar, Sanjay G.; Sutton, Deanna A.

    2010-01-01

    Summary: Melanized or dematiaceous fungi are associated with a wide variety of infectious syndromes. Many are soil organisms and are generally distributed worldwide, though certain species appear to have restricted geographic ranges. Though they are uncommon causes of disease, melanized fungi have been increasingly recognized as important pathogens, with most reports occurring in the past 20 years. The spectrum of diseases with which they are associated has also broadened and includes allergic disease, superficial and deep local infections, pneumonia, brain abscess, and disseminated infection. For some infections in immunocompetent individuals, such as allergic fungal sinusitis and brain abscess, they are among the most common etiologic fungi. Melanin is a likely virulence factor for these fungi. Diagnosis relies on careful microscopic and pathological examination, as well as clinical assessment of the patient, as these fungi are often considered contaminants. Therapy varies depending upon the clinical syndrome. Local infection may be cured with excision alone, while systemic disease is often refractory to therapy. Triazoles such as voriconazole, posaconazole, and itraconazole have the most consistent in vitro activity. Further studies are needed to better understand the pathogenesis and optimal treatment of these uncommon infections. PMID:20930077

  12. Global biogeography of human infectious diseases

    PubMed Central

    Murray, Kris A.; Preston, Nicholas; Allen, Toph; Zambrana-Torrelio, Carlos; Hosseini, Parviez R.; Daszak, Peter

    2015-01-01

    The distributions of most infectious agents causing disease in humans are poorly resolved or unknown. However, poorly known and unknown agents contribute to the global burden of disease and will underlie many future disease risks. Existing patterns of infectious disease co-occurrence could thus play a critical role in resolving or anticipating current and future disease threats. We analyzed the global occurrence patterns of 187 human infectious diseases across 225 countries and seven epidemiological classes (human-specific, zoonotic, vector-borne, non–vector-borne, bacterial, viral, and parasitic) to show that human infectious diseases exhibit distinct spatial grouping patterns at a global scale. We demonstrate, using outbreaks of Ebola virus as a test case, that this spatial structuring provides an untapped source of prior information that could be used to tighten the focus of a range of health-related research and management activities at early stages or in data-poor settings, including disease surveillance, outbreak responses, or optimizing pathogen discovery. In examining the correlates of these spatial patterns, among a range of geographic, epidemiological, environmental, and social factors, mammalian biodiversity was the strongest predictor of infectious disease co-occurrence overall and for six of the seven disease classes examined, giving rise to a striking congruence between global pathogeographic and “Wallacean” zoogeographic patterns. This clear biogeographic signal suggests that infectious disease assemblages remain fundamentally constrained in their distributions by ecological barriers to dispersal or establishment, despite the homogenizing forces of globalization. Pathogeography thus provides an overarching context in which other factors promoting infectious disease emergence and spread are set. PMID:26417098

  13. Advances in the treatment of acute graft-versus-host disease

    PubMed Central

    Qian, Liren; Wu, Zhengcheng; Shen, Jianliang

    2013-01-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) has been widely used for the treatment of hematologic malignant and non-malignant hematologic diseases and other diseases. However, acute graft-versus-host disease (GVHD) is a life-threatening complication of allogeneic transplantation. Acute GVHD may occur in 30% of transplant recipients, which is a syndrome of erythematous skin eruption, cholestatic liver disease and intestinal dysfunction, resulting from the activation of donor T lymphocytes by host antigen-presenting cells, resulting in an immune-mediated inflammatory response. Recent scientific advances in the understanding of the pathogenesis involved in the development of acute GVHD and clinical investigation have provided more effective therapeutic strategies for acute GVHD. This review focuses on major scientific and clinical advances in the treatment of acute GVHD. PMID:23802653

  14. Acute hypoxemia in humans enhances the neutrophil inflammatory response.

    PubMed

    Tamura, Douglas Y; Moore, Ernest E; Partrick, David A; Johnson, Jeffrey L; Offner, Patrick J; Silliman, Christopher C

    2002-04-01

    The neutrophil (PMN) is regarded as a key component in the hyperinflammatory response known as the systemic inflammatory response syndrome. Acute respiratory distress syndrome (ARDS) and subsequent multiple organ failure (MOF) are related to the severity of this hyperinflammation. ICU patients who are at highest risk of developing MOF may have acute hypoxic events that complicate their hospital course. This study was undertaken to evaluate the effects of acute hypoxia and subsequent hypoxemia on circulating PMNs in human volunteers. Healthy subjects were exposed to a changing O2/N2 mixture until their O2 saturation (SaO2) reached a level of 68% saturation. These subjects were then exposed to room air and then returned to their baseline SaO2. PMNs were isolated from pre- and post-hypoxemic arterial blood samples and were then either stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) or PMA alone, or they were primed with L-alpha-phosphatidylcholine, beta-acetyl-gamma-O-alkyl (PAF) followed by fMLP activation. Reactive oxygen species generation as measured by superoxide anion production was enhanced in primed PMNs after hypoxemia. Protease degranulation as measured by elastase release was enhanced in both quiescent PMNs and primed PMNs after fMLP activation following the hypoxemic event. Adhesion molecule upregulation as measured by CD11b/CD18, however, was not significantly changed after hypoxemia. Apoptosis of quiescent PMNs was delayed after the hypoxemic event. TNFalpha, IL-1, IL-6, and IL-8 cytokine levels were unchanged following hypoxemia. These results indicate that relevant acute hypoxemic events observed in the clinical setting enhance several PMN cytotoxic functions and suggest that a transient hypoxemic insult may promote hyperinflammation. PMID:11954825

  15. [Primary human demodicosis. A disease sui generis].

    PubMed

    Hsu, C-K; Zink, A; Wei, K-J; Dzika, E; Plewig, G; Chen, W

    2015-03-01

    Human Demodex mites (Demodex folliculorum and Demodex brevis) are unique in that they are an obligate human ectoparasite that can inhabit the pilosebaceous unit lifelong without causing obvious host immune response in most cases. The mode of symbiosis between humans and human Demodex mites is unclear, while the pathogenicity of human Demodex mites in many inflammatory skin diseases is now better understood. Primary human demodicosis is a skin disease sui generis not associated with local or systemic immunosuppression. Diagnosis is often underestimated and differentiation from folliculitis, papulopustular rosacea and perioral dermatitis is not always straightforward. Dependent on the morphology and degree of inflammation, the clinical manifestations can be classified into spinulate, papulopustular, nodulocystic, crustic and fulminant demodicosis. Therapy success can be achieved only with acaricides/arachidicides. The effective doses, optimal regimen and antimicrobial resistance remain to be determined. PMID:25744530

  16. Reduced myo-inositol and total choline measured with cerebral MRS in acute thyrotoxic Graves' disease.

    PubMed

    Elberling, T V; Danielsen, E R; Rasmussen, A K; Feldt-Rasmussen, U; Waldemar, G; Thomsen, C

    2003-01-14

    Neuropsychiatric symptoms in the acute thyrotoxic phase of Graves' disease suggest involvement of brain processes. Short-echo-time proton MRS was used to measure the cerebral metabolite profile in newly diagnosed and untreated Graves' disease. Sixteen patients with Graves' disease and 18 age- and sex-matched healthy volunteers were studied. The patients had significantly reduced total choline and myo-inositol in the acute phase of Graves' thyrotoxicosis compared with the healthy volunteers. PMID:12525741

  17. Cis-regulatory mutations in human disease

    PubMed Central

    2009-01-01

    Cis-acting regulatory sequences are required for the proper temporal and spatial control of gene expression. Variation in gene expression is highly heritable and a significant determinant of human disease susceptibility. The diversity of human genetic diseases attributed, in whole or in part, to mutations in non-coding regulatory sequences is on the rise. Improvements in genome-wide methods of associating genetic variation with human disease and predicting DNA with cis-regulatory potential are two of the major reasons for these recent advances. This review will highlight select examples from the literature that have successfully integrated genetic and genomic approaches to uncover the molecular basis by which cis-regulatory mutations alter gene expression and contribute to human disease. The fine mapping of disease-causing variants has led to the discovery of novel cis-acting regulatory elements that, in some instances, are located as far away as 1.5 Mb from the target gene. In other cases, the prior knowledge of the regulatory landscape surrounding the gene of interest aided in the selection of enhancers for mutation screening. The success of these studies should provide a framework for following up on the large number of genome-wide association studies that have identified common variants in non-coding regions of the genome that associate with increased risk of human diseases including, diabetes, autism, Crohn's, colorectal cancer, and asthma, to name a few. PMID:19641089

  18. Raman spectroscopy of human saliva for acute myocardial infarction detection

    NASA Astrophysics Data System (ADS)

    Chen, Maowen; Chen, Yuanxiang; Wu, Shanshan; Huang, Wei; Lin, Jinyong; Weng, Guo-Xing; Chen, Rong

    2014-09-01

    Raman spectroscopy is a rapidly non-invasive technique with great potential for biomedical research. The aim of this study was to evaluate the feasibility of using Raman spectroscopy of human saliva for acute myocardial infarction (AMI) detection. Raman spectroscopy measurements were performed on two groups of saliva samples: one group from patients (n=30) with confirmed AMI and the other group from healthy controls (n=31). The diagnostic performance for differentiating AMI saliva from normal saliva was evaluated by multivariate statistical analysis. The combination of principal component analysis (PCA) and linear discriminate analysis (LDA) of the measured Raman spectra separated the spectral features of the two groups into two distinct clusters with little overlaps, rendering the sensitivity of 80.0% and specificity of 80.6%. The results from this exploratory study demonstrated that Raman spectroscopy of human saliva can serve as a potentially clinical tool for rapid AMI detection and screening.

  19. Use of corticosteroids during acute phase of Kawasaki disease.

    PubMed

    Yu, Jeong Jin

    2015-11-01

    In spite of initial intravenous immunoglobulin (IVIG) treatment, a significant number of patients are unresponsive to it and are at a higher risk for coronary artery lesions. Corticosteroids have been used as a secondary drug or used in combination with IVIG. Three options of using corticosteroids for the treatment of patients during the acute phase of Kawasaki disease, have been considered. The first is their use exclusively for patients unresponsive to IVIG treatment. The second is their use in combination with IVIG as the routine first line therapy for all patients. The last is the use in the combination as the first line therapy for selected patients at a high risk being unresponsive to initial IVIG. However, it is uncertain that the corticosteroids as the second line treatment are better than the additional IVIG in patients unresponsive to initial IVIG. The combination of corticosteroids and IVIG as the routine first line therapy also have not enough evidences. The last option of using corticosteroids - the combination of corticosteroids and IVIG in patients at high risk of unresponsiveness, is a properly reasonable treatment strategy. However, there have been no globally standardized predictive models for the unresponsiveness to initial IVIG treatment. Therefore, future investigations to determine the best predictive model are necessary. PMID:26566486

  20. Use of corticosteroids during acute phase of Kawasaki disease

    PubMed Central

    Yu, Jeong Jin

    2015-01-01

    In spite of initial intravenous immunoglobulin (IVIG) treatment, a significant number of patients are unresponsive to it and are at a higher risk for coronary artery lesions. Corticosteroids have been used as a secondary drug or used in combination with IVIG. Three options of using corticosteroids for the treatment of patients during the acute phase of Kawasaki disease, have been considered. The first is their use exclusively for patients unresponsive to IVIG treatment. The second is their use in combination with IVIG as the routine first line therapy for all patients. The last is the use in the combination as the first line therapy for selected patients at a high risk being unresponsive to initial IVIG. However, it is uncertain that the corticosteroids as the second line treatment are better than the additional IVIG in patients unresponsive to initial IVIG. The combination of corticosteroids and IVIG as the routine first line therapy also have not enough evidences. The last option of using corticosteroids - the combination of corticosteroids and IVIG in patients at high risk of unresponsiveness, is a properly reasonable treatment strategy. However, there have been no globally standardized predictive models for the unresponsiveness to initial IVIG treatment. Therefore, future investigations to determine the best predictive model are necessary. PMID:26566486

  1. Acute kidney injury: Renal disease in the ICU.

    PubMed

    Seller-Pérez, G; Más-Font, S; Pérez-Calvo, C; Villa-Díaz, P; Celaya-López, M; Herrera-Gutiérrez, M E

    2016-01-01

    Acute kidney injury (AKI) in the ICU frequently requires costly supportive therapies, has high morbidity, and its long-term prognosis is not as good as it has been presumed so far. Consequently, AKI generates a significant burden for the healthcare system. The problem is that AKI lacks an effective treatment and the best approach relies on early secondary prevention. Therefore, to facilitate early diagnosis, a broader definition of AKI should be established, and a marker with more sensitivity and early-detection capacity than serum creatinine - the most common marker of AKI - should be identified. Fortunately, new classification systems (RIFLE, AKIN or KDIGO) have been developed to solve these problems, and the discovery of new biomarkers for kidney injury will hopefully change the way we approach renal patients. As a first step, the concept of renal failure has changed from being a "static" disease to being a "dynamic process" that requires continuous evaluation of kidney function adapted to the reality of the ICU patient. PMID:27388683

  2. Monitoring of minimal residual disease in acute myeloid leukemia.

    PubMed

    Kern, Wolfgang; Haferlach, Claudia; Haferlach, Torsten; Schnittger, Susanne

    2008-01-01

    Two highly sensitive methods, multiparameter flow cytometry (MFC) and real-time quantitative PCR (RQ-PCR), are increasingly used to monitor minimal residual disease (MRD) and to guide risk-adapted management in acute myeloid leukemia (AML). An independent prognostic impact has been demonstrated for MRD levels obtained by both methods. MFC has been found particularly useful for assessment of early clearance of malignant cells and after consolidation therapy. At the latter checkpoint, MRD levels quantified by RQ-PCR in AML with fusion genes also have the strongest prognostic power. In addition, highly predictive initial expression levels have been identified by RQ-PCR. Both methods are capable of early detection of relapse. Through the use of all available markers including NPM1 mutations and FLT3 mutations in addition to fusion genes, RQ-PCR-based MRD assessment is possible in more than half of patients, whereas MFC is applicable to most AML cases. With a sensitivity of 10(-4) (PML-RARA) to 10(-7) (patient-specific primers, FLT3 and NPM1 mutations), RQ-PCR is more sensitive in most cases. Large clinical trials will determine the exact role and place of immunologic and RQ-PCR-based monitoring of MRD in the therapy of patients with AML. PMID:18000811

  3. Direct micromethod for diagnosis of acute and congenital Chagas' disease.

    PubMed Central

    Feilij, H; Muller, L; Gonzalez Cappa, S M

    1983-01-01

    A microhematocrit concentration method (MH) for immediate diagnosis of Chagas' disease during the acute stage or in congenital cases was standardized. Parasitemia as low as 1,000 parasites per ml was detected, after centrifugation of six 50-microliters capillary tubes, by 10-min microscopic observation of each buffy coat spread between slide and cover glass. Operator's time was reduced by at least one-third when compared with a fresh blood observation (FB). In 12 of the 15 patients studied, diagnosis was performed in 4.9 +/- 3.08 min with MH, whereas 27.0 +/- 12.1 min were necessary when FB was used. In the three remaining patients whose FB results were negative, MH became positive after 13, 16, and 40 min. In our experience, FB proved to be more sensitive than previously reported. Suckling mouse inoculation also proved to be sensitive but, as in xenodiagnosis and in hemoculture, the delay in getting the final result was a limiting factor. PMID:6413530

  4. Human Polyomaviruses in Skin Diseases

    PubMed Central

    Moens, Ugo; Ludvigsen, Maria; Van Ghelue, Marijke

    2011-01-01

    Polyomaviruses are a family of small, nonenveloped viruses with a circular double-stranded DNA genome of ∼5,000 base pairs protected by an icosahedral protein structure. So far, members of this family have been identified in birds and mammals. Until 2006, BK virus (BKV), JC virus (JCV), and simian virus 40 (SV40) were the only polyomaviruses known to circulate in the human population. Their occurrence in individuals was mainly confirmed by PCR and the presence of virus-specific antibodies. Using the same methods, lymphotropic polyomavirus, originally isolated in monkeys, was recently shown to be present in healthy individuals although with much lower incidence than BKV, JCV, and SV40. The use of advanced high-throughput sequencing and improved rolling circle amplification techniques have identified the novel human polyomaviruses KI, WU, Merkel cell polyomavirus, HPyV6, HPyV7, trichodysplasia spinulosa-associated polyomavirus, and HPyV9. The skin tropism of human polyomaviruses and their dermatopathologic potentials are the focus of this paper. PMID:21941687

  5. Surfactant protein D in human lung diseases.

    PubMed

    Hartl, D; Griese, M

    2006-06-01

    The lung is continuously exposed to inhaled pollutants, microbes and allergens. Therefore, the pulmonary immune system has to defend against harmful pathogens, while an inappropriate inflammatory response to harmless particles must be avoided. In the bronchoalveolar space this critical balance is maintained by innate immune proteins, termed surfactant proteins. Among these, surfactant protein D (SP-D) plays a central role in the pulmonary host defence and the modulation of allergic responses. Several human lung diseases are characterized by decreased levels of bronchoalveolar SP-D. Thus, recombinant SP-D has been proposed as a therapeutical option for cystic fibrosis, neonatal lung disease and smoking-induced emphysema. Furthermore, SP-D serum levels can be used as disease activity markers for interstitial lung diseases. This review illustrates the emerging role of SP-D translated from in vitro studies to human lung diseases. PMID:16684127

  6. Extramedullary Disease in Acute Promyelocytic Leukemia: Two-In-One Disease

    PubMed Central

    Albano, Francesco; Specchia, Giorgina

    2011-01-01

    In acute promyelocytic leukemia (APL), extramedullary disease (EMD) is particularly rare and shows special clinical and biological features. It is estimated that about 3–5% of APL patients will suffer extramedullary relapse. The most common site of EMD in APL is the central nervous system (CNS). At present, there are still many issues of EMD in APL needing further clarification, including pathogenesis, risk factors, prognosis and treatment. A better understanding of the biological mechanisms underlying EMD is important to be able to devise more effective CNS prophylaxis and induction-consolidation therapeutic strategies. PMID:22220263

  7. Hemophagocytosis in the Acute Phase of Fatal Kawasaki Disease in a 4 Month-Old Girl

    PubMed Central

    Doğan, Vehbi; Karaaslan, Erhan; Özer, Samet; Gümüşer, Rüveyda; Yılmaz, Resul

    2016-01-01

    Background: Kawasaki disease is a systemic vasculitis predominately affecting coronary arteries. Hemophagocytic lymphohistiocytosis can complicate the course of Kawasaki disease. Rare cases of secondary hemophagocytic lymphohistiocytosis occurring during the acute phase of Kawasaki disease have been reported. Case Report: We report here a 4 month-old girl with diffuse coronary ectasia and secondary hemophagocytic lymphohistiocytosis occurring during the acute phase of incomplete Kawasaki disease. Conclusion: Due to the large overlap in clinical symptoms, the presence of atypical findings for Kawasaki disease should suggest the possible diagnosis of hemophagocytic lymphohistiocytosis in these patients. PMID:27606147

  8. Blood transfusion for the treatment of acute anaemia in inflammatory bowel disease and other digestive diseases

    PubMed Central

    García-Erce, José Antonio; Gomollón, Fernando; Muñoz, Manuel

    2009-01-01

    Allogeneic blood transfusion (ABT) is frequently used as the first therapeutic option for the treatment of acute anaemia in patients with inflammatory bowel disease (IBD), especially when it developed due to gastrointestinal or perioperative blood loss, but is not risk-free. Adverse effects of ABT include, but are not limited to, acute hemolytic reaction (wrong blood or wrong patient), febrile non-hemolytic transfusional reaction, bacterial contamination, transfusion-related acute lung injury, transfusion associated circulatory overload, transfusion-related immuno-modulation, and transmission of almost all infectious diseases (bacteria, virus, protozoa and prion), which might result in increased risk of morbidity and mortality. Unfortunately, the main physiological goal of ABT, i.e. to increase oxygen consumption by the hypoxic tissues, has not been well documented. In contrast, the ABT is usually misused only to increase the haemoglobin level within a fixed protocol [mostly two by two packed red blood cell (PRC) units] independently of the patient’s tolerance to normovolemic anaemia or his clinical response to the transfusion of PRC units according to a “one-by-one” administration schedule. Evidence-based clinical guidelines may promote best transfusion practices by implementing restrictive transfusion protocols, thus reducing variability and minimizing the avoidable risks of transfusion, and the use of autologous blood and pharmacologic alternatives. In this regard, preoperative autologous blood donation (PABD) consistently diminished the frequency of ABT, although its contribution to ABT avoidance is reduced when performed under a transfusion protocol. In addition, interpretation of utility of PABD in surgical IBD patients is hampered by scarcity of published data. However, the role of autologous red blood cells as drug carriers is promising. Finally, it must be stressed that a combination of methods used within well-constructed protocols will offer better

  9. Blood transfusion for the treatment of acute anaemia in inflammatory bowel disease and other digestive diseases.

    PubMed

    García-Erce, José Antonio; Gomollón, Fernando; Muñoz, Manuel

    2009-10-01

    Allogeneic blood transfusion (ABT) is frequently used as the first therapeutic option for the treatment of acute anaemia in patients with inflammatory bowel disease (IBD), especially when it developed due to gastrointestinal or perioperative blood loss, but is not risk-free. Adverse effects of ABT include, but are not limited to, acute hemolytic reaction (wrong blood or wrong patient), febrile non-hemolytic transfusional reaction, bacterial contamination, transfusion-related acute lung injury, transfusion associated circulatory overload, transfusion-related immuno-modulation, and transmission of almost all infectious diseases (bacteria, virus, protozoa and prion), which might result in increased risk of morbidity and mortality. Unfortunately, the main physiological goal of ABT, i.e. to increase oxygen consumption by the hypoxic tissues, has not been well documented. In contrast, the ABT is usually misused only to increase the haemoglobin level within a fixed protocol [mostly two by two packed red blood cell (PRC) units] independently of the patient's tolerance to normovolemic anaemia or his clinical response to the transfusion of PRC units according to a "one-by-one" administration schedule. Evidence-based clinical guidelines may promote best transfusion practices by implementing restrictive transfusion protocols, thus reducing variability and minimizing the avoidable risks of transfusion, and the use of autologous blood and pharmacologic alternatives. In this regard, preoperative autologous blood donation (PABD) consistently diminished the frequency of ABT, although its contribution to ABT avoidance is reduced when performed under a transfusion protocol. In addition, interpretation of utility of PABD in surgical IBD patients is hampered by scarcity of published data. However, the role of autologous red blood cells as drug carriers is promising. Finally, it must be stressed that a combination of methods used within well-constructed protocols will offer better

  10. Oxidants and human disease: some new concepts

    SciTech Connect

    Halliwell, B.

    1987-11-01

    Oxidant species such as superoxide radical (O/sub 2//sup -/), hydrogen peroxide (H/sub 2/O/sub 2/), hydroxyl radical (HO.), and lipid peroxides (LOOH) are becoming increasingly implicated in human disease. However, the question of whether such oxidants are a major cause of tissue injury in human disease or are merely produced during such injury has been difficult to answer because of inadequate experimental techniques, and possibly because of an overemphasis on lipid peroxidation as a mechanism of oxidant injury. Recent developments in methodology, in the authors understanding of the primary mechanism of oxidant toxicity to cells, and in concepts of antioxidant protection are reviewed. Good evidence now exists for some role of oxidant damage to tissues in the pathology of several human diseases, including rheumatoid arthritis, reperfusion injury, immune injury to lung and kidney, and cerebral trauma or ischemia. These have led to promising suggestions for new therapeutic approaches.

  11. Engineering large animal models of human disease.

    PubMed

    Whitelaw, C Bruce A; Sheets, Timothy P; Lillico, Simon G; Telugu, Bhanu P

    2016-01-01

    The recent development of gene editing tools and methodology for use in livestock enables the production of new animal disease models. These tools facilitate site-specific mutation of the genome, allowing animals carrying known human disease mutations to be produced. In this review, we describe the various gene editing tools and how they can be used for a range of large animal models of diseases. This genomic technology is in its infancy but the expectation is that through the use of gene editing tools we will see a dramatic increase in animal model resources available for both the study of human disease and the translation of this knowledge into the clinic. Comparative pathology will be central to the productive use of these animal models and the successful translation of new therapeutic strategies. PMID:26414877

  12. Human Motor Cortex Functional Changes in Acute Stroke: Gender Effects

    PubMed Central

    Di Lazzaro, Vincenzo; Pellegrino, Giovanni; Di Pino, Giovanni; Ranieri, Federico; Lotti, Fiorenza; Florio, Lucia; Capone, Fioravante

    2016-01-01

    The acute phase of stroke is accompanied by functional changes in the activity and interplay of both hemispheres. In healthy subjects, gender is known to impact the functional brain organization. We investigated whether gender influences also acute stroke functional changes. In thirty-five ischemic stroke patients, we evaluated the excitability of the affected (AH) and unaffected hemisphere (UH) by measuring resting and active motor threshold (AMT) and motor-evoked potential amplitude under baseline conditions and after intermittent theta burst stimulation (iTBS) of AH. We also computed an index of the excitability balance between the hemispheres, laterality indexes (LI), to evidence hemispheric asymmetry. AMT differed significantly between AH and UH only in the male group (p = 0.004), not in females (p > 0.200), and both LIAMT and LIRMT were significantly higher in males than in females (respectively p = 0.033 and p = 0.042). LTP-like activity induced by iTBS in AH was more frequent in females. Gender influences the functional excitability changes that take place after human stroke and the level of LTP that can be induced by repetitive stimulation. This knowledge is of high value in the attempt of individualizing to different genders any non-invasive stimulation strategy designed to foster stroke recovery. PMID:26858590

  13. Expression of Tumor Necrosis Factor in Human Acute Cardiac Rejection

    PubMed Central

    Arbustini, Eloisa; Grasso, Maurizia; Diegoli, Marta; Bramerio, Manuela; Foglieni, Andrea Scotti; Albertario, Marco; Martinelli, Luigi; Gavazzi, Antonello; Goggi, Claudio; Campana, Carlo; Vigano, Mario

    1991-01-01

    The authors performed an immunohistochemical study on expression of tumor necrosis factor alpha (TNFα) in endomyocardial biopsies from human cardiac allografts. TNFα immunoreactivity was found in 45% biopsies with mild acute rejection, in 83% biopsies with focal moderate rejection, in 80% biopsies with diffuse moderate rejection. Biopsies with absent rejection did not show immunoreactive cells. In mild rejection, positive cells were few and scanty monocytes and macrophages (MAC-387 and LN5 positive cells) and T lymphocytes (UCHL-1/CD45 RO positive cells) (up to 20% of all infiltrating cells). Expression of major histocompatibility complex (MHC) class II antigens on infiltrating and endothelial cells occurred earlier and independent of TNFα reactivity. Number of immunoreactive cells increased in moderate rejection (up to 50%). Immunoreactivity was also present in nonpigmented macrophages in part of the biopsies with resolving rejection (45%). The authors conclude that TNFα is expressed in acute cardiac rejection by immunologically activated inflammatory cells. Immunoreactive cells increase in number with increasing severity of the reaction. ImagesFigure 1Figure 2Figure 3Figure 4 PMID:1928295

  14. Estrogen receptors and human disease: an update

    PubMed Central

    Burns, Katherine A.

    2016-01-01

    A myriad of physiological processes in mammals are influenced by estrogens and the estrogen receptors (ERs), ERα and ERβ. As we reviewed previously, given the widespread role for estrogen in normal human physiology, it is not surprising that estrogen is implicated in the development or progression of a number of diseases. In this review, we are giving a 5-year update of the literature regarding the influence of estrogens on a number of human cancers (breast, ovarian, colorectal, prostate, and endometrial), endometriosis, fibroids, and cardiovascular disease. A large number of sophisticated experimental studies have provided insights into human disease, but for this review, the literature citations were limited to articles published after our previous review (Deroo and Korach in J Clin Invest 116(3):561–570, 2006) and will focus in most cases on human data and clinical trials. We will describe the influence in which estrogen’s action, through one of or both of the ERs, mediates the aforementioned human disease states. PMID:22648069

  15. Mouse homologues of human hereditary disease.

    PubMed Central

    Searle, A G; Edwards, J H; Hall, J G

    1994-01-01

    Details are given of 214 loci known to be associated with human hereditary disease, which have been mapped on both human and mouse chromosomes. Forty two of these have pathological variants in both species; in general the mouse variants are similar in their effects to the corresponding human ones, but exceptions include the Dmd/DMD and Hprt/HPRT mutations which cause little, if any, harm in mice. Possible reasons for phenotypic differences are discussed. In most pathological variants the gene product seems to be absent or greatly reduced in both species. The extensive data on conserved segments between human and mouse chromosomes are used to predict locations in the mouse of over 50 loci of medical interest which are mapped so far only on human chromosomes. In about 80% of these a fairly confident prediction can be made. Some likely homologies between mapped mouse loci and unmapped human ones are also given. Sixty six human and mouse proto-oncogene and growth factor gene homologies are also listed; those of confirmed location are all in known conserved segments. A survey of 18 mapped human disease loci and chromosome regions in which the manifestation or severity of pathological effects is thought to be the result of genomic imprinting shows that most of the homologous regions in the mouse are also associated with imprinting, especially those with homologues on human chromosomes 11p and 15q. Useful methods of accelerating the production of mouse models of human hereditary disease include (1) use of a supermutagen, such as ethylnitrosourea (ENU), (2) targeted mutagenesis involving ES cells, and (3) use of gene transfer techniques, with production of 'knockout mutations'. PMID:8151633

  16. Does acute exposure to mobile phones affect human attention?

    PubMed

    Russo, Riccardo; Fox, Elaine; Cinel, Caterina; Boldini, Angela; Defeyter, Margaret A; Mirshekar-Syahkal, Dariush; Mehta, Amit

    2006-04-01

    Recent studies have indicated that acute exposure to low level radiofrequency (RF) electromagnetic fields generated by mobile phones affects human cognition. However, the relatively small samples used, in addition to methodological problems, make the outcomes of these studies difficult to interpret. In our study we tested a large sample of volunteers (168) using a series of cognitive tasks apparently sensitive to RF exposure (a simple reaction task, a vigilance task, and a subtraction task). Participants performed those tasks twice, in two different sessions. In one session they were exposed to RFs, with half of subjects exposed to GSM signals and the other half exposed to CW signals, while in the other session they were exposed to sham signals. No significant effects of RF exposure on performance for either GSM or CW were found, independent of whether the phone was positioned on the left or on the right side. PMID:16304701

  17. Human bocavirus in children with acute gastroenteritis in Albania.

    PubMed

    La Rosa, G; Della Libera, S; Iaconelli, M; Donia, D; Cenko, F; Xhelilaj, G; Cozza, P; Divizia, M

    2016-05-01

    Human Bocavirus (HBoV) has been recently identified in association with acute viral gastroenteritis (AGE). The objective of this work was to investigate the prevalence of HBoV in children with AGE in Albania. Stool specimens collected from 142 children were analyzed by amplification of partial NP1 and Vp1/Vp2 genes. HBoV was detected in 13 samples (9.1%), 12 HBoV-1 and one HBoV-2. All HBoV-positive patients were co-infected with rotavirus and/or adenovirus, a finding which might indicate that there is no clear causal association of this agent with diarrhea. Further investigation is needed to assess the pathogenic role of HBoV in childhood diarrhea. PMID:26496439

  18. IMMUNOACTIVATION AT THE CROSSROADS OF HUMAN DISEASES

    PubMed Central

    Margolis, Leonid

    2015-01-01

    It is becoming increasingly clear that immunoactivation, which evolved as a system of host defense against pathogens, can become dysregulated and promote the pathogenesis of diverse diseases with both known and unknown etiologies (e.g., AIDS, age-related macular degeneration, cancer) as well as aging. Immunoactivation seems to be a “common denominator” or general mechanism of pathogenesis, and may explain the association and similarities in pathology among otherwise unrelated human diseases. Identification of general mechanisms of immunoactivation may lead to the development of new therapeutic strategies applicable to many diseases even before detailed knowledge of specific etiology and pathogenesis may be available. PMID:25637756

  19. Longitudinal Transcriptome Analysis Reveals a Sustained Differential Gene Expression Signature in Patients Treated for Acute Lyme Disease

    PubMed Central

    Bouquet, Jerome; Soloski, Mark J.; Swei, Andrea; Cheadle, Chris; Federman, Scot; Billaud, Jean-Noel; Rebman, Alison W.; Kabre, Beniwende; Halpert, Richard; Boorgula, Meher

    2016-01-01

    ABSTRACT Lyme disease is a tick-borne illness caused by the bacterium Borrelia burgdorferi, and approximately 10 to 20% of patients report persistent symptoms lasting months to years despite appropriate treatment with antibiotics. To gain insights into the molecular basis of acute Lyme disease and the ensuing development of post-treatment symptoms, we conducted a longitudinal transcriptome study of 29 Lyme disease patients (and 13 matched controls) enrolled at the time of diagnosis and followed for up to 6 months. The differential gene expression signature of Lyme disease following the acute phase of infection persisted for at least 3 weeks and had fewer than 44% differentially expressed genes (DEGs) in common with other infectious or noninfectious syndromes. Early Lyme disease prior to antibiotic therapy was characterized by marked upregulation of Toll-like receptor signaling but lack of activation of the inflammatory T-cell apoptotic and B-cell developmental pathways seen in other acute infectious syndromes. Six months after completion of therapy, Lyme disease patients were found to have 31 to 60% of their pathways in common with three different immune-mediated chronic diseases. No differential gene expression signature was observed between Lyme disease patients with resolved illness to those with persistent symptoms at 6 months post-treatment. The identification of a sustained differential gene expression signature in Lyme disease suggests that a panel of selected human host-based biomarkers may address the need for sensitive clinical diagnostics during the “window period” of infection prior to the appearance of a detectable antibody response and may also inform the development of new therapeutic targets. PMID:26873097

  20. Therapeutic Approach to the Management of Pediatric Demyelinating Disease: Multiple Sclerosis and Acute Disseminated Encephalomyelitis.

    PubMed

    Brenton, J Nicholas; Banwell, Brenda L

    2016-01-01

    Acquired pediatric demyelinating diseases manifest acutely with optic neuritis, transverse myelitis, acute disseminated encephalomyelitis, or with various other acute deficits in focal or polyfocal areas of the central nervous system. Patients may experience a monophasic illness (as in the case of acute disseminated encephalomyelitis) or one that may manifest as a chronic, relapsing disease [e.g., multiple sclerosis (MS)]. The diagnosis of pediatric MS and other demyelinating disorders of childhood has been facilitated by consensus statements regarding diagnostic definitions. Treatment of pediatric MS has been modeled after data obtained from clinical trials in adult-onset MS. There are now an increasing number of new therapeutic agents for MS, and many will be formally studied for use in pediatric patients. There are important efficacy and safety concerns regarding the use of these therapies in children and young adults. This review will discuss acute management as well as chronic immunotherapies in acquired pediatric demyelination. PMID:26496907

  1. The acute cardiorenal syndrome: burden and mechanisms of disease.

    PubMed

    Nijst, Petra; Mullens, Wilfried

    2014-12-01

    Worsening renal function during the treatment of acute decompensated heart failure, so-called acute cardio-renal syndrome, is very common and complicates the treatment course. The underlying pathophysiology of worsening renal function (WRF) involves variable contributions of renal hemodynamics, neurohormonal activity, and oxidative stress. Historically, WRF has been associated with adverse outcomes. However, emerging data support therapeutic strategies that permit WRF while effectively treating congestion as they are associated with improved outcomes. PMID:25135470

  2. Role of Tyrosine Isomers in Acute and Chronic Diseases Leading to Oxidative Stress - A Review.

    PubMed

    Molnár, Gergő A; Kun, Szilárd; Sélley, Eszter; Kertész, Melinda; Szélig, Lívia; Csontos, Csaba; Böddi, Katalin; Bogár, Lajos; Miseta, Attila; Wittmann, István

    2016-01-01

    Oxidative stress plays a major role in the pathogenesis of a variety of acute and chronic diseases. Measurement of the oxidative stress-related end products may be performed, e.g. that of structural isomers of the physiological para-tyrosine, namely meta- and ortho-tyrosine, that are oxidized derivatives of phenylalanine. Recent data suggest that in sepsis, serum level of meta-tyrosine increases, which peaks on the 2(nd) and 3(rd) days (p<0.05 vs. controls), and the kinetics follows the intensity of the systemic inflammation correlating with serum procalcitonin levels. In a similar study subset, urinary meta-tyrosine excretion correlated with both need of daily insulin dose and the insulin-glucose product in non-diabetic septic cases (p<0.01 for both). Using linear regression model, meta-tyrosine excretion, urinary meta-tyrosine/para-tyrosine, urinary ortho-tyrosine/para-tyrosine and urinary (meta- + orthotyrosine)/ para-tyrosine proved to be markers of carbohydrate homeostasis. In a chronic rodent model, we tried to compensate the abnormal tyrosine isomers using para-tyrosine, the physiological amino acid. Rats were fed a standard high cholesterol-diet, and were given para-tyrosine or vehicle orally. High-cholesterol feeding lead to a significant increase in aortic wall meta-tyrosine content and a decreased vasorelaxation of the aorta to insulin and the glucagon-like peptide-1 analogue, liraglutide, that both could be prevented by administration of para-tyrosine. Concluding, these data suggest that meta- and ortho-tyrosine are potential markers of oxidative stress in acute diseases related to oxidative stress, and may also interfere with insulin action in septic humans. Competition of meta- and ortho-tyrosine by supplementation of para-tyrosine may exert a protective role in oxidative stress-related diseases. PMID:26785996

  3. Role of Tyrosine Isomers in Acute and Chronic Diseases Leading to Oxidative Stress - A Review

    PubMed Central

    Molnár, Gergő A.; Kun, Szilárd; Sélley, Eszter; Kertész, Melinda; Szélig, Lívia; Csontos, Csaba; Böddi, Katalin; Bogár, Lajos; Miseta, Attila; Wittmann, István

    2016-01-01

    Oxidative stress plays a major role in the pathogenesis of a variety of acute and chronic diseases. Measurement of the oxidative stress-related end products may be performed, e.g. that of structural isomers of the physiological para-tyrosine, namely meta- and ortho-tyrosine, that are oxidized derivatives of phenylalanine. Recent data suggest that in sepsis, serum level of meta-tyrosine increases, which peaks on the 2nd and 3rd days (p<0.05 vs. controls), and the kinetics follows the intensity of the systemic inflammation correlating with serum procalcitonin levels. In a similar study subset, urinary meta-tyrosine excretion correlated with both need of daily insulin dose and the insulin-glucose product in non-diabetic septic cases (p<0.01 for both). Using linear regression model, meta-tyrosine excretion, urinary meta-tyrosine/para-tyrosine, urinary ortho-tyrosine/para-tyrosine and urinary (meta- + ortho-tyrosine)/para-tyrosine proved to be markers of carbohydrate homeostasis. In a chronic rodent model, we tried to compensate the abnormal tyrosine isomers using para-tyrosine, the physiological amino acid. Rats were fed a standard high cholesterol-diet, and were given para-tyrosine or vehicle orally. High-cholesterol feeding lead to a significant increase in aortic wall meta-tyrosine content and a decreased vasorelaxation of the aorta to insulin and the glucagon-like peptide-1 analogue, liraglutide, that both could be prevented by administration of para-tyrosine. Concluding, these data suggest that meta- and ortho-tyrosine are potential markers of oxidative stress in acute diseases related to oxidative stress, and may also interfere with insulin action in septic humans. Competition of meta- and ortho-tyrosine by supplementation of para-tyrosine may exert a protective role in oxidative stress-related diseases. PMID:26785996

  4. Age, Predisposing Diseases, and Ultrasonographic Findings in Determining Clinical Outcome of Acute Acalculous Inflammatory Gallbladder Diseases in Children.

    PubMed

    Yi, Dae Yong; Chang, Eun Jae; Kim, Ji Young; Lee, Eun Hye; Yang, Hye Ran

    2016-10-01

    We evaluated clinical factors such as age, gender, predisposing diseases and ultrasonographic findings that determine clinical outcome of acute acalculous inflammatory gallbladder diseases in children. The patients were divided into the four age groups. From March 2004 through February 2014, clinical data from 131 children diagnosed as acute acalculous inflammatory gallbladder disease by ultrasonography were retrospectively reviewed. Systemic infectious diseases were the most common etiology of acute inflammatory gallbladder disease in children and were identified in 50 patients (38.2%). Kawasaki disease was the most common predisposing disease (28 patients, 21.4%). The incidence was highest in infancy and lowest in adolescence. The age groups were associated with different predisposing diseases; noninfectious systemic disease was the most common etiology in infancy and early childhood, whereas systemic infectious disease was the most common in middle childhood and adolescence (P = 0.001). Gallbladder wall thickening was more commonly found in malignancy (100%) and systemic infection (94.0%) (P = 0.002), whereas gallbladder distension was more frequent in noninfectious systemic diseases (60%) (P = 0.000). Ascites seen on ultrasonography was associated with a worse clinical course compared with no ascites (77.9% vs. 37.7%, P = 0.030), and the duration of hospitalization was longer in patients with ascites (11.6 ± 10.7 vs. 8.0 ± 6.6 days, P = 0.020). In conclusion, consideration of age and predisposing disease in addition to ultrasonographic gallbladder findings in children suspected of acute acalculous inflammatory gallbladder disease might result in better outcomes. PMID:27550491

  5. [Human prion diseases in the Czech Republic].

    PubMed

    Rohan, Z; Rusina, R; Marešová, M; Matěj, R

    2015-09-01

    Human prion diseases are a group of very rare diseases with a unique pathogenesis and, due to an inauspicious prognosis and unavailability of therapy, with fatal consequences. The etiopathogenetic background is the presence of pathologically misfolded prion protein, highly resistant to denaturation, the aggregation and presence of which in the brain tissue causes irreversible neuronal damage. The most frequent prion disease in humans is Creutzfeldt-Jakob disease (CJD) which occurs in sporadic, hereditary/familial, or acquired/infectious/iatrogenic forms. A new form of CJD, variant CJD, is considered to be linked to dietary exposure to beef products from cattle infected with bovine spongiform encephalopathy (BSE) and to infection via blood transfusion. The clinical picture of these diseases is characterized by a rapidly progressing dementia, cerebellar and extrapyramidal symptoms, and rather specific MRI, EEG, and CSF findings. Clinically, the diagnosis is described as possible or probable prion disease and needs to be confirmed by neuropathological or immunological investigation of the brain tissue. Epidemiological data from the Czech Republic spanning the last decade are presented. PMID:26448298

  6. Commentary: is Alzheimer's disease uniquely human?

    PubMed Central

    Finch, Caleb E.; Austad, Steven N.

    2015-01-01

    That Alzheimer's disease (AD) might be a human-specific disease was hypothesized by Rapoport in 1989. Apes and humans share an identical amyloid beta (Aβ) peptide amino acid sequence and accumulate considerable Aβ deposits after age 40 years, an age when amyloid plaques are uncommon in humans. Despite their early Aβ buildup, ape brains have not shown evidence dystrophic neurites near plaques. Aging great ape brains also have few neurofibrillary tangles, with one exception of 1 obese chimpanzee euthanized after a stroke who displayed abundant neurofibrillary tangles, but without the typical AD distribution. We discuss the need for more exacting evaluation of neuron density with age, and note husbandry issues that may allow great apes to live to greater ages. We remain reserved about expectations for fully developed AD-like pathology in the great apes of advanced ages and cautiously support Rapoport's hypothesis. PMID:25533426

  7. Endothelial Fas-Ligand in Inflammatory Bowel Diseases and in Acute Appendicitis.

    PubMed

    Kokkonen, Tuomo S; Karttunen, Tuomo J

    2015-12-01

    Fas-mediated induction of apoptosis is a major factor in the selection of lymphocytes and downregulation of immunological processes. In the present study, we have assessed endothelial Fas-ligand (FasL) expression in normal human ileum, appendix, and colon, and compared the expression levels with that in inflammatory bowel disease and in acute appendicitis. In a normal appendix, endothelial FasL levels were constant in almost half of the mucosal vessels; but, in the normal ileum and colon, endothelial FasL was practically restricted to areas in close proximity to lymphatic follicles, and was expressed mainly in the submucosal aspect of the follicles in the vessels with high endothelium. In samples from subjects with either Crohn's disease or ulcerative colitis, the extent of endothelial FasL expression was elevated in the submucosa and associated with an elevated number of lymphoid follicles. In inflammatory bowel disease, ulcers and areas with a high density of mononuclear cells expressing FasL also showed an elevated density of blood vessels with endothelial FasL expression. Although the function of endothelial FasL remains unclear, such a specific expression pattern suggests that endothelial FasL expression has a role in the regulation of lymphocyte access to the peripheral lymphoid tissues, including the intestinal mucosa. PMID:26374830

  8. Prediction of Acute Respiratory Disease in Current and Former Smokers With and Without COPD

    PubMed Central

    Kim, Victor; Regan, Elizabeth; Williams, André A. A.; Santorico, Stephanie A.; Make, Barry J.; Lynch, David A.; Hokanson, John E.; Washko, George R.; Bercz, Peter; Soler, Xavier; Marchetti, Nathaniel; Criner, Gerard J.; Ramsdell, Joe; Han, MeiLan K.; Demeo, Dawn; Anzueto, Antonio; Comellas, Alejandro; Crapo, James D.; Dransfield, Mark; Wells, J. Michael; Hersh, Craig P.; MacIntyre, Neil; Martinez, Fernando; Nath, Hrudaya P.; Niewoehner, Dennis; Sciurba, Frank; Sharafkhaneh, Amir; Silverman, Edwin K.; van Beek, Edwin J. R.; Wilson, Carla; Wendt, Christine; Wise, Robert A.; Curtis, Jeffrey; Kazerooni, Ella; Hanania, Nicola; Alapat, Philip; Bandi, Venkata; Guntupalli, Kalpalatha; Guy, Elizabeth; Lunn, William; Mallampalli, Antara; Trinh, Charles; Atik, Mustafa; DeMeo, Dawn; Hersh, Craig; Jacobson, Francine; Graham Barr, R.; Thomashow, Byron; Austin, John; MacIntyre, Neil; Washington, Lacey; Page McAdams, H.; Rosiello, Richard; Bresnahan, Timothy; McEvoy, Charlene; Tashjian, Joseph; Wise, Robert; Hansel, Nadia; Brown, Robert; Casaburi, Richard; Porszasz, Janos; Fischer, Hans; Budoff, Matt; Sharafkhaneh, Amir; Niewoehner, Dennis; Allen, Tadashi; Rice, Kathryn; Foreman, Marilyn; Westney, Gloria; Berkowitz, Eugene; Bowler, Russell; Friedlander, Adam; Meoni, Eleonora; Criner, Gerard; Kim, Victor; Marchetti, Nathaniel; Satti, Aditi; James Mamary, A.; Steiner, Robert; Dass, Chandra; Bailey, William; Dransfield, Mark; Gerald, Lynn; Nath, Hrudaya; Ramsdell, Joe; Ferguson, Paul; Friedman, Paul; McLennan, Geoffrey; van Beek, Edwin JR; Martinez, Fernando; Han, MeiLan; Thompson, Deborah; Kazerooni, Ella; Wendt, Christine; Allen, Tadashi; Sciurba, Frank; Weissfeld, Joel; Fuhrman, Carl; Bon, Jessica; Anzueto, Antonio; Adams, Sandra; Orozco, Carlos; Santiago Restrepo, C.; Mumbower, Amy; Crapo, James; Silverman, Edwin; Make, Barry; Regan, Elizabeth; Samet, Jonathan; Willis, Amy; Stinson, Douglas; Beaty, Terri; Klanderman, Barbara; Laird, Nan; Lange, Christoph; Ionita, Iuliana; Santorico, Stephanie; Silverman, Edwin; Lynch, David; Schroeder, Joyce; Newell, John; Reilly, John; Coxson, Harvey; Judy, Philip; Hoffman, Eric; San Jose Estepar, Raul; Washko, George; Leek, Rebecca; Zach, Jordan; Kluiber, Alex; Rodionova, Anastasia; Mann, Tanya; Crapo, Robert; Jensen, Robert; Farzadegan, Homayoon; Murphy, James; Everett, Douglas; Wilson, Carla; Hokanson, John

    2014-01-01

    BACKGROUND: The risk factors for acute episodes of respiratory disease in current and former smokers who do not have COPD are unknown. METHODS: Eight thousand two hundred forty-six non-Hispanic white and black current and former smokers in the Genetic Epidemiology of COPD (COPDGene) cohort had longitudinal follow-up (LFU) every 6 months to determine acute respiratory episodes requiring antibiotics or systemic corticosteroids, an ED visit, or hospitalization. Negative binomial regression was used to determine the factors associated with acute respiratory episodes. A Cox proportional hazards model was used to determine adjusted hazard ratios (HRs) for time to first episode and an acute episode of respiratory disease risk score. RESULTS: At enrollment, 4,442 subjects did not have COPD, 658 had mild COPD, and 3,146 had moderate or worse COPD. Nine thousand three hundred three acute episodes of respiratory disease and 2,707 hospitalizations were reported in LFU (3,044 acute episodes of respiratory disease and 827 hospitalizations in those without COPD). Major predictors included acute episodes of respiratory disease in year prior to enrollment (HR, 1.20; 95% CI, 1.15-1.24 per exacerbation), airflow obstruction (HR, 0.94; 95% CI, 0.91-0.96 per 10% change in % predicted FEV1), and poor health-related quality of life (HR, 1.07; 95% CI, 1.06-1.08 for each 4-unit increase in St. George’s Respiratory Questionnaire score). Risks were similar for those with and without COPD. CONCLUSIONS: Although acute episode of respiratory disease rates are higher in subjects with COPD, risk factors are similar, and at a population level, there are more episodes in smokers without COPD. PMID:24945159

  9. Acute aerobic exercise increases brain-derived neurotrophic factor levels in elderly with Alzheimer's disease.

    PubMed

    Coelho, Flávia Gomes de Melo; Vital, Thays Martins; Stein, Angelica Miki; Arantes, Franciel José; Rueda, André Veloso; Camarini, Rosana; Teodorov, Elizabeth; Santos-Galduróz, Ruth Ferreira

    2014-01-01

    Studies indicate the involvement of brain-derived neurotrophic factor (BDNF) in the pathogenesis of Alzheimer's disease (AD). Decreased BDNF levels may constitute a lack of trophic support and contribute to cognitive impairment in AD. The benefits of acute and chronic physical exercise on BDNF levels are well-documented in humans, however, exercise effects on BDNF levels have not been analyzed in older adults with AD. The aim of this study was to investigate the effects of acute aerobic exercise on BDNF levels in older adults with AD and to verify associations among BDNF levels, aerobic fitness, and level of physical activity. Using a controlled design, twenty-one patients with AD (76.3 ± 6.2 years) and eighteen healthy older adults (74.6 ± 4.7 years) completed an acute aerobic exercise. The outcomes included measures of BDNF plasma levels, aerobic fitness (treadmill grade, time to exhaustion, VO2, and maximal lactate) and level of physical activity (Baecke Questionnaire Modified for the Elderly). The independent t-test shows differences between groups with respect to the BDNF plasma levels at baseline (p = 0.04; t = 4.53; df = 37). In two-way ANOVA, a significant effect of time was found (p = 0.001; F = 13.63; df = 37), the aerobic exercise significantly increased BDNF plasma levels in AD patients and healthy controls. A significant correlation (p = 0.04; r = 0.33) was found between BDNF levels and the level of physical activity. The results of our study suggest that aerobic exercise increases BDNF plasma levels in patients with AD and healthy controls. In addition to that, BDNF levels had association with level of physical activity. PMID:24164734

  10. Drug repurposing and human parasitic protozoan diseases

    PubMed Central

    Andrews, Katherine T.; Fisher, Gillian; Skinner-Adams, Tina S.

    2014-01-01

    Parasitic diseases have an enormous health, social and economic impact and are a particular problem in tropical regions of the world. Diseases caused by protozoa and helminths, such as malaria and schistosomiasis, are the cause of most parasite related morbidity and mortality, with an estimated 1.1 million combined deaths annually. The global burden of these diseases is exacerbated by the lack of licensed vaccines, making safe and effective drugs vital to their prevention and treatment. Unfortunately, where drugs are available, their usefulness is being increasingly threatened by parasite drug resistance. The need for new drugs drives antiparasitic drug discovery research globally and requires a range of innovative strategies to ensure a sustainable pipeline of lead compounds. In this review we discuss one of these approaches, drug repurposing or repositioning, with a focus on major human parasitic protozoan diseases such as malaria, trypanosomiasis, toxoplasmosis, cryptosporidiosis and leishmaniasis. PMID:25057459

  11. Roles for retrotransposon insertions in human disease.

    PubMed

    Hancks, Dustin C; Kazazian, Haig H

    2016-01-01

    Over evolutionary time, the dynamic nature of a genome is driven, in part, by the activity of transposable elements (TE) such as retrotransposons. On a shorter time scale it has been established that new TE insertions can result in single-gene disease in an individual. In humans, the non-LTR retrotransposon Long INterspersed Element-1 (LINE-1 or L1) is the only active autonomous TE. In addition to mobilizing its own RNA to new genomic locations via a "copy-and-paste" mechanism, LINE-1 is able to retrotranspose other RNAs including Alu, SVA, and occasionally cellular RNAs. To date in humans, 124 LINE-1-mediated insertions which result in genetic diseases have been reported. Disease causing LINE-1 insertions have provided a wealth of insight and the foundation for valuable tools to study these genomic parasites. In this review, we provide an overview of LINE-1 biology followed by highlights from new reports of LINE-1-mediated genetic disease in humans. PMID:27158268

  12. Major Histocompatibility Complex Genomics and Human Disease

    PubMed Central

    Trowsdale, John; Knight, Julian C.

