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Sample records for incidence pathogenesis differential

  1. Persistent perineal sinus. Incidence, pathogenesis, risk factors, and management

    International Nuclear Information System (INIS)

    Lohsiriwat, V.

    2009-01-01

    This review discusses the incidence, pathogenesis, risk factors, diagnosis, and therapeutic options for persistent perineal sinus (PPS), defined as a perineal wound that remains unhealed more than 6 months after surgery. The incidence of PPS after surgery for inflammatory bowel disease (IBD) ranges from 3% to 70% and after abdominoperineal resection (APR) for Low rectal cancer, it can be up to 30%. These unhealed wounds are frequently related to perioperative pelvic or perineal sepsis. Crohn's disease (CD) and neoadjuvant radiation therapy are also important risk factors. The management of PPS is based on an understanding of pathogenesis and clinical grounds. The advantages and disadvantages of the current therapeutic approaches, including the topical administration of various drugs, vacuum-assisted closure, and perineal reconstruction with a muscle flap or a myocutaneous flap are also discussed. (author)

  2. Differential Virulence and Pathogenesis of West Nile Viruses

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    Emilie Donadieu

    2013-11-01

    Full Text Available West Nile virus (WNV is a neurotropic flavivirus that cycles between mosquitoes and birds but that can also infect humans, horses, and other vertebrate animals. In most humans, WNV infection remains subclinical. However, 20%–40% of those infected may develop WNV disease, with symptoms ranging from fever to meningoencephalitis. A large variety of WNV strains have been described worldwide. Based on their genetic differences, they have been classified into eight lineages; the pathogenic strains belong to lineages 1 and 2. Ten years ago, Beasley et al. (2002 found that dramatic differences exist in the virulence and neuroinvasion properties of lineage 1 and lineage 2 WNV strains. Further insights on how WNV interacts with its hosts have recently been gained; the virus acts either at the periphery or on the central nervous system (CNS, and these observed differences could help explain the differential virulence and neurovirulence of WNV strains. This review aims to summarize the current state of knowledge on factors that trigger WNV dissemination and CNS invasion as well as on the inflammatory response and CNS damage induced by WNV. Moreover, we will discuss how WNV strains differentially interact with the innate immune system and CNS cells, thus influencing WNV pathogenesis.

  3. Transient splenium lesions in presurgical epilepsy patients: incidence and pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Nelles, M.; Falkenhausen, M. von; Urbach, H. [University of Bonn Medical Center, Department of Radiology/Neuroradiology, Bonn (Germany); Bien, C.G.; Kurthen, M. [University of Bonn Medical Center, Department of Epileptology, Bonn (Germany)

    2006-07-15

    Transient splenium corporis callosi (SCC) lesions are related to rapid reduction of antiepileptic drugs (AEDs). The range of substances with predilection for SCC changes, their pathophysiology and their occurrence are still unknown. In a prospective 2-year study an epilepsy-dedicated MRI protocol supplemented by DWI and ADC maps was performed after AED withdrawal for diagnostic seizure provocation in all patients with pharmacoresistant seizures locally admitted to the Department of Epileptology. Of 891 presurgical epilepsy patients, 6 (0.7%) had SCC lesions with cytotoxic edema on DWI. Carbamazepine combined with other AEDs was administered in five of those patients. In the study period we observed identical lesions in a schizophrenic patient treated with olanzapine and citalopram, in a patient with oropharyngeal carcinoma treated with alkylating agents, and in a hypernatremic patient following neurohypophyseal granular cell tumor surgery. Transient SCC lesions are related to rapid AED reduction but may occur in similar conditions with fluid balance alterations. We contribute further clinical data in this field to better classify the pharmaceuticals that are prone to the described cerebral cytotoxic side effects in the SCC and to clarify their incidence among presurgical epilepsy patients. (orig.)

  4. Asthma in elite athletes: pathogenesis, diagnosis, differential diagnoses, and treatment

    DEFF Research Database (Denmark)

    Pedersen, Lars; Elers, Jimmi; Backer, Vibeke

    2011-01-01

    is essential when treating elite athletes. This article is aimed at physicians who diagnose and treat athletes with respiratory symptoms. It focuses on the pathogenesis of asthma and exercise-induced bronchoconstriction in elite athletes and how the diagnosis can be made. Furthermore, treatment of elite......Elite athletes have a high prevalence of asthma and exercise-induced bronchoconstriction. Although respiratory symptoms can be suggestive of asthma, the diagnosis of asthma in elite athletes cannot be based solely on the presence or absence of symptoms; diagnosis should be based on objective...... measurements, such as the eucapnic voluntary hyperpnea test or exercise test. When considering that not all respiratory symptoms are due to asthma, other diagnoses should be considered. Certain regulations apply to elite athletes who require asthma medication for asthma. Knowledge of these regulations...

  5. Asthma in elite athletes: pathogenesis, diagnosis, differential diagnoses, and treatment

    DEFF Research Database (Denmark)

    Pedersen, Lars; Elers, Jimmi; Backer, Vibeke

    2011-01-01

    Elite athletes have a high prevalence of asthma and exercise-induced bronchoconstriction. Although respiratory symptoms can be suggestive of asthma, the diagnosis of asthma in elite athletes cannot be based solely on the presence or absence of symptoms; diagnosis should be based on objective...... measurements, such as the eucapnic voluntary hyperpnea test or exercise test. When considering that not all respiratory symptoms are due to asthma, other diagnoses should be considered. Certain regulations apply to elite athletes who require asthma medication for asthma. Knowledge of these regulations...... is essential when treating elite athletes. This article is aimed at physicians who diagnose and treat athletes with respiratory symptoms. It focuses on the pathogenesis of asthma and exercise-induced bronchoconstriction in elite athletes and how the diagnosis can be made. Furthermore, treatment of elite...