    2015-01-01

    Over several decades, various forms of genomic analysis of the human major histocompatibility complex (MHC) have been extremely successful in picking up many disease associations. This is to be expected, as the MHC region is one of the most gene-dense and polymorphic stretches of human DNA. It also encodes proteins critical to immunity, including several controlling antigen processing and presentation. Single-nucleotide polymorphism genotyping and human leukocyte antigen (HLA) imputation now permit the screening of large sample sets, a technique further facilitated by high-throughput sequencing. These methods promise to yield more precise contributions of MHC variants to disease. However, interpretation of MHC-disease associations in terms of the functions of variants has been problematic. Most studies confirm the paramount importance of class I and class II molecules, which are key to resistance to infection. Infection is likely driving the extreme variation of these genes across the human population, but this has been difficult to demonstrate. In contrast, many associations with autoimmune conditions have been shown to be specific to certain class I and class II alleles. Interestingly, conditions other than infections and autoimmunity are also associated with the MHC, including some cancers and neuropathies. These associations could be indirect, owing, for example, to the infectious history of a particular individual and selective pressures operating at the population level. PMID:23875801

  13. Glial biomarkers in human central nervous system disease.

    PubMed

    Garden, Gwenn A; Campbell, Brian M

    2016-10-01

    There is a growing understanding that aberrant GLIA function is an underlying factor in psychiatric and neurological disorders. As drug discovery efforts begin to focus on glia-related targets, a key gap in knowledge includes the availability of validated biomarkers to help determine which patients suffer from dysfunction of glial cells or who may best respond by targeting glia-related drug mechanisms. Biomarkers are biological variables with a significant relationship to parameters of disease states and can be used as surrogate markers of disease pathology, progression, and/or responses to drug treatment. For example, imaging studies of the CNS enable localization and characterization of anatomical lesions without the need to isolate tissue for biopsy. Many biomarkers of disease pathology in the CNS involve assays of glial cell function and/or response to injury. Each major glia subtype (oligodendroglia, astroglia and microglia) are connected to a number of important and useful biomarkers. Here, we describe current and emerging glial based biomarker approaches for acute CNS injury and the major categories of chronic nervous system dysfunction including neurodegenerative, neuropsychiatric, neoplastic, and autoimmune disorders of the CNS. These descriptions are highlighted in the context of how biomarkers are employed to better understand the role of glia in human CNS disease and in the development of novel therapeutic treatments. GLIA 2016;64:1755-1771. PMID:27228454

  14. The origin recognition complex in human diseases

    PubMed Central

    Shen, Zhen

    2013-01-01

    ORC (origin recognition complex) serves as the initiator for the assembly of the pre-RC (pre-replication complex) and the subsequent DNA replication. Together with many of its non-replication functions, ORC is a pivotal regulator of various cellular processes. Notably, a number of reports connect ORC to numerous human diseases, including MGS (Meier–Gorlin syndrome), EBV (Epstein–Barr virus)-infected diseases, American trypanosomiasis and African trypanosomiasis. However, much of the underlying molecular mechanism remains unclear. In those genetic diseases, mutations in ORC alter its function and lead to the dysregulated phenotypes; whereas in some pathogen-induced symptoms, host ORC and archaeal-like ORC are exploited by these organisms to maintain their own genomes. In this review, I provide detailed examples of ORC-related human diseases, and summarize the current findings on how ORC is involved and/or dysregulated. I further discuss how these discoveries can be generalized as model systems, which can then be applied to elucidating other related diseases and revealing potential targets for developing effective therapies. PMID:23662735

  15. Human endogenous retroviruses in neurologic disease.

    PubMed

    Christensen, Tove

    2016-01-01

    Endogenous retroviruses are pathogenic - in other species than the human. Disease associations for Human Endogenous RetroViruses (HERVs) are emerging, but so far an unequivocal pathogenetic cause-effect relationship has not been established. A role for HERVs has been proposed in neurological and neuropsychiatric diseases as diverse as multiple sclerosis (MS) and schizophrenia (SCZ). Particularly for MS, many aspects of the activation and involvement of specific HERV families (HERV-H/F and HERV-W/MSRV) have been reported, both for cells in the circulation and in the central nervous system. Notably envelope genes and their gene products (Envs) appear strongly associated with the disease. For SCZ, for ALS, and for HIV-associated dementia (HAD), indications are accumulating for involvement of the HERV-K family, and also HERV-H/F and/or HERV-W. Activation is reasonably a prerequisite for causality as most HERV sequences remain quiescent in non-pathological conditions, so the importance of regulatory pathways and epigenetics involved in regulating HERV activation, derepression, and also involvement of retroviral restriction factors, is emerging. HERV-directed antiretrovirals have potential as novel therapeutic paradigms in neurologic disease, particularly in MS. The possible protective or ameliorative effects of antiretroviral therapy in MS are substantiated by reports that treatment of HIV infection may be associated with a significantly decreased risk of MS. Further studies of HERVs, their role in neurologic diseases, and their potential as therapeutic targets are essential. PMID:26818266

  16. Predicting interactome network perturbations in human cancer: application to gene fusions in acute lymphoblastic leukemia

    PubMed Central

    Hajingabo, Leon Juvenal; Daakour, Sarah; Martin, Maud; Grausenburger, Reinhard; Panzer-Grümayer, Renate; Dequiedt, Franck; Simonis, Nicolas; Twizere, Jean-Claude

    2014-01-01

    Genomic variations such as point mutations and gene fusions are directly or indirectly associated with human diseases. They are recognized as diagnostic, prognostic markers and therapeutic targets. However, predicting the functional effect of these genetic alterations beyond affected genes and their products is challenging because diseased phenotypes are likely dependent of complex molecular interaction networks. Using as models three different chromosomal translocations—ETV6-RUNX1 (TEL-AML1), BCR-ABL1, and TCF3-PBX1 (E2A-PBX1)—frequently found in precursor-B-cell acute lymphoblastic leukemia (preB-ALL), we develop an approach to extract perturbed molecular interactions from gene expression changes. We show that the MYC and JunD transcriptional circuits are specifically deregulated after ETV6-RUNX1 and TCF3-PBX1 gene fusions, respectively. We also identified the bulk mRNA NXF1-dependent machinery as a direct target for the TCF3-PBX1 fusion protein. Through a novel approach combining gene expression and interactome data analysis, we provide new insight into TCF3-PBX1 and ETV6-RUNX1 acute lymphoblastic leukemia. PMID:25273558

  17. Longitudinal characterization of dysfunctional T cell-activation during human acute Ebola infection.

    PubMed

    Agrati, C; Castilletti, C; Casetti, R; Sacchi, A; Falasca, L; Turchi, F; Tumino, N; Bordoni, V; Cimini, E; Viola, D; Lalle, E; Bordi, L; Lanini, S; Martini, F; Nicastri, E; Petrosillo, N; Puro, V; Piacentini, M; Di Caro, A; Kobinger, G P; Zumla, A; Ippolito, G; Capobianchi, M R

    2016-01-01

    Data on immune responses during human Ebola virus disease (EVD) are scanty, due to limitations imposed by biosafety requirements and logistics. A sustained activation of T-cells was recently described but functional studies during the acute phase of human EVD are still missing. Aim of this work was to evaluate the kinetics and functionality of T-cell subsets, as well as the expression of activation, autophagy, apoptosis and exhaustion markers during the acute phase of EVD until recovery. Two EVD patients admitted to the Italian National Institute for Infectious Diseases, Lazzaro Spallanzani, were sampled sequentially from soon after symptom onset until recovery and analyzed by flow cytometry and ELISpot assay. An early and sustained decrease of CD4 T-cells was seen in both patients, with an inversion of the CD4/CD8 ratio that was reverted during the recovery period. In parallel with the CD4 T-cell depletion, a massive T-cell activation occurred and was associated with autophagic/apoptotic phenotype, enhanced expression of the exhaustion marker PD-1 and impaired IFN-gamma production. The immunological impairment was accompanied by EBV reactivation. The association of an early and sustained dysfunctional T-cell activation in parallel to an overall CD4 T-cell decline may represent a previously unknown critical point of Ebola virus (EBOV)-induced immune subversion. The recent observation of late occurrence of EBOV-associated neurological disease highlights the importance to monitor the immuno-competence recovery at discharge as a tool to evaluate the risk of late sequelae associated with resumption of EBOV replication. Further studies are required to define the molecular mechanisms of EVD-driven activation/exhaustion and depletion of T-cells. PMID:27031961

  18. Longitudinal characterization of dysfunctional T cell-activation during human acute Ebola infection

    PubMed Central

    Agrati, C; Castilletti, C; Casetti, R; Sacchi, A; Falasca, L; Turchi, F; Tumino, N; Bordoni, V; Cimini, E; Viola, D; Lalle, E; Bordi, L; Lanini, S; Martini, F; Nicastri, E; Petrosillo, N; Puro, V; Piacentini, M; Di Caro, A; Kobinger, G P; Zumla, A; Ippolito, G; Capobianchi, M R

    2016-01-01

    Data on immune responses during human Ebola virus disease (EVD) are scanty, due to limitations imposed by biosafety requirements and logistics. A sustained activation of T-cells was recently described but functional studies during the acute phase of human EVD are still missing. Aim of this work was to evaluate the kinetics and functionality of T-cell subsets, as well as the expression of activation, autophagy, apoptosis and exhaustion markers during the acute phase of EVD until recovery. Two EVD patients admitted to the Italian National Institute for Infectious Diseases, Lazzaro Spallanzani, were sampled sequentially from soon after symptom onset until recovery and analyzed by flow cytometry and ELISpot assay. An early and sustained decrease of CD4 T-cells was seen in both patients, with an inversion of the CD4/CD8 ratio that was reverted during the recovery period. In parallel with the CD4 T-cell depletion, a massive T-cell activation occurred and was associated with autophagic/apoptotic phenotype, enhanced expression of the exhaustion marker PD-1 and impaired IFN-gamma production. The immunological impairment was accompanied by EBV reactivation. The association of an early and sustained dysfunctional T-cell activation in parallel to an overall CD4 T-cell decline may represent a previously unknown critical point of Ebola virus (EBOV)-induced immune subversion. The recent observation of late occurrence of EBOV-associated neurological disease highlights the importance to monitor the immuno-competence recovery at discharge as a tool to evaluate the risk of late sequelae associated with resumption of EBOV replication. Further studies are required to define the molecular mechanisms of EVD-driven activation/exhaustion and depletion of T-cells. PMID:27031961

  19. Acute stress impairs the retrieval of extinction memory in humans

    PubMed Central

    Raio, Candace M.; Brignoni-Perez, Edith; Goldman, Rachel; Phelps, Elizabeth A.

    2014-01-01

    Extinction training is a form of inhibitory learning that allows an organism to associate a previously aversive cue with a new, safe outcome. Extinction does not erase a fear association, but instead creates a competing association that may or may not be retrieved when a cue is subsequently encountered. Characterizing the conditions under which extinction learning is expressed is important to enhancing the treatment of anxiety disorders that rely on extinction-based exposure therapy as a primary treatment technique. The ventromedial prefrontal cortex, which plays an important role in the expression of extinction memory, has been shown to be functionally impaired after stress exposure. Further, recent research in rodents found that exposure to stress led to deficits in extinction retrieval, although this has yet to be tested in humans. To explore how stress might influence extinction retrieval in humans, participants underwent a differential aversive learning paradigm, in which one image was probabilistically paired with an aversive shock while the other image denoted safety. Extinction training directly followed, at which point reinforcement was omitted. A day later, participants returned to the lab and either completed an acute stress manipulation (i.e., cold pressor), or a control task, before undergoing an extinction retrieval test. Skin conductance responses and salivary cortisol concentrations were measured throughout each session as indices of fear arousal and neuroendocrine stress responses, respectively. The efficacy of our stress induction was established by observing significant increases in cortisol for the stress condition only. We examined extinction retrieval by comparing conditioned responses during the last trial of extinction (day 1) with that of the first trial of re-extinction (day 2). Groups did not differ on initial fear acquisition or extinction, however, one day later participants in the stress group (n = 27) demonstrated significantly less

  20. Soluble CD163 is increased in patients with acute pancreatitis independent of disease severity.

    PubMed

    Karrasch, Thomas; Brünnler, Tanja; Hamer, Okka W; Schmid, Karin; Voelk, Markus; Herfarth, Hans; Buechler, Christa

    2015-10-01

    Macrophages are crucially involved in the pathophysiology of acute pancreatitis. Soluble CD163 (sCD163) is specifically released from macrophages and systemic levels are increased in inflammatory diseases. Here, sCD163 was measured in serum of 50 patients with acute pancreatitis to find out possible associations with disease activity. Admission levels of systemic sCD163 were nearly three-fold higher in patients with acute pancreatitis compared to controls. In patients sCD163 did not correlate with C-reactive protein and leukocyte count as established markers of inflammation. Levels were not associated with disease severity assessed by the Schroeder score, Balthazar score, Acute Physiology, Age, and Chronic Health Evaluation (Apache) II score and peripancreatic necrosis score. Soluble CD163 was not related to complications of acute pancreatitis. These data show that serum sCD163 is increased in acute pancreatitis indicating activation of macrophages but is not associated with disease severity and outcome. PMID:26209500

  1. Cardiovascular and cerebrovascular responses to acute hypoxia following exposure to intermittent hypoxia in healthy humans

    PubMed Central

    Foster, Glen E; Brugniaux, Julien V; Pialoux, Vincent; Duggan, Cailean T C; Hanly, Patrick J; Ahmed, Sofia B; Poulin, Marc J

    2009-01-01

    Intermittent hypoxia (IH) is thought to be responsible for many of the long-term cardiovascular consequences associated with obstructive sleep apnoea (OSA). Experimental human models of IH can aid in investigating the pathophysiology of these cardiovascular complications. The purpose of this study was to determine the effects of IH on the cardiovascular and cerebrovascular response to acute hypoxia and hypercapnia in an experimental human model that simulates the hypoxaemia experienced by OSA patients. We exposed 10 healthy, male subjects to IH for 4 consecutive days. The IH profile involved 2 min of hypoxia (nadir = 45.0 mmHg) alternating with 2 min of normoxia (peak = 88.0 mmHg) for 6 h. The cerebral blood flow response and the pressor responses to hypoxia and hypercapnia were assessed after 2 days of sham exposure, after each day of IH, and 4 days following the discontinuation of IH. Nitric oxide derivatives were measured at baseline and following the last exposure to IH. After 4 days of IH, mean arterial pressure increased by 4 mmHg (P < 0.01), nitric oxide derivatives were reduced by 55% (P < 0.05), the pressor response to acute hypoxia increased (P < 0.01), and the cerebral vascular resistance response to hypoxia increased (P < 0.01). IH alters blood pressure and cerebrovascular regulation, which is likely to contribute to the pathogenesis of cardiovascular and cerebrovascular disease in patients with OSA. PMID:19417094

  2. Screening for acute HIV infection in South Africa: finding acute and chronic disease

    PubMed Central

    Bassett, Ingrid V.; Chetty, Senica; Giddy, Janet; Reddy, Shabashini; Bishop, Karen; Lu, Zhigang; Losina, Elena; Freedberg, Kenneth A.; Walensky, Rochelle P.

    2010-01-01

    Background The yield of screening for acute HIV infection among general medical patients in resource-scarce settings remains unclear. Our objective was to evaluate a strategy of pooled HIV plasma RNA to diagnose acute HIV infection in patients with negative or discordant rapid HIV antibody tests in Durban, South Africa. Methods We prospectively enrolled patients with negative or discordant rapid HIV antibody tests from a routine HIV screening program in an outpatient department in Durban with an HIV prevalence of 48%. Study participants underwent venipuncture for pooled qualitative HIV RNA, and if positive, quantitative RNA, enzyme immunoassay and Western Blot (WB). Patients with negative or indeterminate WB and positive quantitative HIV RNA were considered acutely infected. Those with chronic infection (positive RNA and WB) despite negative or discordant rapid HIV tests were considered false negative rapid antibody tests. Results Nine hundred ninety-four participants were enrolled with either negative (N=976) or discordant (N=18) rapid test results. Eleven (1.1%, 95% CI: 0.6–2.0%) had acute HIV infection. Of the 994 patients, an additional 20 (2.0%, 95% CI: 1.3–.3.1%) had chronic HIV infection (false negative rapid test). Conclusions One percent of outpatients with negative or discordant rapid HIV tests in Durban, South Africa had acute HIV infection readily detectable through pooled serum HIV RNA screening. Pooled RNA testing also identified an additional 2% of patients with chronic HIV infection. HIV RNA screening has the potential to identify both acute and chronic HIV infections that are otherwise missed by standard HIV testing algorithms. PMID:20553336

  3. Acute nephritic syndrome

    MedlinePlus

    Glomerulonephritis - acute; Acute glomerulonephritis; Nephritis syndrome - acute ... Acute nephritic syndrome is often caused by an immune response triggered by an infection or other disease. Common causes ...

  4. The Mitochondrial Proteome and Human Disease

    PubMed Central

    Calvo, Sarah E.; Mootha, Vamsi K.

    2015-01-01

    For nearly three decades, the sequence of the human mitochondrial genome (mtDNA) has provided a molecular framework for understanding maternally inherited diseases. However, the vast majority of human mitochondrial disorders are caused by nuclear defects, which is not surprising since the mtDNA encodes only 13 proteins. Advances in genomics, mass spectrometry, and computation have only recently made it possible to systematically identify the complement of over 1,000 proteins that comprise the mammalian mitochondrial proteome. Here, we review recent progress in characterizing the mitochondrial proteome and highlight insights into its complexity, tissue heterogeneity, evolutionary origins, and biochemical versatility. We then discuss how this proteome is being used to discover the genetic basis of respiratory chain disorders as well as to expand our definition of mitochondrial disease. Finally, we explore future prospects and challenges for using the mitochondrial proteome as a foundation for systems analysis of the organelle. PMID:20690818

  5. [Human hantavirus diseases - still neglected zoonoses?].

    PubMed

    Vrbovská, V; Chalupa, P; Straková, P; Hubálek, Z; Rudolf, I

    2015-10-01

    Hantavirus disease is the most common rodent-borne viral infection in the Czech Republic, with a mean annual incidence of 0.02 cases per 100 000 population and specific antibodies detected in 1% of the human population. Four hantaviruses (Puumala, Dobrava-Belgrade, Tula, and Seewis) circulate in this country, of which Puumala virus (responsible for a mild form of hemorrhagic fever with renal syndrome called nephropathia epidemica) and Dobrava-Belgrade virus (causing haemorrhagic fever with renal syndrome) have been proven to cause human disease. The aim of this study is to provide a comprehensive review of the hantaviruses occurring in the Czech Republic, based on the literature published during the past three decades, including their geographical distribution and clinical symptoms. The recent detection of Tula virus in an immunocompromised person as well as reports of Seoul virus infections in Europe highlight the possible emergence of neglected hantavirus infections in the foreseeable future. PMID:26795222

  6. Molecular biology of human muscle disease

    SciTech Connect

    Dunne, P.W.; Epstein, H.F. )

    1991-01-01

    The molecular revolution that is transforming the entire biomedical field has had far-reaching impact in its application to inherited human muscle disease. The gene for Duchenne muscular dystrophy was one of the first cloned without knowledge of the defective protein product. This success was based upon the availability of key chromosomal aberrations that provided molecular landmarks for the disease locus. Subsequent discoveries regarding the mode of expression for this gene, the structure and localization of its protein product dystrophin, and molecular diagnosis of affected and carrier individuals constitute a paradigm for investigation of human genetics. Finding the gene for myotonic muscular dystrophy is requiring the brute force approach of cloning several million bases of DNA, identifying expressed sequences, and characterizing candidate genes. The gene that causes hypertrophic cardiomyopathy has been found serendipitously to be one of the genetic markers on chromosome 14, the {beta} myosin heavy chain.

  7. Renal and urological diseases of the newborn neonatal acute kidney injury.

    PubMed

    Mistry, Kirtida

    2014-01-01

    Survival of critically ill neonates in the intensive care unit has improved over the past decades reflecting improvements in obstetric, delivery room and neonatal intensive care, however, morbidity remains significant. Acute kidney injury is a common occurrence in these neonates and despite improved understanding of the pathophysiology and management of acute kidney injury in full term and preterm infants, the mortality remains as high as 61%. Furthermore, there is growing evidence that despite recovery from the acute injury, these infants are at risk for developing hypertension and chronic kidney disease later in life. Emphasis on improving our capability to detect renal insult and injury early, before renal failure occurs, and identification of novel therapeutic agents to prevent and treat acute kidney injury may impact mortality and morbidity. This review focuses on our current knowledge of acute kidney injury in the newborn, approaches to investigating and managing this complication and what future trends in this field may bring. PMID:25088261

  8. FIRST REPORT OF ACUTE CHAGAS DISEASE BY VECTOR TRANSMISSION IN RIO DE JANEIRO STATE, BRAZIL.

    PubMed

    Sangenis, Luiz Henrique Conde; De Sousa, Andréa Silvestre; Sperandio Da Silva, Gilberto Marcelo; Xavier, Sérgio Salles; Machado, Carolina Romero Cardoso; Brasil, Patrícia; De Castro, Liane; Da Silva, Sidnei; Georg, Ingebourg; Saraiva, Roberto Magalhães; do Brasil, Pedro Emmanuel Alvarenga Americano; Hasslocher-Moreno, Alejandro Marcel

    2015-01-01

    Chagas disease (CD) is an endemic anthropozoonosis from Latin America of which the main means of transmission is the contact of skin lesions or mucosa with the feces of triatomine bugs infected by Trypanosoma cruzi. In this article, we describe the first acute CD case acquired by vector transmission in the Rio de Janeiro State and confirmed by parasitological, serological and PCR tests. The patient presented acute cardiomyopathy and pericardial effusion without cardiac tamponade. Together with fever and malaise, a 3 cm wide erythematous, non-pruritic, papule compatible with a "chagoma" was found on his left wrist. This case report draws attention to the possible transmission of CD by non-domiciled native vectors in non-endemic areas. Therefore, acute CD should be included in the diagnostic workout of febrile diseases and acute myopericarditis in Rio de Janeiro. PMID:26422165

  9. Acute Splenic Sequestration Crisis in a 70-Year-Old Patient With Hemoglobin SC Disease.

    PubMed

    Squiers, John J; Edwards, Anthony G; Parra, Alberto; Hofmann, Sandra L

    2016-01-01

    A 70-year-old African American female with a past medical history significant for chronic bilateral shoulder pain and reported sickle cell trait presented with acute-onset bilateral thoracolumbar pain radiating to her left arm. Two days after admission, Hematology was consulted for severely worsening microcytic anemia and thrombocytopenia. Examination of the patient's peripheral blood smear from admission revealed no cell sickling, spherocytes, or schistocytes. Some targeting was noted. A Coombs test was negative. The patient was eventually transferred to the medical intensive care unit in respiratory distress. Hemoglobin electrophoresis confirmed a diagnosis of hemoglobin SC disease. A diagnosis of acute splenic sequestration crisis complicated by acute chest syndrome was crystallized, and red blood cell exchange transfusion was performed. Further research is necessary to fully elucidate the pathophysiology behind acute splenic sequestration crisis, and the role of splenectomy to treat hemoglobin SC disease patients should be better defined. PMID:27047980

  10. Acute Splenic Sequestration Crisis in a 70-Year-Old Patient With Hemoglobin SC Disease

    PubMed Central

    Squiers, John J.; Edwards, Anthony G.; Parra, Alberto; Hofmann, Sandra L.

    2016-01-01

    A 70-year-old African American female with a past medical history significant for chronic bilateral shoulder pain and reported sickle cell trait presented with acute-onset bilateral thoracolumbar pain radiating to her left arm. Two days after admission, Hematology was consulted for severely worsening microcytic anemia and thrombocytopenia. Examination of the patient’s peripheral blood smear from admission revealed no cell sickling, spherocytes, or schistocytes. Some targeting was noted. A Coombs test was negative. The patient was eventually transferred to the medical intensive care unit in respiratory distress. Hemoglobin electrophoresis confirmed a diagnosis of hemoglobin SC disease. A diagnosis of acute splenic sequestration crisis complicated by acute chest syndrome was crystallized, and red blood cell exchange transfusion was performed. Further research is necessary to fully elucidate the pathophysiology behind acute splenic sequestration crisis, and the role of splenectomy to treat hemoglobin SC disease patients should be better defined. PMID:27047980

  11. The genetics of human skin disease.

    PubMed

    DeStefano, Gina M; Christiano, Angela M

    2014-10-01

    The skin is composed of a variety of cell types expressing specific molecules and possessing different properties that facilitate the complex interactions and intercellular communication essential for maintaining the structural integrity of the skin. Importantly, a single mutation in one of these molecules can disrupt the entire organization and function of these essential networks, leading to cell separation, blistering, and other striking phenotypes observed in inherited skin diseases. Over the past several decades, the genetic basis of many monogenic skin diseases has been elucidated using classical genetic techniques. Importantly, the findings from these studies has shed light onto the many classes of molecules and essential genetic as well as molecular interactions that lend the skin its rigid, yet flexible properties. With the advent of the human genome project, next-generation sequencing techniques, as well as several other recently developed methods, tremendous progress has been made in dissecting the genetic architecture of complex, non-Mendelian skin diseases. PMID:25274756

  12. A Genomic Approach to Human Autoimmune Diseases

    PubMed Central

    Pascual, Virginia; Chaussabel, Damien; Banchereau, Jacques

    2010-01-01

    The past decade has seen an explosion in the use of DNA-based microarrays. These techniques permit to assess RNA abundance on a genome-wide scale. Medical applications emerged in the field of cancer, with studies of both solid tumors and hematological malignancies leading to the development of tests that are now used to personalize therapeutic options. Microarrays have also been used to analyze the blood transcriptome in a wide range of diseases. In human autoimmune diseases, these studies are showing potential for identifying therapeutic targets as well as biomarkers for diagnosis, assessment of disease activity and response to treatment. More quantitative and sensitive high throughput RNA profiling methods are starting to be available and will be necessary for transcriptome analyses to become routine tests in the clinical setting. We expect this to crystallize within the coming decade, as they become part of the personalized medicine armamentarium. PMID:20192809

  13. HECT E3s and human disease

    PubMed Central

    Scheffner, Martin; Staub, Olivier

    2007-01-01

    In a simplified view, members of the HECT E3 family have a modular structure consisting of the C-terminal HECT domain, which is catalytically involved in the attachment of ubiquitin to substrate proteins, and N-terminal extensions of variable length and sequence that mediate the substrate specificity of the respective HECT E3. Although the physiologically relevant substrates of most HECT E3s have remained elusive, it is becoming increasingly clear that HECT E3s play an important role in sporadic and hereditary human diseases including cancer, cardiovascular (Liddle's syndrome) and neurological (Angelman syndrome) disorders, and/or in disease-relevant processes including bone homeostasis, immune response and retroviral budding. Thus, molecular approaches to target the activity of distinct HECT E3s, regulators thereof, and/or of HECT E3 substrates could prove valuable in the treatment of the respective diseases. Publication history: Republished from Current BioData's Targeted Proteins database (TPdb; ). PMID:18047743

  14. Francisella philomiragia Bacteremia in a Patient with Acute Respiratory Insufficiency and Acute-on-Chronic Kidney Disease

    PubMed Central

    Humphries, Romney M.; Mattison, H. Reid; Miles, Jessica E.; Simpson, Edward R.; Corbett, Ian J.; Schmitt, Bryan H.; May, M.

    2015-01-01

    Francisella philomiragia is a very uncommon pathogen of humans. Diseases caused by it are protean and have been reported largely in near-drowning victims and those with chronic granulomatous disease. We present a case of F. philomiragia pneumonia with peripheral edema and bacteremia in a renal transplant patient and review the diverse reports of F. philomiragia infections. PMID:26400786

  15. Life-threatening acute pneumonitis in mixed connective tissue disease: a case report and literature review.

    PubMed

    Rath, Eva; Zandieh, Shahin; Löckinger, Alexander; Hirschl, Mirko; Klaushofer, Klaus; Zwerina, Jochen

    2015-10-01

    Mixed connective tissue disease (MCTD) is a rare connective tissue disease frequently involving the lungs. The main characteristic is a systemic sclerosis-like picture of slowly progressing interstitial lung disease consistent with lung fibrosis, while pulmonary arterial hypertension is rare. Herein, we present a case of a newly diagnosed MCTD patient developing life-threatening acute pneumonitis similar to lupus pneumonitis. Previous literature on this exceptionally rare complication of MCTD is reviewed and differential diagnosis and management discussed. PMID:26142172

  16. Psychiatric Disease and Post-Acute Traumatic Brain Injury.

    PubMed

    Zgaljardic, Dennis J; Seale, Gary S; Schaefer, Lynn A; Temple, Richard O; Foreman, Jack; Elliott, Timothy R

    2015-12-01

    Psychiatric disorders are common following traumatic brain injury (TBI) and can include depression, anxiety, and psychosis, as well as other maladaptive behaviors and personality changes. The epidemiologic data of psychiatric disorders post-TBI vary widely, although the incidence and prevalence rates typically are higher than in the general population. Although the experience of psychiatric symptoms may be temporary and may resolve in the acute period, many patients with TBI can experience psychopathology that is persistent or that develops in the post-acute period. Long-term psychiatric disorder, along with cognitive and physical sequelae and greater risk for substance use disorders, can pose a number of life-long challenges for patients and their caregivers, as they can interfere with participation in rehabilitation as well as limit functional independence in the community. The current review of the literature considers the common psychiatric problems affecting individuals with TBI in the post-acute period, including personality changes, psychosis, executive dysfunction, depression, anxiety, and substance misuse. Although treatment considerations (pharmacological and nonpharmacological) are referred to, an extensive description of such protocols is beyond the scope of the current review. The impact of persistent psychiatric symptoms on perceived caregiver burden and distress is also discussed. PMID:25629222

  17. Proteomic analysis of mitral valve in Lewis rat with acute rheumatic heart disease

    PubMed Central

    Li, Wenting; Zeng, Zhiyu; Gui, Chun; Zheng, Huilei; Huang, Weiqiang; Wei, Heng; Gong, Danping

    2015-01-01

    Rheumatic heart disease (RHD) makes a heavy burden in human lives and economy. The proteomic analysis of acute rheumatic heart disease (ARHD) can provide precious data to study RHD at the early stages, but no one has looked into. So based on our early research we applied the method of continuous GAS stimulation on Lewis rats to duplicate the animal model of ARHD. And the mitral valves of rats in control group (n=10) and ARHD group (n=10) were selected for proteomic analysis of ARHD with the iTRAQ labeling based 2D LC-ESI-MS/MS quantitative technology. We identified 3931 proteins in valve tissue out of which we obtained 395 differentially expressed proteins containing 176 up-regulated proteins and 119 down-regulated proteins. Changes in levels of GAPDH (6.793 times higher than the control group) and CD9 (2.63 times higher than the control group) were confirmed by Western blot or immunohistochemistry. The differentially expressed proteins such as GAPDH, CD9, myosin, collagen and RAC1 may be potential biomarkers for ARHD. Moreover, the mitral valve protein profile shed light on further understanding and investigating ARHD. PMID:26823728

  18. Human autoimmune diseases: a comprehensive update.

    PubMed

    Wang, Lifeng; Wang, Fu-Sheng; Gershwin, M Eric

    2015-10-01

    There have been significant advances in our understanding of human autoimmunity that have led to improvements in classification and diagnosis and, most importantly, research advances in new therapies. The importance of autoimmunity and the mechanisms that lead to clinical disease were first recognized about 50 years ago following the pioneering studies of Macfarlane Burnett and his Nobel Prize-winning hypothesis of the 'forbidden clone'. Such pioneering efforts led to a better understanding not only of autoimmunity, but also of lymphoid cell development, thymic education, apoptosis and deletion of autoreactive cells. Contemporary theories suggest that the development of an autoimmune disease requires a genetic predisposition and environmental factors that trigger the immune pathways that lead, ultimately, to tissue destruction. Despite extensive research, there are no genetic tools that can be used clinically to predict the risk of autoimmune disease. Indeed, the concordance of autoimmune disease in identical twins is 12-67%, highlighting not only a role for environmental factors, but also the potential importance of stochastic or epigenetic phenomena. On the other hand, the identification of cytokines and chemokines, and their cognate receptors, has led to novel therapies that block pathological inflammatory responses within the target organ and have greatly improved the therapeutic effect in patients with autoimmune disease, particularly rheumatoid arthritis. Further advances involving the use of multiplex platforms for diagnosis and identification of new therapeutic agents should lead to major breakthroughs within the next decade. PMID:26212387

  19. Human Immunodeficiency Virus and Liver Disease Forum 2012

    PubMed Central

    Sherman, Kenneth E.; Thomas, David; Chung, Raymond T.

    2013-01-01

    In the U.S. more than 1.1 million individuals are infected with the human immunodeficiency virus (HIV). These patients exhibit a high frequency of coinfections with other hepatotropic viruses and ongoing fibrosis leading to cirrhosis and liver-related mortality. The etiologies of liver disease include viral hepatitis coinfections, drug-related hepatotoxicity, fatty liver disease, and direct and indirect effects from HIV infection including increased bacterial translocation, immune activation, and presence of soluble proteins that modulate the hepatic cytokine environment. New treatments for HCV using direct acting agents appear viable, though issues related to intrinsic toxicities and drug:drug interactions remain. Recent research suggests that acute HCV infection, unrecognized hepatitis D infection, and hepatitis E may all represent emergent areas of concern. Antiretroviral agents, including those used in past years may represent risk factors for hepatic injury and portal hypertension. Key issues in the future include systematic implementation of liver disease management and new treatment in HIV-infected populations with concomitant injection drug use, alcohol use, and low socioeconomic status. PMID:23904401

  20. Elemental diet as primary treatment of acute Crohn's disease: a controlled trial.

    PubMed

    O'Moráin, C; Segal, A W; Levi, A J

    1984-06-23

    Acute exacerbations of Crohn's disease are usually treated with prednisolone or potentially more toxic immunosuppressive drugs or by surgery. In pilot studies replacing the normal diet by a protein free elemental diet also induced remission. A controlled trial was therefore conducted in which 21 patients acutely ill with exacerbations of Crohn's disease were randomised to receive either prednisolone 0.75 mg/kg/day or an elemental diet (Vivonex) for four weeks. Assessment at four and 12 weeks showed that the patients treated with the elemental diet had improved as much as and by some criteria more than the steroid treated group. Elemental diet is a safe and effective treatment for acute Crohn's disease. PMID:6428577

  1. Minimal residual disease analysis by eight-color flow cytometry in relapsed childhood acute lymphoblastic leukemia

    PubMed Central

    Karawajew, Leonid; Dworzak, Michael; Ratei, Richard; Rhein, Peter; Gaipa, Giuseppe; Buldini, Barbara; Basso, Giuseppe; Hrusak, Ondrej; Ludwig, Wolf-Dieter; Henze, Günter; Seeger, Karl; von Stackelberg, Arend; Mejstrikova, Ester; Eckert, Cornelia

    2015-01-01

    Multiparametric flow cytometry is an alternative approach to the polymerase chain reaction method for evaluating minimal residual disease in treatment protocols for primary acute lymphoblastic leukemia. Given considerable differences between primary and relapsed acute lymphoblastic leukemia treatment regimens, flow cytometric assessment of minimal residual disease in relapsed leukemia requires an independent comprehensive investigation. In the present study we addressed evaluation of minimal residual disease by flow cytometry in the clinical trial for childhood relapsed acute lymphoblastic leukemia using eight-color flow cytometry. The major challenge of the study was to reliably identify low amounts of residual leukemic cells against the complex background of regeneration, characteristic of follow-up samples during relapse treatment. In a prospective study of 263 follow-up bone marrow samples from 122 patients with B-cell precursor acute lymphoblastic leukemia, we tested various B-cell markers, adapted the antibody panel to the treatment protocol, and evaluated its performance by a blinded parallel comparison with the polymerase chain reaction data. The resulting eight-color single-tube panel showed a consistently high overall concordance (P<0.001) and, under optimal conditions, sensitivity similar to that of the reference polymerase chain reaction method. Overall, evaluation of minimal residual disease by flow cytometry can be successfully integrated into the clinical management of relapsed childhood acute lymphoblastic leukemia either as complementary to the polymerase chain reaction or as an independent risk stratification tool. ALL-REZ BFM 2002 clinical trial information: NCT00114348 PMID:26001791

  2. Validation of a mouse xenograft model system for gene expression analysis of human acute lymphoblastic leukaemia

    PubMed Central

    2010-01-01

    Background Pre-clinical models that effectively recapitulate human disease are critical for expanding our knowledge of cancer biology and drug resistance mechanisms. For haematological malignancies, the non-obese diabetic/severe combined immunodeficient (NOD/SCID) mouse is one of the most successful models to study paediatric acute lymphoblastic leukaemia (ALL). However, for this model to be effective for studying engraftment and therapy responses at the whole genome level, careful molecular characterisation is essential. Results Here, we sought to validate species-specific gene expression profiling in the high engraftment continuous ALL NOD/SCID xenograft. Using the human Affymetrix whole transcript platform we analysed transcriptional profiles from engrafted tissues without prior cell separation of mouse cells and found it to return highly reproducible profiles in xenografts from individual mice. The model was further tested with experimental mixtures of human and mouse cells, demonstrating that the presence of mouse cells does not significantly skew expression profiles when xenografts contain 90% or more human cells. In addition, we present a novel in silico and experimental masking approach to identify probes and transcript clusters susceptible to cross-species hybridisation. Conclusions We demonstrate species-specific transcriptional profiles can be obtained from xenografts when high levels of engraftment are achieved or with the application of transcript cluster masks. Importantly, this masking approach can be applied and adapted to other xenograft models where human tissue infiltration is lower. This model provides a powerful platform for identifying genes and pathways associated with ALL disease progression and response to therapy in vivo. PMID:20406497

  3. Importance of structural information in predicting human acute toxicity from in vitro cytotoxicity data

    SciTech Connect

    Lee, Soyoung; Park, Keunwan; Ahn, Hee-Sung; Kim, Dongsup

    2010-07-15

    In this study, we tried to assess the utility of the structural information of drugs for predicting human acute toxicity from in vitro basal cytotoxicity, and to interpret the informative quality and the pharmacokinetic meaning of each structural descriptor. For this, human acute toxicity data of 67 drugs were taken from literature with their basal cytotoxicity data, and used to develop predictive models. A series of multiple linear regression analyses were performed to construct feasible regression models by combining molecular descriptors and cytotoxicity data. We found that although the molecular descriptors alone had only moderate correlation with human acute toxicity, they were highly useful for explaining the discrepancy between in vitro cytotoxicity and human acute toxicity. Among many possible models, we selected the most explanatory models by changing the number and the type of combined molecular descriptors. The results showed that our selected models had high predictive power (R{sup 2}: between 0.7 and 0.87). Our analysis indicated that those successful models increased the prediction accuracies by providing the information on human pharmacokinetic parameters which are the major reason for the difference between human acute toxicity and cytotoxicity. In addition, we performed a clustering analysis on selected molecular descriptors to assess their informative qualities. The results indicated that the number of single bonds, the number of hydrogen bond donors and valence connectivity indices are closely related to linking cytotoxicity to acute toxicity, which provides insightful explanation about human toxicity beyond cytotoxicity.

  4. Outcomes before and after the Implementation of a Critical Pathway for Patients with Acute Aortic Disease

    PubMed Central

    Shin, Kyu Chul; Lee, Hye Sun; Park, Joon Min; Joo, Hyun-Chel; Ko, Young-Guk; Park, Incheol

    2016-01-01

    Purpose Acute aortic diseases, such as aortic dissection and aortic aneurysm, can be life-threatening vascular conditions. In this study, we compared outcomes before and after the implementation of a critical pathway (CP) for patients with acute aortic disease at the emergency department (ED). Materials and Methods This was a retrospective observational cohort study. The CP was composed of two phases: PRE-AORTA for early diagnosis and AORTA for prompt treatment. We compared patients who were diagnosed with acute aortic disease between pre-period (January 2010 to December 2011) and post-period (July 2012 to June 2014). Results Ninety-four and 104 patients were diagnosed with acute aortic disease in the pre- and post-periods, respectively. After the implementation of the CP, 38.7% of acute aortic disease cases were diagnosed via PRE-AORTA. The door-to-CT time was reduced more in PRE-AORTA-activated patients [71.0 (61.0, 115.0) min vs. 113.0 (56.0, 170.5) min; p=0.026]. During the post-period, more patients received emergency intervention than during the pre-period (22.3% vs. 36.5%; p=0.029). Time until emergency intervention was reduced in patients, who visited the ED directly, from 378.0 (302.0, 489.0) min in the pre-period to 200.0 (170.0, 299.0) min in the post-period (p=0.001). The number of patients who died in the ED declined from 11 to 4 from the pre-period to the post-period. Hospital mortality decreased from 26.6% to 14.4% in the post-period (p=0.033). Conclusion After the implementation of a CP for patients with acute aortic disease, more patients received emergency intervention within a shorter time, resulting in improved hospital mortality. PMID:26996561

  5. Human Genome Sequencing in Health and Disease

    PubMed Central

    Gonzaga-Jauregui, Claudia; Lupski, James R.; Gibbs, Richard A.

    2013-01-01

    Following the “finished,” euchromatic, haploid human reference genome sequence, the rapid development of novel, faster, and cheaper sequencing technologies is making possible the era of personalized human genomics. Personal diploid human genome sequences have been generated, and each has contributed to our better understanding of variation in the human genome. We have consequently begun to appreciate the vastness of individual genetic variation from single nucleotide to structural variants. Translation of genome-scale variation into medically useful information is, however, in its infancy. This review summarizes the initial steps undertaken in clinical implementation of personal genome information, and describes the application of whole-genome and exome sequencing to identify the cause of genetic diseases and to suggest adjuvant therapies. Better analysis tools and a deeper understanding of the biology of our genome are necessary in order to decipher, interpret, and optimize clinical utility of what the variation in the human genome can teach us. Personal genome sequencing may eventually become an instrument of common medical practice, providing information that assists in the formulation of a differential diagnosis. We outline herein some of the remaining challenges. PMID:22248320

  6. Cell mechanics and human disease states

    NASA Astrophysics Data System (ADS)

    Suresh, Subra

    2006-03-01

    This presentation will provide summary of our very recent studies exploring the effects of biochemical factors, influenced by foreign organisms or in vivo processes, on intracellular structural reorganization, single-cell mechanical response and motility of a population of cells in the context of two human diseases: malaria induced by Plasmodium falciparum merozoites that invade red blood cells, and gastrointestinal cancer metastasis involving epithelial cells. In both cases, particular attention will be devoted to systematic changes induced in specific molecular species in response to controlled alterations in disease state. The role of critical proteins in influencing the mechanical response of human red bloods during the intra-erythrocytic development of P. falciparum merozoites has also been assessed quantitatively using specific protein knock-out experiments by recourse to gene inactivation methods. Single-cell mechanical response characterization entails such tools as optical tweezers and mechanical plate stretchers whereas cell motility assays and cell-population biorheology characterization involves microfluidic channels. The experimental studies are accompanied by three-dimensional computational simulations at the continuum and mesoscopic scales of cell deformation. An outcome of such combined experimental and computational biophysical studies is the realization of how chemical factors influence single-cell mechanical response, cytoadherence, the biorheology of a large population of cells through microchannels representative of in vivo conditions, and the onset and progression of disease states.

  7. The Human Microbiome and Surgical Disease

    PubMed Central

    Morowitz, Michael J.; Babrowski, Trissa; Carlisle, Erica M.; Olivas, Andrea; Romanowski, Kathleen S.; Seal, John B.; Liu, Donald C.; Alverdy, John C.

    2015-01-01

    Objective The purpose of this review article is to summarize what is currently known about microbes associated with the human body and to provide examples of how this knowledge impacts the care of surgical patients. Background Pioneering research over the past decade has demonstrated that human beings live in close, constant contact with dynamic communities of microbial organisms. This new reality has wide-ranging implications for the care of surgical patients. Methods and Results Recent advances in the culture-independent study of the human microbiome are reviewed. To illustrate the translational relevance of these studies to surgical disease, we discuss in detail what is known about the role of microbes in the pathogenesis of obesity, gastrointestinal malignancies, Crohn disease, and perioperative complications including surgical site infections and sepsis. The topics of mechanical bowel preparation and perioperative antibiotics are also discussed. Conclusions Heightened understanding of the microbiome in coming years will likely offer opportunities to refine the prevention and treatment of a wide variety of surgical conditions. PMID:21422915

  8. Conditional Lineage Ablation to Model Human Diseases

    NASA Astrophysics Data System (ADS)

    Lee, Paul; Morley, Gregory; Huang, Qian; Fischer, Avi; Seiler, Stephanie; Horner, James W.; Factor, Stephen; Vaidya, Dhananjay; Jalife, Jose; Fishman, Glenn I.

    1998-09-01

    Cell loss contributes to the pathogenesis of many inherited and acquired human diseases. We have developed a system to conditionally ablate cells of any lineage and developmental stage in the mouse by regulated expression of the diphtheria toxin A (DTA) gene by using tetracycline-responsive promoters. As an example of this approach, we targeted expression of DTA to the hearts of adult mice to model structural abnormalities commonly observed in human cardiomyopathies. Induction of DTA expression resulted in cell loss, fibrosis, and chamber dilatation. As in many human cardiomyopathies, transgenic mice developed spontaneous arrhythmias in vivo, and programmed electrical stimulation of isolated-perfused transgenic hearts demonstrated a strikingly high incidence of spontaneous and inducible ventricular tachycardia. Affected mice showed marked perturbations of cardiac gap junction channel expression and localization, including a subset with disorganized epicardial activation patterns as revealed by optical action potential mapping. These studies provide important insights into mechanisms of arrhythmogenesis and suggest that conditional lineage ablation may have wide applicability for studies of disease pathogenesis.

  9. Low acute hematological toxicity during chemotherapy predicts reduced disease control in advanced Hodgkin's disease.

    PubMed

    Brosteanu, O; Hasenclever, D; Loeffler, M; Diehl, V

    2004-03-01

    Chemotherapy-treated patients with advanced Hodgkin's disease (HD) differ considerably in acute hematotoxicity. Hematotoxicity may be indicative of pharmacological and metabolic heterogeneity. We hypothesized that low hematotoxicity might correlate with reduced systemic dose and thus reduced disease control. A total of 266 patients with advanced HD treated with cyclophosphamide, vincristine, procarbazine, prednisone, doxorubicin, bleomycin, vinblastine, and dacarbazine (COPP-ABVD) were analyzed (HD6 trial of the German Hodgkin's Lymphoma Study Group). The reported WHO grade of leukocytopenia was averaged over chemotherapy cycles given and weighted with the reciprocal dose intensity of the corresponding cycle. The low and high toxicity groups were defined in retrospect as having had an averaged WHO grade of leukocytopenia 2.1, respectively. The independent impact of low hematological toxicity on freedom from treatment failure (FFTF) was assessed multivariately adjusting for the international prognostic score for advanced HD. The results were validated in two independent cohorts [181 patients treated with COPP-ABVD (HD9-trial) and 250 patients treated with COPP-ABV-ifosfamide, methotrexate, etoposide, and prednisone (IMEP) (HD6 trial)]. The 5-year FFTF rates were 68% for patients with high toxicity vs 47% for patients with low toxicity [multivariate relative risk (RR) 2.0, 95% confidence interval (CI) 1.4-3.0, p=0.0002]. Patients with low toxicity received significantly higher nominal dose ( p=0.02) and dose intensity ( p<0.0001). This finding was confirmed in both validation cohorts (multivariate RR 2.1, 95% CI 1.2-3.8, p=0.01 and RR 1.5, 95% CI 1.01-2.26, p=0.04, respectively). Patients with low hematotoxicity have significantly higher failure rates despite higher doses and dose intensity. Hematotoxicity is an independent prognostic factor for treatment outcome. This observation suggests a strategy of individualized dosing adapted to hematotoxicity

  10. The Blood Transcriptome of Experimental Melioidosis Reflects Disease Severity and Shows Considerable Similarity with the Human Disease.

    PubMed

    Conejero, Laura; Potempa, Krzysztof; Graham, Christine M; Spink, Natasha; Blankley, Simon; Salguero, Francisco J; Pankla-Sranujit, Rungnapa; Khaenam, Prasong; Banchereau, Jacques F; Pascual, Virginia; Chaussabel, Damien; Lertmemongkolchai, Ganjana; O'Garra, Anne; Bancroft, Gregory J

    2015-10-01

    Melioidosis, a severe human disease caused by the bacterium Burkholderia pseudomallei, has a wide spectrum of clinical manifestations ranging from acute septicemia to chronic localized illness or latent infection. Murine models have been widely used to study the pathogenesis of infection and to evaluate novel therapies or vaccines, but how faithfully they recapitulate the biology of human melioidosis at a molecular level is not known. In this study, mice were intranasally infected with either high or low doses of B. pseudomallei to generate either acute, chronic, or latent infection and host blood and tissue transcriptional profiles were generated. Acute infection was accompanied by a homogeneous signature associated with induction of multiple innate immune response pathways, such as IL-10, TREM1, and IFN signaling, largely found in both blood and tissue. The transcriptional profile in blood reflected the heterogeneity of chronic infection and quantitatively reflected the severity of disease. Genes associated with fibrosis and tissue remodeling, including matrix metalloproteases and collagen, were upregulated in chronically infected mice with severe disease. Transcriptional signatures of both acute and chronic melioidosis revealed upregulation of iNOS in tissue, consistent with the expression of IFN-γ, but also Arginase-1, a functional antagonist of the iNOS pathway, and was confirmed by immunohistochemistry. Comparison of these mouse blood datasets by pathway and modular analysis with the blood transcriptional signature of patients with melioidosis showed that many genes were similarly perturbed, including Arginase-1, IL-10, TREM1, and IFN signaling, revealing the common immune response occurring in both mice and humans. PMID:26311902

  11. The Blood Transcriptome of Experimental Melioidosis Reflects Disease Severity and Shows Considerable Similarity with the Human Disease

    PubMed Central

    Spink, Natasha; Blankley, Simon; Salguero, Francisco J.; Pankla-Sranujit, Rungnapa; Khaenam, Prasong; Banchereau, Jacques F.; Pascual, Virginia; Chaussabel, Damien; Lertmemongkolchai, Ganjana

    2015-01-01

    Melioidosis, a severe human disease caused by the bacterium Burkholderia pseudomallei, has a wide spectrum of clinical manifestations ranging from acute septicaemia to chronic localized illness or latent infection. Murine models have been widely used to study the pathogenesis of infection and to evaluate novel therapies or vaccines, but how faithfully they recapitulate the biology of human melioidosis at a molecular level is not known. Here, mice were intranasally infected with either high or low doses of B. pseudomallei to generate either acute, chronic or latent infection and host blood and tissue transcriptional profiles were generated. Acute infection was accompanied by a homogeneous signature associated with induction of multiple innate immune response pathways, such as IL10, TREM1 and IFN-signaling, largely found in both blood and tissue. The transcriptional profile in blood reflected the heterogeneity of chronic infection and quantitatively reflected the severity of disease. Genes associated with fibrosis and tissue remodelling, including MMPs and collagen, were upregulated in chronically infected mice with severe disease. Transcriptional signatures of both acute and chronic melioidosis revealed upregulation of iNOS in tissue, consistent with the expression of IFN-γ, but also Arginase-1, a functional antagonist of the iNOS pathway, and was confirmed by immunohistochemistry. Comparison of these mouse blood datasets by pathway and modular analysis with the blood transcriptional signature of patients with melioidosis showed that many genes were similarly perturbed, including Arginase-1, IL10, TREM1 and IFN-signaling, revealing the common immune response occurring in both mice and humans. PMID:26311902

  12. Acute Human Cytomegalovirus Infection with Bleeding in Iran

    PubMed Central

    Pourhossein, Behzad; Yaghmaei, Farhad; Esmaeili, Saber; Banafshi, Omid; Afrasiabian, Shahla; Shirzadi, Mohammad Reza; Schleiss, Mark; Mostafavi, Ehsan

    2014-01-01

    In December 2011, a 42-year-old male farmer was admitted to a hospital in Sanandaj (Western Iran) with fever and anemia in order to check whether he suffered from some infectious diseases. During the first 3 days after admission, the patient gradually developed progressive oliguria, fever, abdominal pain in the right upper quadrant, leukocytosis with toxic granulation, petechiae and ecchymosis, oral bleeding, and vomiting. The sonographic findings revealed splenomegaly and an increase in the thickness of the gall bladder wall. In order to manage the patient and taking into consideration the most probable differential diagnoses, diagnostic tests were performed on two blood samples collected from him, and real-time polymerase chain reaction for human cytomegalovirus was positive. PMID:25562049

  13. Human brain disease recreated in mice

    SciTech Connect

    Marx, J.

    1990-12-14

    In the early 1980s, neurologist Stanley Prusiner suggested that scrapie, an apparently infectious degenerative brain disease of sheep, could be transmitted by prions, infectious particles made just of protein - and containing no nucleic acids. But prion research has come a long way since then. In 1985, the cloning of the gene encoding the prion protein proved that it does in fact exist. And the gene turned out to be widely expressed in the brains of higher organisms, a result suggesting that the prion protein has a normal brain function that can somehow be subverted, leading to brain degeneration. Then studies done during the past 2 years suggested that specific mutations in the prion gene might cause two similar human brain diseases, Gerstmann-Straeussler-Scheinker syndrome (GSS) and Creutzfelt-Jakob disease. Now, Prusiner's group at the University of California, San Francisco, has used genetic engineering techniques to recreate GSS by transplanting the mutated prion gene into mice. Not only will the animal model help neurobiologists answer the many remaining questions about prions and how they work, but it may also shed some light on other neurodegenerative diseases as well.

  14. The Microbiota, Chemical Symbiosis, and Human Disease

    PubMed Central

    Redinbo, Matthew R.

    2014-01-01

    Our understanding of mammalian-microbial mutualism has expanded by combing microbial sequencing with evolving molecular and cellular methods, and unique model systems. Here, the recent literature linking the microbiota to diseases of three of the key mammalian mucosal epithelial compartments – nasal, lung and gastrointestinal (GI) tract – is reviewed with a focus on new knowledge about the taxa, species, proteins and chemistry that promote health and impact progression toward disease. The information presented is further organized by specific diseases now associated with the microbiota:, Staphylococcus aureus infection and rhinosinusitis in the nasal-sinus mucosa; cystic fibrosis (CF), chronic obstructive pulmonary disorder (COPD), and asthma in the pulmonary tissues. For the vast and microbially dynamic GI compartment, several disorders are considered, including obesity, atherosclerosis, Crohn’s disease, ulcerative colitis, drug toxicity, and even autism. Our appreciation of the chemical symbiosis ongoing between human systems and the microbiota continues to grow, and suggest new opportunities for modulating this symbiosis using designed interventions. PMID:25305474

  15. Acute electrophysiological responses of bradykinin-stimulated human fibroblasts.

    PubMed

    Estacion, M

    1991-05-01

    1. Acute responses to bradykinin in human dermal fibroblasts were studied at 20-24 degrees C using both the patch-clamp technique to monitor ion currents and Fura-2 fluorescence to monitor [Ca2+]i. 2. During subconfluent culture, human dermal fibroblasts can express a diversity of ion channels as described in the preceding paper. 3. When GTP (1 mM) was included in the pipette solution, two additional ion channel populations were transiently augmented in response to bradykinin stimulation. 4. The first is a component of outwardly rectifying current which reached maximal induction within 10-15 s after bradykinin addition (1 microM) and then decayed back to near baseline over 60 s. 5. Ion substitution experiments combined with tail current analysis indicate that the outward current is carried predominantly by K+. 6. Video imaging of single-cell Fura-2 fluorescence from both intact cells and patch-clamped cells showed temporal correlation of the K+ current modulation and the Ca2+ transients in response to bradykinin stimulation. 7. The calcium ionophore, ionomycin, caused both an increase in intracellular calcium and the augmentation of the outward K+ current. The amount of additional K+ current was correlated with [Ca2+]i levels and could be elicited even without the presence of GTP in the pipette. 8. Apamin, a blocker of Ca(2+)-activated K+ channels, inhibited (at 1 microM) the ionomycin-induced modulation of K+ current. 9. In addition, an inward current was transiently induced in response to bradykinin. This current was strictly dependent on the presence of GTP in the pipette solution. This current showed little voltage dependence, as evidenced by a linear current vs. voltage relation, and a reversal potential near but measurably more positive than 0 mV. 10. This current could be decoupled from the Ca2+ transient and be irreversibly induced by including GTP gamma S (100 microM) in the pipette solution. 11. Ion substitution experiments show that this is a non

  16. Human Pluripotent Stem Cells for Modelling Human Liver Diseases and Cell Therapy

    PubMed Central

    Dianat, Noushin; Steichen, Clara; Vallier, Ludovic; Weber, Anne; Dubart-Kupperschmitt, Anne

    2013-01-01

    The liver is affected by many types of diseases, including metabolic disorders and acute liver failure. Orthotopic liver transplantation (OLT) is currently the only effective treatment for life-threatening liver diseases but transplantation of allogeneic hepatocytes has now become an alternative as it is less invasive than OLT and can be performed repeatedly. However, this approach is hampered by the shortage of organ donors, and the problems related to the isolation of high quality adult hepatocytes, their cryopreservation and their absence of proliferation in culture. Liver is also a key organ to assess the pharmacokinetics and toxicology of xenobiotics and for drug discovery, but appropriate cell culture systems are lacking. All these problems have highlighted the need to explore other sources of cells such as stem cells that could be isolated, expanded to yield sufficiently large populations and then induced to differentiate into functional hepatocytes. The presence of a niche of “facultative” progenitor and stem cells in the normal liver has recently been confirmed but they display no telomerase activity. The recent discovery that human induced pluripotent stem cells can be generated from somatic cells has renewed hopes for regenerative medicine and in vitro disease modelling, as these cells are easily accessible. We review here the present progresses, limits and challenges for the generation of functional hepatocytes from human pluripotent stem cells in view of their potential use in regenerative medicine and drug discovery. PMID:23444872

  17. Human Rabies with Initial Manifestations that Mimic Acute Brachial Neuritis and Guillain-Barré Syndrome

    PubMed Central

    Mader, Edward C.; Maury, Joaquin S.; Santana-Gould, Lenay; Craver, Randall D.; El-Abassi, Rima; Segura-Palacios, Enrique; Sumner, Austin J.

    2012-01-01

    Introduction Human rabies can be overlooked in places where this disease is now rare. Its diagnosis is further confused by a negative history of exposure (cryptogenic rabies), by a Guillain-Barré syndrome (GBS) type of presentation, or by symptoms indicating another diagnosis, eg, acute brachial neuritis (ABN). Case presentation A 19-year-old Mexican, with no past health problems, presented with a two-day history of left shoulder, arm, and chest pain. He arrived in Louisiana from Mexico five days prior to admission. Of particular importance is the absence of a history of rabies exposure and immunization. On admission, the patient had quadriparesis, areflexia, and elevated protein in the cerebrospinal fluid, prompting a diagnosis of GBS. However, emerging neurological deficits pointed towards acute encephalitis. Rabies was suspected on hospital day 11 after common causes of encephalitis (eg, arboviruses) have been excluded. The patient tested positive for rabies IgM and IgG. He died 17 days after admission. Negri bodies were detected in the patient’s brain and rabies virus antigen typing identified the vampire bat as the source of infection. Conclusion Rabies should be suspected in every patient with a rapidly evolving GBS-like illness—even if there is no history of exposure and no evidence of encephalitis on presentation. The patient’s ABN-like symptoms may be equivalent to the pain experienced by rabies victims near the inoculation site. PMID:22577299

  18. Genetics of CD33 in Alzheimer's disease and acute myeloid leukemia

    PubMed Central

    Malik, Manasi; Chiles, Joe; Xi, Hualin S.; Medway, Christopher; Simpson, James; Potluri, Shobha; Howard, Dianna; Liang, Ying; Paumi, Christian M.; Mukherjee, Shubhabrata; Crane, Paul; Younkin, Steven; Fardo, David W.; Estus, Steven

    2015-01-01

    The CD33 single-nucleotide polymorphism (SNP) rs3865444 has been associated with the risk of Alzheimer's disease (AD). Rs3865444 is in linkage disequilibrium with rs12459419 which has been associated with efficacy of an acute myeloid leukemia (AML) chemotherapeutic agent based on a CD33 antibody. We seek to evaluate the extent to which CD33 genetics in AD and AML can inform one another and advance human disease therapy. We have previously shown that these SNPs are associated with skipping of CD33 exon 2 in brain mRNA. Here, we report that these CD33 SNPs are associated with exon 2 skipping in leukocytes from AML patients and with a novel CD33 splice variant that retains CD33 intron 1. Each copy of the minor rs12459419T allele decreases prototypic full-length CD33 expression by ∼25% and decreases the AD odds ratio by ∼0.10. These results suggest that CD33 antagonists may be useful in reducing AD risk. CD33 inhibitors may include humanized CD33 antibodies such as lintuzumab which was safe but ineffective in AML clinical trials. Here, we report that lintuzumab downregulates cell-surface CD33 by 80% in phorbol-ester differentiated U937 cells, at concentrations as low as 10 ng/ml. Overall, we propose a model wherein a modest effect on RNA splicing is sufficient to mediate the CD33 association with AD risk and suggest the potential for an anti-CD33 antibody as an AD-relevant pharmacologic agent. PMID:25762156

  19. Acute carbon monoxide poisoning alters hemorheological parameters in human.

    PubMed

    Ozturk, Baris; Arihan, Okan; Coskun, Figen; Dikmenoglu-Falkmarken, Neslihan H

    2016-01-01

    Acute carbon monoxide (CO) poisoning seriously hinders oxygen delivery to tissues. This harmful effect of CO may be aggravated by accompanying changes in the viscosity of blood. We had previously reported increased plasma viscosity in people chronically exposed to CO. This study was planned to test our hypothesis that acute CO poisoning increases blood viscosity. For this purpose four main parameters contributing to blood viscosity - hematocrit, erythrocyte deformability, erythrocyte aggregation and plasma viscosity - were determined in patients with acute CO poisoning and compared with healthy controls. Plasma viscosity and erythrocyte aggregation tendency were lower in the CO group (p <  0.05). Erythrocyte deformability was also lower in CO group (p <  0.05). Our results indicate that acute CO poisoning has diverse effects on hemorheological parameters such as attenuating hematocrit value, plasma viscosity, erythrocyte aggregation tendency and erythrocyte deformability. PMID:25536918

  20. Copy number variants, aneuploidies, and human disease.

    PubMed

    Martin, Christa Lese; Kirkpatrick, Brianne E; Ledbetter, David H

    2015-06-01

    In the perinatal setting, chromosome imbalances cause a range of clinically significant disorders and increase the risk for other particular phenotypes. As technologies have improved to detect increasingly smaller deletions and duplications, collectively referred to as copy number variants (CNVs), clinicians are learning the significant role that these types of genomic variants play in human disease and their high frequency in ∼ 1% of all pregnancies. This article highlights key aspects of CNV detection and interpretation used during the course of clinical care in the prenatal and neonatal periods. Early diagnosis and accurate interpretation are important for targeted clinical management. PMID:26042902

  1. Gene Conversion in Human Genetic Disease

    PubMed Central

    Chen, Jian-Min; Férec, Claude; Cooper, David N.

    2010-01-01

    Gene conversion is a specific type of homologous recombination that involves the unidirectional transfer of genetic material from a ‘donor’ sequence to a highly homologous ‘acceptor’. We have recently reviewed the molecular mechanisms underlying gene conversion, explored the key part that this process has played in fashioning extant human genes, and performed a meta-analysis of gene-conversion events known to have caused human genetic disease. Here we shall briefly summarize some of the latest developments in the study of pathogenic gene conversion events, including (i) the emerging idea of minimal efficient sequence homology (MESH) for homologous recombination, (ii) the local DNA sequence features that appear to predispose to gene conversion, (iii) a mechanistic comparison of gene conversion and transient hypermutability, and (iv) recently reported examples of pathogenic gene conversion events. PMID:24710102

  2. Tacrolimus and Methotrexate With or Without Sirolimus in Preventing Graft-Versus-Host Disease in Young Patients Undergoing Donor Stem Cell Transplant for Acute Lymphoblastic Leukemia in Complete Remission

    ClinicalTrials.gov

    2014-01-23

    B-cell Childhood Acute Lymphoblastic Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Graft Versus Host Disease; L1 Childhood Acute Lymphoblastic Leukemia; L2 Childhood Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

  3. The Role of Echocardiography in Coronary Artery Disease and Acute Myocardial Infarction

    PubMed Central

    Esmaeilzadeh, Maryam; Parsaee, Mozhgan; Maleki, Majid

    2013-01-01

    Echocardiography is a non-invasive diagnostic technique which provides information regarding cardiac function and hemodynamics. It is the most frequently used cardiovascular diagnostic test after electrocardiography and chest X-ray. However, in a patient with acute chest pain, Transthoracic Echocardiography is essential both for diagnosing acute coronary syndrome, zeroing on the evaluation of ventricular function and the presence of regional wall motion abnormalities, and for ruling out other etiologies of acute chest pain or dyspnea, including aortic dissection and pericardial effusion. Echocardiography is a versatile imaging modality for the management of patients with chest pain and assessment of left ventricular systolic function, diastolic function, and even myocardial and coronary perfusion and is, therefore, useful in the diagnosis and triage of patients with acute chest pain or dyspnea. This review has focused on the current applications of echocardiography in patients with coronary artery disease and myocardial infarction. PMID:23646042

  4. Acute myocardial infarction following scorpion sting in a case with obstructive coronary artery disease.

    PubMed

    Patra, Soumya; Satish, K; Singla, Vivek; Ravindranath, K S

    2013-01-01

    The occurrence of an acute myocardial infarction (MI) following a scorpion sting has been very rarely reported in the previous literature. Possible pathogenetic mechanisms include severe hypotension due to hypovolaemic shock and coronary spasm with subsequent thrombosis of coronary vessels developed after the release of vasoactive, inflammatory and thrombogenic substances contained in the scorpion venom. All of the previously reported cases had normal coronary angiogram. We report a case of a 65-year-old woman who presented with severe scorpion sting and was treated with prazosin. But a few hours later, she developed acute anterior wall MI. Coronary angiogram revealed the presence of significant stenosis in coronary arteries. As acute MI owing to significant coronary artery disease can be evident after severe scorpion envenomation, so every case of acute coronary syndrome following scorpion sting needs early diagnosis, thorough cardiovascular evaluation and appropriate treatment. PMID:23715842

  5. A challenging diagnosis for potential fatal diseases: recommendations for diagnosing acute porphyrias.

    PubMed

    Ventura, Paolo; Cappellini, Maria Domenica; Biolcati, Gianfranco; Guida, Claudio Carmine; Rocchi, Emilio

    2014-07-01

    Acute porphyrias are a heterogeneous group of metabolic disorders resulting from a variable catalytic defect of four enzymes out of the eight involved in the haem biosynthesis pathway; they are rare and mostly inherited diseases, but in some circumstances, the metabolic disturbance may be acquired. Many different environmental factors or pathological conditions (such as drugs, calorie restriction, hormones, infections, or alcohol abuse) often play a key role in triggering the clinical exacerbation (acute porphyric attack) of these diseases that may often mimic many other more common acute medical and neuropsychiatric conditions and whose delayed diagnosis and treatment may be fatal. In order to obtain an accurate diagnosis of acute porphyria, the knowledge and the use of appropriate diagnostic tools are mandatory, even in order to provide as soon as possible the more effective treatment and to prevent the use of potentially unsafe drugs, which can severely precipitate these diseases, especially in the presence of life-threatening symptoms. In this paper, we provide some recommendations for the diagnostic steps of acute porphyrias by reviewing literature and referring to clinical experience of the board members of the Gruppo Italiano Porfiria (GrIP). PMID:24809927

  6. Antimicrobial peptides in human skin disease

    PubMed Central

    Kenshi, Yamasaki; Richard, L. Gallo

    2009-01-01

    The skin continuously encounters microbial pathogens. To defend against this, cells of the epidermis and dermis have evolved several innate strategies to prevent infection. Antimicrobial peptides are one of the primary mechanisms used by the skin in the early stages of immune defense. In general, antimicrobial peptides have broad antibacterial activity against gram-positive and negative bacteria and also show antifungal and antiviral activity. The antimicrobial activity of most peptides occurs as a result of unique structural characteristics that enable them to disrupt the microbial membrane while leaving human cell membranes intact. However, antimicrobial peptides also act on host cells to stimulate cytokine production, cell migration, proliferation, maturation, and extracellular matrix synthesis. The production by human skin of antimicrobial peptides such as defensins and cathelicidins occurs constitutively but also greatly increases after infection, inflammation or injury. Some skin diseases show altered expression of antimicrobial peptides, partially explaining the pathophysiology of these diseases. Thus, current research suggests that understanding how antimicrobial peptides modify susceptibility to microbes, influence skin inflammation, and modify wound healing, provides greater insight into the pathophysiology of skin disorders and offers new therapeutic opportunities. PMID:18086583

  7. Endovascular Interventions for Acute and Chronic Lower Extremity Deep Venous Disease: State of the Art

    PubMed Central

    Sista, Akhilesh K.; Vedantham, Suresh; Kaufman, John A.

    2015-01-01

    The societal and individual burden caused by acute and chronic lower extremity venous disease is considerable. In the past several decades, minimally invasive endovascular interventions have been developed to reduce thrombus burden in the setting of acute deep venous thrombosis to prevent both short- and long-term morbidity and to recanalize chronically occluded or stenosed postthrombotic or nonthrombotic veins in symptomatic patients. This state-of-the-art review provides an overview of the techniques and challenges, rationale, patient selection criteria, complications, postinterventional care, and outcomes data for endovascular intervention in the setting of acute and chronic lower extremity deep venous disease. Online supplemental material is available for this article. © RSNA, 2015 PMID:26101920

  8. Recent advances in the treatment of colonic diverticular disease and prevention of acute diverticulitis.

    PubMed

    Elisei, Walter; Tursi, Antonio

    2016-01-01

    The incidence of diverticulosis and diverticular disease of the colon is increasing worldwide. Although the majority of patients remains asymptomatic long-life, the prevalence of diverticular disease of the colon, including acute diverticulitis, is substantial and is becoming a significant burden on National Health Systems in terms of direct and indirect costs. Focus is now being drawn on identifying the correct therapeutic approach by testing various treatments. Fiber, non-absorbable antibiotics and probiotics seem to be effective in treating symptomatic and uncomplicated patients, and 5-aminosalicylic acid might help prevent acute diverticulitis. Unfortunately, robust evidence on the effectiveness of a medical strategy to prevent acute diverticulitis recurrence is still lacking. We herein provide a concise review on the effectiveness and future perspectives of these treatments. PMID:26752946

  9. Acute myocardial infarction after heart irradiation in young patients with Hodgkin's disease

    SciTech Connect

    Joensuu, H.

    1989-02-01

    Forty-seven patients younger than 40 years at the time of the diagnosis, and irradiated to the mediastinum for Hodgkin's disease at Turku University Central Hospital from 1977 to 1982, were regularly followed for 56 to 127 months after therapy. Two patients developed an acute myocardial infarction ten and 50 months after cardiac irradiation at the age of only 28 and 24 years, respectively. None of the patients died from lymphoma within five years from the diagnosis, but one of the infarctions was eventually fatal. Since acute myocardial infarction is rare in this age group, the result suggests strongly that prior cardiac irradiation is a risk factor for acute myocardial infarction. The possibility of radiation-induced myocardial infarction should be taken into account both in treatment planning and follow-up of patients with Hodgkin's disease.

  10. Recent advances in the treatment of colonic diverticular disease and prevention of acute diverticulitis

    PubMed Central

    Elisei, Walter; Tursi, Antonio

    2016-01-01

    The incidence of diverticulosis and diverticular disease of the colon is increasing worldwide. Although the majority of patients remains asymptomatic long-life, the prevalence of diverticular disease of the colon, including acute diverticulitis, is substantial and is becoming a significant burden on National Health Systems in terms of direct and indirect costs. Focus is now being drawn on identifying the correct therapeutic approach by testing various treatments. Fiber, non-absorbable antibiotics and probiotics seem to be effective in treating symptomatic and uncomplicated patients, and 5-aminosalicylic acid might help prevent acute diverticulitis. Unfortunately, robust evidence on the effectiveness of a medical strategy to prevent acute diverticulitis recurrence is still lacking. We herein provide a concise review on the effectiveness and future perspectives of these treatments. PMID:26752946

  11. Chronic kidney disease in human immunodeficiency virus infection.

    PubMed

    Fabian, J; Katz, I; Gerntholtz, T; Goetsch, S; Naicker, S

    2007-06-01

    The number of people living with human immunodeficiency virus (HIV) worldwide was estimated to be 39.5 million in 2006, 2.6 million more than in 2004. The manifestations of HIV infection in the kidney are multiple and varied, highlighting the complexity of the disease process. There is a wide spectrum of renal disease that occurs in the course of HIV infection. Biopsy studies reveal varying frequencies of histological patterns. HIV-associated nephropathy (HIVAN) is most common. A biopsy study at Chris Baragwanath Hospital in Soweto, South Africa showed that HIVAN was present in 27% and immune complex disease in 21%. Han et al. studied HIV-positive patients in Durban, South Africa and screened for proteinuria, including microalbuminuria. They found persistent proteinuria in 6%; HIVAN in 21/30 (72.4%) and the prevalence of HIVAN in patients with persistent microalbuminuria was 85.7%. Studies in black patients have shown a higher prevalence of both severe glomerular lesions (focal glomerulosclerosis) and nephrotic range proteinuria with renal dysfunction in the presence of normo-hypotension. There have been no prospective randomised controlled studies with any form of therapy for HIVAN to date. Therapy of HIVAN has included corticosteroids, cyclosporine and antiretroviral therapy (ART). ART appears to be a logical choice in the management of HIV-associated renal disease. Regimens containing protease inhibitors have been shown to be associated with significant slowing of the decline in creatinine clearance. Both peritoneal dialysis and haemodialysis are appropriate treatment modalities for HIV-infected patients with end stage renal disease. The choice of dialysis modality between haemodialysis and peritoneal dialysis is not a factor in predicting survival, if patients are stable on ART. Preliminary short-term data in case reports and small cohorts of liver, kidney, and heart transplant recipients suggest that patient survival rates may be similar to those in HIV

  12. Lymphocyte Activation during Acute Simian/Human Immunodeficiency Virus SHIV89.6PD Infection in Macaques†

    PubMed Central

    Wallace, Marianne; Waterman, Paul M.; Mitchen, Jacque L.; Djavani, Mahmoud; Brown, Charles; Trivedi, Parul; Horejsh, Douglas; Dykhuizen, Marta; Kitabwalla, Moiz; Pauza, C. David

    1999-01-01

    Host-virus interactions control disease progression in human immunodeficiency virus-infected human beings and in nonhuman primates infected with simian or simian/human immunodeficiency viruses (SHIV). These interactions evolve rapidly during acute infection and are key to the mechanisms of viral persistence and AIDS. SHIV89.6PD infection in rhesus macaques can deplete CD4+ T cells from the peripheral blood, spleen, and lymph nodes within 2 weeks after exposure and is a model for virulent, acute infection. Lymphocytes isolated from blood and tissues during the interval of acute SHIV89.6PD infection have lost the capacity to proliferate in response to phytohemagglutinin (PHA). T-cell unresponsiveness to mitogen occurred within 1 week after mucosal inoculation yet prior to massive CD4+ T-cell depletion and extensive virus dissemination. The lack of mitogen response was due to apoptosis in vitro, and increased activation marker expression on circulating T cells in vivo coincided with the appearance of PHA-induced apoptosis in vitro. Inappropriately high immune stimulation associated with rapid loss of mature CD4+ T cells suggested that activation-induced cell death is a mechanism for helper T-cell depletion in the brief period before widespread virus dissemination. Elevated levels of lymphocyte activation likely enhance SHIV89.6PD replication, thus increasing the loss of CD4+ T cells and diminishing the levels of virus-specific immunity that remain after acute infection. The level of surviving immunity may dictate the capacity to control virus replication and disease progression. We describe this level of immune competence as the host set point to show its pivotal role in AIDS pathogenesis. PMID:10559340

  13. HIV and the spectrum of human disease.

    PubMed

    Lucas, Sebastian; Nelson, Ann Marie

    2015-01-01

    Infection with the human immunodeficiency virus (HIV) causes systemic T cell destruction and reduced cell-mediated immunity that leads to a wide range of opportunistic infections and cancers. Second, it directly damages many tissues - gut, brain, lung - through mononuclear cell infection and activation. Third, through immune activation and effects on endothelia, it can cause more subtle systemic organ damage, such as chronic cardiovascular, hepatic, pulmonary and central nervous system disease. Antiretroviral treatment has enabled HIV-infected persons to live with chronic infection, although with some side-effects and mortality, including reactions due to the immune reconstitution inflammatory syndrome (IRIS). As cohorts of infected people get older, age-related diseases will combine with chronic HIV infection to produce disabilities whose scale is not yet understood. HIV is detectable in tissues by immunohistochemistry when infection loads are high, such as at first presentation. Pathologists should proactively consider HIV disease in routine diagnostic work, so as to identify more HIV-infected patients and enable their optimal management. PMID:25251832

  14. [Sweet syndrome (acute febrile neutrophilic dermatosis) and erythema nodosum in Crohn disease].

    PubMed

    Schlegel Gómez, R; Kiesewetter, F; von den Driesch, P; Hornstein, O P

    1990-07-01

    We report on 2 patients who developed an acute febrile neutrophilic dermatosis (Sweet's syndrome) and erythema nodosum in association with Crohn's disease. The first patient showed symmetrical painful erythemas on her cheeks after hemicolectomy. Additionally, red painful nodules appeared on her lower legs. The second patient disclosed typical Sweet's syndrome-like lesions with pustules and plaques on her face, scalp and extremities after activation of Crohn's disease. Simultaneously, erythema nodosum-like lesions appeared on her lower legs. PMID:2144848

  15. [Acute respiratory distress syndrome caused by tropical eosinophilic lung disease: a case in Gabon].

    PubMed

    Chani, M; Iken, M; Eljahiri, Y; Nzenze, J R; Mion, G

    2011-04-01

    The purpose of this report is to describe the case of a 28-year-old woman in whom acute respiratory distress syndrome (ARDS) following cholecystectomy led to the discovery of eosinophilic lung disease. Outcome was favorable after oxygenotherapy and medical treatment using ivermectin and corticosteroids. The case shows that hypereosinophilic syndrome can be the underlying cause of ARDS. PMID:21695880

  16. Iron metabolism and oxidative profile of dogs naturally infected by Ehrlichia canis: Acute and subclinical disease.

    PubMed

    Bottari, Nathieli B; Crivellenti, Leandro Z; Borin-Crivellenti, Sofia; Oliveira, Jéssica R; Coelho, Stefanie B; Contin, Catarina M; Tatsch, Etiane; Moresco, Rafael N; Santana, Aureo E; Tonin, Alexandre A; Tinucci-Costa, Mirela; Da Silva, Aleksandro S

    2016-03-01

    The aim of this study was to evaluate the oxidant profile and iron metabolism in serum of dogs infected by Ehrlichia canis. Banked sera samples of dogs were divided into two groups: negative control (n = 17) and infected by E. canis on acute (n = 24), and subclinical (n = 18) phases of the disease. The eritrogram, leucogram, and platelet counts were evaluate as well as iron, ferritin, and transferrin levels, latent iron binding capacity (LIBC), and transferrin saturation index (TSI) concentration. In addition, the advanced oxidation protein products (AOPP) and ferric reducing ability of plasma (FRAP) in sera were also analyzed. Blood samples were examined for the presence of E. canis by PCR techniques. History and clinical signals were recorded for each dog. During the acute phase of the disease, infected animals showed thrombocytopenia and anemia when compared to healthy animals (P < 0.05) as a consequence of lower iron levels. Ferritin and transferrin levels were higher in both phases (acute and subclinical) of the disease. The AOPP and FRAP levels increased in infected animals on the acute phase; however, the opposite occurred in the subclinical phase. We concluded that dogs naturally infected by E. canis showed changes in the iron metabolism and developed an oxidant status in consequence of disease pathophysiology. PMID:26724737

  17. Experimental Chagas' disease in rhesus monkeys. I. Clinical, parasitological, hematological and anatomo-pathological studies in the acute and indeterminate phase of the disease.

    PubMed

    Bonecini-Almeida, M da G; Galvão-Castro, B; Pessoa, M H; Pirmez, C; Laranja, F

    1990-01-01

    Rhesus monkeys (Macaca mulatta) were infected subcutaneously with 1.0 x 10(4) to 1.5 x 10(4) metacyclic trypomastigotes of Trypanosoma cruzi (Colombian strain). Parasitological and immunological parameters were evaluated in these animals for periods of 1 month to over 3 years. A chagoma was observed between the 3rd and the 13th day after infection (a.i.) and patent parasitaemia between the 13th and 59th day a.i.. Thereafter, parasites were demonstrated only by haemoculture and/or xenodiagnosis. Circulating specific IgM and IgG antibodies were observed as early as in the 2nd week a.i. IgG levels persisted until the end of the experiment, but IgM antibodies were detectable nine months a.i. Haematological alterations comprised leucocytosis and lymphocytosis. Electrocardiographic alterations were minor and transient, similar to those observed in non-lethal human acute Chagas' myocarditis. Myocarditis and myositis, characterized by multiple foci of lympho-histiocyte inflammatory infiltrate, were present in monkeys sacrificed on the 41st, 70th and 76th day but not in the animal sacrificed 3 years and 3 months a. i.. The results suggest that Chagas' disease in rhesus monkeys reproduces the acute and indeterminate phases of human Chagas' disease. PMID:2128360

  18. Evolutionary history of human disease genes reveals phenotypic connections and comorbidity among genetic diseases

    NASA Astrophysics Data System (ADS)

    Park, Solip; Yang, Jae-Seong; Kim, Jinho; Shin, Young-Eun; Hwang, Jihye; Park, Juyong; Jang, Sung Key; Kim, Sanguk

    2012-10-01

    The extent to which evolutionary changes have impacted the phenotypic relationships among human diseases remains unclear. In this work, we report that phenotypically similar diseases are connected by the evolutionary constraints on human disease genes. Human disease groups can be classified into slowly or rapidly evolving classes, where the diseases in the slowly evolving class are enriched with morphological phenotypes and those in the rapidly evolving class are enriched with physiological phenotypes. Our findings establish a clear evolutionary connection between disease classes and disease phenotypes for the first time. Furthermore, the high comorbidity found between diseases connected by similar evolutionary constraints enables us to improve the predictability of the relative risk of human diseases. We find the evolutionary constraints on disease genes are a new layer of molecular connection in the network-based exploration of human diseases.

  19. Significance of Cerebral Blood Flow Analysis in the Acute Stage after Revascularization Surgery for Moyamoya Disease

    PubMed Central

    FUJIMURA, Miki; TOMINAGA, Teiji

    2015-01-01

    Moyamoya disease is a chronic, occlusive cerebrovascular disease with unknown etiology characterized by steno-occlusive changes at the terminal portion of the internal carotid artery, either bilaterally or unilaterally, and an abnormal vascular network at the base of the brain. Surgical revascularization such as extracranial-intracranial (EC-IC) bypass is the preferred procedure for moyamoya disease. Despite the favorable long-term outcome, cerebral infarction and hyperperfusion syndrome are potential complications of this procedure, which can lead to neurological deterioration in the acute stage. In light of the similar clinical presentations between perioperative ischemia and hyperperfusion, it is essential to attempt a prompt cerebral blood flow (CBF) measurement in the acute stage after EC-IC bypass for moyamoya disease to differentiate these distinct pathologies, because the management of cerebral ischemia and hyperperfusion is contradictory to each other. Routine CBF analysis by single-photon emission computed tomography and/or magnetic resonance imaging not only facilitated a safer perioperative management but also provided important information about dynamic pathology of the hemodynamic conversion in the acute stage after revascularization surgery for moyamoya disease. We represent the current status of CBF analysis during the perioperative period of revascularization surgery for moyamoya disease, and sought to discuss its significance and efficacy to avoid surgical complications. PMID:26369873

  20. Soluble DNAM-1, as a Predictive Biomarker for Acute Graft-Versus-Host Disease.

    PubMed

    Kanaya, Minoru; Shibuya, Kazuko; Hirochika, Rei; Kanemoto, Miyoko; Ohashi, Kazuteru; Okada, Masafumi; Wagatsuma, Yukiko; Cho, Yukiko; Kojima, Hiroshi; Teshima, Takanori; Imamura, Masahiro; Sakamaki, Hisashi; Shibuya, Akira

    2016-01-01

    Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Because diagnosis of aGVHD is exclusively based on clinical symptoms and pathological findings, reliable and noninvasive laboratory tests for accurate diagnosis are required. An activating immunoreceptor, DNAM-1 (CD226), is expressed on T cells and natural killer cells and is involved in the development of aGVHD. Here, we identified a soluble form of DNAM-1 (sDNAM-1) in human sera. In retrospective univariate and multivariate analyses of allo-HSCT patients (n = 71) at a single center, cumulative incidences of all grade (grade I-IV) and sgrade II-IV aGVHD in patients with high maximal serum levels of sDNAM-1 (≥30 pM) in the 7 days before allo-HSCT were significantly higher than those in patients with low maximal serum levels of sDNAM-1 (<30 pM) in the same period. However, sDNAM-1 was not associated with other known allo-HSCT complications. Our data suggest that sDNAM-1 is potentially a unique candidate as a predictive biomarker for the development of aGVHD. PMID:27257974

  1. Soluble DNAM-1, as a Predictive Biomarker for Acute Graft-Versus-Host Disease

    PubMed Central

    Kanaya, Minoru; Shibuya, Kazuko; Hirochika, Rei; Kanemoto, Miyoko; Ohashi, Kazuteru; Okada, Masafumi; Wagatsuma, Yukiko; Cho, Yukiko; Kojima, Hiroshi; Teshima, Takanori; Imamura, Masahiro; Sakamaki, Hisashi; Shibuya, Akira

    2016-01-01

    Acute graft-versus-host disease (aGVHD) is a major complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT). Because diagnosis of aGVHD is exclusively based on clinical symptoms and pathological findings, reliable and noninvasive laboratory tests for accurate diagnosis are required. An activating immunoreceptor, DNAM-1 (CD226), is expressed on T cells and natural killer cells and is involved in the development of aGVHD. Here, we identified a soluble form of DNAM-1 (sDNAM-1) in human sera. In retrospective univariate and multivariate analyses of allo-HSCT patients (n = 71) at a single center, cumulative incidences of all grade (grade I–IV) and sgrade II–IV aGVHD in patients with high maximal serum levels of sDNAM-1 (≥30 pM) in the 7 days before allo-HSCT were significantly higher than those in patients with low maximal serum levels of sDNAM-1 (<30 pM) in the same period. However, sDNAM-1 was not associated with other known allo-HSCT complications. Our data suggest that sDNAM-1 is potentially a unique candidate as a predictive biomarker for the development of aGVHD. PMID:27257974

  2. Telomere length in human liver diseases.

    PubMed

    Urabe, Y; Nouso, K; Higashi, T; Nakatsukasa, H; Hino, N; Ashida, K; Kinugasa, N; Yoshida, K; Uematsu, S; Tsuji, T

    1996-10-01

    To determine the role of telomere-mediated gene stability in hepatocarcinogenesis, we examined the telomere length of human liver with or without chronic liver diseases and hepatocellular carcinomas (HCC). The mean telomere restriction fragment (TRF) length of normal liver (n = 13), chronic hepatitis (n = 11), liver cirrhosis (n = 24) and HCC (n = 24) was 7.8 +/- 0.2, 7.1 +/- 0.3, 6.4 +/- 0.2 and 5.2 +/- 0.2 kb, respectively (mean +/- standard error). TRF length decreased with a progression of chronic liver diseases and that in HCC was significantly shorter than that in other chronic liver diseases (p < 0.05). The ratios of TRF length of HCC to that of corresponding surrounding liver of well differentiated (n = 7), moderately differentiated (n = 10) and poorly differentiated (n = 4) HCCs were 0.83 +/- 0.06, 0.75 +/- 0.05 and 0.98 +/- 0.09, respectively. The ratio of poorly differentiated HCC was significantly higher than that of moderately differentiated HCC (p < 0.05). A comparison between the size and telomere length ratio of moderately differentiated HCCs revealed a decrease of the ratio with size until it reached 50 mm in diameter. In contrast, the ratio increased as the size enlarged over 50 mm. These findings suggest that the gene stability of the liver cells mediated by the telomere is reduced as chronic liver disease progresses and that telomerase is activated in poorly differentiated HCC and moderately differentiated HCC over 50 mm in diameter. PMID:8938628

  3. Human thermal bioclimatic conditions associated with acute cardiovascular syndromes in Crete Island, Greece

    NASA Astrophysics Data System (ADS)

    Bleta, Anastasia G.; Nastos, Panagiotis T.

    2013-04-01

    The aim of this study is to quantify the association between bioclimatic conditions and daily counts of admissions for non-fatal acute cardiovascular (acute coronary syndrome, arrhythmia, decompensation of heart failure) syndromes (ACS) registered by the two main hospitals in Heraklion, Crete Island, during a five-year period 2008-2012. The bioclimatic conditions analyzed are based on human thermal bioclimatic indices such as the Physiological Equivalent Temperature (PET) and the Universal Thermal Climate Index (UTCI). Mean daily meteorological parameters, such as air temperature, relative humidity, wind speed and cloudiness, were acquired from the meteorological station of Heraklion (Hellenic National Meteorological Service). These parameters were used as input variables in modeling the aforementioned thermal indices, in order to interpret the grade of the thermo-physiological stress. The PET and UTCI analysis was performed by the use of the radiation and bioclimate model, "RayMan", which is well-suited to calculate radiation fluxes and human biometeorological indices. Generalized linear models (GLM) were applied to time series of daily numbers of outpatients with ACS against bioclimatic variations, after controlling for possible confounders and adjustment for season and trends. The interpretation of the results of this analysis suggests a significant association between cold weather and increased coronary heart disease incidence, especially in the elderly and males. Additionally, heat stress plays an important role in the configuration of daily ACS outpatients, even in temperate climate, as that in Crete Island. In this point it is worth mentioning that Crete Island is frequently affected by Saharan outbreaks, which are associated in many cases with miscellaneous phenomena, such as Föhn winds - hot and dry winds - causing extreme bioclimatic conditions (strong heat stress). Taking into consideration the projected increased ambient temperature in the future, ACS

  4. MicroRNAs in Human Diseases: From Autoimmune Diseases to Skin, Psychiatric and Neurodegenerative Diseases

    PubMed Central

    2011-01-01

    MicroRNAs (miRNAs) are small noncoding RNA molecules that negatively regulate gene expression via degradation or translational repression of their target messenger RNAs (mRNAs). Recent studies have clearly demonstrated that miRNAs play critical roles in several biologic processes, including cell cycle, differentiation, cell development, cell growth, and apoptosis and that miRNAs are highly expressed in regulatory T (Treg) cells and a wide range of miRNAs are involved in the regulation of immunity and in the prevention of autoimmunity. It has been increasingly reported that miRNAs are associated with various human diseases like autoimmune disease, skin disease, neurological disease and psychiatric disease. Recently, the identification of mi- RNAs in skin has added a new dimension in the regulatory network and attracted significant interest in this novel layer of gene regulation. Although miRNA research in the field of dermatology is still relatively new, miRNAs have been the subject of much dermatological interest in skin morphogenesis and in regulating angiogenesis. In addition, miRNAs are moving rapidly onto center stage as key regulators of neuronal development and function in addition to important contributions to neurodegenerative disorder. Moreover, there is now compelling evidence that dysregulation of miRNA networks is implicated in the development and onset of human neruodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease, Tourette's syndrome, Down syndrome, depression and schizophrenia. In this review, I briefly summarize the current studies about the roles of miRNAs in various autoimmune diseases, skin diseases, psychoneurological disorders and mental stress. PMID:22194706

  5. COMPARING BEHAVIORAL DOSE-EFFECT CURVES FOR HUMANS AND LABORATORY ANIMALS ACUTELY EXPOSED TO TOLUENE.

    EPA Science Inventory

    The utility of laboratory animal data in toxicology depends upon the ability to generalize the results quantitatively to humans. To compare the acute behavioral effects of inhaled toluene in humans to those in animals, dose-effect curves were fitted by meta-analysis of published...

  6. Transcriptome Analysis of Human Diabetic Kidney Disease

    PubMed Central

    Woroniecka, Karolina I.; Park, Ae Seo Deok; Mohtat, Davoud; Thomas, David B.; Pullman, James M.; Susztak, Katalin

    2011-01-01

    OBJECTIVE Diabetic kidney disease (DKD) is the single leading cause of kidney failure in the U.S., for which a cure has not yet been found. The aim of our study was to provide an unbiased catalog of gene-expression changes in human diabetic kidney biopsy samples. RESEARCH DESIGN AND METHODS Affymetrix expression arrays were used to identify differentially regulated transcripts in 44 microdissected human kidney samples. DKD samples were significant for their racial diversity and decreased glomerular filtration rate (~25–35 mL/min). Stringent statistical analysis, using the Benjamini-Hochberg corrected two-tailed t test, was used to identify differentially expressed transcripts in control and diseased glomeruli and tubuli. Two different web-based algorithms were used to define differentially regulated pathways. RESULTS We identified 1,700 differentially expressed probesets in DKD glomeruli and 1,831 in diabetic tubuli, and 330 probesets were commonly differentially expressed in both compartments. Pathway analysis highlighted the regulation of Ras homolog gene family member A, Cdc42, integrin, integrin-linked kinase, and vascular endothelial growth factor signaling in DKD glomeruli. The tubulointerstitial compartment showed strong enrichment for inflammation-related pathways. The canonical complement signaling pathway was determined to be statistically differentially regulated in both DKD glomeruli and tubuli and was associated with increased glomerulosclerosis even in a different set of DKD samples. CONCLUSIONS Our studies have cataloged gene-expression regulation and identified multiple novel genes and pathways that may play a role in the pathogenesis of DKD or could serve as biomarkers. PMID:21752957

  7. Tricuspid and mitral regurgitation detected by color flow Doppler in the acute phase of Kawasaki disease

    SciTech Connect

    Suzuki, A.; Kamiya, T.; Tsuchiya, K.; Sato, I.; Arakaki, Y.; Kohata, T.; Ono, Y.

    1988-02-01

    Valvular lesions in the acute phase of Kawasaki disease were studied in 19 children. The patients were intensively observed by color flow Doppler every day from the day of hospitalization up to 12 days after the onset of the disease and 2 or more times a week thereafter, for up to 28 days. Mitral regurgitation (MR) was found in 9 patients (47%) and tricuspid regurgitation (TR) in 10 (53%). MRs were of transient type and confirmed from 7.5 +/- 1.6 (mean +/- standard deviation) to 13.1 +/- 6.5 days after the onset of the disease. Both types of valvular regurgitation were mild. The direction of regurgitation was from the center of valvular coaptation toward the posterior wall of the atrium. Neither valvular prolapse nor valvular deformity was noted. In patients with MR, left ventricular ejection fraction on M-mode echocardiography was significantly lower in the acute phase than in the convalescent phase of the disease (p less than 0.05). Using gallium-67 scintigram, the positive uptake of the isotope was noted in 7 (88%) of 8 patients with MR, but not found at all in 8 patients free of MR. These results suggest that MR and TR are often transient in the acute phase of Kawasaki disease and could be attributed to myocarditis.

  8. Neonatal acute lymphocytic leukaemia: an unusual presentation of a rare disease.

    PubMed

    Palman, Jason; Karam, Maria; Chee, Ying; Kandala, Vijay

    2015-01-01

    Infantile acute lymphocytic leukaemia (ALL) seldom presents within the first month of life. Most are diagnosed before birth. Postnatal diagnoses are easily recognisable when characteristic features are present, namely hepatosplenomegaly, leukaemia cutis or infiltrative disease of the extramedullar and central nervous system. However, some children present with vague and non-specific symptoms masquerading as other diseases. We report an unusual presentation of infantile ALL in a 19-day-old infant, who struggled with feeding after a diagnosis of gastro-oesophageal reflux disease since birth. To the best of our knowledge, this is the youngest case report of neonatal ALL, presenting with vomiting, lethargy and dehydration. The neonate presented to our paediatric assessment unit acutely due to progression of her symptoms. General physical examination was unremarkable apart from signs of lethargy and dehydration. Blood investigation revealed an incidental finding of high white cells, including 90% blast cells. Early diagnosis in this case meant early treatment and a good prognosis. PMID:26178003

  9. Treatment disparities in acute coronary syndromes, heart failure, and kidney disease.

    PubMed

    McCullough, Peter A; Maynard, Robert C

    2011-01-01

    It has been consistently observed that patients with renal dysfunction have more premature, severe, complicated, and fatal cardiovascular disease than age- and sex-matched individuals with normal renal function. There have been 4 major explanations for this finding: (1) positive confounding by third variables associated with chronic kidney disease (CKD), including diabetes mellitus and hypertension; (2) therapeutic nihilism or lesser use of beneficial therapies in CKD; (3) greater toxicities of therapies, such as bleeding from anticoagulants or contrast-induced kidney injury; (4) biological factors which result directly from CKD that work to promote and accelerate cardiovascular disease. In this paper, we focus on the issue of treatment disparities or therapeutic nihilism and its contribution to poor outcomes in the setting of acute coronary syndromes and acutely decompensated heart failure. This issue is important because if we can overcome barriers to the utilization of beneficial treatments, then clinical outcomes should improve over time. PMID:21625092

  10. Coexistence of Acute Crescent Glomerulonephritis and IgG4-Related Kidney Disease

    PubMed Central

    Lu, Zeyuan; Yin, Jianyong; Bao, Hongda; Jiao, Qiong; Wu, Huijuan; Wu, Rui; Xue, Qin; Wang, Niansong; Zhang, Zhigang; Wang, Feng

    2016-01-01

    Introduction IgG4-related disease (IgG4-RD) is a fibroinflammatory disorder that may involve almost each organ or system. IgG4-related kidney disease (IgG4-RKD) refers to renal lesions associated with IgG4-RD. The most frequent morphological type of renal lesions is IgG4-related tubulointerstitial nephritis (IgG4-TIN) which is associated with increased IgG4-positive plasma cell infiltration and interstitial fibrosis. Case Report Herein, we present a rare case with coexisting IgG4-RKD and acute crescent glomerulonephritis with concomitant severe tubulointerstitial lesions instead of classic IgG4-TIN. Conclusion IgG4-RKD and acute crescent glomerulonephritis can occur in the same patient. This case may give us a clearer viewpoint of the disease. PMID:27504450

  11. Acute encephalitis and encephalopathy associated with human parvovirus B19 infection in children.

    PubMed

    Watanabe, Toru; Kawashima, Hideshi

    2015-11-01

    Reports of neurologic manifestations of human parvovirus B19 (B19) infection have been on the rise. Acute encephalitis and encephalopathy is the most common, accounting for 38.8% of total B19-associated neurological manifestations. To date, 34 children with B19 encephalitis and encephalopathy have been reported, which includes 21 encephalitis and 13 encephalopathy cases. Ten (29%) were immunocompromised and 17 (39%) had underlying diseases. Fever at the onset of disease and rash presented in 44.1% and 20.6% of patients, respectively. Neurological manifestations include alteration of consciousness occurred in all patients, seizures in 15 (44.1%) patients, and focal neurologic signs in 12 (35.3%) patients. Anemia and pleocytosis in cerebrospinal fluid (CSF) occurred in 56.3% and 48.1% of patients, respectively. Serum Anti-B19 IgM (82.6%) and CSF B19 DNA (90%) were positive in the majority of cases. Some patients were treated with intravenous immunoglobulins and/or steroids, although an accurate evaluation of the efficacy of these treatment modalities cannot be determined. Nineteen (57.6%) patients recovered completely, 11 (33.3%) patients had some neurological sequelae and 3 (8.8%) patients died. Although the precise pathogenesis underlying the development of B19 encephalitis and encephalopathy is unclear, direct B19 infection or NS1protein of B19 toxicity in the brain, and immune-mediated brain injuries have been proposed. PMID:26566485

  12. Dietary patterns and their association with acute coronary heart disease: Lessons from the REGARDS Study

    PubMed Central

    Al Suwaidi, Jassim

    2015-01-01

    Shikany et al used data from 17,418 participants in the REGARDS study, a national, population-based, longitudinal study of white and black adults aged ≥ 45 years, enrolled between 2003–2007. They examined 536 acute coronary heart disease events at follow-up (median 5.8 years) in relation to five dietary patterns (Convenience, Plant-based, Sweets, Southern, and Alcohol and Salad). After adjustment for baseline variables, the highest consumers of the Southern pattern experienced a 56% higher hazard for acute CHD. PMID:26779528

  13. A rare cause of acute abdominal disease: two reports of caecal diverticulum perforation.

    PubMed

    Çiftci, Fatih; Abdurrahman, İbrahim; Eren, Abdülkadir

    2016-05-01

    Diverticulum of the caecum is a rare lesion. From a clinical point of view, the inflammation it causes can mimic symptoms of acute appendicitis, causing difficulties in diagnosis and thus prescription of appropriate treatment. It is almost impossible to differentiate this disease from acute appendicitis through physical examination alone, and radiological imaging may also prove insufficient. For this reason, it is common to perioperatively diagnose diverticula of the caecum. Two cases of patients who underwent surgery for perforated caecal diverticula are presently described. PMID:27598596

  14. Dietary patterns and their association with acute coronary heart disease: Lessons from the REGARDS Study.

    PubMed

    Al Suwaidi, Jassim

    2015-01-01

    Shikany et al used data from 17,418 participants in the REGARDS study, a national, population-based, longitudinal study of white and black adults aged ≥ 45 years, enrolled between 2003-2007. They examined 536 acute coronary heart disease events at follow-up (median 5.8 years) in relation to five dietary patterns (Convenience, Plant-based, Sweets, Southern, and Alcohol and Salad). After adjustment for baseline variables, the highest consumers of the Southern pattern experienced a 56% higher hazard for acute CHD. PMID:26779528

  15. How I treat acute graft-versus-host disease of the gastrointestinal tract and the liver

    PubMed Central

    2016-01-01

    Treatment of acute graft-versus-host disease (GVHD) has evolved from a one-size-fits-all approach to a more nuanced strategy based on predicted outcomes. Lower and time-limited doses of immune suppression for patients predicted to have low-risk GVHD are safe and effective. In more severe GVHD, prolonged exposure to immunosuppressive therapies, failure to achieve tolerance, and inadequate clinical responses are the proximate causes of GVHD-related deaths. This article presents acute GVHD-related scenarios representing, respectively, certainty of diagnosis, multiple causes of symptoms, jaundice, an initial therapy algorithm, secondary therapy, and defining futility of treatment. PMID:26729898

  16. Acute generalized erythematous pustulosis occurring with Hailey-Hailey disease.

    PubMed

    Deng, April; Lowitt, Mark

    2012-01-01

    A 70-year-old woman urgently presented with severe eruptive skin dermatitis associated with fever and malaise 7 days after taking clindamycin for an unknown skin eruption. She had a 40-year-long history of well-controlled Hailey-Hailey disease. Physical examination revealed erythrodermic skin changes covering more than 80% of the patient's body surface, with hundreds of nonfollicular pustules. Many of the pustules fused into large bullae, involving the intertriginous as well as the extensor areas, sparing the mucosa. Her body temperature was 103 degrees F. Laboratory workup was significant for neutrophilia with a white cell count > 10,000/mm3. PMID:23008946

  17. Celiac disease unmasked by acute severe iron deficiency anemia

    PubMed Central

    Meseeha, Marcelle G.; Attia, Maximos N.; Kolade, Victor O.

    2016-01-01

    The prevalence of celiac disease (CD) appears to be increasing in the United States. However, the proportion of new CD cases with atypical presentations is also rising. We present the case of a 49-year-old woman who was diagnosed with CD in the setting of new, severe iron-deficiency anemia, 13 years into treatment of diarrhea-predominant irritable bowel syndrome associated with chronic mildly elevated liver function tests. While CD and iron deficiency anemia are common, this is a rare presentation of CD. PMID:27406450

  18. Celiac disease unmasked by acute severe iron deficiency anemia.

    PubMed

    Meseeha, Marcelle G; Attia, Maximos N; Kolade, Victor O

    2016-01-01

    The prevalence of celiac disease (CD) appears to be increasing in the United States. However, the proportion of new CD cases with atypical presentations is also rising. We present the case of a 49-year-old woman who was diagnosed with CD in the setting of new, severe iron-deficiency anemia, 13 years into treatment of diarrhea-predominant irritable bowel syndrome associated with chronic mildly elevated liver function tests. While CD and iron deficiency anemia are common, this is a rare presentation of CD. PMID:27406450

  19. The Burden of Acute Disease in Mahajanga, Madagascar – A 21 Month Study

    PubMed Central

    Kannan, Vijay C.; Andriamalala, Clara N.; Reynolds, Teri A.

    2015-01-01

    Background Efforts to develop effective and regionally-appropriate emergency care systems in sub-Saharan Africa are hindered by a lack of data on both the burden of disease in the region and on the state of existing care delivery mechanisms. This study describes the burden of acute disease presenting to an emergency unit in Mahajanga, Madagascar. Methods and Findings Handwritten patient registries on all emergency department patients presenting between 1 January 2011 and 30 September 2012 were reviewed and data entered into a database. Data included age, sex, diagnosis, and disposition. We classified diagnoses into Clinical Classifications Software (CCS) multi-level categories. The population was 53.5% male, with a median age of 31 years. The five most common presenting conditions were 1) Superficial injury; contusion, 2) Open wounds of head; neck; and trunk, 3) Open wounds of extremities, 4) Intracranial injury, and 5) Unspecified injury and poisoning. Trauma accounted for 48%, Infectious Disease for 15%, Mental Health 6.1%, Noncommunicable 29%, and Neoplasms 1.2%. The acuity seen was high, with an admission rate of 43%. Trauma was the most common reason for admission, representing 19% of admitted patients. Conclusions This study describes the burden of acute disease at a large referral center in northern Madagascar. The Centre Hôpitalier Universitaire de Mahajanga sees a high volume of acutely ill and injured patients. Similar to other reports from the region, trauma is the most common pathology observed, though infectious disease was responsible for the majority of adult mortality. Typhoid fever other intestinal infections were the most lethal CCS-coded pathologies. By utilizing a widely understood classification system, we are able to highlight contrasts between Mahajanga’s acute and overall disease burden as well as make comparisons between this region and the rest of the globe. We hope this study will serve to guide the development of context

  20. The Prevalence of Natural Health Product Use in Patients with Acute Cardiovascular Disease

    PubMed Central

    Alherbish, Aws; Charrois, Theresa L.; Ackman, Margaret L.; Tsuyuki, Ross T.; Ezekowitz, Justin A.