  6. Alcoholic Pancreatitis: Pathogenesis, Incidence and Treatment with Special Reference to the Associated Pain

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    Antonio M. Morselli-Labate

    2009-11-01

    Full Text Available Alcoholic pancreatitis continues to stir up controversy. One of the most debated points is whether from onset it is a chronic disease or whether it progresses to a chronic form after repeated episodes of acute pancreatitis. Histological studies on patients with alcoholic pancreatitis have shown that the disease is chronic from onset and that alcoholic acute pancreatitis occurs in a pancreas already damaged by chronic lesions. Genetic factors may also play a role in the pathogenesis of alcoholic disease. The incidence of chronic alcoholic pancreatitis seems to have decreased in the last twenty years. Finally, recent therapeutic studies which have shown medical or surgical approaches capable of reducing the pain episodes in chronic pancreatitis patients will be described.

  7. Understanding mechanisms and the role of differentiation in pathogenesis of Toxoplasma gondii: a review

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    William J Sullivan Jr

    2009-03-01

    Full Text Available Parasite differentiation from proliferating tachyzoites into latent bradyzoites is central to pathogenesis and transmission of the intracellular protozoan pathogen Toxoplasma gondii. The presence of bradyzoite-containing cysts in human hosts and their subsequent rupture can cause life-threatening recrudescence of acute infection in the immunocompromised and cyst formation in other animals contributes to zoonotic transmission and widespread dissemination of the parasite. In this review, we discuss the evidence showing how the clinically relevant process of bradyzoite differentiation is regulated at both transcriptional and post-transcriptional levels. Specific regulatory factors implicated in modulating bradyzoite differentiation include promoter-based cis-elements, epigenetic modifications and protein translation control through eukaryotic initiation factor -2 (eIF2. In addition to a summary of the current state of knowledge in these areas we discuss the pharmacological ramifications and pose some questions for future research.

  8. The role of growth differentiation factor 15 in the pathogenesis of primary myelofibrosis

    International Nuclear Information System (INIS)

    Uchiyama, Tatsuki; Kawabata, Hiroshi; Miura, Yasuo; Yoshioka, Satoshi; Iwasa, Masaki; Yao, Hisayuki; Sakamoto, Soichiro; Fujimoto, Masakazu; Haga, Hironori; Kadowaki, Norimitsu; Maekawa, Taira; Takaori-Kondo, Akifumi

    2015-01-01

    Growth differentiation factor 15 (GDF15) is a pleiotropic cytokine that belongs to the transforming growth factor-β superfamily. Elevated serum concentrations of this cytokine have been reported in patients with various malignancies. To assess the potential roles of GDF15 in hematologic malignancies, we measured its serum levels in patients with these diseases. We found that serum GDF15 levels were elevated in almost all these patients, particularly in patients with primary myelofibrosis (PMF). Immunohistochemical staining of bone marrow (BM) specimens revealed that GDF15 was strongly expressed by megakaryocytes, which may be sources of increased serum GDF15 in PMF patients. Therefore, we further assessed the contribution of GDF15 to the pathogenesis of PMF. Recombinant human (rh) GDF15 enhanced the growth of human BM mesenchymal stromal cells (BM-MSCs), and it enhanced the potential of these cells to support human hematopoietic progenitor cell growth in a co-culture system. rhGDF15 enhanced the growth of human primary fibroblasts, but it did not affect their expression of profibrotic genes. rhGDF15 induced osteoblastic differentiation of BM-MSCs in vitro, and pretreatment of BM-MSCs with rGDF15 enhanced the induction of bone formation in a xenograft mouse model. These results suggest that serum levels of GDF15 in PMF are elevated, that megakaryocytes are sources of this cytokine in BM, and that GDF15 may modulate the pathogenesis of PMF by enhancing proliferation and promoting osteogenic differentiation of BM-MSCs

  9. Differentially expressed microRNA in multiple sclerosis: A window into pathogenesis?

    DEFF Research Database (Denmark)

    Martin, Nellie Anne; Illés, Zsolt

    2014-01-01

    MicroRNA are small non-coding RNA that mediate mRNA translation repression or mRNA degradation, and thereby refine protein expression levels. More than 30–60% of all genes are regulated by microRNA. Exploring disease-related microRNA signatures is an emerging tool in biomarker discovery......, and silencing has already been used in a clinical phase 2a trial. As microRNA regulate translation of more than 100 genes, they could also provide a focused insight into important pathways, and offer a better understanding of diseases with heterogeneous pathogenesis. The number of studies investigating micro......RNA related to multiple sclerosis has increased significantly in recent years. Differentially expressed microRNA have been identified in the whole blood, serum, plasma, cerebrospinal fluid, peripheral blood mononuclear cells, blood-derived cell subsets and brain lesions of patients with multiple sclerosis...