    2011-01-01

    Background Natural health products (NHP) use may have implications with respect to adverse effects, drug interactions and adherence yet the prevalence of NHP use by patients with acute cardiovascular disease and the best method to ascertain this information is unknown. Objective To identify the best method to ascertain information on NHP, and the prevalence of use in a population with acute cardiovascular disease. Methods Structured interviews were conducted with a convenience sample of consecutive patients admitted with acute cardiovascular disease to the University of Alberta Hospital during January 2009. NHP use was explored using structured and open-ended questions based on Health Canada's definition of NHP. The medical record was reviewed, and documentation of NHP use by physicians, nurses, and pharmacists, compared against the gold-standard structured interview. Results 88 patients were interviewed (mean age 62 years, standard deviation [SD 14]; 80% male; 41% admitted for acute coronary syndromes). Common co-morbidities included hypertension (59%), diabetes (26%) and renal impairment (19%). NHP use was common (78% of patients) and 75% of NHP users reported daily use. The category of NHP most commonly used was vitamins and minerals (73%) followed by herbal products (20%), traditional medicines including Chinese medicines (9%), homeopathic preparations (1%) and other products including amino acids, essential fatty acids and probiotics (35%). In a multivariable model, only older age was associated with increased NHP use (OR 1.5 per age decile [95%CI 1.03 to 2.2]). When compared to the interview, the highest rate of NHP documentation was the pharmacist history (41%). NHP were documented in 22% of patients by the physician and 19% by the nurse. Conclusions NHP use is common in patients admitted with acute cardiovascular disease. However, health professionals do not commonly identify NHP as part of the medication profile despite its potential importance. Structured

  1. Negative findings concerning Alcaligenes faecalis as an etiologic agent in acute respiratory disease of turkeys.

    PubMed

    Singer, N; Weisman, Y; Aronovici, A

    1981-01-01

    An acute respiratory disease of turkeys in Israel was first reported in November 1978. Alcaligenes faecalis was isolated from sick turkeys and from chickens not affected by the disease. Plate agglutination tests with A. faecalis antigen of 1,067 turkey and 494 chicken serum samples gave variable results: healthy turkeys gave positive reactions and sick turkeys sometimes gave negative ones. All isolated strains were highly sensitive in vitro drug sensitivity tests, but chemotherapy failed in the field. Pathogenicity trials with A. faecalis, given alone or in combination with Yucaipa virus to 8-day-old turkey poults, failed to reproduce the disease. PMID:7259671

  2. Acute stroke revealing Takayasu's arteritis in a patient with Crohn's disease.

    PubMed

    Lavie, Gil; Zalmanovich, Anat; Golan, Yitzhak; Jonas Kimchi, Tali; Barenboim, Erez

    2016-08-01

    A 36-year-old Caucasian male with Crohn's disease exhibited acute ischaemic stroke as the first manifestation of Takayasu's arteritis. Stroke as the first clinical manifestation of Takayasu's arteritis has been rarely reported. Though rare in Western countries, Takayasu's arteritis should be considered as a possibility in young patients presenting with stroke. Both Takayasu's arteritis and Crohn's disease may increase the risk of ischaemic stroke. Furthermore, their coexistence is much higher than that expected by chance and suggest a pathophysiological link between these diseases. PMID:27075786

  3. Lethal acute demyelinization with encephalo-myelitis as a complication of cured Cushing's disease.

    PubMed

    Chevalier, N; Hieronimus, S; Vandenbos, F; Delmont, E; Cua, E; Cherick, F; Paquis, P; Michiels, J-F; Fenichel, P; Brucker-Davis, F

    2010-12-01

    Cushing's disease is usually associated with higher mortality rate, especially from cardiovascular causes. Development or exacerbation of autoimmune or inflammatory diseases is known to occur in patients with hypercortisolism after cure. We report for the first time a 34-year old woman with a psychiatric background, who developed four months after the surgical cure of Cushing's disease an acute disseminated encephalomyelitis (ADEM) presenting initially as a psychiatric illness. We hypothesize that the recent correction of hypercortisolism triggered ADEM and that the atypical presentation, responsible for diagnosis delay, led to the death of this patient. PMID:20850107

  4. Molecular Analysis of Central Nervous System Disease Spectrum in Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Hicks, Chindo; Sitthi-Amorn, Jitsuda; Douglas, Jessica; Ramani, Ritika; Miele, Lucio; Vijayakumar, Vani; Karlson, Cynthia; Chipeta, James; Megason, Gail

    2016-01-01

    Treatment of the central nervous system (CNS) is an essential therapeutic component in childhood acute lymphoblastic leukemia (ALL). The goal of this study was to identify molecular signatures distinguishing patients with CNS disease from those without the disease in pediatric patients with ALL. We analyzed gene expression data from 207 pediatric patients with ALL. Patients without CNS were classified as CNS1, while those with mild and advanced CNS disease were classified as CNS2 and CNS3, respectively. We compared gene expression levels among the three disease classes. We identified gene signatures distinguishing the three disease classes. Pathway analysis revealed molecular networks and biological pathways dysregulated in response to CNS disease involvement. The identified pathways included the ILK, WNT, B-cell receptor, AMPK, ERK5, and JAK signaling pathways. The results demonstrate that transcription profiling could be used to stratify patients to guide therapeutic decision-making in pediatric ALL. PMID:26997880

  5. Wolbachia endosymbionts and human disease control.

    PubMed

    Slatko, Barton E; Luck, Ashley N; Dobson, Stephen L; Foster, Jeremy M

    2014-07-01

    Most human filarial nematode parasites and arthropods are hosts for a bacterial endosymbiont, Wolbachia. In filaria, Wolbachia are required for normal development, fertility and survival, whereas in arthropods, they are largely parasitic and can influence development and reproduction, but are generally not required for host survival. Due to their obligate nature in filarial parasites, Wolbachia have been a target for drug discovery initiatives using several approaches including diversity and focused library screening and genomic sequence analysis. In vitro and in vivo anti-Wolbachia antibiotic treatments have been shown to have adulticidal activity, a long sought goal of filarial parasite drug discovery. In mosquitoes, it has been shown that the presence of Wolbachia can inhibit the transmission of certain viruses, such as Dengue, Chikungunya, Yellow Fever, West Nile, as well as the infectivity of the malaria-causing protozoan, Plasmodium and filarial nematodes. Furthermore, Wolbachia can cause a form of conditional sterility that can be used to suppress populations of mosquitoes and additional medically important insects. Thus Wolbachia, a pandemic endosymbiont offers great potential for elimination of a wide-variety of devastating human diseases. PMID:25046729

  6. Circadian misalignment increases cardiovascular disease risk factors in humans

    PubMed Central

    Morris, Christopher J.; Purvis, Taylor E.; Hu, Kun; Scheer, Frank A. J. L.

    2016-01-01

    Shift work is a risk factor for hypertension, inflammation, and cardiovascular disease. This increased risk cannot be fully explained by classic risk factors. One of the key features of shift workers is that their behavioral and environmental cycles are typically misaligned relative to their endogenous circadian system. However, there is little information on the impact of acute circadian misalignment on cardiovascular disease risk in humans. Here we show—by using two 8-d laboratory protocols—that short-term circadian misalignment (12-h inverted behavioral and environmental cycles for three days) adversely affects cardiovascular risk factors in healthy adults. Circadian misalignment increased 24-h systolic blood pressure (SBP) and diastolic blood pressure (DBP) by 3.0 mmHg and 1.5 mmHg, respectively. These results were primarily explained by an increase in blood pressure during sleep opportunities (SBP, +5.6 mmHg; DBP, +1.9 mmHg) and, to a lesser extent, by raised blood pressure during wake periods (SBP, +1.6 mmHg; DBP, +1.4 mmHg). Circadian misalignment decreased wake cardiac vagal modulation by 8–15%, as determined by heart rate variability analysis, and decreased 24-h urinary epinephrine excretion rate by 7%, without a significant effect on 24-h urinary norepinephrine excretion rate. Circadian misalignment increased 24-h serum interleukin-6, C-reactive protein, resistin, and tumor necrosis factor-α levels by 3–29%. We demonstrate that circadian misalignment per se increases blood pressure and inflammatory markers. Our findings may help explain why shift work increases hypertension, inflammation, and cardiovascular disease risk. PMID:26858430

  7. Acute dermatitis in farmed trout: an emerging disease.

    PubMed

    Peeler, E J; Ryder, D; Thrush, M A; Mewett, J; Hulland, J; Feist, S W

    2014-12-01

    A new skin condition, known as puffy skin disease (PSD), emerged in farmed rainbow trout Oncorhynchus mykiss (Walbaum) in 2002. The number of new cases increased considerably from 2006. Clinical signs include white or grey skin patches, which become raised and red with excessive mucous production and scale loss. Fish are inappetant and lose condition. Histologically, the key feature is epithelial hyperplasia. We undertook a questionnaire study of trout farmers in England and Wales to investigate prevalence and risk factors. PSD was reported on 37% (n = 49) of rainbow trout sites, located in 28 river catchments. The increase in cases from 2006 onwards was mirrored by the increase in red mark syndrome (RMS). Prevalence and severity of PSD were highest in the summer months. The presence of PSD was associated with RMS (OR = 9.7, P < 0.001). Sites receiving live rainbow trout in the previous 12 months were considerably more likely to have PSD (OR = 5.3. P < 0.01), which suggests an infectious aetiology. The size of affected fish and prevalence varied between farms, indicating that farm-level factors are important. Future research should further investigate the aetiology of PSD and practices to manage the disease. PMID:24720525

  8. Non-invasive ventilation in chronic obstructive pulmonary disease: management of acute type 2 respiratory failure.

    PubMed

    Roberts, C M; Brown, J L; Reinhardt, A K; Kaul, S; Scales, K; Mikelsons, C; Reid, K; Winter, R; Young, K; Restrick, L; Plant, P K

    2008-10-01

    Non-invasive ventilation (NIV) in the management of acute type 2 respiratory failure in patients with chronic obstructive pulmonary disease (COPD) represents one of the major technical advances in respiratory care over the last decade. This document updates the 2002 British Thoracic Society guidance and provides a specific focus on the use of NIV in COPD patients with acute type 2 respiratory failure. While there are a variety of ventilator units available most centres now use bi-level positive airways pressure units and this guideline refers specifically to this form of ventilatory support although many of the principles encompassed are applicable to other forms of NIV. The guideline has been produced for the clinician caring for COPD patients in the emergency and ward areas of acute hospitals. PMID:18975486

  9. Characteristics of acute care utilization of a Delaware adult sickle cell disease patient population.

    PubMed

    Anderson, Nina; Bellot, Jennifer; Senu-Oke, Oluseyi; Ballas, Samir K

    2014-02-01

    Sickle cell disease (SCD) is an inherited blood disorder that is chronic in nature and manifests itself through many facets of the patient's life. Comprehensive specialty centers have the potential to reduce health care costs and improve the quality of care for patients who have chronic medical conditions such as heart failure and SCD. The purpose of this practice inquiry was to analyze de-identified data for acute care episodes involving SCD in order to create a detailed picture of acute care utilization for adult patients in Delaware with SCD from 2007 to 2009. Gaining a better understanding of acute care utilization for adults with SCD may provide evidence to improve access to high-quality health care services for this vulnerable patient population in the state of Delaware. PMID:23965046

  10. The epidemiology and outcome of acute renal failure and the impact on chronic kidney disease.

    PubMed

    Block, Clay A; Schoolwerth, Anton C

    2006-01-01

    Acute renal failure (ARF) is a common condition, especially among the critically ill, and confers a high mortality. Recent publications have highlighted changes in the epidemiology and improvement in mortality that was long thought to be static despite improvements in clinical care. The incidence of ARF is increasing. Efforts, such as the Acute Dialysis Quality Initiative, are being undertaken to establish a consensus definition of ARF, and to distinguish between varying degrees of acute kidney injury. Data are emerging to allow comparison of the epidemiology of ARF across institutions internationally. There is ongoing recognition of the important interaction between ARF and chronic kidney disease. Two brief case reports are offered to help frame the context and clinical impact of this disorder, followed by a review of some of the recent literature that addresses these points. PMID:17150044

  11. Genetic variant associations of human SP-A and SP-D with acute and chronic lung injury

    PubMed Central

    Silveyra, Patricia; Floros, Joanna

    2013-01-01

    Pulmonary surfactant, a lipoprotein complex, maintains alveolar integrity and plays an important role in lung host defense, and control of inflammation. Altered inflammatory processes and surfactant dysfunction are well described events that occur in patients with acute or chronic lung disease that can develop secondary to a variety of insults. Genetic variants of surfactant proteins, including single nucleotide polymorphisms, haplotypes, and other genetic variations have been associated with acute and chronic lung disease throughout life in several populations and study groups. The hydrophilic surfactant proteins SP-A and SP-D, also known as collectins, in addition to their surfactant-related functions, are important innate immunity molecules as these, among others, exhibit the ability to bind and enhance clearance of a wide range of pathogens and allergens. This review focuses on published association studies of human surfactant proteins A and D genetic polymorphisms with respiratory, and non-respiratory diseases in adults, children, and newborns. The potential role of genetic variations in pulmonary disease or pathogenesis is discussed following an evaluation, and comparison of the available literature. PMID:22201752

  12. Cross-host evolution of severe acute respiratory syndrome coronavirus in palm civet and human

    PubMed Central

    Song, Huai-Dong; Tu, Chang-Chun; Zhang, Guo-Wei; Wang, Sheng-Yue; Zheng, Kui; Lei, Lian-Cheng; Chen, Qiu-Xia; Gao, Yu-Wei; Zhou, Hui-Qiong; Xiang, Hua; Zheng, Hua-Jun; Chern, Shur-Wern Wang; Cheng, Feng; Pan, Chun-Ming; Xuan, Hua; Chen, Sai-Juan; Luo, Hui-Ming; Zhou, Duan-Hua; Liu, Yu-Fei; He, Jian-Feng; Qin, Peng-Zhe; Li, Ling-Hui; Ren, Yu-Qi; Liang, Wen-Jia; Yu, Ye-Dong; Anderson, Larry; Wang, Ming; Xu, Rui-Heng; Wu, Xin-Wei; Zheng, Huan-Ying; Chen, Jin-Ding; Liang, Guodong; Gao, Yang; Liao, Ming; Fang, Ling; Jiang, Li-Yun; Li, Hui; Chen, Fang; Di, Biao; He, Li-Juan; Lin, Jin-Yan; Tong, Suxiang; Kong, Xiangang; Du, Lin; Hao, Pei; Tang, Hua; Bernini, Andrea; Yu, Xiao-Jing; Spiga, Ottavia; Guo, Zong-Ming; Pan, Hai-Yan; He, Wei-Zhong; Manuguerra, Jean-Claude; Fontanet, Arnaud; Danchin, Antoine; Niccolai, Neri; Li, Yi-Xue; Wu, Chung-I; Zhao, Guo-Ping

    2005-01-01

    The genomic sequences of severe acute respiratory syndrome coronaviruses from human and palm civet of the 2003/2004 outbreak in the city of Guangzhou, China, were nearly identical. Phylogenetic analysis suggested an independent viral invasion from animal to human in this new episode. Combining all existing data but excluding singletons, we identified 202 single-nucleotide variations. Among them, 17 are polymorphic in palm civets only. The ratio of nonsynonymous/synonymous nucleotide substitution in palm civets collected 1 yr apart from different geographic locations is very high, suggesting a rapid evolving process of viral proteins in civet as well, much like their adaptation in the human host in the early 2002–2003 epidemic. Major genetic variations in some critical genes, particularly the Spike gene, seemed essential for the transition from animal-to-human transmission to human-to-human transmission, which eventually caused the first severe acute respiratory syndrome outbreak of 2002/2003. PMID:15695582

  13. Acute kidney injury in critically ill patients with lung disease: kidney-lung crosstalk

    PubMed Central

    de Abreu, Krasnalhia Lívia Soares; da Silva Junior, Geraldo Bezerra; Muniz, Thalita Diógenes; Barreto, Adller Gonçalves Costa; Lima, Rafael Siqueira Athayde; Holanda, Marcelo Alcântara; Pereira, Eanes Delgado Barros; Libório, Alexandre Braga; Daher, Elizabeth de Francesco

    2013-01-01

    Objective To examine the factors associated with acute kidney injury and outcome in patients with lung disease. Methods A prospective study was conducted with 100 consecutive patients admitted to a respiratory intensive care unit in Fortaleza (CE), Brazil. The risk factors for acute kidney injury and mortality were investigated in a group of patients with lung diseases. Results The mean age of the study population was 57 years, and 50% were male. The incidence of acute kidney injury was higher in patients with PaO2/FiO2<200 mmHg (54% versus 23.7%; p=0.02). Death was observed in 40 cases and the rate of mortality of the acute kidney injury group was higher (62.8% versus 27.6%; p=0.01). The independent factor that was found to be associated with acute kidney injury was PaO2/FiO2<200 mmHg (p=0.01), and the independent risk factors for death were PEEP at admission (OR: 3.6; 95%CI: 1.3-9.6; p=0.009) and need for hemodialysis (OR: 7.9; 95%CI: 2.2-28.3; p=0.001). Conclusion There was a higher mortality rate in the acute kidney injury group. Increased mortality was associated with mechanical ventilation, high PEEP, urea and need for dialysis. Further studies must be performed to better establish the relationship between kidney and lung injury and its impact on patient outcome. PMID:23917978

  14. Carcinoid heart disease from ovarian primary presenting with acute pericarditis and biventricular failure

    PubMed Central

    Vergani, D; Massironi, L; Lombardi, F; Fiorentini, C

    1998-01-01

    A case is described of a 54 year old woman who had acute pericarditis with large exudative effusion accompanied by severe right and left ventricular failure. The patient was finally diagnosed with carcinoid heart disease from an ovarian carcinoid teratoma. She was treated with octreotide—a somatostatin analogue—followed by radical surgical resection of the neoplasm. At one year follow up only mild carcinoid tricuspid regurgitation remained. Only 16 cases of carcinoid heart disease from an ovarian primary have been described in literature. Moreover clinically manifest acute, non-metastatic pericarditis and left heart failure are not considered as possible presentations of carcinoid heart disease, whatever the origin. In a recent series a small pericardial effusion was considered an infrequent and unexpected echocardiographic finding in carcinoid heart patients. One case of "carcinoid pericarditis" has previously been described as a consequence of pericardial metastasis. Left sided heart involvement is usually caused by bronchial carcinoids or patency of foramen ovale; both were excluded in the case presented.

 Keywords: carcinoid heart disease;  ovarian tumour;  acute pericarditis;  heart failure PMID:10065036

  15. Disease emergence and resurgence: the wildlife-human connection

    USGS Publications Warehouse

    Friend, Milton

    2006-01-01

    In 2000, the Global Outbreak Alert and Response Network (GOARN) was organized as a global disease watchdog group to coordinate disease outbreak information and health crisis response. The World Health Organization (WHO) is the headquarters for this network.2 Understandably, the primary focus for WHO is human health. However, diseases such as the H5N1 avian influenza epizootic in Asian bird populations demonstrate the need for integrating knowledge about disease emergence in animals and in humans.

  16. [Acute bacterial exacerbation of chronic obstructive pulmonary disease and biofilm].

    PubMed

    Legnani, Delfino

    2009-07-01

    The lower respiratory tract of patients affected by COPD is constantly colonized by pathogenic microrganisms such as H. influenzae, M. catarrhalis and S. pneumoniae. Role of bacterial colonization of big and small airways in patients affected by COPD is still unclear but it is likely to play a role in directly or indirectly maintaining the vicious circle of infection/inflammation. Colonizer pathogens are capable to stimulate mucus production, to alter the ciliary function by inducing dyskinesia and stasis; in addition, they represent a strong stimulus for neutrophils to come in the airways, which release elastase that, in turn, inhibit the mucus-ciliary function. The same pathogens are responsible for epithelial damage and chronic inflammation, by releasing neutrophilic elastase, leading to the damage progression and obstruction. Recent studies have also shown that infection sustained by H. influenzae is not limited to bronchial mucosa, i.e. surface epithelial cells, but that the pathogen is capable to penetrate cells, so spreading the infection in sub-epithelial cellular layers. In addition, the ability to produce biofilm is another possible defence mechanism which allows them to grow and colonise. Such a mechanism could in part explain the lack of response to antimicrobials and contribute to stimulation of parenchymal inflammatory response, the cause of pathological-anatomic damage which occurs in COPD. The impossibility to eradicate chronic infection and bacterial exacerbations of COPD are likely the elements that promt and worsen obstruction, so determining the disease's progression. PMID:19696555

  17. Acute Graft-versus-Host Disease: Novel Biological Insights.

    PubMed

    Teshima, Takanori; Reddy, Pavan; Zeiser, Robert

    2016-01-01

    Graft-versus-host disease (GVHD) continues to be a leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Recent insights into intestinal homeostasis and uncovering of new pathways and targets have greatly reconciled our understanding of GVHD pathophysiology and will reshape contemporary GVHD prophylaxis and treatment. Gastrointestinal (GI) GVHD is the major cause of mortality. Emerging data indicate that intestinal stem cells (ISCs) and their niche Paneth cells are targeted, resulting in dysregulation of the intestinal homeostasis and microbial ecology. The microbiota and their metabolites shape the immune system and intestinal homeostasis, and they may alter host susceptibility to GVHD. Protection of the ISC niche system and modification of the intestinal microbiota and metabolome to restore intestinal homeostasis may, thus, represent a novel approach to modulate GVHD and infection. Damage to the intestine plays a central role in amplifying systemic GVHD by propagating a proinflammatory cytokine milieu. Molecular targeting to inhibit kinase signaling may be a promising approach to treat GVHD, ideally via targeting the redundant effect of multiple cytokines on immune cells and enterocytes. In this review, we discuss insights on the biology of GI GVHD, interaction of microflora and metabolome with the hosts, identification of potential new target organs, and identification and targeting of novel T cell-signaling pathways. Better understanding of GVHD biology will, thus, pave a way to develop novel treatment strategies with great clinical benefits. PMID:26453971

  18. Acute Q fever: an emerging and endemic disease in southern Taiwan.

    PubMed

    Lai, Chung-Hsu; Huang, Chun-Kai; Chin, Chuen; Chung, Hsing-Chun; Huang, Wu-Shiung; Lin, Chih-Wen; Hsu, Chuan-Yuan; Lin, Hsi-Hsun

    2008-01-01

    Acute Q fever is a worldwide zoonosis caused by Coxiella burnetii infection. In Taiwan, cases of acute Q fever increased during 3 y of observation, especially at Kaohsiung County and City in southern Taiwan. From 15 April 2004 to 15 April 2007, a total of 67 cases of acute Q fever were identified at E-Da hospital located at Kaohsiung County. 19 (28.4%) patients had a history of travel in rural areas and only 1 had been outside southern Taiwan. 21 (31.3%) patients had a history of animal contact. 20 (30.8%) of the 65 examined patients had underlying chronic hepatitis B or hepatitis C virus infection. Fever (98.5%), chills (79.1%), headache (79.1%), relative bradycardia (44.8%), elevated aminotransferases (100%), and thrombocytopenia (74.6%) were common manifestations. 12 (19.0%) cases had abnormal findings on chest X-ray. Fatty liver (50.0%) and hepatomegaly and/or splenomegaly (41.9%) were found by abdominal image examinations. 42 (76.4%) of 55 cases had defervescence within 3 d after treatment, whereas 4 (7.3%) had spontaneous remission. Acute Q fever is an endemic infectious disease with hepatitis rather than pneumonia as the major presentation in southern Taiwan and the emergence of Q fever is due to increased alertness for the disease by physicians. PMID:17852909

  19. Consanguinity, human evolution, and complex diseases

    PubMed Central

    Bittles, A. H.; Black, M. L.

    2010-01-01

    There is little information on inbreeding during the critical early years of human existence. However, given the small founding group sizes and restricted mate choices it seems inevitable that intrafamilial reproduction occurred and the resultant levels of inbreeding would have been substantial. Currently, couples related as second cousins or closer (F ≥ 0.0156) and their progeny account for an estimated 10.4% of the global population. The highest rates of consanguineous marriage occur in north and sub-Saharan Africa, the Middle East, and west, central, and south Asia. In these regions even couples who regard themselves as unrelated may exhibit high levels of homozygosity, because marriage within clan, tribe, caste, or biraderi boundaries has been a long-established tradition. Mortality in first-cousin progeny is ≈3.5% higher than in nonconsanguineous offspring, although demographic, social, and economic factors can significantly influence the outcome. Improving socioeconomic conditions and better access to health care will impact the effects of consanguinity, with a shift from infant and childhood mortality to extended morbidity. At the same time, a range of primarily social factors, including urbanization, improved female education, and smaller family sizes indicate that the global prevalence of consanguineous unions will decline. This shift in marriage patterns will initially result in decreased homozygosity, accompanied by a reduction in the expression of recessive single-gene disorders. Although the roles of common and rare gene variants in the etiology of complex disease remain contentious, it would be expected that declining consanguinity would also be reflected in reduced prevalence of complex diseases, especially in population isolates. PMID:19805052

  20. Advancing swine models for human health and diseases.

    PubMed

    Walters, Eric M; Prather, Randall S

    2013-01-01

    Swine models are relatively new kids on the block for modeling human health and diseases when compared to rodents and dogs. Because of the similarity to humans in size, physiology, and genetics, the pig has made significant strides in advancing the understanding of the human condition, and is thus an excellent choice for an animal model. Recent technological advances to genetic engineering of the swine genome enhance the utility of swine as models of human genetic diseases. PMID:23829105

  1. Trypanosoma cruzi IV Causing Outbreaks of Acute Chagas Disease and Infections by Different Haplotypes in the Western Brazilian Amazonia

    PubMed Central

    Monteiro, Wuelton Marcelo; Magalhães, Laylah Kelre Costa; de Sá, Amanda Regina Nichi; Gomes, Mônica Lúcia; Toledo, Max Jean de Ornelas; Borges, Lara; Pires, Isa; de Oliveira Guerra, Jorge Augusto; Silveira, Henrique; Barbosa, Maria das Graças Vale

    2012-01-01

    Background Chagas disease is an emergent tropical disease in the Brazilian Amazon Region, with an increasing number of cases in recent decades. In this region, the sylvatic cycle of Trypanosoma cruzi transmission, which constitutes a reservoir of parasites that might be associated with specific molecular, epidemiological and clinical traits, has been little explored. The objective of this work is to genetically characterize stocks of T. cruzi from human cases, triatomines and reservoir mammals in the State of Amazonas, in the Western Brazilian Amazon. Methodology/Principal Findings We analyzed 96 T. cruzi samples from four municipalities in distant locations of the State of Amazonas. Molecular characterization of isolated parasites from cultures in LIT medium or directly from vectors or whole human blood was performed by PCR of the non-transcribed spacer of the mini-exon and of the 24 S alfa ribosomal RNA gene, RFLP and sequencing of the mitochondrial cytochrome c oxidase subunit II (COII) gene, and by sequencing of the glucose-phosphate isomerase gene. The T. cruzi parasites from two outbreaks of acute disease were all typed as TcIV. One of the outbreaks was triggered by several haplotypes of the same DTU. TcIV also occurred in isolated cases and in Rhodnius robustus. Incongruence between mitochondrial and nuclear phylogenies is likely to be indicative of historical genetic exchange events resulting in mitochondrial introgression between TcIII and TcIV DTUs from Western Brazilian Amazon. TcI predominated among triatomines and was the unique DTU infecting marsupials. Conclusion/Significance DTU TcIV, rarely associated with human Chagas disease in other areas of the Amazon basin, is the major strain responsible for the human infections in the Western Brazilian Amazon, occurring in outbreaks as single or mixed infections by different haplotypes. PMID:22848457

  2. Human neutrophil peptides: a novel potential mediator of inflammatory cardiovascular diseases

    PubMed Central

    Quinn, Kieran; Henriques, Melanie; Parker, Tom; Slutsky, Arthur S.; Zhang, Haibo

    2016-01-01

    The traditional view of atherosclerosis has recently been expanded from a predominantly lipid retentive disease to a coupling of inflammatory mechanisms and dyslipidemia. Studies have suggested a novel role for polymorphonuclear neutrophil (PMN)-dominant inflammation in the development of atherosclerosis. Human neutrophil peptides (HNPs), also known as α-defensins, are secreted and released from PMN granules upon activation and are conventionally involved in microbial killing. Current evidence suggests an important immunomodulative role for these peptides. HNP levels are markedly increased in inflammatory diseases including sepsis and acute coronary syndromes. They have been found within the intima of human atherosclerotic arteries, and their deposition in the skin correlates with the severity of coronary artery diseases. HNPs form complexes with LDL in solution and increase LDL binding to the endothelial surface. HNPs have also been shown to contribute to endothelial dysfunction, lipid metabolism disorder, and the inhibition of fibrinolysis. Given the emerging relationship between PMN-dominant inflammation and atherosclerosis, HNPs may serve as a link between them and as a biological marker and potential therapeutic target in cardiovascular diseases including coronary artery diseases and acute coronary syndromes. PMID:18805897

  3. [Treatment of acute pelvic inflammatory diseases with a new antibiotic compound preparation (author's transl)].

    PubMed

    Burmucic, R

    1980-11-30

    48 patients with acute pelvic inflammatory diseases (35 cases of acute adnexitis and 13 cases of inflammatory adnexal tumours) were treated with an antibiotic combination of Ampicillin/Oxacillin and Sisomicin. As initial parenteral therapy Ampicillin/Oxacillin 3.0 g was given intravenously twice daily and additionally Sisomicin 75 or 100 mg according to the body-weight was administered intramuscular twice daily. If required a further oral treatment with 500 mg Ampicillin/Dicloxacillin capsules four times a day was carried out. The average duration of parenteral treatment was 6.3 days; together with the oral treatment the duration of antibiotic treatment was 18.5 days. In 43 patients (89.6%) the disease could be cured completely or a distinct improvement could be achieved. Only in 5 cases (10.4%) the results were unsatisfactory. As side-effects allergic reactions were observed in three cases and gastro-enteritis in one case. PMID:7467388

  4. Acute Schistosomiasis in Brazilian Traveler: The Importance of Tourism in The Epidemiology of Neglected Parasitic Diseases

    PubMed Central

    Guiguet Leal, Diego Averaldo; Franco, Regina Maura Bueno; Neves, Maria Francisca; Simões, Luciana Franceschi; Bastos, Letícia Aparecida Duart; Allegretti, Silmara Marques; Zanotti-Magalhães, Eliana Maria; Magalhães, Luiz Augusto

    2012-01-01

    Parasitic infectious diseases acquired in tourist areas may pose a challenge to physicians and to travel medicine practitioners. Acute schistosomiasis may be seen in returning travelers and migrants after primary infection. This form of schistosomiasis is frequently misdiagnosed due to its temporal delay and its nonspecific presentation and might occur even in countries where the disease is endemic, such as in Brazil. The patient developed the acute phase of schistosomiasis with severe clinical manifestations. The quantitative analysis revealed the presence of 240 eggs per gram of stool. The treatment was administered with oxamniquine, and the control of cure of the patient was monitored and was favorable. The present paper aims to emphasize the importance of a detailed clinical history including information regarding travel history. PMID:22844623

  5. Examining acute health outcomes due to ozone exposure and their subsequent relationship to chronic disease outcomes

    SciTech Connect

    Ostro, B.D.

    1993-12-01

    Current evidence indicates that individuals exposed to short term elevations in ambient ozone may experience both upper and lower respiratory effects. Some respiratory symptoms and spirometric changes are mild and reversible in nature, while others involve more severe outcomes, including hospital admissions and emergency room visits. However, many questions remain about the effects of acute ozone exposure and the implications of this exposure for chronic disease outcomes. For example, the identification of sensitive subgroups, the delineation of the entire spectrum of health effects due to exposure to ozone, the potential synergy between viral infections and ozone exposure, and the nature of adaptation to ozone are not well characterized. In addition, studies that examine the association between acute responses to ozone and potential biological indicators of a chronic disease process would be desirable. This paper serves to provide an overview of the types of epidemiologic studies that may be appropriate and factors to consider in addressing these questions. 23 refs.

  6. Subacute radiation dermatitis: a histologic imitator of acute cutaneous graft-versus-host disease

    SciTech Connect

    LeBoit, P.E.

    1989-02-01

    The histopathologic changes of radiation dermatitis have been classified either as early effects (necrotic keratinocytes, fibrin thrombi, and hemorrhage) or as late effects (vacuolar changes at the dermal-epidermal junction, atypical radiation fibroblasts, and fibrosis). Two patients, one exposed to radiation therapeutically and one accidentally, are described. Skin biopsy specimens showed an interface dermatitis characterized by numerous dyskeratotic epidermal cells with lymphocytes in close apposition (satellite cell necrosis); that is, the epidermal changes were similar to those in acute graft-versus-host disease. Because recipients of bone marrow transplants frequently receive total body irradiation as part of their preparatory regimen, the ability of radiation to cause persistent epidermal changes similar to those in acute graft-versus-host disease could complicate the interpretation of posttransplant skin biopsy specimens.

  7. Modified Extracorporeal Photopheresis with Cells from a Healthy Donor for Acute Graft-versus-Host Disease in a Mouse Model

    PubMed Central

    Budde, Holger; Kolb, Susanne; Salinas Tejedor, Laura; Wulf, Gerald; Reichardt, Holger M.; Riggert, Joachim; Legler, Tobias J.

    2014-01-01

    Background Graft-versus-host disease (GvHD) is a major challenge after hematopoietic stem cell transplantation but treatment options for patients are still limited. In many cases first-line treatment with glucocorticoids is not successful. Among second-line therapies the extracorporeal photopheresis (ECP) is frequently performed, due to induction of selective tolerance instead of general immunosuppression. However, for some patients with severe acute GvHD the leukapheresis step of the ECP procedure is physically exhausting and limits the number of ECP cycles. Methods We hypothesized that leukocytes from healthy cell donors could be used as a replacement for ECP leukocytes gained from the GvHD patient. For this purpose we used a well established mouse model of acute GvHD. The ECP therapy was based on cells with the genetic background of the initial donor of the stem cell transplantation. As a precondition we developed a protocol representing conventional ECP in mice equivalent to clinical used ECP setup. Results We could demonstrate that conventional, clinically derived ECP setup is able to alleviate acute GvHD. By using leukocytes obtained from healthy mice with the bone marrow donor’s genetic background we could not observe a statistically significant therapeutic effect. Conclusions Conventional human ECP setup is effective in the mouse model of severe acute GvHD. In addition we could not prove that ECP cells from healthy mice with bone marrow donor’s genetic background are as effective as ECP cells derived from GvHD mice. Based on our findings, new questions arise for further studies, in which the cellular characteristics for ECP mediated immune tolerance are a matter of investigation. PMID:25148404

  8. Haemodialysis is an effective treatment in acute metabolic decompensation of maple syrup urine disease

    PubMed Central

    Atwal, P.S.; Macmurdo, C.; Grimm, P.C.

    2015-01-01

    Acute metabolic decompensation in maple syrup urine disease can occur during intercurrent illness and is a medical emergency. A handful of reports in the medical literature describe the use of peritoneal dialysis and haemodialysis as therapeutic inventions. We report the only patient from our centre to have haemodialysis performed in this setting. Combined with dietary BCAA restriction and calorific support, haemodialysis allows rapid reduction in plasma leucine concentrations considerably faster than conservative methods. PMID:26937409

  9. Haemodialysis is an effective treatment in acute metabolic decompensation of maple syrup urine disease.

    PubMed

    Atwal, P S; Macmurdo, C; Grimm, P C

    2015-09-01

    Acute metabolic decompensation in maple syrup urine disease can occur during intercurrent illness and is a medical emergency. A handful of reports in the medical literature describe the use of peritoneal dialysis and haemodialysis as therapeutic inventions. We report the only patient from our centre to have haemodialysis performed in this setting. Combined with dietary BCAA restriction and calorific support, haemodialysis allows rapid reduction in plasma leucine concentrations considerably faster than conservative methods. PMID:26937409

  10. [Clinical pathway management of acute exacerbations of chronic obstructive pulmonary disease based on state machine].

    PubMed

    Tan, Jian; Hao, Liwei; Cheng, Yuanxiong; Xu, Tongliang; Song, Yingnuo

    2014-04-01

    We propose a clinical pathway of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) based on state machine. Clinical event-driven response was utilized to control workflow execution of the AECOPD clinical pathway. By comparison with the traditional clinical pathway management, clinical numerical results showed that the proposed method was better in hospitalization days, average hospitalization expense and aberration rate, and better handled the variability in the AECOPD clinical pathway execution. PMID:24752111

  11. Molecular Epidemiology of Human Oral Chagas Disease Outbreaks in Colombia

    PubMed Central

    Ramírez, Juan David; Montilla, Marleny; Cucunubá, Zulma M.; Floréz, Astrid Carolina; Zambrano, Pilar; Guhl, Felipe

    2013-01-01

    Background Trypanosoma cruzi, the causative agent of Chagas disease, displays significant genetic variability revealed by six Discrete Typing Units (TcI-TcVI). In this pathology, oral transmission represents an emerging epidemiological scenario where different outbreaks associated to food/beverages consumption have been reported in Argentina, Bolivia, Brazil, Ecuador and Venezuela. In Colombia, six human oral outbreaks have been reported corroborating the importance of this transmission route. Molecular epidemiology of oral outbreaks is barely known observing the incrimination of TcI, TcII, TcIV and TcV genotypes. Methodology and Principal Findings High-throughput molecular characterization was conducted performing MLMT (Multilocus Microsatellite Typing) and mtMLST (mitochondrial Multilocus Sequence Typing) strategies on 50 clones from ten isolates. Results allowed observing the occurrence of TcI, TcIV and mixed infection of distinct TcI genotypes. Thus, a majority of specific mitochondrial haplotypes and allelic multilocus genotypes associated to the sylvatic cycle of transmission were detected in the dataset with the foreseen presence of mitochondrial haplotypes and allelic multilocus genotypes associated to the domestic cycle of transmission. Conclusions These findings suggest the incrimination of sylvatic genotypes in the oral outbreaks occurred in Colombia. We observed patterns of super-infection and/or co-infection with a tailored association with the severe forms of myocarditis in the acute phase of the disease. The transmission dynamics of this infection route based on molecular epidemiology evidence was unraveled and the clinical and biological implications are discussed. PMID:23437405

  12. Association of inflammatory bowel disease risk loci with sarcoidosis, and its acute and chronic subphenotypes.

    PubMed

    Fischer, A; Nothnagel, M; Franke, A; Jacobs, G; Saadati, H R; Gaede, K I; Rosenstiel, P; Schürmann, M; Müller-Quernheim, J; Schreiber, S; Hofmann, S

    2011-03-01

    Sarcoidosis is a complex granulomatous inflammatory disorder that shares several clinical and pathogenic features with inflammatory bowel disease (IBD). Postulating a common genetic basis of inflammatory diseases, we tested 106 single-nucleotide polymorphisms (SNPs) that are known or have been suggested to be associated with IBD for a potential association with sarcoidosis and its acute and chronic subphenotypes. We genotyped 1,996 German sarcoidosis patients, comprising 648 acutely and 1,161 chronically affected individuals, 2,622 control subjects, and 342 German trios with affected offspring using SNPlex™ technology. The nonsynonymous SNP rs11209026 (Arg381Gln) in the interleukin (IL)-23 receptor (IL23R) gene was associated with chronic sarcoidosis (OR 0.63; p = 5.58×10(-5)), which was supported by the result of a transmission disequilibrium test analysis in the independent family sample (OR 0.50; p = 0.031). Marker rs12035082 located at chromosome 1q24.3 was found to be associated with the acute subphenotype (OR 1.36; p = 6.80×10(-7)) and rs916977 (HERC2 locus; OR 1.30; p = 4.49×10(-5)) was associated with sarcoidosis. Our results highlight the potential importance of the IL-23 signalling pathway for the development of chronic sarcoidosis. The finding links sarcoidosis pathogenesis to other inflammatory conditions and may contribute to new hypotheses on disease mechanisms. PMID:20650992

  13. Caroli's disease and congenital hepatic fibrosis associated with polycystic kidney disease. A case presenting with acute focal bacterial nephritis.

    PubMed

    Sung, J M; Huang, J J; Lin, X Z; Ruaan, M K; Lin, C Y; Chang, T T; Shu, H F; Chow, N H

    1992-12-01

    Congenital cystic dilatation of the intrahepatic biliary ducts (Caroli's disease), until recently, has been infrequently recognized. It is often associated with autosomal recessive polycystic kidney disease (ARPKD) and congenital hepatic fibrosis (CHF). We hereby report a case with Caroli's disease, polycystic kidney disease (PKD), and CHF: This 24-year-old female patient initially presented with acute bacterial nephritis (ABN). Renal ultrasonography revealed bilateral enlarged kidneys with multiple cysts. Because her parents showed no renal cyst on ultrasonographic examination, she received further studies. Abdominal ultrasonography showed cystic dilatation of the biliary tree. Computed tomography (CT) with meglumine lotroxinate (biliscopin) infusion study and hepatobiliary scintigraphy confirmed the diagnosis of Caroli's disease. Liver biopsy revealed CHF: The radiographic and scintigraphic pictures are hereby illustrated and CT with biliscopin infusion study is emphasized. We conclude that if radiologic evidence of renal cystic lesions is absent in the parents of patients with PKD, the coexistence of Caroli's disease and CHF should be considered. The clinical pictures of ABN in this patient are also discussed. As far as we know, this is the first reported case of ABN in a patient with PKD and Caroli's disease, and it showed good response to antibiotic therapy. PMID:1468163

  14. [Severe acute respiratory syndrome: the first transmissible disease of the 21st century].

    PubMed

    Nicastri, Emanuele; Petrosillo, Nicola; Macrì, Giulia; Ippolito, Giuseppe

    2003-01-01

    The Severe Acute Respiratory Syndrome (SARS) is the first severe and easily transmissible disease to emerge in the 21st century. It is caused by the infection with a coronavirus, a single strand RNA capsulated virus, recently found in a small mammalian, the masked palm civet. It is likely to represent the source of human infection. The first cases of SARS have been reported in the Chinese province of Guangdong and, since then, probable cases have been reported world wide. The clinical picture is characterized by nonspecific symptoms such as fever, cough or dyspnea in patients affected by air-space opacities (unifocal involvement in the 54.6% of cases) or distress respiratory syndrome and linked to a recent exposure to a SARS case or to a travel/residence in an affected area. The empirical therapy is based on broad-spectrum antibiotics, steroids and ribavirin, but susceptibility testing have failed to demonstrate direct anti-viral activity of ribavirin against SARS-related coronavirus in vitro. The exposure to respiratory droplets and the contact with biologic fluids (respiratory and gastrointestinal secretions) represent the most efficient transmission modality of the SARS-related coronavirus. Hand hygiene is the most simple and cost effective measure of infection control to prevent contagion, and the use of airborne, contact and droplet precaution is strictly recommended to all health care workers taking care of such patients. The spread of SARS, to less developed country with limited resource for public health programs, represent the emerging alarming threat in the new global scenario. PMID:12868234

  15. Further evidence of spontaneous cure in human Chagas disease.

    PubMed

    Dias, João Carlos Pinto; Dias, Emmanuel; Martins-Filho, Olindo Assis; Filho, Olindo M; Vitelli-Avelar, Danielle; Correia, Dalmo; Lages, Eliane; Prata, Aluízio

    2008-01-01

    An acute case of Chagas disease was studied in 1944, with clinical and laboratory follow-up until 2007, in Bambuí, Minas Gerais, Brazil. A five-year-old girl living in a rural hut that was highly infested with Triatoma infestans presented a febrile clinical condition compatible with the acute form of trypanosomiasis. She presented a positive thick blood smear, but never again showed serological and/or parasitological evidence of Trypanosoma cruzi infection, on several occasions. This patient never received any specific treatment and, to this day, she remains completely asymptomatic, with normal findings from clinical, electrocardiographic, X-ray and echocardiographic examinations. PMID:19009195

  16. Pharmacologic prophylaxis regimens for acute graft-versus-host disease: past, present and future.

    PubMed

    Ram, Ron; Storb, Rainer

    2013-08-01

    Abstract Acute graft-versus-host disease (GVHD) has compromised and continues to compromise the benefits associated with allogeneic hematopoietic cell transplant to cure malignant and non-malignant diseases. Pharmacologic interventions to prevent GVHD have emerged as a major objective of research in the immunology and transplant fields. A better understanding of the pathobiology behind the GVHD process has led the way to novel approaches and medications. Here we review the present arsenal of medications used to prevent GVHD, focusing on past experience and the current evidence, and discuss future potential targets. PMID:23278640

  17. Grover disease (transient acantholytic dermatosis) in acute myeloid leukemia on FDG PET/CT.

    PubMed

    Zhu, Hongyun June; Clark, Lindsey N; Deloney, Linda A; McDonald, James E

    2014-02-01

    A 48-year-old man with a newly diagnosed acute myeloid leukemia developed purpuric rash on day 6 after chemotherapy. Skin biopsy on day 8 demonstrated Grover disease. Triamcinolone treatment started on day 10 with subjective improvement on day 15. Initial FDG PET/CT on day 12 demonstrated rarely seen diffuse skin uptake that was interpreted as technical artifact and repeated on day 16. Accurately reviewing both PET and CT imaging would prevent confusion between diffuse cutaneous hypermetabolic activity and a technical artifact. Grover disease usually affects the trunk and may be related to the elimination of chemotherapy agents by sweating. PMID:24152615

  18. Prognosis and Prognostic Scoring Models for Alcoholic Liver Disease and Acute Alcoholic Hepatitis.

    PubMed

    Gholam, Pierre M

    2016-08-01

    Multiple prognostic scoring systems have been developed to predict mortality from acute alcoholic hepatitis. Some systems, such as the modified discriminant function, are specific to alcoholic hepatitis. Others, such as the model for end-stage liver disease, apply to a broad range of liver diseases. Prognostic factors are better at predicting patients who are likely to survive rather than die of this condition at 30 and 90 days. This important shortcoming may be improved by combining scores for better prediction accuracy. PMID:27373611

  19. Nutritional Status of Chronic Obstructive Pulmonary Disease Patients Admitted in Hospital With Acute Exacerbation

    PubMed Central

    Gupta, Barkha; Kant, Surya; Mishra, Rachna; Verma, Sanjay

    2010-01-01

    Background Patients with Chronic Obstructive Pulmonary Disease (COPD) are frequently hospitalized with an acute exacerbation. Patients with COPD often lose weight. Consequently, deterioration in nutritional status (loss of lean body mass) is a likely repercussion of acute exacerbation in hospitalized COPD patients. The study was carried out to assess the nutritional status of COPD patients with acute exacerbation, during the period of hospital admission, and to evaluate the relationships between the nutritional indices and the pulmonary function parameters. Methods A cross sectional observation study constituting 83 COPD patients consecutively hospitalized with acute exacerbation on accrual during a period of one year. Lung function was measured by routine spirometry. Nutritional status was assessed by the measurement of anthropometric parameters. Hospital outcome was also assessed. Statistical analysis was performed using SPSS version 16.0 Independent t-tests and Pearsons correlation coefficient was used. Results Mean body weight was 50.03 ± 9.23 kg. Subjects had approximately 5 kg weight loss in previous six months. All the subjects had low BMI (19.38 ± 3.10) and MUAC (21.18 ± 2.31) that was significantly below the predicted levels. The correlation between body weight and FEV1/FVC% was good (r = 0.648, p = 0.003). BMI was negatively correlated (r = - 0.0103, p= 0.03) with duration of hospital stay. Conclusions The high prevalence of malnutrition among hospitalized COPD patients with acute exacerbation is related to their lung function and hospital outcome such as duration of hospital stay. Keywords Nutritional status; COPD; Acute exacerbation; Hospitalization PMID:21811522

  20. GPR56 identifies primary human acute myeloid leukemia cells with high repopulating potential in vivo.

    PubMed

    Pabst, Caroline; Bergeron, Anne; Lavallée, Vincent-Philippe; Yeh, Jonathan; Gendron, Patrick; Norddahl, Gudmundur L; Krosl, Jana; Boivin, Isabel; Deneault, Eric; Simard, Jessica; Imren, Suzan; Boucher, Geneviève; Eppert, Kolja; Herold, Tobias; Bohlander, Stefan K; Humphries, Keith; Lemieux, Sébastien; Hébert, Josée; Sauvageau, Guy; Barabé, Frédéric

    2016-04-21

    Acute myeloid leukemia (AML) is a genetically heterogeneous hematologic malignancy, which is initiated and driven by a rare fraction of leukemia stem cells (LSCs). Despite the difficulties of identifying a common LSC phenotype, there is increasing evidence that high expression of stem cell gene signatures is associated with poor clinical outcome. Identification of functionally distinct subpopulations in this disease is therefore crucial to dissecting the molecular machinery underlying LSC self-renewal. Here, we combined next-generation sequencing technology with in vivo assessment of LSC frequencies and identified the adhesion G protein-coupled receptor 56 (GPR56) as a novel and stable marker for human LSCs for the majority of AML samples. High GPR56 expression was significantly associated with high-risk genetic subgroups and poor outcome. Analysis of GPR56 in combination with CD34 expression revealed engraftment potential of GPR56(+)cells in both the CD34(-)and CD34(+)fractions, thus defining a novel LSC compartment independent of the CD34(+)CD38(-)LSC phenotype. PMID:26834243

  1. Acute Alithiasic Cholecystitis and Human Herpes Virus Type-6 Infection: First Case.

    PubMed

    Gomes, Maria Miguel; Antunes, Henedina; Lobo, Ana Luísa; Branca, Fernando; Correia-Pinto, Jorge; Moreira-Pinto, João

    2016-01-01

    A three-year-old male child presented with erythematous maculopapular nonpruritic generalized rash, poor feeding, vomiting, and cramping generalized abdominal pain. He was previously healthy and there was no family history of immunologic or other diseases. On examination he was afebrile, hemodynamically stable, with painful palpation of the right upper quadrant and positive Murphy's sign. Laboratory tests revealed elevated inflammatory markers, elevated aminotransferase activity, and features of cholestasis. Abdominal ultrasound showed gallbladder wall thickening of 8 mm with a positive sonographic Murphy's sign, without gallstones or pericholecystic fluid. Acute Alithiasic Cholecystitis (AAC) was diagnosed. Tests for underlying infectious causes were negative except positive blood specimen for Human Herpes Virus Type-6 (HHV-6) by polymerase chain reaction. With supportive therapy the child became progressively less symptomatic with gradual improvement. The child was discharged on the sixth day, asymptomatic and with improved analytic values. Two months later he had IgM negative and IgG positive antibodies (1/160) for HHV-6, which confirmed the diagnosis of previous infection. In a six-month follow-up period he remains asymptomatic. To the best of our knowledge, this represents the first case of AAC associated with HHV-6 infection. PMID:27200203

  2. Acute Alithiasic Cholecystitis and Human Herpes Virus Type-6 Infection: First Case

    PubMed Central

    Lobo, Ana Luísa; Branca, Fernando

    2016-01-01

    A three-year-old male child presented with erythematous maculopapular nonpruritic generalized rash, poor feeding, vomiting, and cramping generalized abdominal pain. He was previously healthy and there was no family history of immunologic or other diseases. On examination he was afebrile, hemodynamically stable, with painful palpation of the right upper quadrant and positive Murphy's sign. Laboratory tests revealed elevated inflammatory markers, elevated aminotransferase activity, and features of cholestasis. Abdominal ultrasound showed gallbladder wall thickening of 8 mm with a positive sonographic Murphy's sign, without gallstones or pericholecystic fluid. Acute Alithiasic Cholecystitis (AAC) was diagnosed. Tests for underlying infectious causes were negative except positive blood specimen for Human Herpes Virus Type-6 (HHV-6) by polymerase chain reaction. With supportive therapy the child became progressively less symptomatic with gradual improvement. The child was discharged on the sixth day, asymptomatic and with improved analytic values. Two months later he had IgM negative and IgG positive antibodies (1/160) for HHV-6, which confirmed the diagnosis of previous infection. In a six-month follow-up period he remains asymptomatic. To the best of our knowledge, this represents the first case of AAC associated with HHV-6 infection. PMID:27200203

  3. Modified skin window technique for the extended characterisation of acute inflammation in humans

    PubMed Central

    Marks, D. J. B.; Radulovic, M.; McCartney, S.; Bloom, S.; Segal, A. W.