  10. Henoch-Schönlein purpura nephritis in children: incidence, pathogenesis and management.

    Science.gov (United States)

    Chen, Jun-Yi; Mao, Jian-Hua

    2015-02-01

    Henoch-Schönlein purpura (HSP) is one of the most common vasculitides in children. It is manifested by skin purpura, arthritis, abdominal pain, renal involvement, etc. Typically, HSP is considered to be self-limiting, although renal involvement (HSP purpura nephritis, HSPN) is the principal cause of morbidity from this disease. For this reason, it is important to clarify the mechanism of onset and clinical manifestations of HSPN and to ascertain the most appropriate treatment for HSPN. In this article, we review the updated pathophysiology and treatment strategies for HSPN. We searched databases including PubMed, Elsevier and Wanfang for the following key words: Henoch-Schönlein purpura, nephritis, mechanism and treatment, and we selected those publications written in English that we judged to be relevant to the topic of this review. Based on the data present in the literature, we reviewed the following topics: 1) the possible pathogenesis of HSPN: several studies suggest that immunoglobulin A immune complexes deposit in the mesangium and induce renal injury; 2) multiple-drug treatment for HSPN: although there have been few evidence-based treatment strategies for HSPN, several studies have suggested that immunosuppressive drugs and multiple drug combination therapy were effective in ameliorating proteinuria and histological severity. HSPN is a severe disease of childhood. To better understand this disease, detailed investigations into the pathogenesis of HSPN and prospective randomized controlled treatment studies on children with severe HSPN are needed.

  11. The syndrome of hemophagocytic lymphohistiocytosis in primary immunodeficiencies: implications for differential diagnosis and pathogenesis.

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    Bode, Sebastian Fn; Ammann, Sandra; Al-Herz, Waleed; Bataneant, Mihaela; Dvorak, Christopher C; Gehring, Stephan; Gennery, Andrew; Gilmour, Kimberly C; Gonzalez-Granado, Luis I; Groß-Wieltsch, Ute; Ifversen, Marianne; Lingman-Framme, Jenny; Matthes-Martin, Susanne; Mesters, Rolf; Meyts, Isabelle; van Montfrans, Joris M; Pachlopnik Schmid, Jana; Pai, Sung-Yun; Soler-Palacin, Pere; Schuermann, Uta; Schuster, Volker; Seidel, Markus G; Speckmann, Carsten; Stepensky, Polina; Sykora, Karl-Walter; Tesi, Bianca; Vraetz, Thomas; Waruiru, Catherine; Bryceson, Yenan T; Moshous, Despina; Lehmberg, Kai; Jordan, Michael B; Ehl, Stephan

    2015-07-01

    Hemophagocytic lymphohistiocytosis is a hyperinflammatory syndrome defined by clinical and laboratory criteria. Current criteria were created to identify patients with familial hemophagocytic lmyphohistiocytosis in immediate need of immunosuppressive therapy. However, these criteria also identify patients with infection-associated hemophagocytic inflammatory states lacking genetic defects typically predisposing to hemophagocytic lymphohistiocytosis. These patients include those with primary immunodeficiencies, in whom the pathogenesis of the inflammatory syndrome may be distinctive and aggressive immunosuppression is contraindicated. To better characterize hemophagocytic inflammation associated with immunodeficiencies, we combined an international survey with a literature search and identified 63 patients with primary immunodeficiencies other than cytotoxicity defects or X-linked lymphoproliferative disorders, presenting with conditions fulfilling current criteria for hemophagocytic lymphohistiocytosis. Twelve patients had severe combined immunodeficiency with immunodeficiencies; (ii) this syndrome can develop despite severe deficiency of T and NK cells, implying that the pathophysiology is distinct and not appropriately described as "lympho"-histiocytosis in these patients; and (iii) current criteria for hemophagocytoc lymphohistiocytosis are insufficient to differentiate hemophagocytic inflammatory syndromes with different pathogeneses. This is important because of implications for therapy, in particular for protocols targeting T cells. Copyright© Ferrata Storti Foundation.

  12. Delayed Chemotherapy-Induced Nausea and Vomiting: Pathogenesis, Incidence, and Current Management.

    Science.gov (United States)

    Rapoport, Bernardo L

    2017-01-01

    Even when chemotherapy-induced nausea and vomiting (CINV) can be effectively controlled in the acute phase, it may still occur in the delayed phase. Identifying at-risk patients is complex and requires consideration of clinical, personal, demographic, and behavioral factors. Delayed CINV has a significant detrimental effect on patients' daily life and is responsible for significant healthcare resource utilization. Patients who do not experience acute CINV are not necessarily exempt from delayed CINV, and healthcare professionals have been shown to underestimate the incidence of delayed CINV. Failure to protect against CINV during the first cycle of chemotherapy is the most significant independent risk factor for delayed CINV during subsequent cycles. Addition of a neurokinin-1 receptor antagonist to antiemetic prophylactic regimens involving a 5-hydroxytryptamine type 3 receptor antagonist and a corticosteroid helps to ameliorate delayed CINV, particularly vomiting. Netupitant and rolapitant are second-generation neurokinin-1 receptor antagonists that provide effective prophylaxis against delayed chemotherapy-induced vomiting and also have an antinausea benefit. All of the neurokinin-1 receptor antagonists with the exception of rolapitant inhibit or induce cytochrome P450 3A4 (CYP3A4), and a reduced dose of dexamethasone (a CYP3A4 substrate) should be administered with aprepitant or netupitant; by contrast, this is not necessary with rolapitant. Here we review specific challenges associated with delayed CINV, its pathophysiology, epidemiology, treatment, and outcomes relative to acute CINV, and its management within the larger context of overall CINV.

  13. Differential glucocorticoid receptor-mediated effects on immunomodulatory gene expression by progestin contraceptives: implications for HIV-1 pathogenesis.

    Science.gov (United States)

    Hapgood, Janet P; Ray, Roslyn M; Govender, Yashini; Avenant, Chanel; Tomasicchio, Michele

    2014-06-01

    Whether hormonal contraceptives increase HIV-1 acquisition, transmission and disease progression are critical questions. Clinical research has been hampered by a lack of understanding that different progestins used in contraception exhibit differential off-target effects via steroid receptors other than the progesterone receptor. Of particular, relevance is the relative effects of medroxyprogesterone acetate (MPA) and norethisterone enanthate (NET-EN), widely used as injectable contraceptives in sub-Saharan Africa. While most high-quality clinical studies find no increased risk for HIV-1 acquisition with oral contraception or injectable NET-EN, most do find an increase with MPA, particularly in young women. Furthermore, mounting evidence from animal, ex vivo and biochemical studies are consistent with MPA acting to increase HIV-1 acquisition and pathogenesis, via mechanisms involving glucocorticoid-like effects on gene expression, in particular genes involved in immune function. We report that MPA, unlike NET and progesterone, represses inflammatory genes in human PBMCs in a dose-dependent manner, via the glucocorticoid receptor (GR), at concentrations within the physiologically relevant range. These and published results collectively suggest that the differential GR activity of MPA versus NET may be a mechanism whereby MPA, unlike NET or progesterone, differentially modulates HIV-1 acquisition and pathogenesis in target cells where the GR is the predominant steroid receptor expressed. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  14. Estrogen deficiency induces the differentiation of IL-17 secreting Th17 cells: a new candidate in the pathogenesis of osteoporosis.

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    Abdul M Tyagi

    Full Text Available Th17 cells produce IL-17, and the latter promotes bone loss in collagen-induced arthritis in mice. Blocking IL-17 action in mouse model of rheumatoid arthritis reduces disease symptoms. These observations suggest that Th17 cells may be involved in the pathogenesis of bone loss. However, the role of Th17 cell in estrogen (E2 deficiency-induced bone loss is still not very clear. We investigated the effect of E2 on Th17 differentiation in vivo and IL-17 mediated regulation of osteoclast and osteoblast differentiation. Additionally, effect of IL-17 functional block under E2 deficiency-induced bone loss was studied. In murine bone marrow cells, E2 suppressed IL-17 mediated osteoclast differentiation. IL-17 inhibited formation of mineralized nodules in osteoblasts and this effect was suppressed by E2. E2 treatment to mouse calvarial osteoblasts inhibited the IL-17-induced production of osteoclastogenic cytokines and NF-kB translocation. In ovariectomized mice, there was increase in the number of Th17 cells, transcription factors promoting Th17 cell differentiation and circulating IL-17 levels. These effects were reversed by E2 supplementation. Treatment of neutralizing IL-17 monoclonal antibody to Ovx mice mitigated the E2 deficiency-induced trabecular bone loss and reversed the decreased osteoprotegerin-to-receptor activator of nuclear factor kappa B ligand (RANKL transcript levels in long bones, increased osteoclast differentiation from the bone marrow precursor cells and decreased osteoblast differentiation from the bone marrow stromal cells. Our findings indicate that E2 deficiency leads to increased differentiation of Th17 cells with attendant up regulation of STAT3, ROR-γt and ROR-α and downregulation of Foxp3 which antagonizes Th17 cell differentiation. Increased IL-17 production in turn induces bone loss by increasing pro-osteoclastogenic cytokines including TNF-α, IL-6 and RANKL from osteoblasts and functional block of IL-17 prevents bone

  15. Differential Thiol-Based Switches Jump-Start Vibrio cholerae Pathogenesis

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    Zhi Liu

    2016-01-01

    Full Text Available Bacterial pathogens utilize gene expression versatility to adapt to environmental changes. Vibrio cholerae, the causative agent of cholera, encounters redox-potential changes when it transitions from oxygen-rich aquatic reservoirs to the oxygen-limiting human gastrointestinal tract. We previously showed that the virulence regulator AphB uses thiol-based switches to sense the anoxic host environment and transcriptionally activate the key virulence activator tcpP. Here, by performing a high-throughput transposon sequencing screen in vivo, we identified OhrR as another regulator that enables V. cholerae rapid anoxic adaptation. Like AphB, reduced OhrR binds to and regulates the tcpP promoter. OhrR and AphB displayed differential dynamics in response to redox-potential changes: OhrR is reduced more rapidly than AphB. Furthermore, OhrR thiol modification is required for rapid activation of virulence and successful colonization. This reveals a mechanism whereby bacterial pathogens employ posttranslational modifications of multiple transcription factors to sense and adapt to dynamic environmental changes.

  16. Incidence and survival differences of differentiated thyroid cancer among younger women

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    Boltz MM

    2013-11-01

    Full Text Available Melissa M Boltz,1 Laura M Enomoto,1,2 Rollyn M Ornstein,3 Brian D Saunders,1,4 Christopher S Hollenbeak1,2,51Department of Surgery, 2Division of Outcomes Research and Quality, The Pennsylvania State University, College of Medicine, 3Department of Pediatrics, Division of Adolescent Medicine and Eating Disorders, The Pennsylvania State University, Hershey Children’s Hospital, 4Division of General Surgery Specialties and Surgical Oncology, 5Department of Public Health Sciences, The Pennsylvania State University, College of Medicine, Hershey, PA, USAAbstract: Differentiated thyroid cancer is the most common endocrine malignancy, with an estimated 60,220 new cases diagnosed in the United States in 2013. For reasons that are unclear, differentiated thyroid cancer is three times more common in females than in males. However, among adolescent and young adult females between ages 15–39 years, differentiated thyroid cancer remains under-recognized. The disparity in cancer incidence and outcomes in this population may be secondary to the tumor's biology, and risk factors unique to women. This review summarizes the incidence and survival rates of thyroid cancer in women younger than 45 years of age, as well as the pathophysiology, etiology, risk factors, prognosis, and current and emerging treatment options for this patient population.Keywords: differentiated thyroid cancer, young adult women, adolescents, incidence, risk factors, treatment

  17. Incidence of symptomatic salivary disease in patients with differentiated thyroid cancer treated with radioactive iodine

    International Nuclear Information System (INIS)