    2009-01-01

    Objective To modify the skin window technique for extended analysis of acute inflammatory responses in humans, and demonstrate its applicability for investigating disease. Subjects 15 healthy subjects and 5 Crohn’s patients. Treatment Skin windows, created by dermal abrasion, were overlaid for various durations with filter papers saturated in saline, 100 ng/ml muramyl dipeptide (MDP) or 10 μg/ml interleukin-8 (IL-8). Methods Exuded leukocytes were analyzed by microscopy, immunoblot, DNA-bound transcription factor arrays and RT-PCR. Inflammatory mediators were quantified by ELISA. Results Infiltrating leukocytes were predominantly neutrophils. Numerous secreted mediators were detectable. MDP and IL-8 enhanced responses. Many signalling proteins were phosphorylated with differential patterns in Crohn’s patients, notably PKC α/β hyperphosphorylation (11.3 ± 3.1 vs 1.2 ± 0.9 units, P < 0.02). Activities of 44 transcription factors were detectable, and sufficient RNA isolated for expression analysis of over 400 genes. Conclusions The modifications enable broad characterisation of inflammatory responses and administration of exogenous immunomodulators. PMID:17522815

  4. Intestinal Microbiota-Kidney Cross Talk in Acute Kidney Injury and Chronic Kidney Disease

    PubMed Central

    Noel, Sanjeev; Martina-Lingua, Maria N.; Bandapalle, Samatha; Pluznick, Jennifer; Hamad, Abdel Rahim A.; Peterson, Daniel A.; Rabb, Hamid

    2016-01-01

    The pathophysiology of acute kidney injury (AKI) involves multiple and overlapping immunological, biochemical, and hemodynamic mechanisms that modulate the effects of both the initial insult and the subsequent repair. Limited but recent experimental data have revealed that the intestinal microbiota significantly affects outcomes in AKI. Additional evidence shows significant changes in the intestinal microbiota in chronic kidney disease patients and in experimental AKI. In this minireview, we discuss the current status of the effect of intestinal microbiota on kidney diseases, the immunomodulatory effects of intestinal microbiota, and the potential mechanisms by which microbiota can modify kidney diseases and vice versa. We also propose future studies to clarify the role of intestinal microbiota in kidney diseases and to explore how the modification of gut microbiota may be a potential therapeutic tool. PMID:25343838

  5. Adalimumab-induced acute interstitial lung disease in a patient with rheumatoid arthritis*

    PubMed Central

    Dias, Olívia Meira; Pereira, Daniel Antunes Silva; Baldi, Bruno Guedes; Costa, André Nathan; Athanazio, Rodrigo Abensur; Kairalla, Ronaldo Adib; Carvalho, Carlos Roberto Ribeiro

    2014-01-01

    The use of immunobiological agents for the treatment of autoimmune diseases is increasing in medical practice. Anti-TNF therapies have been increasingly used in refractory autoimmune diseases, especially rheumatoid arthritis, with promising results. However, the use of such therapies has been associated with an increased risk of developing other autoimmune diseases. In addition, the use of anti-TNF agents can cause pulmonary complications, such as reactivation of mycobacterial and fungal infections, as well as sarcoidosis and other interstitial lung diseases (ILDs). There is evidence of an association between ILD and the use of anti-TNF agents, etanercept and infliximab in particular. Adalimumab is the newest drug in this class, and some authors have suggested that its use might induce or exacerbate preexisting ILDs. In this study, we report the first case of acute ILD secondary to the use of adalimumab in Brazil, in a patient with rheumatoid arthritis and without a history of ILD. PMID:24626274

  6. The effects of acute alcohol administration on the human brain: Insights from neuroimaging

    PubMed Central

    Bjork, James M.; Gilman, Jodi M.

    2014-01-01

    Over the last quarter century, researchers have peered into the living human brain to develop and refine mechanistic accounts of alcohol-induced behavior, as well as neurobiological mechanisms for development and maintenance of addiction. These in vivo neuroimaging studies generally show that acute alcohol administration affects brain structures implicated in motivation and behavior control, and that chronic intoxication is correlated with structural and functional abnormalities in these same structures, where some elements of these decrements normalize with extended sobriety. In this review, we will summarize recent findings about acute human brain responses to alcohol using neuroimaging techniques, and how they might explain behavioral effects of alcohol intoxication. We then briefly address how chronic alcohol intoxication (as inferred from cross-sectional differences between various drinking populations and controls) may yield individual brain differences between drinking subjects that may confound interpretation of acute alcohol administration effects. PMID:23978384

  7. Computations of uncertainty mediate acute stress responses in humans

    PubMed Central

    de Berker, Archy O.; Rutledge, Robb B.; Mathys, Christoph; Marshall, Louise; Cross, Gemma F.; Dolan, Raymond J.; Bestmann, Sven

    2016-01-01

    The effects of stress are frequently studied, yet its proximal causes remain unclear. Here we demonstrate that subjective estimates of uncertainty predict the dynamics of subjective and physiological stress responses. Subjects learned a probabilistic mapping between visual stimuli and electric shocks. Salivary cortisol confirmed that our stressor elicited changes in endocrine activity. Using a hierarchical Bayesian learning model, we quantified the relationship between the different forms of subjective task uncertainty and acute stress responses. Subjective stress, pupil diameter and skin conductance all tracked the evolution of irreducible uncertainty. We observed a coupling between emotional and somatic state, with subjective and physiological tuning to uncertainty tightly correlated. Furthermore, the uncertainty tuning of subjective and physiological stress predicted individual task performance, consistent with an adaptive role for stress in learning under uncertain threat. Our finding that stress responses are tuned to environmental uncertainty provides new insight into their generation and likely adaptive function. PMID:27020312

  8. Analogue peptides for the immunotherapy of human acute myeloid leukemia.

    PubMed

    Hofmann, Susanne; Mead, Andrew; Malinovskis, Aleksandrs; Hardwick, Nicola R; Guinn, Barbara-Ann

    2015-11-01

    The use of peptide vaccines, enhanced by adjuvants, has shown some efficacy in clinical trials. However, responses are often short-lived and rarely induce notable memory responses. The reason is that self-antigens have already been presented to the immune system as the tumor develops, leading to tolerance or some degree of host tumor cell destruction. To try to break tolerance against self-antigens, one of the methods employed has been to modify peptides at the anchor residues to enhance their ability to bind major histocompatibility complex molecules, extending their exposure to the T-cell receptor. These modified or analogue peptides have been investigated as stimulators of the immune system in patients with different cancers with variable but sometimes notable success. In this review we describe the background and recent developments in the use of analogue peptides for the immunotherapy of acute myeloid leukemia describing knowledge useful for the application of analogue peptide treatments for other malignancies. PMID:26438084

  9. Human Pluripotent Stem Cells: Applications and Challenges in Neurological Diseases

    PubMed Central

    Hibaoui, Youssef; Feki, Anis

    2012-01-01

    The ability to generate human pluripotent stem cells (hPSCs) holds great promise for the understanding and the treatment of human neurological diseases in modern medicine. The hPSCs are considered for their in vitro use as research tools to provide relevant cellular model for human diseases, drug discovery, and toxicity assays and for their in vivo use in regenerative medicine applications. In this review, we highlight recent progress, promises, and challenges of hPSC applications in human neurological disease modeling and therapies. PMID:22934023

  10. Cyclosporine and methotrexate-related pharmacogenomic predictors of acute graft-versus-host disease

    PubMed Central

    Laverdière, Isabelle; Guillemette, Chantal; Tamouza, Ryad; Loiseau, Pascale; de Latour, Regis Peffault; Robin, Marie; Couture, Félix; Filion, Alain; Lalancette, Marc; Tourancheau, Alan; Charron, Dominique; Socié, Gérard; Lévesque, Éric

    2015-01-01

    Effective immunosuppression is mandatory to prevent graft-versus-host disease and to achieve a successful clinical outcome of hematopoietic stem cell transplantation. Here we tested whether germline single nucleotide polymorphisms in 20 candidate genes related to methotrexate and cyclosporine metabolism and activity influence the incidence of graft-versus-host disease in patients who undergo stem cell transplantation for hematologic disorders. Recipient genetic status of the adenosine triphosphate-binding cassette sub-family C1 and adenosine triphosphate-binding cassette sub-family C2 transporters, 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/ inosine monophosphate cyclohydrolase within the methotrexate pathway, and nuclear factor of activated T cells (cytoplasmic 1) loci exhibit a remarkable influence on severe acute graft-versus-host disease prevalence. Indeed, an increased risk of acute graft-versus-host disease was observed in association with single nucleotide polymorphisms located in 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase (hazard ratio=3.04; P=0.002), nuclear factor of activated T cells (cytoplasmic 1) (hazard ratio=2.69; P=0.004), adenosine triphosphate-binding cassette sub-family C2 (hazard ratio=3.53; P=0.0018) and adenosine triphosphate-binding cassette sub-family C1 (hazard ratio=3.67; P=0.0005). While donor single nucleotide polymorphisms of dihydrofolate reductase and solute carrier family 19 (member 1) genes are associated with a reduced risk of acute graft-versus-host disease (hazard ratio=0.32–0.41; P=0.0009–0.008), those of nuclear factor of activated T cells (cytoplasmic 2) are found to increase such risk (hazard ratio=3.85; P=0.0004). None of the tested single nucleotide polymorphisms was associated with the occurrence of chronic graft-versus-host disease. In conclusion, by targeting drug-related biologically relevant genes, this work emphasizes the potential

  11. Cyclosporine and methotrexate-related pharmacogenomic predictors of acute graft-versus-host disease.

    PubMed

    Laverdière, Isabelle; Guillemette, Chantal; Tamouza, Ryad; Loiseau, Pascale; Peffault de Latour, Regis; Robin, Marie; Couture, Félix; Filion, Alain; Lalancette, Marc; Tourancheau, Alan; Charron, Dominique; Socié, Gérard; Lévesque, Éric

    2015-02-01

    Effective immunosuppression is mandatory to prevent graft-versus-host disease and to achieve a successful clinical outcome of hematopoietic stem cell transplantation. Here we tested whether germline single nucleotide polymorphisms in 20 candidate genes related to methotrexate and cyclosporine metabolism and activity influence the incidence of graft-versus-host disease in patients who undergo stem cell transplantation for hematologic disorders. Recipient genetic status of the adenosine triphosphate-binding cassette sub-family C1 and adenosine triphosphate-binding cassette sub-family C2 transporters, 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/ inosine monophosphate cyclohydrolase within the methotrexate pathway, and nuclear factor of activated T cells (cytoplasmic 1) loci exhibit a remarkable influence on severe acute graft-versus-host disease prevalence. Indeed, an increased risk of acute graft-versus-host disease was observed in association with single nucleotide polymorphisms located in 5-aminoimidazole-4-carboxamide ribonucleotide formyltransferase/inosine monophosphate cyclohydrolase (hazard ratio=3.04; P=0.002), nuclear factor of activated T cells (cytoplasmic 1) (hazard ratio=2.69; P=0.004), adenosine triphosphate-binding cassette sub-family C2 (hazard ratio=3.53; P=0.0018) and adenosine triphosphate-binding cassette sub-family C1 (hazard ratio=3.67; P=0.0005). While donor single nucleotide polymorphisms of dihydrofolate reductase and solute carrier family 19 (member 1) genes are associated with a reduced risk of acute graft-versus-host disease (hazard ratio=0.32-0.41; P=0.0009-0.008), those of nuclear factor of activated T cells (cytoplasmic 2) are found to increase such risk (hazard ratio=3.85; P=0.0004). None of the tested single nucleotide polymorphisms was associated with the occurrence of chronic graft-versus-host disease. In conclusion, by targeting drug-related biologically relevant genes, this work emphasizes the potential role of

  12. Mouse models of acute, chemical itch and pain in humans

    PubMed Central

    LaMotte, Robert H.; Shimada, Steven G.; Sikand, Parul

    2011-01-01

    In psychophysical experiments, humans use different verbal responses to pruritic and algesic chemical stimuli to indicate the different qualities of sensation they feel. A major challenge for behavioral models in the mouse of chemical itch and pain in humans is to devise experimental protocols that provide the opportunity for the animal to exhibit a multiplicity of responses as well. One basic criterion is that chemicals that evoke primarily itch or pain in humans should elicit different types of responses when applied in the same way to the mouse. Meeting this criterion is complicated by the fact that the type of behavioral responses exhibited by the mouse depends in part on the site of chemical application such as the nape of the neck which evokes only scratching with the hind paw vs. the hind limb which elicits licking and biting. Here, we review to what extent mice behaviorally differentiate chemicals that elicit itch vs. pain in humans. PMID:21929688

  13. Particle-induced pulmonary acute phase response may be the causal link between particle inhalation and cardiovascular disease

    PubMed Central

    Saber, Anne T; Jacobsen, Nicklas R; Jackson, Petra; Poulsen, Sarah Søs; Kyjovska, Zdenka O; Halappanavar, Sabina; Yauk, Carole L; Wallin, Håkan; Vogel, Ulla

    2014-01-01

    Inhalation of ambient and workplace particulate air pollution is associated with increased risk of cardiovascular disease. One proposed mechanism for this association is that pulmonary inflammation induces a hepatic acute phase response, which increases risk of cardiovascular disease. Induction of the acute phase response is intimately linked to risk of cardiovascular disease as shown in both epidemiological and animal studies. Indeed, blood levels of acute phase proteins, such as C-reactive protein and serum amyloid A, are independent predictors of risk of cardiovascular disease in prospective epidemiological studies. In this review, we present and review emerging evidence that inhalation of particles (e.g., air diesel exhaust particles and nanoparticles) induces a pulmonary acute phase response, and propose that this induction constitutes the causal link between particle inhalation and risk of cardiovascular disease. Increased levels of acute phase mRNA and proteins in lung tissues, bronchoalveolar lavage fluid and plasma clearly indicate pulmonary acute phase response following pulmonary deposition of different kinds of particles including diesel exhaust particles, nanoparticles, and carbon nanotubes. The pulmonary acute phase response is dose-dependent and long lasting. Conversely, the hepatic acute phase response is reduced relative to lung or entirely absent. We also provide evidence that pulmonary inflammation, as measured by neutrophil influx, is a predictor of the acute phase response and that the total surface area of deposited particles correlates with the pulmonary acute phase response. We discuss the implications of these findings in relation to occupational exposure to nanoparticles. How to cite this article: WIREs Nanomed Nanobiotechnol 2014, 6:517–531. doi: 10.1002/wnan.1279 PMID:24920450

  14. Ambient air pollution particles and the acute exacerbation of chronic obstructive pulmonary disease

    EPA Science Inventory

    Investigation has repeatedly demonstrated an association between exposure to ambient air pollution particles and numerous indices of human morbidity and mortality. Individuals with chronic obstructive pulmonary disease (COPD) are among those with an increased sensitivity to air p...

  15. Vitamin E in human health and disease.

    PubMed

    Clarke, Michael W; Burnett, John R; Croft, Kevin D

    2008-01-01

    Vitamin E in nature is comprised of a family of tocopherols and tocotrienols. The most studied of these is alpha-tocopherol (alpha-TOH), because this form is retained within the body, and vitamin E deficiency is corrected with this supplement. alpha-TOH is a lipid-soluble antioxidant required for the preservation of cell membranes, and it potentially acts as a defense against oxidative stress. Many studies have investigated the metabolism, transport, and efficacy alpha-TOH in the prevention of sequelae associated with cardiovascular disease (CVD). Supplementation with vitamin E is considered to provide health benefits against CVD through its antioxidant activity, the prevention of lipoprotein oxidation, and the inhibition of platelet aggregation. However, the results from large prospective, randomized, placebo-controlled clinical trials with alpha-TOH have been largely negative. A recent meta-analysis suggests that alpha-TOH supplements may actually increase all-cause mortality; however, the mechanism for this increased risk is unknown. In vitro studies performed in human cell cultures and animal models suggest that vitamin E might increase the hepatic production of cytochrome P450s and MDR1. Induction of CYP3A4 or MDR1 by vitamin E could potentially lower the efficacy of any drug metabolized by CYP3A4 or MDR1. Other possibilities include an adverse effect of alpha-TOH on blood pressure in high-risk populations. Because of the wide popularity and use of vitamin E supplements, further research into potential adverse effects is clearly warranted. PMID:18712629

  16. Human milk proresolving mediators stimulate resolution of acute inflammation.

    PubMed

    Arnardottir, H; Orr, S K; Dalli, J; Serhan, C N

    2016-05-01

    Human milk contains nutrients and bioactive products relevant to infant development and immunological protection. Here, we investigated the proresolving properties of milk using human milk lipid mediator isolates (HLMIs) and determined their impact on resolution programs in vivo and with human macrophages. HLMIs reduced the maximum neutrophil numbers (14.6±1.2 × 10(6)-11.0±1.0 × 10(6) cells per exudate) and shortened the resolution interval (Ri; 50% neutrophil reduction) by 54% compared with peritonitis. Using rigorous liquid-chromatography tandem-mass spectrometry (LC-MS-MS)-based lipid mediator (LM) metabololipidomics, we demonstrated that human milk possesses a proresolving LM-specialized proresolving mediator (LM-SPM) signature profile, containing SPMs (e.g. resolvins (Rv), protectins (PDs), maresins (MaRs), and lipoxins (LXs)) at bioactive levels (pico-nanomolar concentrations) that enhanced human macrophage efferocytosis and bacterial containment. SPMs identified in human milk included D-series Rvs (e.g., RvD1, RvD2, RvD3, AT-RvD3, and RvD4), PD1, MaR1, E-series Rvs (e.g. RvE1, RvE2, and RvE3), and LXs (LXA4 and LXB4). Of the SPMs identified in human milk, RvD2 and MaR1 (50 ng per mouse) individually shortened Ri by ∼75%. Milk from mastitis gave higher leukotriene B4 and prostanoids and lower SPM levels. Taken together, these findings provide evidence that human milk has proresolving actions via comprehensive LM-SPM profiling, describing a potentially novel mechanism in maternal-infant biochemical imprinting. PMID:26462421

  17. Human Milk Proresolving Mediators Stimulate Resolution of Acute Inflammation

    PubMed Central

    Dalli, Jesmond; Serhan, Charles N

    2015-01-01

    Human milk contains nutrients and bioactive products relevant to infant development and immunological protection. Here, we investigated the pro-resolving properties of milk using human milk lipid mediator isolates (HLMI) and determined their impact on resolution programs in vivo and with human macrophages. HLMI reduced maximum neutrophil numbers (14.6±1.2×106 to 11.0±1.0×106 cells/exudate) and shortened the resolution interval (Ri; 50% neutrophil reduction) 54% compared to peritonitis. Using rigorous liquid-chromatography tandem-mass spectrometry (LC-MS-MS)-based lipid mediator (LM) metabololipidomics, we demonstrated that human milk possesses a proresolving LM-SPM signature profile, containing specialized proresolving mediators (SPM; e.g. resolvins, protectins, maresins and lipoxins) at bioactive levels (pico-nanomolar concentrations) that enhanced human macrophage efferocytosis and bacterial containment. SPM identified in human milk included D-series resolvins, (e.g. Resolvin (Rv) D1, RvD2, RvD3, AT-RvD3 and RvD4), Protectin (PD)1, Maresin (MaR)1, E-series resolvins (e.g. RvE1, RvE2 and RvE3) and lipoxins (LXA4 and LXB4). Of the SPM identified in human milk, RvD2 and MaR1 (50 ng/mouse) individually shortened Ri ~75%. Milk from mastitis gave higher LTB4 and prostanoids and lower SPM levels. Taken together, these findings provide evidence that human milk has pro-resolving actions via comprehensive LM-SPM profiling, describing a potentially novel mechanism in maternal-infant biochemical imprinting. PMID:26462421

  18. Geographic Distribution and Expansion of Human Lyme Disease, United States

    PubMed Central

    2015-01-01

    Lyme disease occurs in specific geographic regions of the United States. We present a method for defining high-risk counties based on observed versus expected number of reported human Lyme disease cases. Applying this method to successive periods shows substantial geographic expansion of counties at high risk for Lyme disease. PMID:26196670

  19. Treatment strategies in the left main coronary artery disease associated with acute coronary syndromes.

    PubMed

    Karabulut, Ahmet; Cakmak, Mahmut

    2015-10-01

    Significant left main coronary artery (LMCA) stenosis is not rare and reported 3 to 10% of patients undergoing coronary angiography. Unprotected LMCA intervention is a still clinical challenge and surgery is still going to be a traditional management method in many cardiac centers. With a presentation of drug eluting stent (DES), extensive use of IVUS and skilled operators, number of such interventions increased rapidly which lead to change in recommendation in the guidelines regarding LMCA procedures in the stable angina (Class 2a recommendation for ostial and shaft lesion and class 2b recommendation for distal bifurcation lesion). However, there was not clear consensus about the management of unprotected LMCA lesion associated with acute myocardial infarction (MI) with a LMCA culprit lesion itself or distinct culprit lesion of other major coronary arteries. Surgery could be preferred as an obligatory management strategy even in the high risk patients. With this review, we aimed to demonstrate treatment strategies of LMCA disease associated with acute coronary syndrome, particularly acute myocardial infarction (MI). In addition, we presented a short case series with LMCA lesion and ST elevated acute MI in which culprit lesion placed either in the left anterior descending artery or circumflex artery. We reviewed the current medical literature and propose simple algorithm for management. PMID:26557745

  20. [Complementary treatment of acute heart failure in patients with diabetes, chronic obstructive pulmonary disease or anemia].

    PubMed

    Carrasco Sánchez, Francisco Javier; Recio Iglesias, Jesús; Grau Amorós, Jordi

    2014-03-01

    Diabetes, chronic obstructive pulmonary disease (COPD) and anemia are comorbidities with a high prevalence and impact in heart failure (HF). The presence of these comorbidities considerably worsens the prognosis of HF. Diabetic patients have a higher likelihood of developing symptoms of HF and both the treatment of diabetes and that of acute HF are altered by the coexistence of both entities. The glycemic targets in patients with acute HF are not well-defined, but could show a U-shaped relationship. Stress hyperglycemia in non-diabetic patients with HF could also have a deleterious effect on the medium-term prognosis. The inter-relationship between COPD and HF hampers diagnosis due to the overlap between the symptoms and signs of both entities and complementary investigations. The treatment of acute HF is also altered by the presence of COPD. Anemia is highly prevalent and is often the direct cause of decompensated HF, the most common cause being iron deficiency anemia. Iron replacement therapy, specifically intravenous forms, has helped to improve the prognosis of acute HF. PMID:24930086

  1. Fatal Outcome of Multiple Clinical Presentations of Human Herpesvirus 8-related Disease After Solid Organ Transplantation.

    PubMed

    Vijgen, Sandrine; Wyss, Caroline; Meylan, Pascal; Bisig, Bettina; Letovanec, Igor; Manuel, Oriol; Pascual, Manuel; de Leval, Laurence

    2016-01-01

    Kaposi sarcoma is the most common human herpesvirus 8 (HHV-8)-related disease described after solid organ transplantation. Multicentric Castleman disease and hemophagocytic syndrome are other potential HHV-8-induced entities but are less frequently reported. We describe the case of a liver transplant recipient who presented with an acute febrile illness 1 year after transplantation with a rapidly fatal outcome. Autopsy revealed 3 distinct HHV-8-related entities: Kaposi sarcoma, HHV-8-associated multicentric Castleman disease with microlymphomas and a severe hemophagocytic syndrome. Retrospective serologic tests suggested that HHV-8 was likely transmitted by the seropositive donor at the time of transplantation. To our knowledge, this is the first case of copresentation of 3 clinical presentations of HHV-8-mediated human disease in the post-transplant setting. Considering the absence of systematic screening of organ donors/recipients for HHV-8 infection, HHV-8-related illness should be suspected in transplant recipients who present with acute febrile illness, systemic symptoms, lymphadenopathies, and/or multiorgan failure to rapidly document the diagnosis and provide timely an adequate treatment. PMID:26120765

  2. Knowledge of Acute Human Immnuodeficiency Virus Infection among Gay and Bisexual Male College Students

    ERIC Educational Resources Information Center

    Grin, Benjamin; Chan, Philip A.; Operario, Don

    2013-01-01

    Objective: To examine human immunodeficiency virus (HIV)-related knowledge, attitudes, and behaviors in at-risk college men who have sex with men (MSM), focusing on knowledge about acute HIV infection (AHI). Participants and Methods: A one-time anonymous survey was administered to college students attending a lesbian, gay, bisexual, transgender,…

  3. The value of acute toxicity testing of pharmaceuticals for estimation of human response.

    PubMed

    Barle, Ester Lovšin; Looser, Roland; Cerne, Manica; Bechter, Rudolf

    2012-04-01

    The determination of single high doses of active pharmaceutical ingredients (API) is used mostly to fulfill regulatory demands. Oral LD(50) values in animals for over 300 API were compared to the minimal effective therapeutic doses (METD) in humans in order to find a correlation between animal and human data. The highest correlation between human METD and animal LD(50) was found for the dog (R=0.323), the lowest for the rat (0.287). It was determined that acute oral LD(50) of rats have poor correlation with the METD, and cannot be used as a classification criteria into official acute toxic categories. Only 13% of API has been classified as fatal if swallowed according to the EU CLP regulation, none of the substances with very low therapeutic dose have been identified as EU CLP acute toxicity category 1. Substances with very low therapeutic doses, which could potentially have toxic effects in humans, are not identified with the use of oral LD(50) and current classification system. We propose that the acute toxicity based on rat LD(50) dose is not used as a basis for classification of pharmaceuticals, and that the METD is applied as basis for classification. PMID:22306828

  4. A QUANTITATIVE COMPARISON OF THE EFFECTS OF ACUTE INHALED TOLUENE IN HUMAN RATS

    EPA Science Inventory

    The effects of acute exposure to toluene have been explored more thoroughly than other hydrocarbon solvents. These effects have been experimentally studied in humans and other species, e.g., rats, as well as in a number of in vitro preparations. The existence ofdosimetric and eff...

  5. Characteristics and outcomes of chronic liver disease patients with acute deteriorated liver function by severity of underlying liver disease

    PubMed Central

    Hong, Yun Soo; Sinn, Dong Hyun; Gwak, Geum-Youn; Cho, Juhee; Kang, Danbee; Paik, Yong-Han; Choi, Moon Seok; Lee, Joon Hyeok; Koh, Kwang Cheol; Paik, Seung Woon

    2016-01-01

    AIM: To analyze characteristics and outcome of patients with acute-on-chronic liver failure (ACLF) according to the severity of underlying liver disease. METHODS: One hundred and sixty-seven adult patients with chronic liver disease and acute deteriorated liver function, defined by jaundice and coagulopathy, were analyzed. Predisposition, type of injury, response, organ failure, and survival were analyzed and compared between patients with non-cirrhosis (type A), cirrhosis (type B) and cirrhosis with previous decompensation (type C). RESULTS: The predisposition was mostly hepatitis B in type A, while it was alcoholic liver disease in types B and C. Injury was mostly hepatic in type A, but was non-hepatic in type C. Liver failure, defined by CLIF-SOFA, was more frequent in types A and B, and circulatory failure was more frequent in type C. The 30-d overall survival rate (85.3%, 81.1% and 83.7% for types A, B and C, respectively, P = 0.31) and the 30-d transplant-free survival rate (55.9%, 65.5% and 62.5% for types A, B and C, respectively P = 0.33) were not different by ACLF subtype, but 1-year overall survival rate were different (85.3%, 71.7% and 58.7% for types A, B and C, respectively, P = 0.02). CONCLUSION: There were clear differences in predisposition, type of injury, accompanying organ failure and long-term mortality according to spectrum of chronic liver disease, implying classifying subtype according to the severity of underlying liver disease is useful for defining, clarifying and comparing ACLF. PMID:27076763

  6. Serum metabolomics study of the acute graft rejection in human renal transplantation based on liquid chromatography-mass spectrometry.

    PubMed

    Zhao, Xinjie; Chen, Jihong; Ye, Lei; Xu, Guowang

    2014-05-01

    Acute graft rejection is one of the most common and serious postcomplications in renal transplantation. A noninvasive method is needed to specifically monitor acute graft rejection. We investigated metabolic alterations of acute graft rejection in human renal transplantation by applying a metabolomics approach. Sera from 11 acute graft rejection subjects and 16 nonacute graft rejection subjects were analyzed by a nontargeted liquid chromatography-mass spectrometry (LC-MS) metabolomics approach including both hydrophilic interaction chromatography and reversed-phase liquid chromatography separations. Discriminative metabolites of acute graft rejection after transplantation were detected, including creatinine, kynurenine, uric acid, polyunsaturated fatty acid, phosphatidylcholines, sphingomyelins, lysophosphatidylcholines, etc. The lower level of serum dehydroepiandrosterone sulfate was found in the acute graft rejection group before transplantation. The results revealed comprehensive metabolic abnormalities in acute graft rejection. The findings are valuable for the clinic noninvasive diagnosis or therapy of acute graft rejection. PMID:24641727

  7. Role of TNF in sickness behavior and allodynia during the acute phase of Chagas' disease.

    PubMed

    Rodríguez-Angulo, H; Thomas, L E; Castillo, E; Cárdenas, E; Mogollón, F; Mijares, A

    2013-08-01

    Chagas disease, caused by the intracellular protozoan Trypanosoma cruzi, is associated with inflammation, discomfort and pain during the acute phase. The influence of TNF-α (tumor necrosis factor) in this disease outcome is controversial. In this way, the aim of this work was to determine the role of the TNF-α blocker etanercept in the pain, discomfort, and survival during the Chagas' acute phase of mice experimentally infected with a wild virulent strain of T. cruzi. The infection with this wild strain was responsible for a severe visceral inflammation and said parasite showed a tropism in peritoneal fluid cells. Etanercept was able to restore spontaneous vertical and horizontal activities during the second week after infection and to abolish mechanical allodynia during the first week after infection. Finally, etanercept delayed the mortality without any effect on the parasitemia rates. This is the first report that correlates sickness behavior and allodynia with TNF-α and suggests that this cytokine may play an important role in the physiopathology of the acute phase. PMID:23684908

  8. Hepatic steatosis depresses alpha-1-antitrypsin levels in human and rat acute pancreatitis

    PubMed Central

    Wang, Qian; Du, Jianjun; Yu, Pengfei; Bai, Bin; Zhao, Zhanwei; Wang, Shiqi; Zhu, Junjie; Feng, Quanxin; Gao, Yun; Zhao, Qingchuan; Liu, Chaoxu

    2015-01-01

    Hepatic steatosis (HS) can exacerbate acute pancreatitis (AP). This study aimed to investigate the relation between α1-antitrypsin (AAT) and acute pancreatitis when patients have HS. Using proteomic profiling, we identified 18 differently expressed proteins pots in the serum of rats with or without HS after surgical establishment of AP. AAT was found to be one of the significantly down-regulated proteins. AAT levels were significantly lower in hepatic steatosis acute pancreatitis (HSAP) than in non-HSAP (NHSAP) (P < 0.001). To explore the clinical significance of these observations, we measured the levels of AAT in the serum of 240 patients with HSAP, NHSAP, fatty liver disease (FLD), or no disease. Compared with healthy controls, serum AAT levels in patients with NHSAP were significantly higher (P < 0.01), while in patients with HSAP serum AAT levels were significantly lower (P < 0.01). Further studies showed that acute physiology and chronic health evaluation (APACHE-II) scores were negatively correlated with serum AAT levels (r = −0.85, P < 0.01). In conclusion, low serum levels of AAT in patients with HSAP are correlated with disease severity and AAT may represent a potential target for therapies aiming to improve pancreatitis. PMID:26634430

  9. Hepatic steatosis depresses alpha-1-antitrypsin levels in human and rat acute pancreatitis.

    PubMed

    Wang, Qian; Du, Jianjun; Yu, Pengfei; Bai, Bin; Zhao, Zhanwei; Wang, Shiqi; Zhu, Junjie; Feng, Quanxin; Gao, Yun; Zhao, Qingchuan; Liu, Chaoxu

    2015-01-01

    Hepatic steatosis (HS) can exacerbate acute pancreatitis (AP). This study aimed to investigate the relation between α1-antitrypsin (AAT) and acute pancreatitis when patients have HS. Using proteomic profiling, we identified 18 differently expressed proteins pots in the serum of rats with or without HS after surgical establishment of AP. AAT was found to be one of the significantly down-regulated proteins. AAT levels were significantly lower in hepatic steatosis acute pancreatitis (HSAP) than in non-HSAP (NHSAP) (P < 0.001). To explore the clinical significance of these observations, we measured the levels of AAT in the serum of 240 patients with HSAP, NHSAP, fatty liver disease (FLD), or no disease. Compared with healthy controls, serum AAT levels in patients with NHSAP were significantly higher (P < 0.01), while in patients with HSAP serum AAT levels were significantly lower (P < 0.01). Further studies showed that acute physiology and chronic health evaluation (APACHE-II) scores were negatively correlated with serum AAT levels (r = -0.85, P < 0.01). In conclusion, low serum levels of AAT in patients with HSAP are correlated with disease severity and AAT may represent a potential target for therapies aiming to improve pancreatitis. PMID:26634430

  10. [Bronchial asthma and chronic obstructive pulmonary disease with acute exacerbation: preclinical differential diagnostic and emergency treatment].

    PubMed

    Friege, B; Friege, L; Pelz, J; Weber, M; von Spiegel, T; Schröder, S

    2009-06-01

    Chronic obstructive pulmonary disease (COPD) and bronchial asthma are the most common causes of obstructive pulmonary diseases and acute dyspnoea. In the preclinical emergency situation a distinction between bronchial asthma and exacerbated COPD is difficult because symptoms are similar. Although the preclinical measures differ only marginally, a differential diagnosis from other causes of respiratory obstruction and acute dyspnoea, such as cardiac decompensation, anaphylaxis, aspiration of foreign bodies, tension pneumothorax and inhalation trauma is necessary because alternative treatment options are required. In the treatment of COPD and bronchial asthma inhalative bronchodilatory beta(2)-mimetics are the first choice especially for serious obstructive emergencies because there is an unfavorable relationship between effect and side-effects for the intravenous route. Dosable aerosols, nebulization and if necessary, continuous nebulization, are appropriate application forms even for serious obstructive crises with the need of a respirator. In these cases a minimal inspiratory flow in patients is not required. Theophylline only plays a minor role to beta(2)-mimetics and anticholinergics as a bronchodilator in asthma and COPD guidelines, even in serious obstructive diseases. For severe asthma attacks the administration of magnesium is a possible additional option. Systemic intravenous administration of steroids has an anti-inflammatory effect and for this reason is the second column of treatment for both diseases. Invasive ventilation remains a last resort to ensure respiratory function and indications for this are given in patients with clinical signs of impending exhaustion of breathing. PMID:19424670

  11. Protein biomarkers associated with acute renal failure and chronic kidney disease.

    PubMed

    Perco, P; Pleban, C; Kainz, A; Lukas, A; Mayer, G; Mayer, B; Oberbauer, R

    2006-11-01

    Acute renal failure (ARF) as well as chronic kidney disease (CKD) are currently categorized according to serum creatinine concentrations. Serum creatinine, however, has shortcomings because of its low predictive values. The need for novel markers for the early diagnosis and prognosis of renal diseases is imminent, particularly for markers reflecting intrinsic organ injury in stages when glomerular filtration is not impaired. This review summarizes protein markers discussed in the context of ARF as well as CKD, and provides an overview on currently available discovery results following 'omics' techniques. The identified set of candidate marker proteins is discussed in their cellular and functional context. The systematic review of proteomics and genomics studies revealed 56 genes to be associated with acute or chronic kidney disease. Context analysis, i.e. correlation of biological processes and molecular functions of reported kidney markers, revealed that 15 genes on the candidate list were assigned to the most significant ontology groups: immunity and defence. Other significantly enriched groups were cell communication (14 genes), signal transduction (22 genes) and apoptosis (seven genes). Among 24 candidate protein markers, nine proteins were also identified by gene expression studies. Next generation candidate marker proteins with improved diagnostic and prognostic values for kidney diseases will be derived from whole genome scans and protemics approaches. Prospective validation still remains elusive for all proposed candidates. PMID:17032342

  12. Acute Effect of Hookah Smoking on the Human Coronary Microcirculation.

    PubMed

    Nelson, Michael D; Rezk-Hanna, Mary; Rader, Florian; Mason, O'Neil R; Tang, Xiu; Shidban, Sarah; Rosenberry, Ryan; Benowitz, Neal L; Tashkin, Donald P; Elashoff, Robert M; Lindner, Jonathan R; Victor, Ronald G

    2016-06-01

    Hookah (water pipe) smoking is a major new understudied epidemic affecting youth. Because burning charcoal is used to heat the tobacco product, hookah smoke delivers not only nicotine but also large amounts of charcoal combustion products, including carbon-rich nanoparticles that constitute putative coronary vasoconstrictor stimuli and carbon monoxide, a known coronary vasodilator. We used myocardial contrast echocardiography perfusion imaging with intravenous lipid shelled microbubbles in young adult hookah smokers to determine the net effect of smoking hookah on myocardial blood flow. In 9 hookah smokers (age 27 ± 5 years, mean ± SD), we measured myocardial blood flow velocity (β), myocardial blood volume (A), myocardial blood flow (A × β) as well as myocardial oxygen consumption (MVO2) before and immediately after 30 minutes of ad lib hookah smoking. Myocardial blood flow did not decrease with hookah smoking but rather increased acutely (88 ± 10 to 120 ± 19 a.u./s, mean ± SE, p = 0.02), matching a mild increase in MVO2 (6.5 ± 0.3 to 7.6 ± 0.4 ml·minute(-1), p <0.001). This was manifested primarily by increased myocardial blood flow velocity (0.7 ± 0.1 to 0.9 ± 0.1 second(-1), p = 0.01) with unchanged myocardial blood volume (133 ± 7 to 137 ± 7 a.u., p = ns), the same pattern of coronary microvascular response seen with a low-dose β-adrenergic agonist. Indeed, with hookah, the increased MVO2 was accompanied by decreased heart rate variability, an indirect index of adrenergic overactivity, and eliminated by β-adrenergic blockade (i.v. propranolol). In conclusion, nanoparticle-enriched hookah smoke either is not an acute coronary vasoconstrictor stimulus or its vasoconstrictor effect is too weak to overcome the physiologic dilation of coronary microvessels matching mild cardiac β-adrenergic stimulation. PMID:27067622

  13. Acute Monocytic Leukemia Masquerading Behçet's Disease-Like Illness at Onset in an Elderly Female

    PubMed Central

    Koba, Shigeru; Sekioka, Toshio; Takeda, Sorou; Miyagawa-Hayashino, Aya; Nishimura, Keisuke

    2016-01-01

    A previously healthy 74-year-old Japanese female was hospitalized with fever and high C-reactive protein. She developed palatal herpangina-like aphthous ulcers, localized intestinal wall thickening, terminal ileum ulcers, and an erythematous acneiform rash; thus Behçet's disease-like illness was suspected. Significant peripheral blood acute monocytosis developed during her hospitalization and acute monocytic leukemia (FAB M5b) with normal karyotype was diagnosed. By immunostaining, the infiltrating cells in the skin and the terminal ileum were identified as monocytic leukemic cells. This case exhibited a unique initial presentation of Behçet's disease-like illness associated with acute monocytic leukemia. PMID:27610252

  14. Acute Monocytic Leukemia Masquerading Behçet's Disease-Like Illness at Onset in an Elderly Female.

    PubMed

    Koba, Shigeru; Sekioka, Toshio; Takeda, Sorou; Miyagawa-Hayashino, Aya; Nishimura, Keisuke; Imashuku, Shinsaku

    2016-01-01

    A previously healthy 74-year-old Japanese female was hospitalized with fever and high C-reactive protein. She developed palatal herpangina-like aphthous ulcers, localized intestinal wall thickening, terminal ileum ulcers, and an erythematous acneiform rash; thus Behçet's disease-like illness was suspected. Significant peripheral blood acute monocytosis developed during her hospitalization and acute monocytic leukemia (FAB M5b) with normal karyotype was diagnosed. By immunostaining, the infiltrating cells in the skin and the terminal ileum were identified as monocytic leukemic cells. This case exhibited a unique initial presentation of Behçet's disease-like illness associated with acute monocytic leukemia. PMID:27610252

  15. Acute human herpesvirus-6A infection of human mesothelial cells modulates HLA molecules.

    PubMed

    Caselli, Elisabetta; Campioni, Diana; Cavazzini, Francesco; Gentili, Valentina; Bortolotti, Daria; Cuneo, Antonio; Di Luca, Dario; Rizzo, Roberta

    2015-09-01

    Human herpesvirus 6A (HHV-6A) causes ubiquitous infections and has been associated with several diseases in immunosuppressed and immune dysregulated individuals. Although considered a lymphotropic virus, HHV-6A has the potential to infect many cell types, inducing important alterations in the infected cell. In our search for additional potential targets for HHV-6A infection, we analyzed the susceptibility of human mesothelial cells to viral infection. HHV-6A infection was performed and analyzed on primary human mesothelial cells isolated from serous cavity fluid, infected in vitro with a cell-free HHV-6A inoculum. The results demonstrated that mesothelial cells are susceptible to in vitro HHV-6A infection, and more importantly, that the virus induces an alteration of HLA expression on the cell surface, inducing HLA class II and HLA-G de novo expression. Since mesothelial cells play a pivotal role in many processes, including inflammation and antigen presentation, we speculate that, in vivo, this virus-induced perturbation might be correlated to alterations in mesothelium functions. PMID:26085284

  16. Baroreflex Responses to Acute Changes in Blood Volume in Humans

    NASA Technical Reports Server (NTRS)

    Thompson, Cynthia A.; Tatro, Dana L.; Ludwig, David A.; Convertino, Victor A.

    1990-01-01

    To test the hypothesis that acute changes in plasma volume affect the stimulus-response relations of high- and low- pressure baroreflexes, eight men (27-44 yr old) underwent measurements for carotid-cardiac and cardiopulmonary baro- reflex responses under the following three volemic conditions: hypovolemic, normovolemic, and hypervolemic. The stimulus- response relation of the carotid-cardiac response curve was generated using a neck cuff device, which delivered pressure changes between +40 and -65 mmHg in continuous steps of 15 mmHg. The stimulus-response relationships of the cardiopulmonary baroreflex were studied by measurements of Forearm Vascular Resistance (FVR) and Peripheral Venotis Pressure (PVP) during low levels of lower body negative pressure (O to -20 mmHg). Altered vascular volume had no effect on response relations of the carotid-cardiac baroreflex but did alter the gain of the cardiopulmonary baroreflex (-7.93 q 1.71, -4.36 q 1.38, and -2.56 q 1.59 peripheral resistance units/mmHg for hypovolemic, normovolemic, and hypervolemic, respectively) independent of shifts in baseline FVR and PVP. These results indicate greater demand for vasoconstriction for equal reductions in venous pressure during progressive hypovolemia; this condition may compromise the capacity to provide adequate peripheral resistance during severe orthostatic stress. Fluid loading before reentry after spaceflight may act to restore vasoconstrictive capacity of the cardiopulnionary baroreflex but may not be an effective countermeasure against potential post- flight impairment of the carotid-cardiac baroreflex.

  17. Baroreflex Responses to Acute Changes in Blood Volume in Humans

    NASA Technical Reports Server (NTRS)

    Thompson, Cynthia A.; Tatro, Dana L.; Ludwig, David A.; Convertino, Victor A.

    1990-01-01

    To test the hypothesis that acute changes in plasma volume affect the stimulus-response relations of high- and low- pressure baroreflexes, eight men (27-44 yr old) underwent measurements for carotid-cardiac and cardiopulmonary baro-reflex responses under the following three volemic conditions: hypovolemic, normovolemic, and hypervolemic. The stimulus- response relation of the carotid-cardiac response curve was generated using a neck cuff device, which delivered pressure changes between +40 and -65 mmHg in continuous steps of 15 mmHg. The stimulus-response relationship, of the cardio-pulmonary baroreflex were studied by measurements of Forearm Vascular Resistance (FVR) and Peripheral Venous Pressure (PVP) during low levels of lower body negative pressure (O to -20 mmHg). The results indicate greater demand for vasoconstriction for equal reductions in venous pressure during progressive hypovolemia; this condition may compromise the capacity to provide adequate peripheral resistance during severe orthostatic stress. Fluid loading before reentry after spaceflight may act to restore vasoconstrictive capacity of the cardiopulmonary baroreflex but may not be an effective countermeasure against potential post- flight impairment of the carotid-cardiac baroreflex.

  18. Acute Physiological and Behavioral Effects of Intranasal Methamphetamine in Humans

    PubMed Central

    Hart, Carl L; Gunderson, Erik W; Perez, Audrey; Kirkpatrick, Matthew G; Thurmond, Andrew; Comer, Sandra D; Foltin, Richard W

    2016-01-01

    Intranasal methamphetamine abuse has increased dramatically in the past decade, yet only one published study has investigated its acute effects under controlled laboratory conditions. Thus, the current study examined the effects of single-dose intranasal methamphetamine administration on a broad range of behavioral and physiological measures. Eleven nontreatment-seeking methamphetamine abusers (two females, nine males) completed this four-session, in-patient, within-participant, double-blind study. During each session, one of four intranasal methamphetamine doses (0, 12, 25, and 50 mg/70 kg) was administered and methamphetamine plasma concentrations, cardiovascular, subjective, and psychomotor/cognitive performance effects were assessed before drug administration and repeatedly thereafter. Following drug administration, methamphetamine plasma concentrations systematically increased for 4 h postdrug administration then declined. Methamphetamine dose dependently increased cardiovascular measures and ‘positive’ subjective effects, with peaks occurring approximately 5–15 min after drug administration, when plasma levels were still ascending. In addition, cognitive performance on less complicated tasks was improved by all active methamphetamine doses, whereas performance on more complicated tasks was improved only by the intermediate doses (12 and 25 mg). These results show that intranasal methamphetamine produced predictable effects on multiple behavioral and physiological measures before peak plasma levels were observed. Of interest is the dissociation between methamphetamine plasma concentrations with cardiovascular measures and positive subjective effects, which might have important implications for potential toxicity after repeated doses. PMID:17851535

  19. Extracellular RNAs: development as biomarkers of human disease

    PubMed Central

    Quinn, Joseph F.; Patel, Tushar; Wong, David; Das, Saumya; Freedman, Jane E.; Laurent, Louise C.; Carter, Bob S.; Hochberg, Fred; Keuren-Jensen, Kendall Van; Huentelman, Matt; Spetzler, Robert; Kalani, M. Yashar S.; Arango, Jorge; Adelson, P. David; Weiner, Howard L.; Gandhi, Roopali; Goilav, Beatrice; Putterman, Chaim; Saugstad, Julie A.

    2015-01-01

    Ten ongoing studies designed to test the possibility that extracellular RNAs may serve as biomarkers in human disease are described. These studies, funded by the NIH Common Fund Extracellular RNA Communication Program, examine diverse extracellular body fluids, including plasma, serum, urine and cerebrospinal fluid. The disorders studied include hepatic and gastric cancer, cardiovascular disease, chronic kidney disease, neurodegenerative disease, brain tumours, intracranial haemorrhage, multiple sclerosis and placental disorders. Progress to date and the plans for future studies are outlined. PMID:26320940

  20. Extracellular RNAs: development as biomarkers of human disease.

    PubMed

    Quinn, Joseph F; Patel, Tushar; Wong, David; Das, Saumya; Freedman, Jane E; Laurent, Louise C; Carter, Bob S; Hochberg, Fred; Van Keuren-Jensen, Kendall; Huentelman, Matt; Spetzler, Robert; Kalani, M Yashar S; Arango, Jorge; Adelson, P David; Weiner, Howard L; Gandhi, Roopali; Goilav, Beatrice; Putterman, Chaim; Saugstad, Julie A

    2015-01-01

    Ten ongoing studies designed to test the possibility that extracellular RNAs may serve as biomarkers in human disease are described. These studies, funded by the NIH Common Fund Extracellular RNA Communication Program, examine diverse extracellular body fluids, including plasma, serum, urine and cerebrospinal fluid. The disorders studied include hepatic and gastric cancer, cardiovascular disease, chronic kidney disease, neurodegenerative disease, brain tumours, intracranial haemorrhage, multiple sclerosis and placental disorders. Progress to date and the plans for future studies are outlined. PMID:26320940

  1. Noninvasive mechanical ventilation in chronic obstructive pulmonary disease and in acute cardiogenic pulmonary edema.

    PubMed

    Rialp Cervera, G; del Castillo Blanco, A; Pérez Aizcorreta, O; Parra Morais, L

    2014-03-01

    Noninvasive ventilation (NIV) with conventional therapy improves the outcome of patients with acute respiratory failure due to hypercapnic decompensation of chronic obstructive pulmonary disease (COPD) or acute cardiogenic pulmonary edema (ACPE). This review summarizes the main effects of NIV in these pathologies. In COPD, NIV improves gas exchange and symptoms, reducing the need for endotracheal intubation, hospital mortality and hospital stay compared with conventional oxygen therapy. NIV may also avoid reintubation and may decrease the length of invasive mechanical ventilation. In ACPE, NIV accelerates the remission of symptoms and the normalization of blood gas parameters, reduces the need for endotracheal intubation, and is associated with a trend towards lesser mortality, without increasing the incidence of myocardial infarction. The ventilation modality used in ACPE does not affect the patient prognosis. PMID:23158869

  2. The value of assessment tests in patients with acute exacerbation of chronic obstructive pulmonary disease.

    PubMed

    Zhao, Yun-feng; Jiang, Yan-ping; Zhou, Lin-fu; Wu, Xue-ling

    2014-05-01

    The aim of our study was to investigate the chronic obstructive pulmonary disease (COPD) assessment test (CAT), serum copeptin, procalcitonin and C-reactive protein (CRP) levels as potential predictive factors for recurrence of acute exacerbation and all-cause mortality in 6 months of COPD inpatients. One hundred fifty-nine patients who met the inclusion criteria were enrolled and followed up for 6 months. The CAT scores, serum copeptin, procalcitonin and CRP levels were measured on admission and 14 days and 3 months later in all patients. The primary endpoint was recurrence of acute exacerbation in 6 months. The secondary endpoint was all-cause mortality after 6 months. The CAT scores, serum copeptin, procalcitonin and CRP levels were significantly elevated on admission and stabilized at 14 days (P < 0.01). In a univariate logistic regression analysis, CAT scores (odds ratio [OR] = 1.10), forced expiratory volume in 1 second % (OR = 1.01), serum copeptin (OR = 1.32) and CRP levels (OR = 1.01) were significantly related to recurrence of acute exacerbation in 6 months (P < 0.05). In a multivariate logistic regression model, increasing CAT scores (OR = 1.10) and serum copeptin levels (OR = 1.29) were still associated with an increased odds of exacerbation (P < 0.05). In a univariate logistic regression analysis, increasing CAT scores (OR = 1.19), forced expiratory volume in 1 second % (OR = 1.05), serum copeptin levels (OR = 1.44) and hospitalization in the previous years (OR = 1.24) were significant determinants of death over a follow-up period of 6 months (P < 0.05). But only serum copeptin (OR = 1.53) and CAT scores (OR = 1.37) were associated with mortality in multivariate logistic regression analysis. Hence, high CAT scores and serum copeptin levels link with recurrence of acute exacerbation and all-cause mortality during 6 months in patients with acute exacerbation of COPD. PMID:24270077

  3. Functional Roles of Protein Nitration in Acute and Chronic Liver Diseases

    PubMed Central

    Abdelmegeed, Mohamed A.; Song, Byoung-Joon

    2014-01-01

    Nitric oxide, when combined with superoxide, produces peroxynitrite, which is known to be an important mediator for a number of diseases including various liver diseases. Peroxynitrite can modify tyrosine residue(s) of many proteins resulting in protein nitration, which may alter structure and function of each target protein. Various proteomics and immunological methods including mass spectrometry combined with both high pressure liquid chromatography and 2D PAGE have been employed to identify and characterize nitrated proteins from pathological tissue samples to determine their roles. However, these methods contain a few technical problems such as low efficiencies with the detection of a limited number of nitrated proteins and labor intensiveness. Therefore, a systematic approach to efficiently identify nitrated proteins and characterize their functional roles is likely to shed new insights into understanding of the mechanisms of hepatic disease pathophysiology and subsequent development of new therapeutics. The aims of this review are to briefly describe the mechanisms of hepatic diseases. In addition, we specifically describe a systematic approach to efficiently identify nitrated proteins to study their causal roles or functional consequences in promoting acute and chronic liver diseases including alcoholic and nonalcoholic fatty liver diseases. We finally discuss translational research applications by analyzing nitrated proteins in evaluating the efficacies of potentially beneficial agents to prevent or treat various diseases in the liver and other tissues. PMID:24876909

  4. Generation of improved humanized mouse models for human infectious diseases

    PubMed Central

    Brehm, Michael A.; Wiles, Michael V.; Greiner, Dale L.; Shultz, Leonard D.

    2014-01-01

    The study of human-specific infectious agents has been hindered by the lack of optimal small animal models. More recently development of novel strains of immunodeficient mice has begun to provide the opportunity to utilize small animal models for the study of many human-specific infectious agents. The introduction of a targeted mutation in the IL2 receptor common gamma chain gene (IL2rgnull) in mice already deficient in T and B cells led to a breakthrough in the ability to engraft hematopoietic stem cells, as well as functional human lymphoid cells and tissues, effectively creating human immune systems in immunodeficient mice. These humanized mice are becoming increasingly important as pre-clinical models for the study of human immunodeficiency virus-1 (HIV-1) and other human-specific infectious agents. However, there remain a number of opportunities to further improve humanized mouse models for the study of human-specific infectious agents. This is being done by the implementation of innovative technologies, which collectively will accelerate the development of new models of genetically modified mice, including; i) modifications of the host to reduce innate immunity, which impedes human cell engraftment; ii) genetic modification to provide human-specific growth factors and cytokines required for optimal human cell growth and function; iii) and new cell and tissue engraftment protocols. The development of “next generation” humanized mouse models continues to provide exciting opportunities for the establishment of robust small animal models to study the pathogenesis of human-specific infectious agents, as well as for testing the efficacy of therapeutic agents and experimental vaccines. PMID:24607601

  5. Targeting xenobiotic receptors PXR and CAR in human diseases

    PubMed Central

    Banerjee, Monimoy; Robbins, Delira; Chen, Taosheng

    2014-01-01

    Nuclear receptors such as the pregnane X receptor (PXR) and constitutive androstane receptor (CAR) are xenobiotic receptors regulating not only drug metabolism and disposition but also various human diseases such as cancer, diabetes, inflammatory disease, metabolic disease and liver diseases, suggesting that PXR and CAR are promising targets for drug discovery. Consequently, there is an urgent need to discover and develop small molecules that target these PXR- and/or CAR-mediated human-disease-related pathways for relevant therapeutic applications. This review proposes approaches to target PXR and CAR, either individually or simultaneously, in the context of various human diseases, taking into consideration the structural differences between PXR and CAR. PMID:25463033

  6. Monitoring minimal residual disease in acute myeloid leukaemia: a review of the current evolving strategies

    PubMed Central

    Ommen, Hans Beier

    2016-01-01

    Several disease-monitoring techniques are available for the physician treating acute myeloid leukaemia (AML). Besides immunohistochemistry assisted light microscopy, the past 20 years have seen the development and preclinical perfection of a number of techniques, most notably quantitative polymerase chain reaction (PCR) and multicolor flow cytometry. Late additions to the group of applicable assays include next generation sequencing and digital PCR. In this review the principles of use of these modalities at three different time points during the AML disease course are discussed, namely at the time of treatment evaluation, pretransplantation and postconsolidation. The drawbacks and pitfalls of each different technique are delineated. The evidence or lack of evidence for minimal residual disease guided treatment decisions is discussed. Lastly, future strategies in the MRD field are suggested and commented upon. PMID:26834951

  7. Acute Fatty Liver of Pregnancy and its Differentiation from Other Liver Diseases in Pregnancy

    PubMed Central

    Maier, J. T.; Schalinski, E.; Häberlein, C.; Gottschalk, U.; Hellmeyer, L.

    2015-01-01

    Background: There are a number of threatening liver diseases that occur during pregnancy. Acute fatty liver of pregnancy is a rare disease associated with high maternal and foetal mortality. Case Report: We report on a young gravida 1 woman who presented to our level 1 perinatal centre in the 36 + 5 week of pregnancy with an isolated elevation of transaminases together with diffuse upper abdominal complaints. After comprehensive diagnostic work-up we performed an emergency delivery by Caesarean section. This was followed by interdisciplinary management. Discussion: The differentiation from other liver diseases seems not to be obvious in all cases. Here we consider the following differential diagnoses: hyperemesis gravidarum, intrahepatic gestational cholestasis, preeclampsia, HELLP syndrome. Conclusion: Rapid diagnosis and delivery as well as interdisciplinary aftercare are necessary in order to reduce maternal and foetal mortality. PMID:26366005

  8. Neonatal herpes simplex virus type-1 central nervous system disease with acute retinal necrosis.

    PubMed

    Fong, Choong Yi; Aye, Aye Mya Min; Peyman, Mohammadreza; Nor, Norazlin Kamal; Visvaraja, Subrayan; Tajunisah, Iqbal; Ong, Lai Choo

    2014-04-01

    We report a case of neonatal herpes simplex virus (HSV)-1 central nervous system disease with bilateral acute retinal necrosis (ARN). An infant was presented at 17 days of age with focal seizures. Cerebrospinal fluid polymerase chain reaction was positive for HSV-1 and brain magnetic resonance imaging showed cerebritis. While receiving intravenous acyclovir therapy, the infant developed ARN with vitreous fluid polymerase chain reaction positive for HSV-1 necessitating intravitreal foscarnet therapy. This is the first reported neonatal ARN secondary to HSV-1 and the first ARN case presenting without external ocular or cutaneous signs. Our report highlights that infants with neonatal HSV central nervous system disease should undergo a thorough ophthalmological evaluation to facilitate prompt diagnosis and immediate treatment of this rapidly progressive sight-threatening disease. PMID:24378951

  9. Impaired sympathetic vascular regulation in humans after acute dynamic exercise.

    PubMed Central

    Halliwill, J R; Taylor, J A; Eckberg, D L

    1996-01-01

    1. The reduction in vascular resistance which accompanies acute dynamic exercise does not subside immediately during recovery, resulting in a post-exercise hypotension. This sustained vasodilatation suggests that sympathetic vascular regulation is altered after exercise. 2. Therefore, we assessed the baroreflex control of sympathetic outflow in response to arterial pressure changes, and transduction of sympathetic activity into vascular resistance during a sympatho-excitatory stimulus (isometric handgrip exercise) after either exercise (60 min cycling at 60% peak aerobic power (VO2,peak)) or sham treatment (60 min seated rest) in nine healthy subjects. 3. Both muscle sympathetic nerve activity and calf vascular resistance were reduced after exercise (-29.7 +/- 8.8 and -25.3 +/- 9.1%, both P < 0.05). The baroreflex relation between diastolic pressure and sympathetic outflow was shifted downward after exercise (post-exercise intercept, 218 +/- 38 total integrated activity (heartbeat)-1; post-sham intercept, 318 +/- 51 total integrated activity (heartbeat)-1, P < 0.05), indicating less sympathetic outflow across all diastolic pressures. Further, the relation between sympathetic activity and vascular resistance was attenuated after exercise (post-exercise slope, 0.0031 +/- 0.0007 units (total integrated activity)-1 min; post-sham slope, 0.0100 +/- 0.0033 units (total integrated activity)-1 min, P < 0.05), indicating less vasoconstriction with any increase in sympathetic activity. 4. Thus, both baroreflex control of sympathetic outflow and the transduction of sympathetic activity into vascular resistance are altered after dynamic exercise. We conclude that the vasodilation which underlies post-exercise hypotension results from both neural and vascular phenomena. Images Figure 7 PMID:8866370

  10. Acute effects of acrolein in human volunteers during controlled exposure

    PubMed Central

    Dwivedi, Aishwarya M.; Johanson, Gunnar; Lorentzen, Johnny C.; Palmberg, Lena; Sjögren, Bengt; Ernstgård, Lena

    2015-01-01

    Abstract Context: Acrolein is a reactive aldehyde mainly formed by combustion. The critical effect is considered to be irritation of the eyes and airways; however, the scarce data available make it difficult to assess effect levels. Objective: The aim of the study was to determine thresholds for acute irritation for acrolein. Methods: Nine healthy volunteers of each sex were exposed at six occasions for 2 h at rest to: clean air, 15 ppm ethyl acetate (EA), and 0.05 ppm and 0.1 ppm acrolein with and without EA (15 ppm) to mask the potential influence of odor. Symptoms related to irritation and central nervous system effects were rated on 100-mm Visual Analogue Scales. Results: The ratings of eye irritation were slightly but significantly increased during exposure to acrolein in a dose-dependent manner (p < 0.001, Friedman test) with a median rating of 8 mm (corresponding to “hardly at all”) at the 0.1 ppm condition and with no influence from EA. No significant exposure-related effects were found for pulmonary function, or nasal swelling, nor for markers of inflammation and coagulation in blood (IL-6, C-reactive protein, serum amyloid A, fibrinogen, factor VIII, von Willebrand factor, and Clara cell protein) or induced sputum (cell count, differential cell count, IL-6 and IL-8). Blink frequency recorded by electromyography was increased during exposure to 0.1 ppm acrolein alone but not during any of the other five exposure conditions. Conclusion: Based on subjective ratings, the present study showed minor eye irritation by exposure to 0.1 ppm acrolein. PMID:26635308

  11. Impaired sympathetic vascular regulation in humans after acute dynamic exercise

    NASA Technical Reports Server (NTRS)

    Halliwill, J. R.; Taylor, J. A.; Eckberg, D. L.

    1996-01-01

    1. The reduction in vascular resistance which accompanies acute dynamic exercise does not subside immediately during recovery, resulting in a post-exercise hypotension. This sustained vasodilatation suggests that sympathetic vascular regulation is altered after exercise. 2. Therefore, we assessed the baroreflex control of sympathetic outflow in response to arterial pressure changes, and transduction of sympathetic activity into vascular resistance during a sympatho-excitatory stimulus (isometric handgrip exercise) after either exercise (60 min cycling at 60% peak aerobic power (VO2,peak)) or sham treatment (60 min seated rest) in nine healthy subjects. 3. Both muscle sympathetic nerve activity and calf vascular resistance were reduced after exercise (-29.7 +/- 8.8 and -25.3 +/- 9.1%, both P < 0.05). The baroreflex relation between diastolic pressure and sympathetic outflow was shifted downward after exercise (post-exercise intercept, 218 +/- 38 total integrated activity (heartbeat)-1; post-sham intercept, 318 +/- 51 total integrated activity (heartbeat)-1, P < 0.05), indicating less sympathetic outflow across all diastolic pressures. Further, the relation between sympathetic activity and vascular resistance was attenuated after exercise (post-exercise slope, 0.0031 +/- 0.0007 units (total integrated activity)-1 min; post-sham slope, 0.0100 +/- 0.0033 units (total integrated activity)-1 min, P < 0.05), indicating less vasoconstriction with any increase in sympathetic activity. 4. Thus, both baroreflex control of sympathetic outflow and the transduction of sympathetic activity into vascular resistance are altered after dynamic exercise. We conclude that the vasodilation which underlies post-exercise hypotension results from both neural and vascular phenomena.

  12. Impact of Preexisting Interstitial Lung Disease on Acute, Extensive Radiation Pneumonitis: Retrospective Analysis of Patients with Lung Cancer

    PubMed Central

    Ozawa, Yuichi; Abe, Takefumi; Omae, Minako; Matsui, Takashi; Kato, Masato; Hasegawa, Hirotsugu; Enomoto, Yasunori; Ishihara, Takeaki; Inui, Naoki; Yamada, Kazunari; Yokomura, Koshi; Suda, Takafumi

    2015-01-01

    Introduction This study investigated the clinical characteristics and predictive factors for developing acute extended radiation pneumonitis with a focus on the presence and radiological characteristics of preexisting interstitial lung disease. Methods Of 1429 irradiations for lung cancer from May 2006 to August 2013, we reviewed 651 irradiations involving the lung field. The presence, compatibility with usual interstitial pneumonia, and occupying area of preexisting interstitial lung disease were retrospectively evaluated by pretreatment computed tomography. Cases of non-infectious, non-cardiogenic, acute respiratory failure with an extended bilateral shadow developing within 30 days after the last irradiation were defined as acute extended radiation pneumonitis. Results Nine (1.4%) patients developed acute extended radiation pneumonitis a mean of 6.7 days after the last irradiation. Although preexisting interstitial lung disease was found in 13% of patients (84 patients), 78% of patients (7 patients) with acute extended radiation pneumonitis cases had preexisting interstitial lung disease, which resulted in incidences of acute extended radiation pneumonitis of 0.35 and 8.3% in patients without and with preexisting interstitial lung disease, respectively. Multivariate logistic analysis indicated that the presence of preexisting interstitial lung disease (odds ratio = 22.6; 95% confidence interval = 5.29–155; p < 0.001) and performance status (≥2; odds ratio = 4.22; 95% confidence interval = 1.06–20.8; p = 0.049) were significant predictive factors. Further analysis of the 84 patients with preexisting interstitial lung disease revealed that involvement of more than 10% of the lung field was the only independent predictive factor associated with the risk of acute extended radiation pneumonitis (odds ratio = 6.14; 95% confidence interval = 1.0–37.4); p = 0.038). Conclusions Pretreatment computed tomography evaluations of the presence of and area size occupied

  13. Plasma levels of microRNA in chronic kidney disease: patterns in acute and chronic exercise.

    PubMed

    Van Craenenbroeck, Amaryllis H; Ledeganck, Kristien J; Van Ackeren, Katrijn; Jürgens, Angelika; Hoymans, Vicky Y; Fransen, Erik; Adams, Volker; De Winter, Benedicte Y; Verpooten, Gert A; Vrints, Christiaan J; Couttenye, Marie M; Van Craenenbroeck, Emeline M

    2015-12-15

    Exercise training is an effective way to improve exercise capacity in chronic kidney disease (CKD), but the underlying mechanisms are only partly understood. In healthy subjects (HS), microRNA (miRNA or miR) are dynamically regulated following exercise and have, therefore, been suggested as regulators of cardiovascular adaptation to exercise. However, these effects were not studied in CKD before. The effect of acute exercise (i.e., an acute exercise bout) was assessed in 32 patients with CKD and 12 age- and sex-matched HS (study 1). miRNA expression in response to chronic exercise (i.e., a 3-mo exercise training program) was evaluated in 40 CKD patients (study 2). In a subgroup of study 2, the acute-exercise induced effect was evaluated at baseline and at follow-up. Plasma levels of a preselected panel miRNA, involved in exercise adaptation processes such as angiogenesis (miR-126, miR-210), inflammation (miR-21, miR-146a), hypoxia/ischemia (miR-21, miR-210), and progenitor cells (miR-150), were quantified by RT-PCR. Additionally, seven miRNA involved in similar biological processes were quantified in the subgroup of study 2. Baseline, studied miRNA were comparable in CKD and HS. Following acute exercise, miR-150 levels increased in both CKD (fold change 2.12 ± 0.39, P = 0.002; and HS: fold change 2.41 ± 0.48 P = 0.018, P for interaction > 0.05). miR-146a acutely decreased in CKD (fold change 0.92 ± 0.13, P = 0.024), whereas it remained unchanged in HS. Levels of miR-21, miR-126, and miR-210 remained unaltered. Chronic exercise did not elicit a significant change in the studied miRNA levels. However, an acute exercise-induced decrease in miR-210 was observed in CKD patients, only after training (fold change 0.76 ± 0.15). The differential expression in circulating miRNA in response to acute and chronic exercise may point toward a physiological role in cardiovascular adaptation to exercise, also in CKD. PMID:26475583

  14. Exploring the evolutionary rate differences between human disease and non-disease genes.

    PubMed

    Chakraborty, Sandip; Panda, Arup; Ghosh, Tapash Chandra

    2016-07-01

    Comparisons of evolutionary features between human disease and non-disease genes have a wide implication to understand the genetic basis of human disease genes. However, it has not yet been resolved whether disease genes evolve at slower or faster rate than the non-disease genes. To resolve this controversy, here we integrated human disease genes from several databases and compared their protein evolutionary rates with non-disease genes in both housekeeping and tissue-specific group. We noticed that in tissue specific group, disease genes evolve significantly at a slower rate than non-disease genes. However, we found no significant difference in evolutionary rates between disease and non-disease genes in housekeeping group. Tissue specific disease genes have a higher protein complex number, elevated gene expression level and are also associated with conserve biological processes. Finally, our regression analysis suggested that protein complex number followed by protein multifunctionality independently modulates the evolutionary rate of human disease genes. PMID:26562439

  15. Functional Analysis of the Human Genome:. Study of Genetic Disease

    NASA Astrophysics Data System (ADS)

    Tsui, Lap-Chee

    2003-04-01

    I will divide my remarks into 3 parts. First, I will give a brief summary of the Human Genome Project. Second, I will describe our work on human chromosome 7 to illustrate how we could contribute to the Project and disease research. Third, I would like to bring across the argument that study of genetic disease is an integral component of the Human Genome Project. In particular, I will use cystic fibrosis as an example to elaborate why I consider disease study is a part of functional genomics.

  16. Human milk anti-inflammatory component contents during acute mastitis.

    PubMed

    Buescher, E S; Hair, P S

    2001-06-15

    Mastitis is a common complication of human lactation. We examined milk specimens from eight women with clinical mastitis to determine their content of anti-inflammatory components. Antioxidant activity (spontaneous cytochrome c reducing activity), selected pro-inflammatory cytokines (IL-6, IL-1beta), selected endogenous cytokine control molecules (sIL-6R, sIL-1RII, and sTNFRI), lactoferrin, Na(+):K(+) ratios, and milk bioactivities that cause shedding of sIL-1RII from human polymorphonuclear leukocytes (PMN), suppress PMN aggregation, and suppress PMN adherence responses were not increased compared to normal milks. Neither the bioactivities that deplete PMN intracellular Ca(2+) stores nor those that block Ca(2+) influx into fMLP-stimulated PMN were significantly increased in mastitis milks. In contrast, levels of TNFalpha, sTNFRII, and IL-1RA and bioactivities that cause shedding of sTNFRI from human PMN were significantly increased compared to normal milks. Mastitis milk has the same anti-inflammatory components and characteristics of normal milk, with elevations in selected components/activities that may help protect the nursing infant from developing clinical illness due to feeding on mastitis milk. PMID:11520075

  17. Circulating long noncoding RNAs as novel biomarkers of human diseases.

    PubMed

    Jiang, Xiaoying; Lei, Ronghui; Ning, Qilan

    2016-07-01

    Long noncoding RNAs (lncRNAs) are a kind of noncoding RNAs which are longer than ˜200 nucleotides, lacking of protein-encoding capacity and are implicated in the pathogenesis of various diseases. Recently, it was demonstrated that lncRNAs could be released into the circulation and be stable in blood. Circulating lncRNAs have been reported to have potential in distinguishing patients from healthy individuals. Therefore, the detection of circulating lncRNAs may be valuable for improving the diagnosis and prognosis of various diseases. This review summarized the current understanding of circulating lncRNAs as novel biomarkers of various human diseases, such as cancer, cardiovascular diseases, nervous system diseases and other diseases, which highlighted the significance of circulating lncRNAs as novel diagnostic and prognostic biomarkers of human diseases. PMID:27347748

  18. Omeprazole does not Potentiate Acute Oxygen Toxicity in Fetal Human Pulmonary Microvascular Endothelial Cells Exposed to Hyperoxia

    PubMed Central

    Patel, Ananddeep; Zhang, Shaojie; Moorthy, Bhagavatula; Shivanna, Binoy

    2015-01-01

    Hyperoxia contributes to the pathogenesis of broncho-pulmonary dysplasia (BPD), which is a developmental lung disease of premature infants that is characterized by an interruption of lung alveolar and pulmonary vascular development. Omeprazole (OM) is a proton pump inhibitor that is used to treat humans with gastric acid related disorders. Earlier we observed that OM-mediated aryl hydrocarbon receptor (AhR) activation attenuates acute hyperoxic lung injury in adult mice and oxygen toxicity in adult human lung cells. However, our later studies in newborn mice demonstrated that OM potentiates hyperoxia-induced developmental lung injury. Whether OM exerts a similar toxicity in primary human fetal lung cells is unknown. Hence, we tested the hypothesis that OM potentiates hyperoxia-induced cytotoxicity and ROS generation in the human fetal lung derived primary human pulmonary microvascular endothelial cells (HPMEC). OM activated AhR as evident by a dose-dependent increase in cytochrome P450 (CYP) 1A1 mRNA levels in OM-treated cells. Furthermore, OM at a concentration of 100 μM (OM 100) increased NADP(H) quinone oxidoreductase 1 (NQO1) expression. Surprisingly, hyperoxia decreased rather than increase the NQO1 protein levels in OM 100-treated cells. Exposure to hyperoxia increased cytotoxicity and hydrogen peroxide (H2O2) levels. Interestingly, OM 100-treated cells exposed to air had increased H2O2 levels. However, hyperoxia did not further augment H2O2 levels in OM 100-treated cells. Additionally, hyperoxia-mediated oxygen toxicity was similar in both vehicle- and OM-treated cells. These findings contradict our hypothesis and support the hypothesis that OM does not potentiate acute hyperoxic injury in HPMEC in vitro. PMID:26779382

  19. Pulmonary fibrosis following pneumonia due to acute Legionnaires' disease. Clinical, ultrastructural, and immunofluorescent study.

    PubMed

    Chastre, J; Raghu, G; Soler, P; Brun, P; Basset, F; Gibert, C

    1987-01-01

    During a recent nosocomial outbreak, 20 critically ill patients with acute Legionnaires' disease were admitted to the intensive care unit of Hopital Bichat, Paris. Pulmonary specimens were obtained at surgery or immediately after death in 12 patients and were examined by light, immunofluorescent, and electron microscopy. Five of these 12 patients showed evidence of pulmonary fibrosis. In all of these five patients, infection with Legionella pneumophila was evidenced by bacteriologic methods, and other diseases known to cause fibrosis were excluded. The condition of four patients deteriorated rapidly with respiratory failure, and they died with pulmonary fibrosis. Only one patient finally recovered but was left with pulmonary sequelae. Two distinctive morphologic patterns were observed, one in which interstitial fibrosis was predominant and one in which intra-alveolar organization and fibrosis were also present. The alveolar epithelial lining and the basement membranes were disrupted in all patients, as evidenced by ultrastructural observations and by immunofluorescent studies showing gaps in the distribution of type 4 collagen and laminin. Types 1 and 3 collagen accumulated in areas corresponding to thickened interstitium and intra-alveolar fibrosis. Thus, some patients who survive the acute pneumonia of Legionnaires' disease may develop pulmonary fibrosis, and this process may lead to functional impairment or death despite prompt and appropriate treatment. PMID:3539546

  20. Development of minimal residual disease-directed therapy in acute myeloid leukemia.

    PubMed

    Freeman, Sylvie D; Jovanovic, Jelena V; Grimwade, David

    2008-08-01

    The last three decades have seen major advances in understanding the genetic basis of acute myeloid leukemia (AML). Comprehensive molecular and cytogenetic analysis can distinguish biologically and prognostically distinct disease subsets that demand differing treatment approaches. Definition of these pretreatment characteristics coupled with morphological response to induction chemotherapy provides the framework for current risk-stratification schemes, aimed at identifying subgroups most (and least) likely to benefit from allogeneic transplant. However, since such parameters lack the precision to distinguish the individual patient likely to be cured with conventional therapy from those destined to relapse, there has been considerable interest in development of multiparameter flow cytometry, identifying leukemia-associated aberrant phenotypes, and real-time quantitative polymerase chain reaction (RQ-PCR) detecting leukemia-specific targets (eg, fusion gene transcripts, NPM1 mutation) or genes overexpressed in AML (eg, WT1), to provide a more precise measure of disease response. Minimal residual disease (MRD) monitoring has been shown to be a powerful independent prognostic factor and is now routinely used to guide therapy in patients with the acute promyelocytic leukemia (APL) subtype. We consider the challenges involved in extending this concept, to develop a more tailored personalized medicine approach to improve the management and outcome of other forms of AML. PMID:18692689

  1. Successful cord blood transplantation in an adult acute lymphoblastic leukemia patient with congenital heart disease.

    PubMed

    Kowata, Shugo; Fujishima, Yukiteru; Suzuki, Yuzo; Tsukushi, Yasuhiko; Oyake, Tatsuo; Togawa, Ryou; Oyama, Kotaro; Ikai, Akio; Ito, Shigeki; Ishida, Yoji

    2016-08-01

    Recent advances in surgical corrections and supportive care for congenital heart disease have resulted in increasing numbers of adult survivors who may develop hematological malignancies. Treatments including chemotherapy for such patients may cause serious hemodynamic or cardiac complications, especially in those receiving stem cell transplantation. We present a 29-year-old woman with acute lymphoblastic leukemia and congenital heart disease. She had been diagnosed with pulmonary atresia with an intact ventricular septum at birth, and the anomaly was surgically corrected according to the Fontan technique at age 9 years. Her induction chemotherapy required modifications due to poor cardiac status with Fontan circulation. However, after surgical procedures including total cavopulmonary connection and aortic valve replacement at first complete remission, her cardiac status was significantly improved. Subsequently, she underwent cord blood stem cell transplantation at the third complete remission. She required intensive supportive care for circulatory failure as a pre-engraftment immune reaction and stage III acute graft versus host disease of the gut, but recovered from these complications. She was discharged on day 239, and remained in complete remission at 1-year post-transplantation. PMID:27599417

  2. Serial assessment of laser Doppler flow during acute pain crises in sickle cell disease

    PubMed Central

    Shi, Patricia Ann; Manwani, Deepa; Olowokure, Olugbenga; Nandi, Vijay

    2014-01-01

    Changes in basal laser Doppler flowmetry (LDF) of skin blood flow in sickle cell disease are reported to have pathophysiologic relevance in pain crisis. This is the first study to strictly control for LDF variability in determining the value of serial, basal (unprovoked) skin LDF as a practical method to assess resolution of acute pain crisis in sickle cell patients. Daily LDF measurements were repeated on the exact same skin areas of the calf and forehead throughout each of 12 hospital admissions for uncomplicated acute pain crisis. A progressive increase in perfusion was observed in the calf throughout hospitalization as pain crisis resolved, but measurement reproducibility in the calf was poor. Reproducibility in the forehead was better, but no significant trend over time in perfusion was seen. There was no significant correlation between perfusion and pain scores over time. There was also no significant pattern of LDF oscillations over time. In conclusion, only perfusion units and not oscillatory pattern of LDF has probable pathophysiological significance in sickle cell disease vaso-occlusion. The reproducibility of basal skin LDF specifically in sickle cell disease needs to be confirmed. PMID:24857171

  3. Human immunodeficiency virus (HIV) infection in a child presenting as acute disseminated encephalomyelitis.

    PubMed

    Tullu, Milind S; Patil, Dhananjay P; Muranjan, Mamta N; Kher, Archana S; Lahiri, Keya R

    2011-01-01

    Acute disseminated encephalomyelitis is an extremely rare occurrence in human immunodeficiency virus (HIV) infection. We describe an 8-year-old male child who presented with weakness of both lower limbs for 10 days and focal convulsions for 2 days. The child had left, upper motor neuron facial palsy, lower limb hypotonia, and exaggerated deep tendon reflexes. Enzyme-linked immunosorbent assay antibodies for HIV tested positive and the CD4 count was 109 cells/µL. The magnetic resonance imaging (MRI, brain) revealed extensive confluent hyperintensities (on T2-weighted images) in left parietal, right temporal, and right occipital regions of the white matter, and similar signals were seen in right lentiform nucleus and right posterior thalami, suggesting acute disseminated encephalomyelitis. There was transient improvement with intravenous methyl prednisolone. The patient succumbed to the illness. Perinatally transmitted pediatric HIV infection presenting with acute disseminated encephalomyelitis has not yet been reported in the medical literature. PMID:20656677

  4. "Miniguts" from plucked human hair meet Crohn's disease.

    PubMed

    Hohwieler, M; Renz, S; Liebau, S; Lin, Q; Lechel, A; Klaus, J; Perkhofer, L; Zenke, M; Seufferlein, T; Illing, A; Müller, M; Kleger, A

    2016-08-01

    Human pluripotent stem cells represent a powerful tool to study human embryonic development and disease but also open up novel strategies for cell replacement therapies. Their capacity to give rise to every cell type of the human body, meanwhile, enables researchers to generate high yields of mesodermal, ectodermal, but also endodermal-derived tissues such as hepatic, pancreatic, or intestinal cells. Another progress in the field came with the advent of 3-dimensional culture conditions, so-called organoids, which facilitate maturation of stem cells and in turn more faithfully recapitulate human tissue architecture. While several studies reported the derivation of organoid cultures from adult intestinal tissue, the derivation of intestinal organoids derived from plucked human hair of Crohn's disease patients has not been reported. The current research project reports such successful generation and characterization of induced pluripotent stem cells (iPSCs) derived from hair sheet keratinocyte cultures of a patient with Crohn's disease. Stepwise differentiation along the intestinal lineage showed no differences in intermediate stages such as definitive endoderm formation. We also directed the patterned primitive gut tube toward intestinal organoids resembling the cellular architecture of human "miniguts". As expected from current pathophysiological knowledge on Crohn's disease, there were no obvious morphological differences in the "miniguts" derived from healthy control and diseased patient-induced pluripotent stem cells. Taken together, our platform will enable for detailed and complementary phenotyping of the pathophysiology of Crohn's disease in a novel disease-in-a-dish format. PMID:27415403

  5. IgG4-related disease manifesting as an acute gastric-pericardial fistula.

    PubMed

    Frydman, James; Grunner, Shahar; Kluger, Yoram

    2014-11-28

    IgG4-related disease is a recently recognized entity linked initially to autoimmune pancreatitis and has been subsequently described in nearly every organ system. Men over the age of 50 represent the most affected demographic group and a comprehensive set of diagnostic criteria has been developed to aid treating clinicians. Though elevated levels of IgG4 in the serum are suggestive of the disease, definitive diagnosis is made on histopathology. Treatment is tailored to the clinical presentation with corticosteroid therapy known to have proven efficacy. Gastric manifestations of the IgG4-related disease primarily come in two varieties, notably chronic ulceration or pseudotumor formation. Autoimmune pancreatitis conveys increased risk for IgG4-related disease of the stomach, which is independent of Helicobacter pylori status. In this case report, we present an acute gastric-pericardial fistula secondary to IgG4-related disease that required urgent operative management. To our knowledge, this is the first report in the medical literature describing this complication of IgG4-related disease. PMID:25469052

  6. IgG4-related disease manifesting as an acute gastric-pericardial fistula

    PubMed Central

    Frydman, James; Grunner, Shahar; Kluger, Yoram

    2014-01-01

    IgG4-related disease is a recently recognized entity linked initially to autoimmune pancreatitis and has been subsequently described in nearly every organ system. Men over the age of 50 represent the most affected demographic group and a comprehensive set of diagnostic criteria has been developed to aid treating clinicians. Though elevated levels of IgG4 in the serum are suggestive of the disease, definitive diagnosis is made on histopathology. Treatment is tailored to the clinical presentation with corticosteroid therapy known to have proven efficacy. Gastric manifestations of the IgG4-related disease primarily come in two varieties, notably chronic ulceration or pseudotumor formation. Autoimmune pancreatitis conveys increased risk for IgG4-related disease of the stomach, which is independent of Helicobacter pylori status. In this case report, we present an acute gastric-pericardial fistula secondary to IgG4-related disease that required urgent operative management. To our knowledge, this is the first report in the medical literature describing this complication of IgG4-related disease. PMID:25469052

  7. Clofarabine and Cytarabine in Treating Patients With Acute Myeloid Leukemia With Minimal Residual Disease

    ClinicalTrials.gov

    2013-05-07

    Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia

  8. Acute exudative polymorphous vitelliform maculopathy in a patient with Lyme disease.

    PubMed

    Singh, Ravi S J; Tran, Lac H; Kim, Judy E

    2013-01-01

    Acute exudative polymorphous vitelli-form maculopathy (AEPVM) is a rare condition of unclear etiology that has been seen in association with respiratory and viral infections. It has also been reported as a paraneoplastic phenomenon in older individuals. The authors report the first case of AEPVM associated with Lyme disease with over 3.5 years of follow-up. Multimodality serial imaging suggested the lesions began as multiple serous detachments followed by accumulation of photoreceptor outer segments in the subretinal space that gradually resolved over time and gave rise to the characteristic fundus findings at various stages. PMID:24044715

  9. Glucocorticoids Acutely Increase Brown Adipose Tissue Activity in Humans, Revealing Species-Specific Differences in UCP-1 Regulation.

    PubMed

    Ramage, Lynne E; Akyol, Murat; Fletcher, Alison M; Forsythe, John; Nixon, Mark; Carter, Roderick N; van Beek, Edwin J R; Morton, Nicholas M; Walker, Brian R; Stimson, Roland H

    2016-07-12

    The discovery of brown adipose tissue (BAT) in adult humans presents a new therapeutic target for metabolic disease; however, little is known about the regulation of human BAT. Chronic glucocorticoid excess causes obesity in humans, and glucocorticoids suppress BAT activation in rodents. We tested whether glucocorticoids regulate BAT activity in humans. In vivo, the glucocorticoid prednisolone acutely increased (18)fluorodeoxyglucose uptake by BAT (measured using PET/CT) in lean healthy men during mild cold exposure (16°C-17°C). In addition, prednisolone increased supraclavicular skin temperature (measured using infrared thermography) and energy expenditure during cold, but not warm, exposure in lean subjects. In vitro, glucocorticoids increased isoprenaline-stimulated respiration and UCP-1 in human primary brown adipocytes, but substantially decreased isoprenaline-stimulated respiration and UCP-1 in primary murine brown and beige adipocytes. The highly species-specific regulation of BAT function by glucocorticoids may have important implications for the translation of novel treatments to activate BAT to improve metabolic health. PMID:27411014

  10. First outbreak of West Nile virus neuroinvasive disease in humans, Croatia, 2012.

    PubMed

    Pem-Novosel, Iva; Vilibic-Cavlek, Tatjana; Gjenero-Margan, Ira; Pandak, Nenad; Peric, Ljiljana; Barbic, Ljubo; Listes, Eddy; Cvitkovic, Ante; Stevanovic, Vladimir; Savini, Giovanni

    2014-01-01

    Between September 6 and 21, 2012, seven human cases of West Nile virus (WNV) neuroinvasive infection were laboratory confirmed in Croatia. The median patient age was 62 years (range 48-77). Five patients presented with meningoencephalitis and two patients with meningoencephalitis followed by acute flaccid paralysis. Four of them had an underlying disease (hypertension). Using enzyme-linked immunosorbent assay (ELISA), WNV-specific immunoglobulin M (IgM) and IgG antibodies of low avidity were detected in six patients, whereas one showed only IgM antibodies. All samples were confirmed using plaque-reduction neutralization and microneutralization tests. Five patients recovered fully. Before human cases were reported, acute asymptomatic WNV infection was demonstrated by detection of IgM antibodies in sentinel horses. Moreover, an increased WNV IgG seropositivity in horses was detected in counties where human cases occurred. Adulticidal and larvicidal treatments were administered immediately in the respective places of residence. The end of the warm season contributed to the fact that there were no new cases of WNV disease recorded. PMID:24283515

  11. Improved human disease candidate gene prioritization using mouse phenotype

    PubMed Central

    Chen, Jing; Xu, Huan; Aronow, Bruce J; Jegga, Anil G

    2007-01-01

    Background The majority of common diseases are multi-factorial and modified by genetically and mechanistically complex polygenic interactions and environmental factors. High-throughput genome-wide studies like linkage analysis and gene expression profiling, tend to be most useful for classification and characterization but do not provide sufficient information to identify or prioritize specific disease causal genes. Results Extending on an earlier hypothesis that the majority of genes that impact or cause disease share membership in any of several functional relationships we, for the first time, show the utility of mouse phenotype data in human disease gene prioritization. We study the effect of different data integration methods, and based on the validation studies, we show that our approach, ToppGene , outperforms two of the existing candidate gene prioritization methods, SUSPECTS and ENDEAVOUR. Conclusion The incorporation of phenotype information for mouse orthologs of human genes greatly improves the human disease candidate gene analysis and prioritization. PMID:17939863

  12. Engineering Large Animal Species to Model Human Diseases.

    PubMed

    Rogers, Christopher S

    2016-01-01

    Animal models are an important resource for studying human diseases. Genetically engineered mice are the most commonly used species and have made significant contributions to our understanding of basic biology, disease mechanisms, and drug development. However, they often fail to recreate important aspects of human diseases and thus can have limited utility as translational research tools. Developing disease models in species more similar to humans may provide a better setting in which to study disease pathogenesis and test new treatments. This unit provides an overview of the history of genetically engineered large animals and the techniques that have made their development possible. Factors to consider when planning a large animal model, including choice of species, type of modification and methodology, characterization, production methods, and regulatory compliance, are also covered. © 2016 by John Wiley & Sons, Inc. PMID:27367161

  13. The human microbiome in rheumatic autoimmune diseases: A comprehensive review.

    PubMed

    Coit, Patrick; Sawalha, Amr H

    2016-09-01

    The human microbiome consists of the total diversity of microbiota and their genes. High-throughput sequencing has allowed for inexpensive and rapid evaluation of taxonomic representation and functional capability of the microbiomes of human body sites. Autoimmune and inflammatory rheumatic diseases are characterized by dysbiosis of the microbiome. Microbiome dysbiosis can be influenced by host genetics and environmental factors. Dysbiosis is also associated with shifts in certain functional pathways. The goal of this article is to provide a current and comprehensive review of the unique characteristics of the microbiome of patients with autoimmune and inflammatory rheumatic diseases, measured using high-throughput sequencing. We also highlight the need for broader studies utilizing a longitudinal approach to better understand how the human microbiome contributes to disease susceptibility, and to characterize the role of the interaction between host genetics and microbial diversity in the pathogenesis of autoimmune diseases, disease manifestations, and progression. PMID:27493014

  14. Endothelial-cell injury in cutaneous acute graft-versus-host disease.

    PubMed Central

    Dumler, J. S.; Beschorner, W. E.; Farmer, E. R.; Di Gennaro, K. A.; Saral, R.; Santos, G. W.

    1989-01-01

    The presence of an erythematous skin rash and hemorrhagic complications in acute graft-versus-host disease (GVHD) suggest that the vasculature may be involved in the immunopathologic process. We reviewed endothelial and vascular histopathologic changes on light microscopy and on immunoperoxidase stained sections of skin biopsies obtained from 41 HLA-identical allogeneic marrow transplant recipients with at least grade 2 GVHD. Biopsies taken from 14 allogeneic HLA-identical bone marrow transplant recipients who never developed GVHD were used as controls. Sections were evaluated for evidence of immunologic vascular injury using the rank file analysis of histologic features, expression of HLA-DR antigen, and the distribution of fibrin and factor VIII-related antigen (F VIII RAg). Patients with acute GVHD had significantly greater intimal lymphocytic infiltrates, perivascular nuclear dust deposition, perivascular F VIII Rag extravasation and deposition and vascular proliferation than controls. We find significantly greater endothelial injury in GVHD patients, which may represent primary immunologic injury to the vasculature. The clinical findings in acute GVHD probably result from cumulative endothelial as well as epithelial injury. Images Figure 1 Figure 2 Figure 3 PMID:2596572

  15. Methanobactin reverses acute liver failure in a rat model of Wilson disease.

    PubMed

    Lichtmannegger, Josef; Leitzinger, Christin; Wimmer, Ralf; Schmitt, Sabine; Schulz, Sabine; Kabiri, Yaschar; Eberhagen, Carola; Rieder, Tamara; Janik, Dirk; Neff, Frauke; Straub, Beate K; Schirmacher, Peter; DiSpirito, Alan A; Bandow, Nathan; Baral, Bipin S; Flatley, Andrew; Kremmer, Elisabeth; Denk, Gerald; Reiter, Florian P; Hohenester, Simon; Eckardt-Schupp, Friedericke; Dencher, Norbert A; Adamski, Jerzy; Sauer, Vanessa; Niemietz, Christoph; Schmidt, Hartmut H J; Merle, Uta; Gotthardt, Daniel Nils; Kroemer, Guido; Weiss, Karl Heinz; Zischka, Hans

    2016-07-01

    In Wilson disease (WD), functional loss of ATPase copper-transporting β (ATP7B) impairs biliary copper excretion, leading to excessive copper accumulation in the liver and fulminant hepatitis. Current US Food and Drug Administration- and European Medicines Agency-approved pharmacological treatments usually fail to restore copper homeostasis in patients with WD who have progressed to acute liver failure, leaving liver transplantation as the only viable treatment option. Here, we investigated the therapeutic utility of methanobactin (MB), a peptide produced by Methylosinus trichosporium OB3b, which has an exceptionally high affinity for copper. We demonstrated that ATP7B-deficient rats recapitulate WD-associated phenotypes, including hepatic copper accumulation, liver damage, and mitochondrial impairment. Short-term treatment of these rats with MB efficiently reversed mitochondrial impairment and liver damage in the acute stages of liver copper accumulation compared with that seen in untreated ATP7B-deficient rats. This beneficial effect was associated with depletion of copper from hepatocyte mitochondria. Moreover, MB treatment prevented hepatocyte death, subsequent liver failure, and death in the rodent model. These results suggest that MB has potential as a therapeutic agent for the treatment of acute WD. PMID:27322060

  16. Clinical outcome of Fitz-Hugh-Curtis syndrome mimicking acute biliary disease

    PubMed Central

    Woo, Seong Yong; Kim, Jin Il; Cheung, Dae Young; Cho, Se Hyun; Park, Soo-Heon; Han, Joon-Yeol; Kim, Jae Kwang

    2008-01-01

    AIM: To analyze the clinical characteristics of patients diagnosed with Fitz-Hugh-Curtis syndrome. METHODS: The clinical courses of patients that visited St. Mary’s Hospital with abdominal pain from January 2005 to December 2006 and were diagnosed with Fitz-Hugh-Curtis syndrome were examined. RESULTS: Fitz-Hugh-Curtis syndrome was identified in 22 female patients of childbearing age; their mean age was 31.0 ± 8.1 years. Fourteen of these cases presented with pain in the upper right abdomen alone or together with pain in the lower abdomen, and six patients presented with pain only in the lower abdomen. The first impression at the time of visit was acute cholecystitis or cholangitis in 10 patients and acute appendicitis or pelvic inflammatory disease in eight patients. Twenty-one patients were diagnosed by abdominal computer tomography (CT), and the results of abdominal sonography were normal for 10 of these patients. Chlamydia trichomatis was isolated from 18 patients. Two patients underwent laparoscopic adhesiotomy and 20 patients were completely cured by antibiotic treatment. CONCLUSION: For women of childbearing age with acute pain in the upper right abdomen alone or together with pain in the lower abdomen, Fitz-Hugh-Curtis syndrome should be considered during differential diagnosis. Moreover, in cases suspected to be Fitz-Hugh-Curtis syndrome, abdominal CT, rather than abdominal sonography, assists in the diagnosis. PMID:19058334

  17. Proteomic Biomarkers for Acute Interstitial Lung Disease in Gefitinib-Treated Japanese Lung Cancer Patients

    PubMed Central

    Kawakami, Takao; Nagasaka, Keiko; Takami, Sachiko; Wada, Kazuya; Tu, Hsiao-Kun; Otsuji, Makiko; Kyono, Yutaka; Dobashi, Tae; Komatsu, Yasuhiko; Kihara, Makoto; Akimoto, Shingo; Peers, Ian S.; South, Marie C.; Higenbottam, Tim; Fukuoka, Masahiro; Nakata, Koichiro; Ohe, Yuichiro; Kudoh, Shoji; Clausen, Ib Groth; Nishimura, Toshihide; Marko-Varga, György; Kato, Harubumi

    2011-01-01

    Interstitial lung disease (ILD) events have been reported in Japanese non-small-cell lung cancer (NSCLC) patients receiving EGFR tyrosine kinase inhibitors. We investigated proteomic biomarkers for mechanistic insights and improved prediction of ILD. Blood plasma was collected from 43 gefitinib-treated NSCLC patients developing acute ILD (confirmed by blinded diagnostic review) and 123 randomly selected controls in a nested case-control study within a pharmacoepidemiological cohort study in Japan. We generated ∼7 million tandem mass spectrometry (MS/MS) measurements with extensive quality control and validation, producing one of the largest proteomic lung cancer datasets to date, incorporating rigorous study design, phenotype definition, and evaluation of sample processing. After alignment, scaling, and measurement batch adjustment, we identified 41 peptide peaks representing 29 proteins best predicting ILD. Multivariate peptide, protein, and pathway modeling achieved ILD prediction comparable to previously identified clinical variables; combining the two provided some improvement. The acute phase response pathway was strongly represented (17 of 29 proteins, p = 1.0×10−25), suggesting a key role with potential utility as a marker for increased risk of acute ILD events. Validation by Western blotting showed correlation for identified proteins, confirming that robust results can be generated from an MS/MS platform implementing strict quality control. PMID:21799770

  18. Acute behavioural comparisons of toluene and ethanol in human subjects.

    PubMed Central

    Echeverria, D; Fine, L; Langolf, G; Schork, T; Sampaio, C

    1991-01-01

    and eye irritation also increased in a dose-response manner. The greatest effect was found for an increasing number of observations of sleep. A range of 2 to 7% decrements suggest the ACGIH TLV of 100 ppm toluene may be a good estimate of the biological threshold supporting a re-evaluation of the TLV. At 0.66 g EtOH/kg body weight symptoms and performance decrements were 6.6% for digit span, 9.2% for pattern recognition, 4.0% for continuous performance, 7.9% for symbol-digit, 16.5% for finger tapping, 6.2% for critical tracking, and 5.2% for the one hole test. The EtOH equivalents at 150 ppm toluene for digit span (0.56g EtOH/kg/body weight), the latency for pattern recognition (0.66 g EtOH kg body weight), and the one hole element "move" (0.37 g EtOH kg body weight) show that the first two measures would be affected at or above the 50 mg% blood alcohol concentration. This concentration is recognised as the lowest alcohol concentration associated with increased numbers of automobile accidents. The results suggest that EtOH may be a useful acute standard to compare the effects of various industrial solvents and support investigating an association between exposure to solvents and increased risk to safety in industry. PMID:1954153

  19. Suppression of Swine NK Cell Function During Acute Infection with Foot-and-Mouth Disease Virus (FMDV)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease virus (FMDV) infects cloven-hoofed animals and causes an economically devastating disease. This highly acute infection has multiple negative effects on the innate response, presumably contributing to the rapid spread of virus within the host. Understanding the regulation of in...

  20. Early Diagnosis and Management of Acute Vertigo from Vestibular Migraine and Ménière's Disease.

    PubMed

    Seemungal, Barry; Kaski, Diego; Lopez-Escamez, Jose Antonio

    2015-08-01

    Vestibular migraine is the most common cause of acute episodic vestibular symptoms after benign paroxysmal positional vertigo. In contrast, Ménière's disease is an uncommon disorder. For both conditions, early and accurate diagnosis (or its exclusion) enables the correct management of patients with acute episodic vestibular symptoms. Long-term management of migraine requires changes in lifestyle to avoid triggers of migraine and/or prophylactic drugs if attacks become too frequent. The long-term management of Ménière's disease also involves lifestyle changes (low salt diet), medications (betahistine, steroids), and ablative therapy applied to the diseased ear (eg, intratympanic gentamicin). PMID:26231275

  1. Soluble Fn14 Is Detected and Elevated in Mouse and Human Kidney Disease

    PubMed Central

    Campanholle, Gabriela; Nagiec, Eva E.; Wang, Ju; Syed, Jameel; O’Neil, Shawn P.; Zhan, Yutian; Brenneman, Karrie; Homer, Bruce; Neubert, Hendrik; Karim, Riyez; Pullen, Nick; Evans, Steven M.; Fleming, Margaret; Chockalingam, Priya; Lin, Lih-Ling

    2016-01-01

    The cytokine TWEAK and its cognate receptor Fn14 are members of the TNF/TNFR superfamily and are upregulated in tissue injury to mediate local tissue responses including inflammation and tissue remodeling. We found that in various models of kidney disease, Fn14 expression (mRNA and protein) is upregulated in the kidney. These models include: lupus nephritis mouse models (Nephrotoxic serum Transfer Nephritis and MRL.Faslpr/lpr), acute kidney injury models (Ischemia reperfusion injury and Folic acid injury), and a ZSF-1 diabetic nephropathy rat model. Fn14 expression levels correlate with disease severity as measured by disease histology. We have also shown for the first time the detection of soluble Fn14 (sFn14) in the urine and serum of mice. Importantly, we found the sFn14 levels are markedly increased in the diseased mice and are correlated with disease biomarkers including proteinuria and MCP-1. We have also detected sFn14 in human plasma and urine. Moreover, sFn14 levels, in urine are significantly increased in DN patients and correlated with proteinuria and MCP-1 levels. Thus our data not only confirm the up-regulation of Fn14/TWEAK pathway in kidney diseases, but also suggest a novel mechanism for its regulation by the generation of sFn14. The correlation of sFn14 levels and disease severity suggest that sFn14 may serve as a potential biomarker for both acute and chronic kidney diseases. PMID:27171494

  2. Acute oral ulcers.

    PubMed

    Lehman, Julia S; Rogers, Roy S

    2016-01-01

    Accurate diagnosis of acute oral ulcers can be challenging. Important historic details include the pattern of recurrence, anatomic areas of involvement within the mouth and elsewhere on the mucocutaneous surface, associated medical symptoms or comorbidities, and symptomology. Careful mucocutaneous examination is essential. When necessary, biopsy at an active site without ulceration is generally optimal. Depending on the clinical scenario, supplemental studies that may be useful include cultures; perilesional biopsy for direct immunofluorescence testing; and evaluation for infectious diseases, gluten sensitivity, inflammatory bowel disease, human immunodeficiency virus infection, connective tissue diseases, or hematinic deficiencies. Clinicians should maintain a broad differential diagnosis when evaluating patients with acute oral ulcers. PMID:27343961

  3. Chronic and acute risk assessment of human exposed to novaluron-bifenthrin mixture in cabbage.

    PubMed

    Shi, Kaiwei; Li, Li; Li, Wei; Yuan, Longfei; Liu, Fengmao

    2016-09-01

    Based on the dissipation and residual level in cabbage determined by gas chromatography coupled with an electron capture detector (GC-ECD), chronic and acute risk assessments of the novaluron and bifenthrin were investigated. At different spiked levels, mean recoveries were between 81 and 108 % with relative standard deviations (RSDs) from 1.1 to 6.8 %. The limit of quantification (LOQ) was 0.01 mg kg(-1), and good linearity with correlation coefficient (>0.9997) were obtained. The half-lives of novaluron and bifenthrin in cabbage were in the range of 3.2~10 days. Based on the consumption data in China, the risk quotients (RQs) of novaluron and bifenthrin were all below 100 %. The chronic and acute risk of novaluron in cabbage was relatively low, while bifenthrin exerts higher acute risk to humans than chronic risk. The obtained results indicated that the use of novaluron-bifenthrin mixture does not seem to pose any chronic or acute risk to humans even if cabbages are consumed at high application dosages and short preharvest interval (PHI). PMID:27550439

  4. Human leukocyte antigen-DRB1 polymorphism in childhood acute lymphoblastic leukemia

    PubMed Central

    EL ANSARY, MERVAT M.; MOHAMMED, LAMIAA A.; HASSAN, TAMER H.; BARAKA, AHMED; AHMED, ALSHYMAA A.

    2015-01-01

    Similar to autoimmune diseases, there are clear associations between resistance or susceptibility to cancer and the classic human leukocyte antigen (HLA) profile of an individual. HLA-associated susceptibility to childhood acute lymphoblastic leukemia (ALL) may provide clues to leukemogenesis in general and to the role of other risk factors. The present study aimed to determine the association between the HLA-DRB1 genotype and susceptibility to ALL in children and to assess the prognostic value of HLA-DRB1 alleles in these patients. This study included 50 ALL patients who were consecutively admitted to the Pediatric Oncology Unit of Zagazig University Hospital and 50 gender-matched healthy volunteers as a control group. The patients were subjected to full clinical history, thorough clinical examination and routine laboratory investigations. Molecular HLA-DRB1 typing for patients and controls using the reverse sequence-specific oligonucleotide probe technique was performed. HLA-DRB1*04 allele frequency was significantly higher in female patients compared to that in female controls (P=0.03) and in patients aged <10 years compared to those aged ≥10 years at the time of diagnosis (P=0.01). HLA-DRB1*11 allele frequency was significantly higher in high-risk compared to standard-risk patients (P=0.01) and in refractory patients compared to those who achieved remission (P=0.02). In conclusion, the HLA-DRB1*04 allele appears to be a female-specific susceptibility factor for the acquisition of childhood ALL and it may affect the age of onset of ALL. In addition, the HLA-DRB1*11 allele may be of prognostic significance in childhood ALL. However, further larger studies are required to support the conclusions drawn from this study. PMID:25798280

  5. Skin Diseases: Cross-section of human skin

    MedlinePlus

    Skip Navigation Bar Home Current Issue Past Issues Skin Diseases Cross-section of human skin Past Issues / Fall 2008 Table of Contents For ... Logical Images, Inc. I n the areas of skin health and skin diseases, the NIH's National Institute ...

  6. Mitochondrion-Permeable Antioxidants to Treat ROS-Burst-Mediated Acute Diseases

    PubMed Central

    Zhang, Zhong-Wei; Xu, Xiao-Chao; Liu, Ting; Yuan, Shu

    2016-01-01

    Reactive oxygen species (ROS) play a crucial role in the inflammatory response and cytokine outbreak, such as during virus infections, diabetes, cancer, cardiovascular diseases, and neurodegenerative diseases. Therefore, antioxidant is an important medicine to ROS-related diseases. For example, ascorbic acid (vitamin C, VC) was suggested as the candidate antioxidant to treat multiple diseases. However, long-term use of high-dose VC causes many side effects. In this review, we compare and analyze all kinds of mitochondrion-permeable antioxidants, including edaravone, idebenone, α-Lipoic acid, carotenoids, vitamin E, and coenzyme Q10, and mitochondria-targeted antioxidants MitoQ and SkQ and propose astaxanthin (a special carotenoid) to be the best antioxidant for ROS-burst-mediated acute diseases, like avian influenza infection and ischemia-reperfusion. Nevertheless, astaxanthins are so unstable that most of them are inactivated after oral administration. Therefore, astaxanthin injection is suggested hypothetically. The drawbacks of the antioxidants are also reviewed, which limit the use of antioxidants as coadjuvants in the treatment of ROS-associated disorders. PMID:26649144

  7. Acute alcoholic hepatitis, end stage alcoholic liver disease and liver transplantation: an Italian position statement.