    Goni E, Ignacio; Selt A, Guillermo Vander; Ruiz A, Catalina; Leon R, Augusto; Solar G, Antonieta; Orellana B, Catalina

    2015-01-01

    Background: The radioactive iodine therapy for differentiated thyroid cancer can produce severe and frequent salivary symptoms, during the treatment or later. Aim: To analyze the incidence, severity and characteristics of the salivary signs and symptoms in these patients. Patients and Method: Retrospective and descriptive anal isis of 106 patients with confirmed diagnosis of differentiated thyroid cancer, treated with surgery and radioactive iodine, that completed a telephonic survey for the evaluation of salivary symptoms. Results: 26 (24.52%) patients presented with salivary symptoms or signs after the radioactive iodine therapy (mean 5 months). The average doses of I 131 was 128,5 mCi. Xerostomy, pain, xeroftalmy, inflammation, sialoadenitis and dysgeusia, were the most frequent clinical symptoms. Conclusions: After radioactive iodine therapy the salivary symptoms and signs incidence is high. We conclude that the indication for this treatment must be selective, but in accordance with the oncological risk of each patient

  18. Measurements of double differential charged particle emission cross sections by incident D-T neutrons

    International Nuclear Information System (INIS)

    Kondoh, Takehiro; Takahashi, Akito; Nishizawa, Hiroshi.

    1995-01-01

    Double differential cross sections for nat Ni(n,xα) and nat Cu(n,xα) reactions with 14.1 MeV incident neutrons were measured based on the E-TOF two dimensional analysis. Measured data were compared with the other experimental data reported by N. Ito et al. and by S.M. Grimes et al, evaluated data of the ENDF/B-VI and SINCROS-II calculation. Concerning the nat Ni(n,xα) reaction, it was observed in this experiment that the angular distributions of α-particle emission showed a forward-peaked tendency except for the low energy region. (author)

  19. Intra-Articular Synovial Sarcomas: Incidence and Differentiating Features from Localized Pigmented Villonodular Synovitis

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    D. Nordemar

    2015-01-01

    Full Text Available Purpose. To determine the incidence of intra-articular synovial sarcomas and investigate if any radiological variables can differentiate them from localized (unifocal pigmented villonodular synovitis (PVNS and if multivariate data analysis could be used as a complementary clinical tool. Methods. Magnetic resonance images and radiographs of 7 cases of intra-articular synovial sarcomas and 14 cases of localized PVNS were blindedly reviewed. Variables analyzed were size, extra-articular growth, tumor border, blooming, calcification, contrast media enhancement, effusion, bowl of grapes sign, triple signal intensity sign, synovial low signal intensity, synovitis, age, and gender. Univariate and multivariate data analysis, the method of partial least squares-discriminant analysis (PLS-DA, were used. Register data on all synovial sarcomas were extracted for comparison. Results. The incidence of intra-articular synovial sarcomas was 3%. PLS-DA showed that age, effusion, size, and gender were the most important factors for discrimination between sarcomas and localized PVNS. No sarcomas were misclassified as PVNS with PLS-DA, while some PVNS were misclassified as sarcomas. Conclusions. The most important variables in differentiating intra-articular sarcomas from localized PVNS were age, effusion, size, and gender. Multivariate data analysis can be helpful as additive information to avoid a biopsy, if the tumor is classified as most likely being PVNS.

  20. Mycobacterium tuberculosis TlyA Protein Negatively Regulates T Helper (Th) 1 and Th17 Differentiation and Promotes Tuberculosis Pathogenesis*

    Science.gov (United States)

    Rahman, Md. Aejazur; Sobia, Parveen; Dwivedi, Ved Prakash; Bhawsar, Aakansha; Singh, Dhiraj Kumar; Sharma, Pawan; Moodley, Prashini; Van Kaer, Luc; Bishai, William R; Das, Gobardhan

    2015-01-01

    Mycobacterium tuberculosis, the causative agent of tuberculosis, is an ancient pathogen and a major cause of death worldwide. Although various virulence factors of M. tuberculosis have been identified, its pathogenesis remains incompletely understood. TlyA is a virulence factor in several bacterial infections and is evolutionarily conserved in many Gram-positive bacteria, but its function in M. tuberculosis pathogenesis has not been elucidated. Here, we report that TlyA significantly contributes to the pathogenesis of M. tuberculosis. We show that a TlyA mutant M. tuberculosis strain induces increased IL-12 and reduced IL-1β and IL-10 cytokine responses, which sharply contrasts with the immune responses induced by wild type M. tuberculosis. Furthermore, compared with wild type M. tuberculosis, TlyA-deficient M. tuberculosis bacteria are more susceptible to autophagy in macrophages. Consequently, animals infected with the TlyA mutant M. tuberculosis organisms exhibited increased host-protective immune responses, reduced bacillary load, and increased survival compared with animals infected with wild type M. tuberculosis. Thus, M. tuberculosis employs TlyA as a host evasion factor, thereby contributing to its virulence. PMID:25847237

  1. NF-κB2 mutation targets survival, proliferation and differentiation pathways in the pathogenesis of plasma cell tumors

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    McCarthy Brian A

    2012-05-01

    Full Text Available Abstract Background Abnormal NF-κB2 activation has been implicated in the pathogenesis of multiple myeloma, a cancer of plasma cells. However, a causal role for aberrant NF-κB2 signaling in the development of plasma cell tumors has not been established. Also unclear is the molecular mechanism that drives the tumorigenic process. We investigated these questions by using a transgenic mouse model with lymphocyte-targeted expression of p80HT, a lymphoma-associated NF-κB2 mutant, and human multiple myeloma cell lines. Methods We conducted a detailed histopathological characterization of lymphomas developed in p80HT transgenic mice and microarray gene expression profiling of p80HT B cells with the goal of identifying genes that drive plasma cell tumor development. We further verified the significance of our findings in human multiple myeloma cell lines. Results Approximately 40% of p80HT mice showed elevated levels of monoclonal immunoglobulin (M-protein in the serum and developed plasma cell tumors. Some of these mice displayed key features of human multiple myeloma with accumulation of plasma cells in the bone marrow, osteolytic bone lesions and/or diffuse osteoporosis. Gene expression profiling of B cells from M-protein-positive p80HT mice revealed aberrant expression of genes known to be important in the pathogenesis of multiple myeloma, including cyclin D1, cyclin D2, Blimp1, survivin, IL-10 and IL-15. In vitro assays demonstrated a critical role of Stat3, a key downstream component of IL-10 signaling, in the survival of human multiple myeloma cells. Conclusions These findings provide a mouse model for human multiple myeloma with aberrant NF-κB2 activation and suggest a molecular mechanism for NF-κB2 signaling in the pathogenesis of plasma cell tumors by coordinated regulation of plasma cell generation, proliferation and survival.

  2. NF-κB2 mutation targets survival, proliferation and differentiation pathways in the pathogenesis of plasma cell tumors

    International Nuclear Information System (INIS)

    McCarthy, Brian A; Ding, Han-Fei; Yang, Liqun; Ding, Jane; Ren, Mingqiang; King, William; ElSalanty, Mohammed; Zakhary, Ibrahim; Sharawy, Mohamed; Cui, Hongjuan

    2012-01-01

    Abnormal NF-κB2 activation has been implicated in the pathogenesis of multiple myeloma, a cancer of plasma cells. However, a causal role for aberrant NF-κB2 signaling in the development of plasma cell tumors has not been established. Also unclear is the molecular mechanism that drives the tumorigenic process. We investigated these questions by using a transgenic mouse model with lymphocyte-targeted expression of p80HT, a lymphoma-associated NF-κB2 mutant, and human multiple myeloma cell lines. We conducted a detailed histopathological characterization of lymphomas developed in p80HT transgenic mice and microarray gene expression profiling of p80HT B cells with the goal of identifying genes that drive plasma cell tumor development. We further verified the significance of our findings in human multiple myeloma cell lines. Approximately 40% of p80HT mice showed elevated levels of monoclonal immunoglobulin (M-protein) in the serum and developed plasma cell tumors. Some of these mice displayed key features of human multiple myeloma with accumulation of plasma cells in the bone marrow, osteolytic bone lesions and/or diffuse osteoporosis. Gene expression profiling of B cells from M-protein-positive p80HT mice revealed aberrant expression of genes known to be important in the pathogenesis of multiple myeloma, including cyclin D1, cyclin D2, Blimp1, survivin, IL-10 and IL-15. In vitro assays demonstrated a critical role of Stat3, a key downstream component of IL-10 signaling, in the survival of human multiple myeloma cells. These findings provide a mouse model for human multiple myeloma with aberrant NF-κB2 activation and suggest a molecular mechanism for NF-κB2 signaling in the pathogenesis of plasma cell tumors by coordinated regulation of plasma cell generation, proliferation and survival

  3. Differential Deposition for Surface Figure Corrections in Grazing Incidence X-Ray Optics

    Science.gov (United States)

    Ramsey, Brian D.; Kilaru, Kiranmayee; Atkins, Carolyn; Gubarev, Mikhail V.; Broadway, David M.

    2015-01-01

    Differential deposition corrects the low- and mid- spatial-frequency deviations in the axial figure of Wolter-type grazing incidence X-ray optics. Figure deviations is one of the major contributors to the achievable angular resolution. Minimizing figure errors can significantly improve the imaging quality of X-ray optics. Material of varying thickness is selectively deposited, using DC magnetron sputtering, along the length of optic to minimize figure deviations. Custom vacuum chambers are built that can incorporate full-shell and segmented Xray optics. Metrology data of preliminary corrections on a single meridian of full-shell x-ray optics show an improvement of mid-spatial frequencies from 6.7 to 1.8 arc secs HPD. Efforts are in progress to correct a full-shell and segmented optics and to verify angular-resolution improvement with X-ray testing.

  4. Associations of Circulating Growth Differentiation Factor-15 and ST2 Concentrations With Subclinical Vascular Brain Injury and Incident Stroke

    DEFF Research Database (Denmark)

    Andersson, Charlotte; Preis, Sarah R; Beiser, Alexa

    2015-01-01

    BACKGROUND AND PURPOSE: Growth differentiation factor-15 (GDF-15) and soluble (s)ST2 are markers of cardiac and vascular stress. We investigated the associations between circulating concentrations of these biomarkers and incident stroke and subclinical vascular brain injury in a sample from the F...

  5. Genistein in the diet reduces the incidence of poorly differentiated prostatic adenocarcinoma in transgenic mice (TRAMP).