    PubMed

    Testino, Gianni; Burra, Patrizia; Bonino, Ferruccio; Piani, Francesco; Sumberaz, Alessandro; Peressutti, Roberto; Giannelli Castiglione, Andrea; Patussi, Valentino; Fanucchi, Tiziana; Ancarani, Ornella; De Cerce, Giovanna; Iannini, Anna Teresa; Greco, Giovanni; Mosti, Antonio; Durante, Marilena; Babocci, Paola; Quartini, Mariano; Mioni, Davide; Aricò, Sarino; Baselice, Aniello; Leone, Silvia; Lozer, Fabiola; Scafato, Emanuele; Borro, Paolo

    2014-10-28

    Alcoholic liver disease encompasses a broad spectrum of diseases ranging from steatosis steatohepatitis, fibrosis, and cirrhosis to hepatocellular carcinoma. Forty-four per cent of all deaths from cirrhosis are attributed to alcohol. Alcoholic liver disease is the second most common diagnosis among patients undergoing liver transplantation (LT). The vast majority of transplant programmes (85%) require 6 mo of abstinence prior to transplantation; commonly referred to as the "6-mo rule". Both in the case of progressive end-stage liver disease (ESLD) and in the case of severe acute alcoholic hepatitis (AAH), not responding to medical therapy, there is a lack of evidence to support a 6-mo sobriety period. It is necessary to identify other risk factors that could be associated with the resumption of alcohol drinking. The "Group of Italian Regions" suggests that: in a case of ESLD with model for end-stage liver disease < 19 a 6-mo abstinence period is required; in a case of ESLD, a 3-mo sober period before LT may be more ideal than a 6-mo period, in selected patients; and in a case of severe AAH, not responding to medical therapies (up to 70% of patients die within 6 mo), LT is mandatory, even without achieving abstinence. The multidisciplinary transplant team must include an addiction specialist/hepato-alcohologist. Patients have to participate in self-help groups. PMID:25356027

  8. Mitochondrion-Permeable Antioxidants to Treat ROS-Burst-Mediated Acute Diseases.

    PubMed

    Zhang, Zhong-Wei; Xu, Xiao-Chao; Liu, Ting; Yuan, Shu

    2016-01-01

    Reactive oxygen species (ROS) play a crucial role in the inflammatory response and cytokine outbreak, such as during virus infections, diabetes, cancer, cardiovascular diseases, and neurodegenerative diseases. Therefore, antioxidant is an important medicine to ROS-related diseases. For example, ascorbic acid (vitamin C, VC) was suggested as the candidate antioxidant to treat multiple diseases. However, long-term use of high-dose VC causes many side effects. In this review, we compare and analyze all kinds of mitochondrion-permeable antioxidants, including edaravone, idebenone, α-Lipoic acid, carotenoids, vitamin E, and coenzyme Q10, and mitochondria-targeted antioxidants MitoQ and SkQ and propose astaxanthin (a special carotenoid) to be the best antioxidant for ROS-burst-mediated acute diseases, like avian influenza infection and ischemia-reperfusion. Nevertheless, astaxanthins are so unstable that most of them are inactivated after oral administration. Therefore, astaxanthin injection is suggested hypothetically. The drawbacks of the antioxidants are also reviewed, which limit the use of antioxidants as coadjuvants in the treatment of ROS-associated disorders. PMID:26649144

  9. Acute graft-versus-host disease: Are we close to bringing the bench to the bedside?

    PubMed Central

    Sung, Anthony D.; Chao, Nelson J.

    2013-01-01

    Graft-versus-host disease (GVHD) is a major complication of allogeneic hematopoietic stem cell transplant (AHSCT) associated with significant morbidity and mortality. This review focuses on the pathophysiology, prevention, and treatment of acute GVHD. Specifically, we explain how new discoveries in immunology have expanded our understanding of GVHD, in which tissue damage from chemotherapy or radiation results in cytokine release, activating T cells, resulting in proliferation and differentiation, trafficking to target organs, and tissue destruction and inflammation. Insights into the mechanisms of this disease relate directly to the development of preventive strategies and therapies, such as immunosuppression, calcineurin inhibitors, T-cell depletion, CCR5 antagonists, gut decontamination, extracorporeal photopheresis, and more. Understanding the immunobiology of GVHD and developing effective preventions and treatments are critical to the continuing success of AHSCT. PMID:24309532

  10. Quantitative assessment of relative roles of drivers of acute respiratory diseases.

    PubMed

    Goswami, Prashant; Baruah, Jurismita

    2014-01-01

    Several thousands of people, including children, suffer from acute respiratory disease (ARD) every year worldwide. Pro-active planning and mitigation for these diseases require identification of the major drivers in a location-specific manner. While the importance of air pollutants in ARD has been extensively studied and emphasized, the role of weather variables has been less explored. With Delhi with its large population and pollution as a test case, we examine the relative roles of air pollution and weather (cold days) in ARD. It is shown that both the number of cold days and air pollution play important roles in ARD load; however, the number of cold days emerges as the major driver. These conclusions are consistent with analyses for several other states in India. The robust association between ARD load and cold days provides basis for estimating and predicting ARD load through dynamical model, as well as impact of climate change. PMID:25322687

  11. Quantitative assessment of relative roles of drivers of acute respiratory diseases

    NASA Astrophysics Data System (ADS)

    Goswami, Prashant; Baruah, Jurismita

    2014-10-01

    Several thousands of people, including children, suffer from acute respiratory disease (ARD) every year worldwide. Pro-active planning and mitigation for these diseases require identification of the major drivers in a location-specific manner. While the importance of air pollutants in ARD has been extensively studied and emphasized, the role of weather variables has been less explored. With Delhi with its large population and pollution as a test case, we examine the relative roles of air pollution and weather (cold days) in ARD. It is shown that both the number of cold days and air pollution play important roles in ARD load; however, the number of cold days emerges as the major driver. These conclusions are consistent with analyses for several other states in India. The robust association between ARD load and cold days provides basis for estimating and predicting ARD load through dynamical model, as well as impact of climate change.

  12. First presentation of Addison's disease as hyperkalaemia in acute kidney injury.

    PubMed

    Maki, Sara; Kramarz, Caroline; Maria Heister, Paula; Pasha, Kamran

    2016-01-01

    Addison's disease is a rare endocrine disorder that frequently presents with non-specific symptoms, but may deteriorate rapidly into life-threatening Addisonian crisis if left untreated. Diagnosis can be difficult in patients without a suggestive medical history. We describe a case of a 37-year-old man who was admitted with acute kidney injury and hyperkalaemia, resistant to treatment with insulin/dextrose and calcium gluconate. On clinical examination, he was found to be hyperpigmented; a subsequent random serum cortisol of 49 nmol/L affirmed the preliminary diagnosis of Addison's disease. The patient's hyperkalaemia improved on treatment with hydrocortisone, and a follow-up morning adrenocorticotropic hormone of 1051 ng/L confirmed the diagnosis. PMID:27170604

  13. Human mitochondrial oxidative capacity is acutely impaired following burn trauma

    PubMed Central

    Cree, Melanie G.; Fram, Ricki Y.; Herndon, David N.; Qian, Ting; Angel, Carlos; Green, Justin M.; Mlcak, Ronald; Aarsland, Asle; Wolfe, Robert R.

    2008-01-01

    Background Mitochondrial proteins and genes are damaged after burn injury in animals but have not previously been assessed in human burn patients. Methods The rates of maximal muscle mitochondrial oxidative capacity(ATP production) and uncoupled oxidation(heat production) for both palmitate and pyruvate were measured in muscle biopsies from 40 children sustaining burns >40% body surface area and from 13 healthy children controls. Results Maximal mitochondrial oxidation of pyruvate and palmitate were reduced in burn patients compared to controls (4.0±0.2:1.9±0.1 µmolO2/citrate synthase activity/mg protein/min pyruvate; Control:Burn;P<0.001 and 3.0±0.1:0.9±0.03 µmolO2/citrate synthase activity/mg protein/min palmatyl CoA; Control:Burn;P=0.003). Uncoupled oxidation was the same between groups. Conclusions The maximal coupled mitochondrial oxidative capacity is severely impaired after burn injury, although there are no alterations in the rate of uncoupled oxidative capacity. It may be that the ratio of these indicates that a larger portion of energy production in trauma patients is wasted through uncoupling, rather than used for healing. PMID:18639661

  14. Multifractal detrended fluctuation analysis of human gait diseases

    PubMed Central

    Dutta, Srimonti; Ghosh, Dipak; Chatterjee, Sucharita

    2013-01-01

    In this paper multifractal detrended fluctuation analysis (MFDFA) is used to study the human gait time series for normal and diseased sets. It is observed that long range correlation is primarily responsible for the origin of multifractality. The study reveals that the degree of multifractality is more for normal set compared to diseased set. However, the method fails to distinguish between the two diseased sets. PMID:24109454

  15. Escin sodium induces apoptosis of human acute leukemia Jurkat T cells.

    PubMed

    Zhang, Zhenzhen; Gao, Jian; Cai, Xueting; Zhao, Youlong; Wang, Yafei; Lu, Wuguang; Gu, Zhenhua; Zhang, Shuangquan; Cao, Peng

    2011-12-01

    Escin sodium has been used in the clinic as an antioedematous, antiexudative and vasoprotective agent for many years and has shown excellent tolerability. However, little is known about its anticancer activity. This is a report for the first time that escin sodium exerts a cytotoxic effect on human acute leukemia Jurkat T cells via the induction of apoptosis rather than cell cycle arrest. Escin sodium activated the initiator caspase-8, -9, and the effector caspase-3, degraded poly (ADP-ribose) polymerase (PARP) and attenuated the expression of Bcl-2. In addition, escin sodium inhibited the growth of cancer cells in a selective manner with Jurkat cells most sensitive to it. Taken together, the data show that escin sodium possesses potent apoptogenic activity toward human acute leukemia Jurkat T cells. PMID:21452372

  16. Seven-year national survey of Kawasaki disease and acute rheumatic fever.

    PubMed

    Taubert, K A; Rowley, A H; Shulman, S T

    1994-08-01

    To assess the frequency of hospital encoded diagnoses of acute rheumatic fever (ARF) and Kawasaki disease (KD), the two leading causes of acquired heart disease in children in the United States, we performed a survey of the medical record departments of United States children's hospitals and of general hospitals that have at least 400 beds and a pediatric ward. With a simple questionnaire, data were gathered for the years 1984 through 1990 by ICD.9CM codes, with a 58% response rate. About 8000 diagnoses of KD and 6000 diagnoses of ARF were encoded during the study period. Encoded diagnoses of both KD and ARF showed yearly fluctuations in the earlier years (1984 through 1987). For KD there was a general trend toward increasing numbers after 1986. These data are consistent with increased physician awareness and diagnosis of KD. For ARF a gradual decline was observed between 1986 and 1990. About 80% of ARF diagnoses were reported from general hospitals. The much smaller pool of encoded diagnoses of ARF at the children's hospitals showed a 56% increase from 1985 to 1986. These data suggest that the highly publicized increase in cases of acute rheumatic fever in the United States during the mid-1980s may reflect focal rather than nationwide increased activity and that nationally the number of diagnoses of ARF actually may have continued to decline gradually from 1984 through 1990. PMID:7970970

  17. [The usefulness of the Peak Flow Meter for assessing patients with acute respiratory disease].

    PubMed

    Alvarez Torices, J C; Diego Domínguez, F; Franch Nadal, J; Alvarez Guisasola, F; Pablo Pons, M L

    1990-11-01

    The aim of the study was to evaluate the utility of the extrahospital use of "Peak Flow Meter" (PFM) in patients with an acute respiratory disease. 70 patients were studied. PFM, arterial gasometry, physical examination and dyspnea evaluation were performed on all of them. The PFM were posteriorly transformed into the rate related to the ideal result, following the Nunn and Gregg equation (1989). We found an association between the PFM rate and the different arterial blood gas test results, and a relation to the degree of dyspnea and the listening of sibilant rales. There was more significance with the rate of PFM than with the PFM transformed in all cases, and only association was found between arterial blood changes and PFM. We concluded that all patients with an acute respiratory disease with a rate of PFM greater than 50% should be evaluated carefully because of the probability of existing hypoxemia, and those with rate of less than 20% must be referred to hospital. PMID:2103210

  18. Gastroesophageal Reflux Disease Increases Infant Acute Respiratory Illness Severity, but not Childhood Asthma.

    PubMed

    Valet, Robert S; Carroll, Kecia N; Gebretsadik, Tebeb; Minton, Patricia A; Woodward, Kimberly B; Liu, Zhouwen; Hartert, Tina V

    2014-03-01

    It is unknown whether gastroesophageal reflux disease (GERD) during infancy affects infant bronchiolitis severity or childhood asthma inception. Four hundred thirty-two infants presenting with acute respiratory illness due to bronchiolitis or upper respiratory infection were studied. The primary exposure was the parental report of a previous GERD diagnosis. Outcomes included bronchiolitis severity at initial presentation and childhood asthma diagnosis at age 4. Infants with parentally reported GERD had a higher bronchiolitis severity score (range=0-12, clinically significant difference=0.5), indicating more severe disease, than infants without reported GERD (median 5.5 [interquartile range 3.5-9.0] among those with reported GERD versus 4.0 [1.0-7.0] among those without, P=0.005). This association persisted after adjusting for infant age, race, gender, and secondhand smoke exposure by a propensity score (adjusted odds ratio [OR] 1.99, 95% confidence interval [CI] 1.14-3.46, P=0.02). The parental report of GERD during infancy was not associated with the parental report of asthma diagnosis at age 4. GERD during infancy may contribute to acute respiratory illness severity, but is not associated with asthma diagnosis at age 4. Future prospective studies are needed to confirm these findings. PMID:24669353

  19. A Puzzle of Vestibular Physiology in a Meniere's Disease Acute Attack

    PubMed Central

    Martinez-Lopez, Marta; Manrique-Huarte, Raquel; Perez-Fernandez, Nicolas

    2015-01-01

    The aim of this paper is to present for the first time the functional evaluation of each of the vestibular receptors in the six semicircular canals in a patient diagnosed with Meniere's disease during an acute attack. A 54-year-old lady was diagnosed with left Meniere's disease who during her regular clinic review suffers an acute attack of vertigo, with fullness and an increase of tinnitus in her left ear. Spontaneous nystagmus and the results in the video head-impulse test (vHIT) are shown before, during, and after the attack. Nystagmus was initially left beating and a few minutes later an upbeat component was added. No skew deviation was observed. A decrease in the gain of the vestibuloocular reflex (VOR) and the presence of overt saccades were observed when the stimuli were in the plane of the left superior semicircular canal. At the end of the crisis nystagmus decreased and vestibuloocular reflex returned to almost normal. A review of the different possibilities to explain these findings points to a hypothetical utricular damage. PMID:26167320

  20. Acute and chronic disease associated with naturally occurring T-2 mycotoxicosis in sheep.

    PubMed

    Ferreras, M C; Benavides, J; García-Pariente, C; Delgado, L; Fuertes, M; Muñoz, M; García-Marín, J F; Pérez, V

    2013-02-01

    A flock of approximately 1,000 sheep were exposed intermittently to food contaminated with T-2 toxin (T-2), a potent type-A trichothecene mycotoxin produced primarily by Fusarium sporotrichioides and Fusarium poae. In the acute stage of the intoxication, affected sheep developed anorexia, decreased water consumption, ruminal atony, soft faeces and apathy. One hundred and ninety of the exposed sheep died. The main gross lesions observed in animals dying during the acute disease were rumenitis and ulcerative abomasitis, depletion of lymphocytes in lymphoid organs, necrosis of the exocrine pancreas, myocarditis and intense oedema of the skin and brain. Sheep developing the chronic stage of disease showed weight loss and reproductive inefficiency and the main pathological features observed in animals dying during this stage were gastrointestinal inflammation, myocardial fibrosis and necrotic and suppurative lesions in the oral cavity. Opportunistic infections (e.g. mycotic mastitis or parasitic pneumonia) were also identified in these animals. Increased serum concentrations of lactate dehydrogenase and creatine kinase were observed, most likely related to heart lesions. T-2 toxins were detected in all samples of the diet of these animals that were analyzed. The changes in the sheep reported here are similar to those described previously in experimental studies. Lesions observed in the present animals suggest an additional cardiotoxic effect of T-2 in sheep. PMID:22819015

  1. Purified human C1-esterase inhibitor is safe in acute relapses of neuromyelitis optica

    PubMed Central

    Levy, Michael

    2014-01-01

    Objective: To minimize complement-mediated damage in acute relapses of neuromyelitis optica (NMO) by adding treatment with a complement inhibitor, purified C1-esterase inhibitor, to the current standard of care (high-dose glucocorticoids). Method: We conducted an open-label phase 1b safety and proof-of-concept trial in 10 patients with NMO–immunoglobulin G seropositive NMO or NMO spectrum disease (NMOSD) who presented with acute transverse myelitis and/or optic neuritis. In addition to treating with 1 g of daily IV methylprednisolone, we infused 2,000 units of C1-esterase inhibitor daily for 3 days, beginning on day 1 of hospitalization. The primary outcome measure was safety, and the secondary efficacy measure was change in Expanded Disability Status Scale (EDSS) scores. Results: Ten patients with NMO/NMOSD were enrolled, 7 of whom presented with acute transverse myelitis and 3 with acute optic neuritis. C1-esterase inhibitor proved to be safe in all 10 patients, with no serious adverse events recorded. There were no thromboembolic events or related lab abnormalities in any of the subjects. EDSS scores dropped from a median of 4.5 on admission to 4.0 on discharge and then down to 2.5 on 30-day follow-up. All but 1 patient returned to preattack EDSS or better and only 2 patients required escalation to plasmapheresis. Conclusions: C1-esterase inhibitor is a safe add-on therapy for patients with NMO/NMOSD presenting with acute transverse myelitis and optic neuritis. Preliminary evidence suggests a promising benefit with C1-esterase inhibitor in reducing neurologic damage and improving outcomes. A placebo-controlled trial is necessary to confirm these findings. Classification of evidence: This study provides Class IV evidence that for patients with NMO with acute transverse myelitis or optic neuritis, C1-esterase inhibitor is safe and improves disability. PMID:25340061

  2. Integrated Genomic and Network-Based Analyses of Complex Diseases and Human Disease Network.

    PubMed

    Al-Harazi, Olfat; Al Insaif, Sadiq; Al-Ajlan, Monirah A; Kaya, Namik; Dzimiri, Nduna; Colak, Dilek

    2016-06-20

    A disease phenotype generally reflects various pathobiological processes that interact in a complex network. The highly interconnected nature of the human protein interaction network (interactome) indicates that, at the molecular level, it is difficult to consider diseases as being independent of one another. Recently, genome-wide molecular measurements, data mining and bioinformatics approaches have provided the means to explore human diseases from a molecular basis. The exploration of diseases and a system of disease relationships based on the integration of genome-wide molecular data with the human interactome could offer a powerful perspective for understanding the molecular architecture of diseases. Recently, subnetwork markers have proven to be more robust and reliable than individual biomarker genes selected based on gene expression profiles alone, and achieve higher accuracy in disease classification. We have applied one of these methodologies to idiopathic dilated cardiomyopathy (IDCM) data that we have generated using a microarray and identified significant subnetworks associated with the disease. In this paper, we review the recent endeavours in this direction, and summarize the existing methodologies and computational tools for network-based analysis of complex diseases and molecular relationships among apparently different disorders and human disease network. We also discuss the future research trends and topics of this promising field. PMID:27318646

  3. Membrane Traffic and Muscle: Lessons from Human Disease

    PubMed Central

    Dowling, James J.; Gibbs, Elizabeth M.; Feldman, Eva L.

    2010-01-01

    Like all mammalian tissues, skeletal muscle is dependent on membrane traffic for proper development and homeostasis. This fact is underscored by the observation that several human diseases of the skeletal muscle are caused by mutations in gene products of the membrane trafficking machinery. An examination of these diseases and the proteins that underlie them is instructive both in terms of determining disease pathogenesis and of understanding the normal aspects of muscle biology regulated by membrane traffic. This review highlights our current understanding of the trafficking genes responsible for human myopathies. PMID:18266915

  4. Megalin and cubilin in proximal tubule protein reabsorption: from experimental models to human disease.

    PubMed

    Nielsen, Rikke; Christensen, Erik Ilsø; Birn, Henrik

    2016-01-01

    Proximal tubule protein uptake is mediated by 2 receptors, megalin and cubilin. These receptors rescue a variety of filtered ligands, including biomarkers, essential vitamins, and hormones. Receptor gene knockout animal models have identified important functions of the receptors and have established their essential role in modulating urinary protein excretion. Rare genetic syndromes associated with dysfunction of these receptors have been identified and characterized, providing additional information on the importance of these receptors in humans. Using various disease models in combination with receptor gene knockout, the implications of receptor dysfunction in acute and chronic kidney injury have been explored and have pointed to potential new roles of these receptors. Based on data from animal models, this paper will review current knowledge on proximal tubule endocytic receptor function and regulation, and their role in renal development, protein reabsorption, albumin uptake, and normal renal physiology. These findings have implications for the pathophysiology and diagnosis of proteinuric renal diseases. We will examine the limitations of the different models and compare the findings to phenotypic observations in inherited human disorders associated with receptor dysfunction. Furthermore, evidence from receptor knockout mouse models as well as human observations suggesting a role of protein receptors for renal disease will be discussed in light of conditions such as chronic kidney disease, diabetes, and hypertension. PMID:26759048

  5. Knowledge and Awareness of Acute Human Immunodeficiency Virus Infection Among Mobile App-Using Men Who Have Sex With Men: A Missed Public Health Opportunity

    PubMed Central

    Siegler, Aaron J.; Sanchez, Travis; Sineath, R. Craig; Grey, Jeremy; Kahle, Erin; Sullivan, Patrick S.

    2015-01-01

    In a national online survey, we assessed awareness and knowledge of acute human immunodeficiency virus (HIV) infection manifestation among 1748 men who have sex with men (MSM). Only 39% of respondents were aware that acute HIV infection may be accompanied by symptoms. Education and increased access to acute HIV testing may facilitate MSM to appropriately seek acute HIV testing. PMID:26034766

  6. Alpha1-antichymotrypsin activity correlates with and may modulate matrix metalloproteinase-9 in human acute wounds.

    PubMed

    Reiss, Matthew J; Han, Yuan-Ping; Garner, Warren L

    2009-01-01

    Matrix metalloproteinase-9 (MMP-9) plays a central role in many physiologic processes including acute and the chronic wounds. MMP-9 is not routinely expressed in healthy tissues but is promptly expressed as a proenzyme and converted into active enzyme after tissue injury. The mechanisms involved, including the activators and inhibitors for this enzyme in human tissue remain largely obscure. We recently identified alpha1-antichymotrypsin (alpha1-ACT), an acute phase factor, as a potent inhibitor controlling activation of pro-MMP-9 by human skin. The aim of this study is to establish the clinical relevance of the inhibitor in cutaneous wound healing. Fluids from acute burn blisters and conditioned media from skin explants of burn patients were analyzed. We observed that the presence pro-MMP-9 and its activation correlated with the proximity to and degree of injury. Early after trauma, massive levels of wound alpha1-ACT were associated with an absence of pro-MMP-9 activation. Conversely, the active MMP-9 occurs simultaneously with inactivation of alpha1-ACT. Our results suggest a role for alpha1-ACT as a physiologic inhibitor of MMP-9 activation in human wound healing. PMID:19660051

  7. 'Laminopathies': A wide spectrum of human diseases

    SciTech Connect

    Worman, Howard J. . E-mail: hjw14@columbia.edu; Bonne, Gisele

    2007-06-10

    Mutations in genes encoding the intermediate filament nuclear lamins and associated proteins cause a wide spectrum of diseases sometimes called 'laminopathies.' Diseases caused by mutations in LMNA encoding A-type lamins include autosomal dominant Emery-Dreifuss muscular dystrophy and related myopathies, Dunnigan-type familial partial lipodystrophy, Charcot-Marie-Tooth disease type 2B1 and developmental and accelerated aging disorders. Duplication in LMNB1 encoding lamin B1 causes autosomal dominant leukodystrophy and mutations in LMNB2 encoding lamin B2 are associated with acquired partial lipodystrophy. Disorders caused by mutations in genes encoding lamin-associated integral inner nuclear membrane proteins include X-linked Emery-Dreifuss muscular dystrophy, sclerosing bone dysplasias, HEM/Greenberg skeletal dysplasia and Pelger-Huet anomaly. While mutations and clinical phenotypes of 'laminopathies' have been carefully described, data explaining pathogenic mechanisms are only emerging. Future investigations will likely identify new 'laminopathies' and a combination of basic and clinical research will lead to a better understanding of pathophysiology and the development of therapies.

  8. Evaluation of Border Entry Screening for Infectious Diseases in Humans

    PubMed Central

    Antão, Catarina; Hall, Robert

    2015-01-01

    In response to the severe acute respiratory syndrome (SARS) pandemic of 2003 and the influenza pandemic of 2009, many countries instituted border measures as a means of stopping or slowing the spread of disease. The measures, usually consisting of a combination of border entry/exit screening, quarantine, isolation, and communications, were resource intensive, and modeling and observational studies indicate that border screening is not effective at detecting infectious persons. Moreover, border screening has high opportunity costs, financially and in terms of the use of scarce public health staff resources during a time of high need. We discuss the border-screening experiences with SARS and influenza and propose an approach to decision-making for future pandemics. We conclude that outbreak-associated communications for travelers at border entry points, together with effective communication with clinicians and more effective disease control measures in the community, may be a more effective approach to the international control of communicable diseases. PMID:25625224

  9. Colorectal Disorders in Acute Human Immunodeficiency Virus Infection: A Case Series

    PubMed Central

    Panichsillapakit, Theppharit; Patel, Derek; Santangelo, Joanne; Richman, Douglas D.; Little, Susan J.; Smith, Davey M.

    2016-01-01

    Background. The gastrointestinal (GI) tract is important in the pathogenesis of human immunodeficiency virus (HIV) infection. We report a case series of lower GI endoscopic and histopathologic findings of HIV-infected individuals after presentation with acute infection. Methods. We performed a retrospective case review of individuals infected with HIV who enrolled between August 2010 and April 2013 in a primary infection treatment trial. All participants started the trial during acute infection and underwent colonoscopy with biopsies at baseline and after the start of antiretroviral treatment. Results. Twenty acutely infected individuals were included in the study (mean age, 33 years; range, 20–54 years). All participants were male who reported having receptive anal sex as an HIV risk factor. Nine individuals (45%) had at least 1 finding by colorectal pathology; 1 person had 2 diagnoses (diverticulosis and focal active proctitis). The histopathological findings revealed anal dysplasia in 3 cases: 2 had high-grade anal intraepithelial neoplasia (AIN) and 1 had low-grade AIN. Two persons had a colorectal polyp, 1 hyperplastic and 1 adenomatous. Three persons were diagnosed with diverticulosis, and 2 persons were diagnosed with proctitis, including 1 with focal active proctitis and 1 with cytomegalovirus proctitis. Conclusions. To our knowledge, this is the first case series report of lower GI disorders in acute HIV-infected individuals. Although the causal relationship remains uncertain, we describe the endoscopic findings that were observed during acute HIV infection among men who have sex with men. Understanding the prevalence of these pathologies may likely shed light on how acute HIV infection damages the lower GI tract. PMID:26925432

  10. The Impact of Fusarium Mycotoxins on Human and Animal Host Susceptibility to Infectious Diseases

    PubMed Central

    Antonissen, Gunther; Martel, An; Pasmans, Frank; Ducatelle, Richard; Verbrugghe, Elin; Vandenbroucke, Virginie; Li, Shaoji; Haesebrouck, Freddy; Van Immerseel, Filip; Croubels, Siska

    2014-01-01

    Contamination of food and feed with mycotoxins is a worldwide problem. At present, acute mycotoxicosis caused by high doses is rare in humans and animals. Ingestion of low to moderate amounts of Fusarium mycotoxins is common and generally does not result in obvious intoxication. However, these low amounts may impair intestinal health, immune function and/or pathogen fitness, resulting in altered host pathogen interactions and thus a different outcome of infection. This review summarizes the current state of knowledge about the impact of Fusarium mycotoxin exposure on human and animal host susceptibility to infectious diseases. On the one hand, exposure to deoxynivalenol and other Fusarium mycotoxins generally exacerbates infections with parasites, bacteria and viruses across a wide range of animal host species. Well-known examples include coccidiosis in poultry, salmonellosis in pigs and mice, colibacillosis in pigs, necrotic enteritis in poultry, enteric septicemia of catfish, swine respiratory disease, aspergillosis in poultry and rabbits, reovirus infection in mice and Porcine Reproductive and Respiratory Syndrome Virus infection in pigs. However, on the other hand, T-2 toxin has been shown to markedly decrease the colonization capacity of Salmonella in the pig intestine. Although the impact of the exposure of humans to Fusarium toxins on infectious diseases is less well known, extrapolation from animal models suggests possible exacerbation of, for instance, colibacillosis and salmonellosis in humans, as well. PMID:24476707

  11. The impact of Fusarium mycotoxins on human and animal host susceptibility to infectious diseases.

    PubMed

    Antonissen, Gunther; Martel, An; Pasmans, Frank; Ducatelle, Richard; Verbrugghe, Elin; Vandenbroucke, Virginie; Li, Shaoji; Haesebrouck, Freddy; Van Immerseel, Filip; Croubels, Siska

    2014-02-01

    Contamination of food and feed with mycotoxins is a worldwide problem. At present, acute mycotoxicosis caused by high doses is rare in humans and animals. Ingestion of low to moderate amounts of Fusarium mycotoxins is common and generally does not result in obvious intoxication. However, these low amounts may impair intestinal health, immune function and/or pathogen fitness, resulting in altered host pathogen interactions and thus a different outcome of infection. This review summarizes the current state of knowledge about the impact of Fusarium mycotoxin exposure on human and animal host susceptibility to infectious diseases. On the one hand, exposure to deoxynivalenol and other Fusarium mycotoxins generally exacerbates infections with parasites, bacteria and viruses across a wide range of animal host species. Well-known examples include coccidiosis in poultry, salmonellosis in pigs and mice, colibacillosis in pigs, necrotic enteritis in poultry, enteric septicemia of catfish, swine respiratory disease, aspergillosis in poultry and rabbits, reovirus infection in mice and Porcine Reproductive and Respiratory Syndrome Virus infection in pigs. However, on the other hand, T-2 toxin has been shown to markedly decrease the colonization capacity of Salmonella in the pig intestine. Although the impact of the exposure of humans to Fusarium toxins on infectious diseases is less well known, extrapolation from animal models suggests possible exacerbation of, for instance, colibacillosis and salmonellosis in humans, as well. PMID:24476707

  12. Polymicrobial Interactions: Impact on Pathogenesis and Human Disease

    PubMed Central

    Peters, Brian M.; Jabra-Rizk, Mary Ann; O'May, Graeme A.; Costerton, J. William

    2012-01-01

    Summary: Microorganisms coexist in a complex milieu of bacteria, fungi, archaea, and viruses on or within the human body, often as multifaceted polymicrobial biofilm communities at mucosal sites and on abiotic surfaces. Only recently have we begun to appreciate the complicated biofilm phenotype during infection; moreover, even less is known about the interactions that occur between microorganisms during polymicrobial growth and their implications in human disease. Therefore, this review focuses on polymicrobial biofilm-mediated infections and examines the contribution of bacterial-bacterial, bacterial-fungal, and bacterial-viral interactions during human infection and potential strategies for protection against such diseases. PMID:22232376

  13. Novel management of acute or secondary biliary liver conditions using hepatically differentiated human dental pulp cells.

    PubMed

    Ishkitiev, Nikolay; Yaegaki, Ken; Imai, Toshio; Tanaka, Tomoko; Fushimi, Naho; Mitev, Vanyo; Okada, Mio; Tominaga, Noriko; Ono, Sachie; Ishikawa, Hiroshi

    2015-02-01

    The current definitive treatment for acute or chronic liver condition, that is, cirrhosis, is liver transplantation from a limited number of donors, which might cause complications after donation. Hence, bone marrow stem cell transplantation has been developed, but the risk of carcinogenesis remains. We have recently developed a protocol for hepatic differentiation of CD117(+) stem cells from human exfoliated deciduous teeth (SHED). In the present study, we examine whether SHED hepatically differentiated (hd) in vitro could be used to treat acute liver injury (ALI) and secondary biliary cirrhosis. The CD117(+) cell fraction was magnetically separated from SHED and then differentiated into hepatocyte-like cells in vitro. The cells were transplanted into rats with either ALI or induced secondary biliary cirrhosis. Engraftment of human liver cells was determined immunohistochemically and by in situ hybridization. Recovery of liver function was examined by means of histochemical and serological tests. Livers of transplanted animals were strongly positive for human immunohistochemical factors, and in situ hybridization confirmed engraftment of human hepatocytes. The tests for recovery of liver function confirmed the presence of human hepatic markers in the animals' blood serum and lack of fibrosis and functional integration of transplanted human cells into livers. No evidence of malignancy was found. We show that in vitro hdSHED engraft morphologically and functionally into the livers of rats having acute injury or secondary biliary cirrhosis. SHED are readily accessible adult stem cells, capable of proliferating in large numbers before differentiating in vitro. This makes SHED an appropriate and safe stem cell source for regenerative medicine. PMID:25234861

  14. Association between Floods and Acute Cardiovascular Diseases: A Population-Based Cohort Study Using a Geographic Information System Approach

    PubMed Central

    Vanasse, Alain; Cohen, Alan; Courteau, Josiane; Bergeron, Patrick; Dault, Roxanne; Gosselin, Pierre; Blais, Claudia; Bélanger, Diane; Rochette, Louis; Chebana, Fateh

    2016-01-01

    Background: Floods represent a serious threat to human health beyond the immediate risk of drowning. There is few data on the potential link between floods and direct consequences on health such as on cardiovascular health. This study aimed to explore the impact of one of the worst floods in the history of Quebec, Canada on acute cardiovascular diseases (CVD). Methods: A cohort study with a time series design with multiple control groups was built with the adult population identified in the Quebec Integrated Chronic Disease Surveillance System. A geographic information system approach was used to define the study areas. Logistic regressions were performed to compare the occurrence of CVD between groups. Results: The results showed a 25%–27% increase in the odds in the flooded population in spring 2011 when compared with the population in the same area in springs 2010 and 2012. Besides, an increase up to 69% was observed in individuals with a medical history of CVD. Conclusion: Despite interesting results, the association was not statistically significant. A possible explanation to this result can be that the population affected by the flood was probably too small to provide the statistical power to answer the question, and leaves open a substantial possibility for a real and large effect. PMID:26828511

  15. Acute coronary syndrome (ACS) registry--leading the charge for National Cardiovascular Disease (NCVD) Database.

    PubMed

    Chin, S P; Jeyaindran, S; Azhari, R; Wan Azman, W A; Omar, I; Robaayah, Z; Sim, K H

    2008-09-01

    Coronary artery disease is one of the most rampant non-communicable diseases in the world. It begins indolently as a fatty streak in the lining of the artery that soon progresses to narrow the coronary arteries and impair myocardial perfusion. Often the atherosclerotic plaque ruptures and causes sudden thrombotic occlusion and acute ST-elevation myocardial infarction (STEMI), non-ST-elevation MI (NSTEMI) or unstable angina (UA). This phenomenon is called acute coronary syndrome (ACS) and is the leading cause of death not only in Malaysia but also globally. In order for us to tackle this threat to the health of our nation we must arm ourselves with reliable and accurate information to assess current burden of disease resources available and success of current strategies. The acute coronary syndrome (ACS) registry is the flagship of the National Cardiovascular Disease Database (NCVD) and is the result of the dedicated and untiring efforts of doctors and nurses in both public and private medical institutions and hospitals around the country, ably guided and supported by the National Heart Association, the National Heart Foundation, the Clinical Research Centre and the Ministry of Health of Malaysia. Analyses of data collected throughout 2006 from 3422 patients with ACS admitted to the 12 tertiary cardiac centres and general hospitals spanning nine states in Malaysia in this first report has already revealed surprising results. Mean age of patients was 59 years while the most consistent risk factor for STEMI was active smoking. Utilization of medications was high generally. Thirty-day mortality for STEMI was 11%, for NSTEMI 8% and UA 4%. Thrombolysis (for STEMI only) reduced in-hospital and 30-day mortality by nearly 50%. Percutaneous coronary intervention or PCI also reduced 30-day mortality for patients with non-ST elevation MI and unstable angina. The strongest determinants of mortality appears to be Killip Class and age of the patient. Fewer women received

  16. Impacts of gut bacteria on human health and diseases.

    PubMed

    Zhang, Yu-Jie; Li, Sha; Gan, Ren-You; Zhou, Tong; Xu, Dong-Ping; Li, Hua-Bin

    2015-01-01

    Gut bacteria are an important component of the microbiota ecosystem in the human gut, which is colonized by 1014 microbes, ten times more than the human cells. Gut bacteria play an important role in human health, such as supplying essential nutrients, synthesizing vitamin K, aiding in the digestion of cellulose, and promoting angiogenesis and enteric nerve function. However, they can also be potentially harmful due to the change of their composition when the gut ecosystem undergoes abnormal changes in the light of the use of antibiotics, illness, stress, aging, bad dietary habits, and lifestyle. Dysbiosis of the gut bacteria communities can cause many chronic diseases, such as inflammatory bowel disease, obesity, cancer, and autism. This review summarizes and discusses the roles and potential mechanisms of gut bacteria in human health and diseases. PMID:25849657

  17. Impacts of Gut Bacteria on Human Health and Diseases

    PubMed Central

    Zhang, Yu-Jie; Li, Sha; Gan, Ren-You; Zhou, Tong; Xu, Dong-Ping; Li, Hua-Bin

    2015-01-01

    Gut bacteria are an important component of the microbiota ecosystem in the human gut, which is colonized by 1014 microbes, ten times more than the human cells. Gut bacteria play an important role in human health, such as supplying essential nutrients, synthesizing vitamin K, aiding in the digestion of cellulose, and promoting angiogenesis and enteric nerve function. However, they can also be potentially harmful due to the change of their composition when the gut ecosystem undergoes abnormal changes in the light of the use of antibiotics, illness, stress, aging, bad dietary habits, and lifestyle. Dysbiosis of the gut bacteria communities can cause many chronic diseases, such as inflammatory bowel disease, obesity, cancer, and autism. This review summarizes and discusses the roles and potential mechanisms of gut bacteria in human health and diseases. PMID:25849657

  18. Human Microbiome and its Association With Health and Diseases.

    PubMed

    Althani, Asmaa A; Marei, Hany E; Hamdi, Wedad S; Nasrallah, Gheyath K; El Zowalaty, Mohamed E; Al Khodor, Souhaila; Al-Asmakh, Maha; Abdel-Aziz, Hassan; Cenciarelli, Carlo

    2016-08-01

    Human microbiota are distinct communities of microorganisms that resides at different body niches. Exploration of the human microbiome has become a reality due to the availability of powerful metagenomics and metatranscriptomic analysis technologies. Recent advances in sequencing and bioinformatics over the past decade help provide a deep insight into the nature of the host-microbial interactions and identification of potential deriver genes and pathways associated with human health, well-being, and predisposition to different diseases. In the present review, we outline recent studies devoted to elucidate the possible link between the microbiota and various type of diseases. The present review also highlights the potential utilization of microbiota as a potential therapeutic option to treat a wide array of human diseases. J. Cell. Physiol. 231: 1688-1694, 2016. © 2015 Wiley Periodicals, Inc. PMID:26660761

  19. Golgi glycosylation and human inherited diseases.

    PubMed

    Freeze, Hudson H; Ng, Bobby G

    2011-09-01

    The Golgi factory receives custom glycosylates and dispatches its cargo to the correct cellular locations. The process requires importing donor substrates, moving the cargo, and recycling machinery. Correctly glycosylated cargo reflects the Golgi's quality and efficiency. Genetic disorders in the specific equipment (enzymes), donors (nucleotide sugar transporters), or equipment recycling/reorganization components (COG, SEC, golgins) can all affect glycosylation. Dozens of human glycosylation disorders fit these categories. Many other genes, with or without familiar names, well-annotated pedigrees, or likely homologies will join the ranks of glycosylation disorders. Their broad and unpredictable case-by-case phenotypes cross the traditional medical specialty boundaries. The gene functions in patients may be elusive, but their common feature may include altered glycosylation that provide clues to Golgi function. This article focuses on a group of human disorders that affect protein or lipid glycosylation. Readers may find it useful to generalize some of these patient-based, translational observations to their own research. PMID:21709180

  20. Golgi Glycosylation and Human Inherited Diseases

    PubMed Central

    Freeze, Hudson H.; Ng, Bobby G.

    2011-01-01

    The Golgi factory receives custom glycosylates and dispatches its cargo to the correct cellular locations. The process requires importing donor substrates, moving the cargo, and recycling machinery. Correctly glycosylated cargo reflects the Golgi's quality and efficiency. Genetic disorders in the specific equipment (enzymes), donors (nucleotide sugar transporters), or equipment recycling/reorganization components (COG, SEC, golgins) can all affect glycosylation. Dozens of human glycosylation disorders fit these categories. Many other genes, with or without familiar names, well-annotated pedigrees, or likely homologies will join the ranks of glycosylation disorders. Their broad and unpredictable case-by-case phenotypes cross the traditional medical specialty boundaries. The gene functions in patients may be elusive, but their common feature may include altered glycosylation that provide clues to Golgi function. This article focuses on a group of human disorders that affect protein or lipid glycosylation. Readers may find it useful to generalize some of these patient-based, translational observations to their own research. PMID:21709180

  1. Animal Models of Human Granulocyte Diseases

    PubMed Central

    Schäffer, Alejandro A.; Klein, Christoph

    2012-01-01

    In vivo animal models have proven very useful to understand basic biological pathways of the immune system, a prerequisite for the development of innovate therapies. This manuscript addresses currently available models for defined human monogenetic defects of neutrophil granulocytes, including murine, zebrafish and larger mammalian species. Strengths and weaknesses of each system are summarized, and clinical investigators may thus be inspired to develop further lines of research to improve diagnosis and therapy by use of the appropriate animal model system. PMID:23351993

  2. Role of Cellular Magnesium in Human Diseases

    PubMed Central

    Long, Samantha; Romani, Andrea MP

    2015-01-01

    Magnesium is required for many of the major organs to function and plays a crucial role in human and mammalian physiology. Magnesium is essential for the structure of bones and teeth, acts as a cofactor for more than 300 enzymes in the body, including binding to ATP for kinase reactions, and affects permeability of excitable membranes and neuromuscular transmission. Despite these essential roles, much is still unknown about magnesium physiology and homeostasis. Currently, nutritionists believe that the general population intakes insufficient magnesium daily through the diet. The effects of magnesium deficiency are, for the most part undetected, and simple, widespread assessments of magnesium intake remain unavailable for humans. Many of the patients admitted to hospitals or medical care facilities are unaware of their low magnesium levels. Moreover, because magnesium is predominantly an intracellular cation (>99%), serum magnesium levels remain a poor predictor of tissue magnesium content and availability. This review will discuss the effects of magnesium deficiency in various pathologies affecting the human population. The underlying causes for magnesium depletion in major physiological systems will be examined along with the involved signaling pathways and the main roles of magnesium homeostasis. Where possible (e.g. alcoholism), the implications of administering supplemental magnesium will be discussed. Ultimately, this review will advocate for the necessity of identifying easy and reproducible methods to assess serum and cellular magnesium levels and to identify magnesium deficiency in order to alleviate related pathological conditions. PMID:25839058

  3. T Cell Immunity to the Alkyl Hydroperoxide Reductase of Burkholderia pseudomallei: A Correlate of Disease Outcome in Acute Melioidosis

    PubMed Central

    Reynolds, Catherine; Goudet, Amélie; Jenjaroen, Kemajittra; Sumonwiriya, Manutsanun; Rinchai, Darawan; Musson, Julie; Overbeek, Saskia; Makinde, Julia; Quigley, Kathryn; Manji, Jiten; Spink, Natasha; Yos, Pagnarith; Wuthiekanun, Vanaporn; Bancroft, Gregory; Robinson, John; Lertmemongkolchai, Ganjana; Dunachie, Susanna; Maillere, Bernard; Holden, Matthew; Altmann, Daniel

    2015-01-01

    There is an urgent need for a better understanding of adaptive immunity to Burkholderia pseudomallei, the causative agent of melioidosis that is frequently associated with sepsis or death in patients in Southeast Asia and Northern Australia. The imperative to identify vaccine targets is driven both by the public health agenda in these regions and biological threat concerns. In several intracellular bacterial pathogens, alkyl hydroperoxidase reductases are upregulated as part of the response to host oxidative stress, and they can stimulate strong adaptive immunity. We show that alkyl hydroperoxidase reductase (AhpC) of B. pseudomallei is strongly immunogenic for T cells of ‘humanized’ HLA transgenic mice and seropositive human donors. Some T cell epitopes, such as p6, are able to bind diverse HLA class II heterodimers and stimulate strong T cell immunity in mice and humans. Importantly, patients with acute melioidosis who survive infection show stronger T cell responses to AhpC relative to those who do not. Although the sequence of AhpC is virtually invariant among global B. pseudomallei clinical isolates, a Cambodian isolate varies only in C-terminal truncation of the p6 T cell epitope, raising the possibility of selection by host immunity. This variant peptide is virtually unable to stimulate T cell immunity. For an infection in which there has been debate about centrality of T cell immunity in defense, these observations support a role for T cell immunity to AhpC in disease protection. PMID:25862821

  4. Current and Emerging Biomarkers of Cell Death in Human Disease

    PubMed Central

    Li, Kongning; Wu, Deng; Chen, Xi; Zhang, Ting; Zhang, Lu; Yi, Ying; Miao, Zhengqiang; Jin, Nana; Bi, Xiaoman; Wang, Hongwei; Wang, Dong

    2014-01-01

    Cell death is a critical biological process, serving many important functions within multicellular organisms. Aberrations in cell death can contribute to the pathology of human diseases. Significant progress made in the research area enormously speeds up our understanding of the biochemical and molecular mechanisms of cell death. According to the distinct morphological and biochemical characteristics, cell death can be triggered by extrinsic or intrinsic apoptosis, regulated necrosis, autophagic cell death, and mitotic catastrophe. Nevertheless, the realization that all of these efforts seek to pursue an effective treatment and cure for the disease has spurred a significant interest in the development of promising biomarkers of cell death to early diagnose disease and accurately predict disease progression and outcome. In this review, we summarize recent knowledge about cell death, survey current and emerging biomarkers of cell death, and discuss the relationship with human diseases. PMID:24949464

  5. Nephropathy in dietary hyperoxaluria: A potentially preventable acute or chronic kidney disease

    PubMed Central

    Glew, Robert H; Sun, Yijuan; Horowitz, Bruce L; Konstantinov, Konstantin N; Barry, Marc; Fair, Joanna R; Massie, Larry; Tzamaloukas, Antonios H

    2014-01-01

    Hyperoxaluria can cause not only nephrolithiasis and nephrocalcinosis, but also renal parenchymal disease histologically characterized by deposition of calcium oxalate crystals throughout the renal parenchyma, profound tubular damage and interstitial inflammation and fibrosis. Hyperoxaluric nephropathy presents clinically as acute or chronic renal failure that may progress to end-stage renal disease (ESRD). This sequence of events, well recognized in the past in primary and enteric hyperoxalurias, has also been documented in a few cases of dietary hyperoxaluria. Estimates of oxalate intake in patients with chronic dietary hyperoxaluria who developed chronic kidney disease or ESRD were comparable to the reported average oxalate content of the diets of certain populations worldwide, thus raising the question whether dietary hyperoxaluria is a primary cause of ESRD in these regions. Studies addressing this question have the potential of improving population health and should be undertaken, alongside ongoing studies which are yielding fresh insights into the mechanisms of intestinal absorption and renal excretion of oxalate, and into the mechanisms of development of oxalate-induced renal parenchymal disease. Novel preventive and therapeutic strategies for treating all types of hyperoxaluria are expected to develop from these studies. PMID:25374807

  6. Residual Disease in a Novel Xenograft Model of RUNX1-Mutated, Cytogenetically Normal Acute Myeloid Leukemia

    PubMed Central

    Sivagnanalingam, Umayal; Balys, Marlene; Eberhardt, Allison; Wang, Nancy; Myers, Jason R.; Ashton, John M.; Becker, Michael W.; Calvi, Laura M.; Mendler, Jason H.

    2015-01-01

    Cytogenetically normal acute myeloid leukemia (CN-AML) patients harboring RUNX1 mutations have a dismal prognosis with anthracycline/cytarabine-based chemotherapy. We aimed to develop an in vivo model of RUNX1-mutated, CN-AML in which the nature of residual disease in this molecular disease subset could be explored. We utilized a well-characterized patient-derived, RUNX1-mutated CN-AML line (CG-SH). Tail vein injection of CG-SH into NOD scid gamma mice led to leukemic engraftment in the bone marrow, spleen, and peripheral blood within 6 weeks. Treatment of leukemic mice with anthracycline/cytarabine-based chemotherapy resulted in clearance of disease from the spleen and peripheral blood, but persistence of disease in the bone marrow as assessed by flow cytometry and secondary transplantation. Whole exome sequencing of CG-SH revealed mutations in ASXL1, CEBPA, GATA2, and SETBP1, not previously reported. We conclude that CG-SH xenografts are a robust, reproducible in vivo model of CN-AML in which to explore mechanisms of chemotherapy resistance and novel therapeutic approaches. PMID:26177509

  7. Controversial results of therapy with mesenchymal stem cells in the acute phase of canine distemper disease.

    PubMed

    Pinheiro, A O; Cardoso, M T; Vidane, A S; Casals, J B; Passarelli, D; Alencar, A L F; Sousa, R L M; Fantinato-Neto, P; Oliveira, V C; Lara, V M; Ambrósio, C E

    2016-01-01

    Distemper disease is an infectious disease reported in several species of domestic and wild carnivores. The high mortality rate of animals infected with canine distemper virus (CDV) treated with currently available therapies has driven the study of new efficacious treatments. Mesenchymal stem cell (MSC)-based therapy is a promising therapeutic option for many degenerative, hereditary, and inflammatory diseases. Therefore, the aim of this study was to characterize stem cells derived from the canine fetal olfactory epithelium and to assess the systemic response of animals infected with CDV to symptomatic therapy and treatment with MSCs. Eight domestic mongrel dogs (N = 8) were divided into two groups: support group (SG) (N = 5) and support group + cell therapy (SGCT) (N = 3), which were monitored over 15 days. Blood samples were collected on days 0, 6, 9, 12, and 15 to assess blood count and serum biochemistry (urea, creatinine, alanine transferase, alkaline phosphatase, gamma-glutamyl transferase, total protein, albumin, and globulin), and urine samples were obtained on days 0 and 15 for urinary evaluation (urine I). The results showed a high mortality rate (SG = 4 and SGCT = 2), providing inadequate data on the clinical course of CDV infection. MSC therapy resulted in no significant improvement when administered during the acute phase of canine distemper disease, and a prevalence of animals with high mortality rate was found in both groups due to the severity of symptoms. PMID:27323085

  8. Glycosphingolipid analysis in a naturally occurring ovine model of acute neuronopathic Gaucher disease.

    PubMed

    Karageorgos, Litsa; Hein, Leanne; Rozaklis, Tina; Adams, Melissa; Duplock, Stephen; Snel, Marten; Hemsley, Kim; Kuchel, Tim; Smith, Nicholas; Hopwood, John J

    2016-07-01

    Gaucher disease arises from mutations in the β-glucocerebrosidase gene which encodes an enzyme required for the lysosomal catabolism of glucosylceramide. We have identified a naturally occurring mutation in the β-glucocerebrosidase gene in sheep that leads to Gaucher disease with acute neurological symptoms. Here we have examined the clinical phenotype at birth and subsequently quantified lipids in Gaucher lamb brain, in order to characterise the disorder. Enzyme activity assessments showed that a reduction in β-glucocerebrosidase activity to 1-5% of wild-type occurs consistently across newborn Gaucher lamb brain regions. We analyzed glucosylceramide, glucosylsphingosine, bis(monoacylglycero)phosphate and ganglioside profiles in brain, liver, and spleen, and observed 30- to 130-fold higher glucosylceramide, and 500- to 2000-fold higher glucosylsphingosine concentrations in Gaucher diseased lambs compared to wild-type. Significant increases of bis(monoacylglycero)phosphate and gangliosides [GM1, GM2, GM3] concentrations were also detected in the brain. As these glycosphingolipids are involved in many cellular events, an imbalance or disruption of the cell membrane lipid homeostasis would be expected to impair normal neuronal function. To our knowledge, this is the first detailed analysis of glycosphingolipids in various brain regions in a large animal model of neuronal disease, which permits the mechanistic investigation of lipid deregulation and their contribution to neurodegenerative process. PMID:26976737

  9. Interneurons in the human olfactory system in Alzheimer's disease.

    PubMed

    Saiz-Sanchez, Daniel; Flores-Cuadrado, Alicia; Ubeda-Bañon, Isabel; de la Rosa-Prieto, Carlos; Martinez-Marcos, Alino

    2016-02-01

    The principal olfactory structures display Alzheimer's disease (AD) related pathology at early stages of the disease. Consequently, olfactory deficits are among the earliest symptoms. Reliable olfactory tests for accurate clinical diagnosis are rarely made. In addition, neuropathological analysis postmortem of olfactory structures is often not made. Therefore, the relationship between the clinical features and the underlying pathology is poorly defined. Traditionally, research into Alzheimer's disease has focused on the degeneration of cortical temporal projection neurons and cholinergic neurons. Recent evidence has demonstrated the neurodegeneration of interneuron populations in AD. This review provides an updated overview of the pathological involvement of interneuron populations in the human olfactory system in Alzheimer's disease. PMID:26616239

  10. Acute regulation of tight junction ion selectivity in human airway epithelia

    PubMed Central

    Flynn, Andrea N.; Itani, Omar A.; Moninger, Thomas O.; Welsh, Michael J.