    Science.gov (United States)

    Mentor-Marcel, R; Lamartiniere, C A; Eltoum, I E; Greenberg, N M; Elgavish, A

    2001-09-15

    Latent prostate tumors are commonly found with similar frequency in many countries and ethnic groups. In contrast, aggressive prostate cancer (PC) is significantly less prevalent among Asian men, where the intake of soy products is very high. High consumption of foods containing soy results in high plasma, urine, and prostatic fluid concentrations of phytoestrogens, including genistein. The objective of the present study was to test the hypothesis that dietary genistein might prevent PC progression in a transgenic mouse model of PC (TRAMP). By 28-30 weeks of age, all TRAMP mice in the study had developed prostate tumors, with about half of them displaying well-differentiated prostatic adenocarcinoma (WD, score 4), and the other half divided between moderately differentiated (MD, score 5) and poorly differentiated adenocarcinoma (PD, score 6). Two lines of evidence supported the possibility that prostates with PD may represent a more advanced stage of PC in TRAMP mice: (a) the weight of prostates with PD was two orders of magnitude higher than that of prostates with WD or MD; and (b) expression of androgen receptor transcripts was altered in PD as compared with WD and MD. To test the potential of genistein to prevent the incidence of mice with PD, starting at 5-6 weeks of age, transgenic males were fed a phytoestrogen-free diet (AIN-76A) containing 0, 100, 250, or 500 mg of genistein per kg AIN-76A (25, 10, 17, and 7 mice/group, respectively). Mice were on the diet until they were 28-30 weeks of age. Each mouse was weighed once a week throughout the study. At necropsy, selected organs were weighed and prepared for histopathological evaluation. Serum levels of genistein in mice on diet containing 0, 250, or 500 mg of genistein per kg AIN-76A were 52.4 +/- 32.7, 138.9 +/- 69.6, and 397.3 +/- 104.9 nM, respectively, comparable with those found in Asian men on regular soy diet (276 nM). Using body and organ weights as indicators, dietary genistein had no toxic effect on

  6. Differential expression of the pr1A gene in Metarhizium anisopliae and Metarhizium acridum across different culture conditions and during pathogenesis

    Directory of Open Access Journals (Sweden)

    Mariele Porto Carneiro Leão

    2015-03-01

    Full Text Available The entomopathogenic fungi of the genus Metarhizium have several subtilisin-like proteases that are involved in pathogenesis and these have been used to investigate genes that are differentially expressed in response to different growth conditions. The identification and characterization of these proteases can provide insight into how the fungus is capable of infecting a wide variety of insects and adapt to different substrates. In addition, the pr1A gene has been used for the genetic improvement of strains used in pest control. In this study we used quantitative RT-PCR to assess the relative expression levels of the pr1A gene in M. anisopliae and M. acridum during growth in different culture conditions and during infection of the sugar cane borer, Diatraea saccharalis Fabricius. We also carried out a pathogenicity test to assess the virulence of both species against D. saccharalis and correlated the results with the pattern of pr1A gene expression. This analysis revealed that, in both species, the pr1A gene was differentially expressed under the growth conditions studied and during the pathogenic process. M. anisopliae showed higher expression of pr1A in all conditions examined, when compared to M. acridum. Furthermore, M. anisopliae showed a greater potential to control D. saccharalis. Taken together, our results suggest that these species have developed different strategies to adapt to different growing conditions.

  7. Antigenically diverse swine-origin H1N1 variant influenza viruses exhibit differential ferret pathogenesis and transmission phenotypes.

    Science.gov (United States)

    Pulit-Penaloza, Joanna A; Jones, Joyce; Sun, Xiangjie; Jang, Yunho; Thor, Sharmi; Belser, Jessica A; Zanders, Natosha; Creager, Hannah M; Ridenour, Callie; Wang, Li; Stark, Thomas J; Garten, Rebecca; Chen, Li-Mei; Barnes, John; Tumpey, Terrence M; Wentworth, David E; Maines, Taronna R; Davis, C Todd

    2018-03-14

    Influenza A(H1) viruses circulating in swine represent an emerging virus threat as zoonotic infections occur sporadically following exposure to swine. A fatal infection caused by an H1N1 variant (H1N1v) virus was detected in a patient with reported exposure to swine and who presented with pneumonia, respiratory failure, and cardiac arrest. To understand the genetic and phenotypic characteristics of the virus, genome sequence analysis, antigenic characterization, and ferret pathogenesis and transmissibility experiments were performed. Antigenic analysis of the virus isolated from the fatal case, A/Ohio/09/2015, demonstrated significant antigenic drift away from classical swine H1N1 variant viruses and H1N1 pandemic 2009 viruses. A substitution in the H1 hemagglutinin (G155E) was identified that likely impacted antigenicity, and reverse genetics was employed to understand the molecular mechanism of antibody escape. Reversion of the substitution to 155G, in a reverse genetics A/Ohio/09/2015 virus, showed that this residue was central to the loss of hemagglutination inhibition by ferret antisera raised against a prototypical H1N1 pandemic 2009 virus (A/California/07/2009), as well as gamma lineage classical swine H1N1 viruses, demonstrating the importance of this residue for antibody recognition of this H1 lineage. When analyzed in the ferret model, A/Ohio/09/2015 and another H1N1v virus (A/Iowa/39/2015), as well as A/California/07/2009, replicated efficiently in the respiratory tract of ferrets. The two H1N1v viruses transmitted efficiently among cohoused ferrets, but respiratory droplet transmission studies showed that A/California/07/2009 transmitted through the air more efficiently. Pre-existing immunity to A/California/07/2009 did not fully protect ferrets from challenge with A/Ohio/09/2015. IMPORTANCE Human infections with classical swine influenza A(H1N1) viruses that circulate in pigs continue to occur in the United States following exposure to swine. To

  8. Astrovirus Pathogenesis

    Directory of Open Access Journals (Sweden)

    Cydney Johnson

    2017-01-01

    Full Text Available Astroviruses are a major cause of diarrhea in the young, elderly, and the immunocompromised. Since the discovery of human astrovirus type 1 (HAstV-1 in 1975, the family Astroviridae has expanded to include two more human clades and numerous mammalian and avian-specific genotypes. Despite this, there is still little known about pathogenesis. The following review highlights the current knowledge of astrovirus pathogenesis, and outlines the critical steps needed to further astrovirus research, including the development of animal models of cell culture systems.