    2009-01-01

    Electrolyte transport through and between airway epithelial cells controls the quantity and composition of the overlying liquid. Many studies have shown acute regulation of transcellular ion transport in airway epithelia. However, whether ion transport through tight junctions can also be acutely regulated is poorly understood both in airway and other epithelia. To investigate the paracellular pathway, we used primary cultures of differentiated human airway epithelia and assessed expression of claudins, the primary determinants of paracellular permeability, and measured transepithelial electrical properties, ion fluxes, and La3+ movement. Like many other tissues, airway epithelia expressed multiple claudins. Moreover, different cell types in the epithelium expressed the same pattern of claudins. To evaluate tight junction regulation, we examined the response to histamine, an acute regulator of airway function. Histamine stimulated a rapid and transient increase in the paracellular Na+ conductance, with a smaller increase in Cl− conductance. The increase was mediated by histamine H1 receptors and depended on an increase in intracellular Ca2+ concentration. These results suggest that ion flow through the paracellular pathway can be acutely regulated. Such regulation could facilitate coupling of the passive flow of counter ions to active transcellular transport, thereby controlling net transepithelial salt and water transport. PMID:19208806

  11. Human physiological responses to cold exposure: Acute responses and acclimatization to prolonged exposure.

    PubMed

    Castellani, John W; Young, Andrew J

    2016-04-01

    Cold exposure in humans causes specific acute and chronic physiological responses. This paper will review both the acute and long-term physiological responses and external factors that impact these physiological responses. Acute physiological responses to cold exposure include cutaneous vasoconstriction and shivering thermogenesis which, respectively, decrease heat loss and increase metabolic heat production. Vasoconstriction is elicited through reflex and local cooling. In combination, vasoconstriction and shivering operate to maintain thermal balance when the body is losing heat. Factors (anthropometry, sex, race, fitness, thermoregulatory fatigue) that influence the acute physiological responses to cold exposure are also reviewed. The physiological responses to chronic cold exposure, also known as cold acclimation/acclimatization, are also presented. Three primary patterns of cold acclimatization have been observed, a) habituation, b) metabolic adjustment, and c) insulative adjustment. Habituation is characterized by physiological adjustments in which the response is attenuated compared to an unacclimatized state. Metabolic acclimatization is characterized by an increased thermogenesis, whereas insulative acclimatization is characterized by enhancing the mechanisms that conserve body heat. The pattern of acclimatization is dependent on changes in skin and core temperature and the exposure duration. PMID:26924539

  12. Perihepatic nodes detected by point-of-care ultrasound in acute hepatitis and acute-on-chronic liver disease

    PubMed Central

    Feng, I Che; Wang, Szu Jen; Sheu, Ming Jen; Koay, Lok-Beng; Lin, Ching Yih; Ho, Chung Han; Sun, Chi Shu; Kuo, Hsing Tao

    2015-01-01

    AIM: To study the manifestations of perihepatic lymph nodes during the episode of acute hepatitis flare by point-of-care ultrasonography. METHODS: One hundred and seventy-six patients with an episode of acute hepatitis flare (ALT value > 5 × upper normal limit) were enrolled retrospectively. Diagnosis of etiology of the acute hepatitis flare was based on chart records and serological and virological assays. The patients were categorized into two groups (viral origin and non-viral origin) and further defined into ten subgroups according to the etiologies. An ultrasonograpy was performed within 2 h to 72 h (median, 8 h). The maximum size of each noticeable lymph node was measured. Correlation between clinical parameters and nodal manifestations was analyzed RESULTS: Enlarged lymph nodes (width ≥ 5mm) were noticeable in 110 (62.5%) patients, mostly in acute on chronic hepatitis B (54.5%). The viral group had a higher prevalence rate (89/110 = 80.9%) and larger nodal size (median, 7 mm) than those of the non-viral group (21/66 = 31.8%; median, 0 mm) (P < 0.001 for both). Meanwhile, there were significant differences in the nodal size between acute and chronic viral groups (P < 0.01), and between acute hepatitis A and non-hepatitis A viral groups (P < 0.001). In logistical regression analysis, the nodal width still showed strong significance in multivariate analysis (P < 0.0001) to stratify the two groups. The area under the curve of ROC was 0.805, with a sensitivity of 80.9%, a specificity of 68.2%, positive predictive value of 80.92%, negative predictive value of 68.18%, and an accuracy of 76.14%. CONCLUSION: Point-of-care ultrasonography to detect perihepatic nodal change is valuable for clarifying the etiologies in an episode of acute hepatitis flare. PMID:26640338

  13. Soluble cell adhesion molecules in human Chagas' disease: association with disease severity and stage of infection.

    PubMed

    Laucella, S; De Titto, E H; Segura, E L; Orn, A; Rottenberg, M E

    1996-12-01

    Formation of inflammatory lesions, one of the pathologic consequences of infection with Trypanosoma cruzi, involves intricate cell-cell interactions in which cell adhesion molecules (CAMs) are involved. Sera from 56 Chagas' disease patients grouped according to disease severity were studied for the presence of soluble intercellular adhesion molecule-1 (s-ICAM-1), soluble endothelial selectin (s-E-selectin), soluble vascular cell adhesion molecule-1 (s-VCAM-1), soluble platelet selectin (s-P-selectin), and s-CD44 were studied to determine if they could be used alone or in different combinations as markers for specific diagnostic procedures. Comparisons were made between congenitally, acutely, and chronically infected patients and aged-matched, noninfected individuals, as well as between patients with chronic Chagas' disease grouped according to the severity of their heart-related pathology. No differences in levels of s-CAMs were detected between sera from children with congenital T. cruzi infection and sera from noninfected infants born from chagasic mothers. In contrast, titers of s-ICAM-1, s-VCAM-1, s-selectin, and s-CD44 but not s-P-selectin were significantly increased in sera from patients during the acute phase of infection with T. cruzi. Titers of s-VCAM-1 and s-P-selectin were increased in chronically infected patients. A positive association with disease severity in sera from patients with chronic disease was observed for the levels of s-P-selectin. In contrast, we found no association between clinical symptoms and levels of s-VCAM-1. Patients with chronic disease with severe cardiopathy also showed diminished levels of s-CD44 in comparison with healthy controls or patients with mild disease. The results are discussed in the context of pathology of Chagas' disease. PMID:9025689

  14. Reprogramming of primary human Philadelphia chromosome-positive B cell acute lymphoblastic leukemia cells into nonleukemic macrophages.

    PubMed

    McClellan, James Scott; Dove, Christopher; Gentles, Andrew J; Ryan, Christine E; Majeti, Ravindra

    2015-03-31

    BCR-ABL1(+) precursor B-cell acute lymphoblastic leukemia (BCR-ABL1(+) B-ALL) is an aggressive hematopoietic neoplasm characterized by a block in differentiation due in part to the somatic loss of transcription factors required for B-cell development. We hypothesized that overcoming this differentiation block by forcing cells to reprogram to the myeloid lineage would reduce the leukemogenicity of these cells. We found that primary human BCR-ABL1(+) B-ALL cells could be induced to reprogram into macrophage-like cells by exposure to myeloid differentiation-promoting cytokines in vitro or by transient expression of the myeloid transcription factor C/EBPα or PU.1. The resultant cells were clonally related to the primary leukemic blasts but resembled normal macrophages in appearance, immunophenotype, gene expression, and function. Most importantly, these macrophage-like cells were unable to establish disease in xenograft hosts, indicating that lineage reprogramming eliminates the leukemogenicity of BCR-ABL1(+) B-ALL cells, and suggesting a previously unidentified therapeutic strategy for this disease. Finally, we determined that myeloid reprogramming may occur to some degree in human patients by identifying primary CD14(+) monocytes/macrophages in BCR-ABL1(+) B-ALL patient samples that possess the BCR-ABL1(+) translocation and clonally recombined VDJ regions. PMID:25775523

  15. Animal models of human granulocyte diseases.

    PubMed

    Schäffer, Alejandro A; Klein, Christoph

    2013-02-01

    In vivo animal models have proven very useful to the understanding of basic biologic pathways of the immune system, a prerequisite for the development of innovate therapies. This article addresses currently available models for defined human monogenetic defects of neutrophil granulocytes, including murine, zebrafish, and larger mammalian species. Strengths and weaknesses of each system are summarized, and clinical investigators may thus be inspired to develop further lines of research to improve diagnosis and therapy by use of the appropriate animal model system. PMID:23351993

  16. Rapidly Escalating Hepcidin and Associated Serum Iron Starvation Are Features of the Acute Response to Typhoid Infection in Humans

    PubMed Central

    Darton, Thomas C.; Blohmke, Christoph J.; Giannoulatou, Eleni; Waddington, Claire S.; Jones, Claire; Sturges, Pamela; Webster, Craig; Drakesmith, Hal; Pollard, Andrew J.; Armitage, Andrew E.

    2015-01-01

    Background Iron is a key pathogenic determinant of many infectious diseases. Hepcidin, the hormone responsible for governing systemic iron homeostasis, is widely hypothesized to represent a key component of nutritional immunity through regulating the accessibility of iron to invading microorganisms during infection. However, the deployment of hepcidin in human bacterial infections remains poorly characterized. Typhoid fever is a globally significant, human-restricted bacterial infection, but understanding of its pathogenesis, especially during the critical early phases, likewise is poorly understood. Here, we investigate alterations in hepcidin and iron/inflammatory indices following experimental human typhoid challenge. Methodology/Principal Findings Fifty study participants were challenged with Salmonella enterica serovar Typhi and monitored for evidence of typhoid fever. Serum hepcidin, ferritin, serum iron parameters, C-reactive protein (CRP), and plasma IL-6 and TNF-alpha concentrations were measured during the 14 days following challenge. We found that hepcidin concentrations were markedly higher during acute typhoid infection than at baseline. Hepcidin elevations mirrored the kinetics of fever, and were accompanied by profound hypoferremia, increased CRP and ferritin, despite only modest elevations in IL-6 and TNF-alpha in some individuals. During inflammation, the extent of hepcidin upregulation associated with the degree of hypoferremia. Conclusions/Significance We demonstrate that strong hepcidin upregulation and hypoferremia, coincident with fever and systemic inflammation, are hallmarks of the early innate response to acute typhoid infection. We hypothesize that hepcidin-mediated iron redistribution into macrophages may contribute to S. Typhi pathogenesis by increasing iron availability for macrophage-tropic bacteria, and that targeting macrophage iron retention may represent a strategy for limiting infections with macrophage-tropic pathogens such as S

  17. Mouse models of human disease: An evolutionary perspective.

    PubMed

    Perlman, Robert L

    2016-01-01

    The use of mice as model organisms to study human biology is predicated on the genetic and physiological similarities between the species. Nonetheless, mice and humans have evolved in and become adapted to different environments and so, despite their phylogenetic relatedness, they have become very different organisms. Mice often respond to experimental interventions in ways that differ strikingly from humans. Mice are invaluable for studying biological processes that have been conserved during the evolution of the rodent and primate lineages and for investigating the developmental mechanisms by which the conserved mammalian genome gives rise to a variety of different species. Mice are less reliable as models of human disease, however, because the networks linking genes to disease are likely to differ between the two species. The use of mice in biomedical research needs to take account of the evolved differences as well as the similarities between mice and humans. PMID:27121451

  18. Diagnostic accuracy of porcine acute phase proteins in meat juice for detecting disease at abattoir.

    PubMed

    Gutiérrez, A M; Martínez-Subiela, S; Cerón, J J

    2015-07-01

    The aim of this work was to evaluate whether acute phase protein (APP) determinations could assist Official Veterinarians carrying out work in slaughterhouses. To test this hypothesis, the diagnostic accuracy of APP determinations in meat juice of pigs was analysed to differentiate between healthy and diseased pigs. One hundred and one pigs of two different origins were classified into two groups according to their health status (healthy and diseased pigs), which was determined by a veterinary clinical examination on the farm. To assess the pigs' immune status, against the main porcine diseases, serological analyses were monitored. A general idea of the degree of disease coverage was analysed by examining organ lesions postmortem. Haptoglobin (Hp) and C reactive protein (CRP) were measured in meat juice samples. 72.13 per cent of pigs appeared to be seropositive for the porcine respiratory and reproductive syndrome virus, and almost 86.2 per cent of them had concomitant infections with other pathogens, such as Porcine circovirus type 2 or Swine influenza virus. Median Hp and CRP concentrations were significantly higher in diseased animals at different stages of the production chain, when compared with levels found in healthy finishing pigs (P<0.0001). Receiver operating characteristic analysis showed the highest sensitivity-specificity pairs, nearly 80-90 per cent, at cut-off levels of 83 and 10 µg/ml for Hp and CRP determinations, respectively, with high AUCs 0.9. This cut-off could be useful for veterinary inspections at the time of slaughter, to differentiate between the carcase of a healthy animal and the carcase of an animal suffering from a systemic disease, which should be completely condemned. PMID:26101294

  19. Genetic regulation of human brain development: lessons from Mendelian diseases

    PubMed Central

    Dixon-Salazar, Tracy J.; Gleeson, Joseph G.

    2016-01-01

    One of the fundamental goals in human genetics is to link gene function to phenotype, yet the function of the majority of the genes in the human body is still poorly understood. This is especially true for the developing human brain. The study of human phenotypes that result from inherited, mutated alleles is the most direct evidence for the requirement of a gene in human physiology. Thus, the study of Mendelian central nervous system(CNS) diseases can be an extremely powerful approach to elucidate such phenotypic/genotypic links and to increase our understanding of the key components required for development of the human brain. In this review, we highlight examples of how the study of inherited neurodevelopmental disorders contributes to our knowledge of both the “normal” and diseased human brain, as well as elaborate on the future of this type of research. Mendelian disease research has been, and will continue to be, key to understanding the molecular mechanisms that underlie human brain function, and will ultimately form a basis for the design of intelligent, mechanism-specific treatments for nervous system disorders. PMID:21062301

  20. Research priorities for Chagas disease, human African trypanosomiasis and leishmaniasis.

    PubMed

    2012-01-01

    This report provides a review and analysis of the research landscape for three diseases - Chagas disease, human African trypanosomiasis and leishmaniasis - that disproportionately afflict poor and remote populations with limited access to health services. It represents the work of the disease reference group on Chagas Disease, Human African Trypanosomiasis and Leishmaniasis (DRG3) which was established to identify key research priorities through review of research evidence and input from stakeholders' consultations. The diseases, which are caused by related protozoan parasites, are described in terms of their epidemiology and diseases burden, clinical forms and pathogenesis, HIV coinfection, diagnosis, drugs and drug resistance, vaccines, vector control, and health-care interventions. Priority areas for research are identified based on criteria such as public health relevance, benefit and impact on poor populations and equity, and feasibility. The priorities are found in the areas of diagnostics, drugs, vector control, asymptomatic infection, economic analysis of treatment and vector control methods, and in some specific issues such as surveillance methods or transmission-blocking vaccines for particular diseases. This report will be useful to researchers, policy and decision-makers, funding bodies, implementation organizations, and civil society. This is one of ten disease and thematic reference group reports that have come out of the TDR Think Tank, all of which have contributed to the development of the Global Report for Research on Infectious Diseases of Poverty, available at: www.who.int/tdr/stewardship/global_report/en/index.html. PMID:23484340

  1. Candida albicans Biofilms and Human Disease

    PubMed Central

    Nobile, Clarissa J.; Johnson, Alexander D.

    2016-01-01

    In humans, microbial cells (including bacteria, archaea, and fungi) greatly outnumber host cells. Candida albicans is the most prevalent fungal species of the human microbiota; this species asymptomatically colonizes many areas of the body, particularly the gastrointestinal and genitourinary tracts of healthy individuals. Alterations in host immunity, stress, resident microbiota, and other factors can lead to C. albicans overgrowth, causing a wide range of infections, from superficial mucosal to hematogenously disseminated candidiasis. To date, most studies of C. albicans have been carried out in suspension cultures; however, the medical impact of C. albicans (like that of many other microorganisms) depends on its ability to thrive as a biofilm, a closely packed community of cells. Biofilms are notorious for forming on implanted medical devices, including catheters, pacemakers, dentures, and prosthetic joints, which provide a surface and sanctuary for biofilm growth. C. albicans biofilms are intrinsically resistant to conventional antifungal therapeutics, the host immune system, and other environmental perturbations, making biofilm-based infections a significant clinical challenge. Here, we review our current knowledge of biofilms formed by C. albicans and closely related fungal species. PMID:26488273

  2. FISH CONSUMPTION, METHYLMERCURY, AND HUMAN HEART DISEASE.

    SciTech Connect

    LIPFERT, F.W.; SULLIVAN, T.M.

    2005-09-21

    Environmental mercury continues to be of concern to public health advocates, both in the U.S. and abroad, and new research continues to be published. A recent analysis of potential health benefits of reduced mercury emissions has opened a new area of public health concern: adverse effects on the cardiovascular system, which could account for the bulk of the potential economic benefits. The authors were careful to include caveats about the uncertainties of such impacts, but they cited only a fraction of the applicable health effects literature. That literature includes studies of the potentially harmful ingredient (methylmercury, MeHg) in fish, as well as of a beneficial ingredient, omega-3 fatty acids or ''fish oils''. The U.S. Food and Drug Administration (FDA) recently certified that some of these fat compounds that are primarily found in fish ''may be beneficial in reducing coronary heart disease''. This paper briefly summarizes and categorizes the extensive literature on both adverse and beneficial links between fish consumption and cardiovascular health, which are typically based on studies of selected groups of individuals (cohorts). Such studies tend to comprise the ''gold standard'' of epidemiology, but cohorts tend to exhibit a great deal of variability, in part because of the limited numbers of individuals involved and in part because of interactions with other dietary and lifestyle considerations. Note that eating fish will involve exposure to both the beneficial effects of fatty acids and the potentially harmful effects of contaminants like Hg or PCBs, all of which depend on the type of fish but tend to be correlated within a population. As a group, the cohort studies show that eating fish tends to reduce mortality, especially due to heart disease, for consumption rates up to about twice weekly, above which the benefits tend to level off. A Finnish cohort study showed increased mortality risks in the highest fish-consuming group ({approx}3 times

  3. Fifth (human parvovirus) and sixth (herpesvirus 6) diseases.

    PubMed

    Koch, W C

    2001-06-01

    Fifth (erythema infectiosum) and sixth (roseola infantum) diseases are common rash illnesses of childhood that have long been recognized in clinical medicine. The discovery of the viruses that cause these illnesses has revealed relationships with other syndromes. Primary infection with the agent of erythema infectiosum, human parvovirus B19, is associated with transient aplastic crisis in hemolytic anemia, arthropathy in adults, chronic anemia in immunocompromised patients, and nonimmune fetal hydrops in pregnant women. The only documented illness associated with primary infection with human herpesvirus 6 is roseola or exanthema subitum in young children. However, reactivated infections in adults and immunocompromised patients may be associated with serious illness such as encephalitis/encephalopathy, and bone marrow suppression leading to transplant failure or graft-versus-host disease. Diagnostic studies for both viruses have been limited, although reliable serologic tests for human parvovirus B19 have recently become available. Diagnosis of human herpesvirus 6 remains problematic, because current tests cannot differentiate primary from reactivated disease. This is more of an issue for the putative relationship of these viruses to more chronic conditions, such as rheumatologic disease for human parvovirus B19 and multiple sclerosis for human herpesvirus 6. The relationship between the viruses and these conditions remains controversial, and better diagnostic tests and further information on viral pathogenesis for both viruses are required in order to make a reliable judgment in this regard. PMID:11964854

  4. Drosophila tools and assays for the study of human diseases.

    PubMed

    Ugur, Berrak; Chen, Kuchuan; Bellen, Hugo J

    2016-03-01

    Many of the internal organ systems of Drosophila melanogaster are functionally analogous to those in vertebrates, including humans. Although humans and flies differ greatly in terms of their gross morphological and cellular features, many of the molecular mechanisms that govern development and drive cellular and physiological processes are conserved between both organisms. The morphological differences are deceiving and have led researchers to undervalue the study of invertebrate organs in unraveling pathogenic mechanisms of diseases. In this review and accompanying poster, we highlight the physiological and molecular parallels between fly and human organs that validate the use of Drosophila to study the molecular pathogenesis underlying human diseases. We discuss assays that have been developed in flies to study the function of specific genes in the central nervous system, heart, liver and kidney, and provide examples of the use of these assays to address questions related to human diseases. These assays provide us with simple yet powerful tools to study the pathogenic mechanisms associated with human disease-causing genes. PMID:26935102

  5. Drosophila tools and assays for the study of human diseases

    PubMed Central

    Ugur, Berrak; Chen, Kuchuan; Bellen, Hugo J.

    2016-01-01

    ABSTRACT Many of the internal organ systems of Drosophila melanogaster are functionally analogous to those in vertebrates, including humans. Although humans and flies differ greatly in terms of their gross morphological and cellular features, many of the molecular mechanisms that govern development and drive cellular and physiological processes are conserved between both organisms. The morphological differences are deceiving and have led researchers to undervalue the study of invertebrate organs in unraveling pathogenic mechanisms of diseases. In this review and accompanying poster, we highlight the physiological and molecular parallels between fly and human organs that validate the use of Drosophila to study the molecular pathogenesis underlying human diseases. We discuss assays that have been developed in flies to study the function of specific genes in the central nervous system, heart, liver and kidney, and provide examples of the use of these assays to address questions related to human diseases. These assays provide us with simple yet powerful tools to study the pathogenic mechanisms associated with human disease-causing genes. PMID:26935102

  6. [Relationship between child day-care attendance and acute infectious disease. A systematic review].

    PubMed

    Ochoa Sangrador, Carlos; Barajas Sánchez, M Verisima; Muñoz Martín, Beatriz

    2007-01-01

    Child day-care attendance is considered to be an acute early childhood disease risk factor, the studies available however not affording the possibility of fully quantifying this risk. A systematic review of clinical trials and cohort studies was conducted, in which the effects child day-care attendance had on the health of young children based on the Cochrane Collaboration, PubMed and Spanish Medical Index databases, without any time or language-related limits, were analyzed and rounded out with analyses of referenced works and an additional EMBASE search. The methodological quality was evaluated by means of personalized criteria. Pooling measures (relative risks, incidence density ratios and weighted mean differences) were calculated with their confidence intervals, assuming random effects models. A significant increase was found to exist of a risk consistent over time and among different social and geographical environments. Considering the most methodologically-stringent studies with adjusted effect estimates, child day-care attendance was related to an increased risk of upper respiratory tract infection (RR=1,88), acute otitis media (RR=1,58), otitis media with fluid draining (RR=2,43), lower respiratory tract infections (overall RR=210; acute pneumonia RR=1.70; broncholitis RR=1,80; bronchitis RR=2,10) and gastroenteritis (RR=1,40). Child day-care attendance could be responsible for 33%-50% of the episodes of respiratory infection and gastroenteritis among the exposed population. In conclusion, it can be said that the risk for childhood health attributable to the child day-care attendance is discreet but of high-impact. This information has some major implications for research, clinical practice, healthcare authorities and society as a whole. PMID:17639680

  7. Pulmonary Artery Dilation and Right Ventricular Function in Acute Kawasaki Disease.

    PubMed

    Numano, Fujito; Shimizu, Chisato; Tremoulet, Adriana H; Dyar, Dan; Burns, Jane C; Printz, Beth F

    2016-03-01

    Coronary artery inflammation and aneurysm formation are the most common complications of Kawasaki disease (KD). Valvulitis and myocarditis are also well described and may lead to valvar regurgitation and left ventricular dysfunction. However, functional changes in the right heart have rarely been reported. We noted several acute KD patients with dilated pulmonary arteries (PA) and thus sought to systematically characterize PA size and right-heart function in an unselected cohort of KD patients cared for at a single clinical center. Clinical, laboratory, and echocardiographic data from 143 acute KD subjects were analyzed. PA dilation was documented in 23 subjects (16.1 %); these subjects had higher median right ventricle myocardial performance index (RV MPI), higher ratio of early tricuspid inflow velocity to tricuspid annular early diastolic velocity (TV E/e'), and lower median TV e' velocity compared to the non-PA dilation group (0.50 vs 0.38 p < 0.01, 4.2 vs 3.6 p < 0.05, and 13.5 vs 15.2 cm/s p < 0.01, respectively). Almost all subjects with PA dilation had improved PA Z-score, RV MPI, and TV E/e' in the subacute phase (p < 0.01). There were no significant differences in indices of left ventricle function between PA dilation group and non-PA dilation group. In summary, PA dilation was documented in 16 % of acute KD subjects. These subjects were more likely to have echocardiographic indices consistent with isolated RV dysfunction that improved in the subacute phase. The long-term consequence of these findings will require longitudinal studies of this patient population. PMID:26681305

  8. Acute analgesic effects of nicotine and tobacco in humans: a meta-analysis.

    PubMed

    Ditre, Joseph W; Heckman, Bryan W; Zale, Emily L; Kosiba, Jesse D; Maisto, Stephen A

    2016-07-01

    Although animal models have consistently demonstrated acute pain inhibitory effects of nicotine and tobacco, human experimental studies have yielded mixed results. The main goal of this meta-analysis was to quantify the effects of nicotine/tobacco administration on human experimental pain threshold and tolerance ratings. A search of PubMed and PsycINFO online databases identified 13 eligible articles, including k = 21 tests of pain tolerance (N = 393) and k = 15 tests of pain threshold (N = 339). Meta-analytic integration for both threshold and tolerance outcomes revealed that nicotine administered through tobacco smoke and other delivery systems (eg, patch, nasal spray) produced acute analgesic effects that may be characterized as small to medium in magnitude (Hedges g = 0.35, 95% confidence interval = 0.21-0.50). Publication bias-corrected estimates remained significant and indicated that these effects may be closer to small. Sex composition was observed to be a significant moderator, such that pain threshold effects were more robust among samples that included more men than women. These results help to clarify a mixed literature and may ultimately help to inform the treatment of both pain and nicotine dependence. Pain and tobacco smoking are both highly prevalent and comorbid conditions. Current smoking has been associated with more severe chronic pain and physical impairment. Acute nicotine-induced analgesia could make smoking more rewarding and harder to give up. Future research should use dynamic measures of experimental pain reactivity and further explore biopsychosocial mechanisms of action. PMID:27023418

  9. Use of Humanized Mice to Study the Pathogenesis of Autoimmune and Inflammatory Diseases

    PubMed Central

    Koboziev, Iurii; Jones-Hall, Yava; Valentine, John F.; Webb, Cynthia Reinoso; Furr, Kathryn L.; Grisham, Matthew B.

    2015-01-01

    Animal models of disease have been used extensively by the research community for the past several decades to better understand the pathogenesis of different diseases as well as assess the efficacy and toxicity of different therapeutic agents. Retrospective analyses of numerous preclinical intervention studies using mouse models of acute and chronic inflammatory diseases reveal a generalized failure to translate promising interventions or therapeutics into clinically-effective treatments in patients. Although several possible reasons have been suggested to account for this generalized failure to translate therapeutic efficacy from the laboratory bench to the patient’s bedside, it is becoming increasingly apparent that the mouse immune system may not adequately recapitulate the immuno-pathological mechanisms observed in human diseases. Indeed, it is well-known that >80 major differences exist between mouse and human immunology; all of which contribute to significant differences in immune system development, activation and responses to challenges in innate and adaptive immunity. This inconvenient reality has prompted investigators to attempt to humanize the mouse immune system in order to address important, human-specific questions that are impossible to study in patients. The successful long-term engraftment of human hemato-lymphoid cells in mice would provide investigators with a relatively inexpensive, small animal model to study clinically-relevant mechanisms as well as facilitate the evaluation of human-specific therapies in vivo. The discovery that targeted mutation of the IL-2 receptor common gamma chain in lymphopenic mice allows for the long-term engraftment of functional human immune cells has advanced greatly our ability to humanize the mouse immune system. The objective of this review is to present a brief overview of the recent advances that have been made in the development and use of humanized mice with special emphasis on autoimmune and chronic

  10. Human Disease Insight: An integrated knowledge-based platform for disease-gene-drug information.

    PubMed

    Tasleem, Munazzah; Ishrat, Romana; Islam, Asimul; Ahmad, Faizan; Hassan, Md Imtaiyaz

    2016-01-01

    The scope of the Human Disease Insight (HDI) database is not limited to researchers or physicians as it also provides basic information to non-professionals and creates disease awareness, thereby reducing the chances of patient suffering due to ignorance. HDI is a knowledge-based resource providing information on human diseases to both scientists and the general public. Here, our mission is to provide a comprehensive human disease database containing most of the available useful information, with extensive cross-referencing. HDI is a knowledge management system that acts as a central hub to access information about human diseases and associated drugs and genes. In addition, HDI contains well-classified bioinformatics tools with helpful descriptions. These integrated bioinformatics tools enable researchers to annotate disease-specific genes and perform protein analysis, search for biomarkers and identify potential vaccine candidates. Eventually, these tools will facilitate the analysis of disease-associated data. The HDI provides two types of search capabilities and includes provisions for downloading, uploading and searching disease/gene/drug-related information. The logistical design of the HDI allows for regular updating. The database is designed to work best with Mozilla Firefox and Google Chrome and is freely accessible at http://humandiseaseinsight.com. PMID:26631432

  11. Improved accuracy of acute graft-versus-host disease staging among multiple centers.

    PubMed

    Levine, John E; Hogan, William J; Harris, Andrew C; Litzow, Mark R; Efebera, Yvonne A; Devine, Steven M; Reshef, Ran; Ferrara, James L M

    2014-01-01

    The clinical staging of acute graft-versus-host disease (GVHD) varies significantly among bone marrow transplant (BMT) centers, but adherence to long-standing practices poses formidable barriers to standardization among centers. We have analyzed the sources of variability and developed a web-based remote data entry system that can be used by multiple centers simultaneously and that standardizes data collection in key areas. This user-friendly, intuitive interface resembles an online shopping site and eliminates error-prone entry of free text with drop-down menus and pop-up detailed guidance available at the point of data entry. Standardized documentation of symptoms and therapeutic response reduces errors in grade assignment and allows creation of confidence levels regarding the diagnosis. Early review and adjudication of borderline cases improves consistency of grading and further enhances consistency among centers. If this system achieves widespread use it may enhance the quality of data in multicenter trials to prevent and treat acute GVHD. PMID:25455279

  12. Improved accuracy of acute graft-versus-host disease staging among multiple centers

    PubMed Central

    Levine, John E.; Hogan, William J.; Harris, Andrew C.; Litzow, Mark R.; Efebera, Yvonne A.; Devine, Steven M.; Reshef, Ran; Ferrara, James L.M.

    2015-01-01

    The clinical staging of acute graft-versus-host disease (GVHD) varies significantly among bone marrow transplant (BMT) centers, but adherence to long-standing practices poses formidable barriers to standardization among centers. We have analyzed the sources of variability and developed a web-based remote data entry system that can be used by multiple centers simultaneously and that standardizes data collection in key areas. This user-friendly, intuitive interface resembles an online shopping site and eliminates error-prone entry of free text with drop-down menus and pop-up detailed guidance available at the point of data entry. Standardized documentation of symptoms and therapeutic response reduces errors in grade assignment and allows creation of confidence levels regarding the diagnosis. Early review and adjudication of borderline cases improves consistency of grading and further enhances consistency among centers. If this system achieves widespread use it may enhance the quality of data in multicenter trials to prevent and treat acute GVHD. PMID:25455279

  13. Acute and chronic Legionnaires' disease and co-existent tuberculosis: a trial of erythromycin.

    PubMed

    Hamedani, P; Hafeez, S; Ali, J; Memon, R; Ali, S; Ali, M; Ansari, M; Raza, R

    1989-01-01

    To assess the prevalence of Legionnaires' disease, 115 patients with 'difficult-to-treat' chest infections were screened for Legionnella pneumophila. The results were positive in 10 (37%) of 27 patients with pulmonary tuberculosis, 15 (22%) of 68 with a recent onset acute respiratory infection, and 7 (35%) of 20 patients with history of a chronic respiratory infection. These 32 patients were enrolled in an open therapeutic trial of erythromycin. Less severe cases (17 of 32) received erythromycin stearate orally (500 mg 4-times daily) for up to 28 days, while severe cases were treated for the first few days with intravenous erythromycin lactobionate (4 g/day). Weekly chest X-ray examinations revealed prompt resolution. Most patients had no signs and symptoms detectable after 7 days, and none persisted up to 28 days. There were no therapeutic failures and microbiological tests on Day 28 were negative for Legionella pneumophila. It is suggested that the possibility of co-existing legionellosis should be considered in all patients with difficult to treat acute and chronic chest infections, particularly in developing countries where tuberculosis is very common, and treatment instituted or supplemented with erythromycin as the drug of choice. PMID:2680287

  14. Loss of Ifnar1 in Pancreatic Acinar Cells Ameliorates the Disease Course of Acute Pancreatitis.

    PubMed

    Miller, Katharina J; Raulefs, Susanne; Kong, Bo; Steiger, Katja; Regel, Ivonne; Gewies, Andreas; Kleeff, Jörg; Michalski, Christoph W

    2015-01-01

    Type I interferon constitutes an essential component of the combinational therapy against viral disease. Acute pancreatitis is one side effect of type I interferon-based therapy, implying that activation of type I interferon signaling affects the homeostasis and integrity of pancreatic acinar cells. Here, we investigated the role of type I interferon signaling in pancreatic acinar cells using a caerulein-induced murine model of acute pancreatitis. Pancreas-specific ablation of interferon (alpha and beta) receptor 1 (Ifnar1) partially protected animals from caerulein-induced pancreatitis, as demonstrated by reduced tissue damage. Profiling of infiltrating immune cells revealed that this dampened tissue damage response correlated with the number of macrophages in the pancreas. Pharmacologic depletion of macrophages reversed the protective effect of Ifnar1 deficiency. Furthermore, expression of chemokine (C-C motif) ligand 2 (Ccl2), a potent factor for macrophage recruitment, was significantly increased in the Ifnar1-deficient pancreas. Thus, type I interferon signaling in pancreatic acinar cells controls pancreatic homeostasis by affecting the macrophage-mediated inflammatory response in the pancreas. PMID:26618925

  15. Acute Respiratory Failure in Critically Ill Patients with Interstitial Lung Disease

    PubMed Central

    Zafrani, Lara; Lemiale, Virginie; Lapidus, Nathanael; Lorillon, Gwenael; Schlemmer, Benoît; Azoulay, Elie

    2014-01-01

    Background Patients with chronic known or unknown interstitial lung disease (ILD) may present with severe respiratory flares that require intensive management. Outcome data in these patients are scarce. Patients and Methods Clinical and radiological features were collected in 83 patients with ILD-associated acute respiratory failure (ARF). Determinants of hospital mortality and response to corticosteroid therapy were identified by logistic regression. Results Hospital and 1-year mortality rates were 41% and 54% respectively. Pulmonary hypertension, computed tomography (CT) fibrosis and acute kidney injury were independently associated with mortality (odds ratio (OR) 4.55; 95% confidence interval (95%CI) (1.20–17.33); OR, 7.68; (1.78–33.22) and OR 10.60; (2.25–49.97) respectively). Response to steroids was higher in patients with shorter time from hospital admission to corticosteroid therapy. Patients with fibrosis on CT had lower response to steroids (OR, 0.03; (0.005–0.21)). In mechanically ventilated patients, overdistension induced by high PEEP settings was associated with CT fibrosis and hospital mortality. Conclusion Mortality is high in ILD-associated ARF. CT and echocardiography are valuable prognostic tools. Prompt corticosteroid therapy may improve survival. PMID:25115557

  16. Spectroscopy techniques for human disease diagnosis

    NASA Astrophysics Data System (ADS)

    Navas-Moreno, Maria

    2011-12-01

    Modern medicine would benefit from the pursuit of new, more specific and easier to implement diagnosis tools. In recent years, Raman scattering, surface-enhanced Raman scattering and fluorescence spectroscopy have proven to be successful diagnostic techniques for a wide range of diseases including atherosclerosis, kidney stones, bone diseases, diabetes, and a wide collection of neoplasms. Optical spectroscopy has several advantages over more traditional diagnostic methods (i.e., histopathology, quantitative PCR, etc.) such as faster data analysis, nonspecific sample preparation, nonspecific labels/reagents/antibodies usage requirements, and immediate on-site implementation. In the present work, label-free in vitro fluorescence and surface enhanced Raman scattering (SERS) spectroscopy have been used to differentiate between blood cells of patients affected with myeloproliferative neoplasms (MPN) and those of healthy subjects. The SERS technique has also been applied to hemoglobin variants as well as to serum obtained from patients affected with chronic heart failure who positively or negatively responded to the seasonal influenza vaccine. We found that spectral ratios of the background fluorescence intensity that accompanies the SERS spectra of granulocytes serve as excellent markers for the presence of MPNs. In addition, we also found expression dysregulation of two hypoxia induced factor regulated genes, which correlates with our results obtained by SERS spectroscopy assay in MPN patients and supports the presence of the Warburg effect in MPNs. We hypothesize that SERS measures metabolic change in granulocytes through two possible mechanisms: (i) Changes in dielectric properties of the environment surrounding the silver-cell interface; and (ii) changes in flavin adenine dinucleotide concentrations, which in turn changes the relative contribution of the autofluorescence to the emission spectrum. These hypotheses are supported by SERS measurement of 2-deoxy

  17. Molecular and genetic inflammation networks in major human diseases.

    PubMed

    Zhao, Yongzhong; Forst, Christian V; Sayegh, Camil E; Wang, I-Ming; Yang, Xia; Zhang, Bin

    2016-07-19

    It has been well-recognized that inflammation alongside tissue repair and damage maintaining tissue homeostasis determines the initiation and progression of complex diseases. Albeit with the accomplishment of having captured the most critical inflammation-involved molecules, genetic susceptibilities, epigenetic factors, and environmental factors, our schemata on the role of inflammation in complex diseases remain largely patchy, in part due to the success of reductionism in terms of research methodology per se. Omics data alongside the advances in data integration technologies have enabled reconstruction of molecular and genetic inflammation networks which shed light on the underlying pathophysiology of complex diseases or clinical conditions. Given the proven beneficial role of anti-inflammation in coronary heart disease as well as other complex diseases and immunotherapy as a revolutionary transition in oncology, it becomes timely to review our current understanding of the molecular and genetic inflammation networks underlying major human diseases. In this review, we first briefly discuss the complexity of infectious diseases and then highlight recently uncovered molecular and genetic inflammation networks in other major human diseases including obesity, type II diabetes, coronary heart disease, late onset Alzheimer's disease, Parkinson's disease, and sporadic cancer. The commonality and specificity of these molecular networks are addressed in the context of genetics based on genome-wide association study (GWAS). The double-sword role of inflammation, such as how the aberrant type 1 and/or type 2 immunity leads to chronic and severe clinical conditions, remains open in terms of the inflammasome and the core inflammatome network features. Increasingly available large Omics and clinical data in tandem with systems biology approaches have offered an exciting yet challenging opportunity toward reconstruction of more comprehensive and dynamic molecular and genetic

  18. Mogamulizumab Treatment Prior to Allogeneic Hematopoietic Stem Cell Transplantation Induces Severe Acute Graft-versus-Host Disease.

    PubMed

    Sugio, Takeshi; Kato, Koji; Aoki, Takatoshi; Ohta, Takanori; Saito, Noriyuki; Yoshida, Shuro; Kawano, Ichiro; Henzan, Hideho; Kadowaki, Masanori; Takase, Ken; Muta, Tsuyoshi; Miyawaki, Kohta; Yamauchi, Takuji; Shima, Takahiro; Takashima, Shuichiro; Mori, Yasuo; Yoshimoto, Goichi; Kamezaki, Kenjiro; Takenaka, Katsuto; Iwasaki, Hiromi; Ogawa, Ryosuke; Ohno, Yuju; Eto, Tetsuya; Kamimura, Tomohiko; Miyamoto, Toshihiro; Akashi, Koichi

    2016-09-01

    Mogamulizumab (MOG), a humanized anti-CC chemokine receptor 4 (CCR4) monoclonal antibody, has recently played an important role in the treatment of adult T cell leukemia/lymphoma (ATLL). Because CCR4 is expressed on normal regulatory T cells as well as on ATLL cells, MOG may accelerate graft-versus-host disease (GVHD) by eradicating regulatory T cells in patients with allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, there is limited information about its safety and efficacy in patients treated with MOG before allo-HSCT. In the present study, 25 patients with ATLL were treated with MOG before allo-HSCT, after which 18 patients (72%) achieved remission. The overall survival and progression-free survival at 1 year post-transplantation were 20.2% (95% CI, 6.0% to 40.3%) and 15.0% (95% CI, 4.3% to 32.0%), respectively. The cumulative incidence of acute GVHD was 64.0% (95% CI, 40.7% to 80.1%) for grade II-IV and 34.7% (95% CI, 15.8% to 54.4%) for grade III-IV. The cumulative incidence of transplantation-related mortality (TRM) was 49.0% (95% CI, 27.0% to 67.8%). Six of 7 patients with acute GVHD grade III-IV died from GVHD, which was the leading cause of death. In particular, a shorter interval from the last administration of MOG to allo-HSCT was associated with more severe GVHD. MOG use before allo-HSCT may decrease the ATLL burden; however, it is associated with an increase in TRM due to severe GVHD. Because MOG is a potent anti-ATLL agent, new treatment protocols should be developed to integrate MOG at suitable doses and timing of administration to minimize unwanted GVHD development. PMID:27220263

  19. The neurocircuitry of illicit psychostimulant addiction: acute and chronic effects in humans

    PubMed Central

    Taylor, Sara B; Lewis, Candace R; Olive, M Foster

    2013-01-01

    Illicit psychostimulant addiction remains a significant problem worldwide, despite decades of research into the neural underpinnings and various treatment approaches. The purpose of this review is to provide a succinct overview of the neurocircuitry involved in drug addiction, as well as the acute and chronic effects of cocaine and amphetamines within this circuitry in humans. Investigational pharmacological treatments for illicit psychostimulant addiction are also reviewed. Our current knowledge base clearly demonstrates that illicit psychostimulants produce lasting adaptive neural and behavioral changes that contribute to the progression and maintenance of addiction. However, attempts at generating pharmacological treatments for psychostimulant addiction have historically focused on intervening at the level of the acute effects of these drugs. The lack of approved pharmacological treatments for psychostimulant addiction highlights the need for new treatment strategies, especially those that prevent or ameliorate the adaptive neural, cognitive, and behavioral changes caused by chronic use of this class of illicit drugs. PMID:24648786

  20. Neutrophil gelatinase-associated lipocalin: a promising biomarker for human acute kidney injury

    PubMed Central

    Devarajan, Prasad

    2010-01-01

    Acute kidney injury (AKI) is a common and serious condition, the diagnosis of which depends on serum creatinine measurements. Unfortunately, creatinine is a delayed and unreliable indicator of AKI. The lack of early biomarkers has crippled our ability to translate promising experimental therapies to human AKI. Fortunately, understanding the early stress response of the kidney to acute injuries has revealed a number of potential biomarkers. The discovery, translation and validation of neutrophil gelatinase-associated lipocalin, arguably the most promising novel AKI biomarker, are reviewed in this article. Neutrophil gelatinase-associated lipocalin is emerging as an excellent standalone troponin-like biomarker in the plasma and urine for the prediction of AKI, monitoring clinical trials in AKI and for the prognosis of AKI in several common clinical scenarios. PMID:20406069

  1. Antibodies targeting human IL1RAP (IL1R3) show therapeutic effects in xenograft models of acute myeloid leukemia

    PubMed Central

    Ågerstam, Helena; Karlsson, Christine; Hansen, Nils; Sandén, Carl; Askmyr, Maria; von Palffy, Sofia; Högberg, Carl; Rissler, Marianne; Wunderlich, Mark; Juliusson, Gunnar; Richter, Johan; Sjöström, Kjell; Bhatia, Ravi; Mulloy, James C.; Järås, Marcus; Fioretos, Thoas

    2015-01-01

    Acute myeloid leukemia (AML) is associated with a poor survival rate, and there is an urgent need for novel and more efficient therapies, ideally targeting AML stem cells that are essential for maintaining the disease. The interleukin 1 receptor accessory protein (IL1RAP; IL1R3) is expressed on candidate leukemic stem cells in the majority of AML patients, but not on normal hematopoietic stem cells. We show here that monoclonal antibodies targeting IL1RAP have strong antileukemic effects in xenograft models of human AML. We demonstrate that effector-cell–mediated killing is essential for the observed therapeutic effects and that natural killer cells constitute a critical human effector cell type. Because IL-1 signaling is important for the growth of AML cells, we generated an IL1RAP-targeting antibody capable of blocking IL-1 signaling and show that this antibody suppresses the proliferation of primary human AML cells. Hence, IL1RAP can be efficiently targeted with an anti-IL1RAP antibody capable of both achieving antibody-dependent cellular cytotoxicity and blocking of IL-1 signaling as modes of action. Collectively, these results provide important evidence in support of IL1RAP as a target for antibody-based treatment of AML. PMID:26261316

  2. Acute kidney injury after using contrast during cardiac catheterization in children with heart disease.

    PubMed

    Hwang, Young Ju; Hyun, Myung Chul; Choi, Bong Seok; Chun, So Young; Cho, Min Hyun

    2014-08-01

    Acute kidney injury (AKI) is closely associated with the mortality of hospitalized patients and long-term development of chronic kidney disease, especially in children. The purpose of our study was to assess the evidence of contrast-induced AKI after cardiac catheterization in children with heart disease and evaluate the clinical usefulness of candidate biomarkers in AKI. A total of 26 children undergoing cardiac catheterization due to various heart diseases were selected and urine and blood samples were taken at 0 hr, 6 hr, 24 hr, and 48 hr after cardiac catheterization. Until 48 hr after cardiac catheterization, there was no significant increase in serum creatinine level in all patients. Unlike urine kidney injury molecule-1, IL-18 and neutrophil gelatinase-associated lipocalin, urine liver-type fatty acid-binding protein (L-FABP) level showed biphasic pattern and the significant difference in the levels of urine L-FABP between 24 and 48 hr. We suggest that urine L-FABP can be one of the useful biomarkers to detect subclinical AKI developed by the contrast before cardiac surgery. PMID:25120320

  3. Acute phase proteins in naturally occurring respiratory disease of feedlot cattle.

    PubMed

    Idoate, Ignacio; Vander Ley, Brian; Schultz, Loren; Heller, Meera

    2015-02-15

    The aim of this study was to evaluate three acute phase proteins (APP) [haptoglobin (HPT), lipopolysaccharide binding protein (LBP) and transferrin (Tf)] in feedlot cattle with naturally occurring respiratory disease diagnosed by a calf health scoring chart (CHSC). Seventy-seven beef calves were observed for signs of Bovine Respiratory Disease (BRD) during the first 28 days after arrival at the feedlot. Fourteen cases and pen matched controls were selected based on the CHSC. BRD cases were defined as a score of ≥ 5, while controls were defined as a score ≤ 4. The mean CHSC score in cases was 6.9 which was significantly greater than the controls 2.8 (P < 0.01). Mean plasma LBP and HPT concentrations were significantly greater in cases than controls (P < 0.01). Our study results show that measurement of HPT and LBP could be useful in detecting respiratory disease in feedlot conditions. Transferrin concentrations between the two groups were not statistically different. PMID:25599608

  4. High prevalence of and potential mechanisms for chronic kidney disease in patients with acute intermittent porphyria.

    PubMed

    Pallet, Nicolas; Mami, Iadh; Schmitt, Caroline; Karim, Zoubida; François, Arnaud; Rabant, Marion; Nochy, Dominique; Gouya, Laurent; Deybach, Jean-Charles; Xu-Dubois, Yichum; Thervet, Eric; Puy, Hervé; Karras, Alexandre

    2015-08-01

    Acute intermittent porphyria (AIP) is a genetic disorder of the synthesis of heme caused by a deficiency in hydroxymethylbilane synthase (HMBS), leading to the overproduction of the porphyrin precursors δ-aminolevulinic acid and porphobilinogen. The aim of this study is to describe the clinical and biological characteristics, the renal pathology, and the cellular mechanisms of chronic kidney disease associated with AIP. A total of 415 patients with HMBS deficiency followed up in the French Porphyria Center were enrolled in 2003 in a population-based study. A follow-up study was conducted in 2013, assessing patients for clinical, biological, and histological parameters. In vitro models were used to determine whether porphyrin precursors promote tubular and endothelial cytotoxicity. Chronic kidney disease occurred in up to 59% of the symptomatic AIP patients, with a decline in the glomerular filtration rate of ~1 ml/min per 1.73 m(2) annually. Proteinuria was absent in the vast majority of the cases. The renal pathology was a chronic tubulointerstitial nephropathy, associated with a fibrous intimal hyperplasia and focal cortical atrophy. Our experimental data provide evidence that porphyrin precursors promote endoplasmic reticulum stress, apoptosis, and epithelial phenotypic changes in proximal tubular cells. In conclusion, the diagnosis of chronic kidney disease associated with AIP should be considered in cases of chronic tubulointerstitial nephropathy and/or focal cortical atrophy with severe proliferative arteriosclerosis. PMID:25830761

  5. Chronic inflammatory systemic diseases: An evolutionary trade-off between acutely beneficial but chronically harmful programs.

    PubMed

    Straub, Rainer H; Schradin, Carsten

    2016-01-01

    It has been recognized that during chronic inflammatory systemic diseases (CIDs) maladaptations of the immune, nervous, endocrine and reproductive system occur. Maladaptation leads to disease sequelae in CIDs. The ultimate reason of disease sequelae in CIDs remained unclear because clinicians do not consider bodily energy trade-offs and evolutionary medicine. We review the evolution of physiological supersystems, fitness consequences of genes involved in CIDs during different life-history stages, environmental factors of CIDs, energy trade-offs during inflammatory episodes and the non-specificity of CIDs. Incorporating bodily energy regulation into evolutionary medicine builds a framework to better understand pathophysiology of CIDs by considering that genes and networks used are positively selected if they serve acute, highly energy-consuming inflammation. It is predicted that genes that protect energy stores are positively selected (as immune memory). This could explain why energy-demanding inflammatory episodes like infectious diseases must be terminated within 3-8 weeks to be adaptive, and otherwise become maladaptive. Considering energy regulation as an evolved adaptive trait explains why many known sequelae of different CIDs must be uniform. These are, e.g. sickness behavior/fatigue/depressive symptoms, sleep disturbance, anorexia, malnutrition, muscle wasting-cachexia, cachectic obesity, insulin resistance with hyperinsulinemia, dyslipidemia, alterations of steroid hormone axes, disturbances of the hypothalamic-pituitary-gonadal (HPG) axis, hypertension, bone loss and hypercoagulability. Considering evolved energy trade-offs helps us to understand how an energy imbalance can lead to the disease sequelae of CIDs. In the future, clinicians must translate this knowledge into early diagnosis and symptomatic treatment in CIDs. PMID:26817483

  6. Systematic discovery of nonobvious human disease models through orthologous phenotypes.

    PubMed

    McGary, Kriston L; Park, Tae Joo; Woods, John O; Cha, Hye Ji; Wallingford, John B; Marcotte, Edward M

    2010-04-01

    Biologists have long used model organisms to study human diseases, particularly when the model bears a close resemblance to the disease. We present a method that quantitatively and systematically identifies nonobvious equivalences between mutant phenotypes in different species, based on overlapping sets of orthologous genes from human, mouse, yeast, worm, and plant (212,542 gene-phenotype associations). These orthologous phenotypes, or phenologs, predict unique genes associated with diseases. Our method suggests a yeast model for angiogenesis defects, a worm model for breast cancer, mouse models of autism, and a plant model for the neural crest defects associated with Waardenburg syndrome, among others. Using these models, we show that SOX13 regulates angiogenesis, and that SEC23IP is a likely Waardenburg gene. Phenologs reveal functionally coherent, evolutionarily conserved gene networks-many predating the plant-animal divergence-capable of identifying candidate disease genes. PMID:20308572

  7. Gene-Environment Interactions in Human Disease: Nuisance or Opportunity?

    PubMed Central

    Ober, Carole; Vercelli, Donata

    2010-01-01

    Many environmental risk factors for common, complex human diseases have been revealed by epidemiologic studies, but how genotypes at specific loci modulate individual responses to environmental risk factors is largely unknown. Gene-environment interactions will be missed in genome-wide association studies and may account for some of the ‘missing heritability’ for these diseases. In this review, we focus on asthma as a model disease for studying gene-environment interactions because of relatively large numbers of candidate gene-environment interactions with asthma risk in the literature. Identifying these interactions using genome-wide approaches poses formidable methodological problems and elucidating molecular mechanisms for these interactions has been challenging. We suggest that studying gene-environment interactions in animal models, while more tractable, is not likely to shed light on the genetic architecture of human diseases. Lastly, we propose avenues for future studies to find gene-environment interactions. PMID:21216485

  8. Zebrafish Models of Human Liver Development and Disease