  9. Measurement of double differential cross sections of secondary neutrons in the incident energy range 9-13 MeV

    International Nuclear Information System (INIS)

    Tang Hongqing; Qi Bujia; Zhou Zuying; Sa Jun; Ke Zunjian; Sui Qingchang; Xia Haihong; Shen Guanren

    1992-01-01

    The status and technique of double differential cross section measurement of secondary neutrons in the incident neutron energy range 9 to 13 MeV is reviewed with emphasis on the work done at CIAE. There are scarce measurements of secondary neutron double differential cross sections in this energy region up to now. A main difficulty for this is lack of an applicable monoenergetic neutron source. When monoenergetic neutron energy reaches 8 Me/v, the break-up neutrons from the d + D or p + T reaction starts to become significant. It is difficult to get a pure secondary neutron spectrum induced only by monoenergetic neutrons. To solve this problem an abnormal fast neutron TOF facility was designed and tested. Double differential neutron emission cross sections of 238 U and 209 Bi at 10 MeV were obtained by combining the data measured by both normal and abnormal TOF spectrometers and a good agreement between measurement and calculation was achieved

  10. The Development of a Differential Deposition Technique for Figure Correction in Grazing Incidence Optics

    Data.gov (United States)

    National Aeronautics and Space Administration — We propose the development of a physical-vapor-deposition coating technique to correct residual figure errors in grazing-incidence optics. The process involves...

  11. Total and Differential Leukocyte Counts in Relation to Incidence of Diabetes Mellitus: A Prospective Population-Based Cohort Study

    Science.gov (United States)

    Borné, Yan; Smith, J. Gustav; Nilsson, Peter M.; Melander, Olle; Hedblad, Bo; Engström, Gunnar

    2016-01-01

    Objective High concentrations of leukocytes in blood have been associated with diabetes mellitus. This prospective study aimed to explore whether total and differential leukocyte counts are associated with incidence of diabetes. A missense variant R262W in the SH2B3 (SH2B adaptor protein 3) gene, coding for a protein that negatively regulates hematopoietic cell proliferation, was also studied in relation to incidence of diabetes. Methods and Results Leukocyte count and its subtypes (neutrophils, lymphocytes and mixed cells) were analyzed in 26,667 men and women, 45–73 years old, from the population-based Malmö Diet and Cancer study. Information about the R262W polymorphism (rs3184504) in SH2B3 was genotyped in 24,489 subjects. Incidence of diabetes was studied during a mean follow-up of 14 years. Cox proportional hazards regression was used to examine incidence of diabetes by total and differential leukocyte counts. Mendelian randomization analysis using R262W as an instrumental variable was performed with two-stage least squares regression. A total of 2,946 subjects developed diabetes during the follow-up period. After taking several possible confounders into account, concentrations of total leukocyte count, neutrophils and lymphocytes were all significantly associated with incidence of diabetes. The adjusted hazard ratios (95% confidence interval; quartile 4 vs quartile 1) were 1.37 (1.22–1.53) for total leukocytes, 1.33 (1.19–1.49) for neutrophils and 1.29 (1.15–1.44) for lymphocytes. The R262W polymorphism was strongly associated with leukocytes (0.11x109 cells/l per T allele, p = 1.14 x10-12), lymphocytes (p = 4.3 x10-16), neutrophils (p = 8.0 x10-6) and mixed cells (p = 3.0 x10-6). However, there was no significant association between R262W and fasting glucose, HbA1c or incidence of diabetes. Conclusions Concentrations of total leukocytes, neutrophils and lymphocytes are associated with incidence of diabetes. However, the lack of association with the

  12. Concepts in viral pathogenesis II

    Energy Technology Data Exchange (ETDEWEB)

    Notkins, A.L.; Oldstone, M.B.A.

    1986-01-01

    This paper contains papers divided among 10 sections. The section titles are: Viral Structure and Function; Viral Constructs; Oncogenes, Transfection, and Differentiation; Viral Tropism and Entry into Cells; Immune Recognition of Viruses; Evolving Concepts in Viral Pathogenesis Illustrated by Selected Plant and Animal Models; Evolving Concepts in Viral Pathogenesis Illustrated by Selected Diseases in Humans; New Trends in Diagnosis and Epidemiology; and Vaccines and Antiviral Therapy.

  13. Molecular pathogenesis of intrahepatic cholangiocarcinoma

    DEFF Research Database (Denmark)

    Andersen, Jesper Bøje

    2014-01-01

    Cholangiocarcinoma (CCA) is an orphan cancer of the hepatobiliary tract, the incidence of which has increased in the past decade. The molecular pathogenesis of this treatment-refractory disease is poorly understood. Desmoplasia is a key causal feature of CCA; however, a majority of tumors develop...

  14. Fruits and vegetables intake differentially affects estrogen receptor negative and positive breast cancer incidence rates.

    Science.gov (United States)

    Olsen, Anja; Tjønneland, Anne; Thomsen, Birthe L; Loft, Steffen; Stripp, Connie; Overvad, Kim; Møller, Susanne; Olsen, Jørgen H

    2003-07-01

    Despite intensive research, the evidence for a protective effect of fruits and vegetables on breast cancer risk remains inconclusive. Other risk factors for breast cancer seem to vary with the estrogen receptor status of the breast tumor, and it is thus possible that the inconsistent results regarding a preventive effect of fruits and vegetables are due to lack of controlling for estrogen receptor status. The objective of this study was to investigate the effect of fruit and vegetable intake on postmenopausal breast cancer and explore whether the estrogen receptor status of the tumor modifies this relation. Postmenopausal women (n = 23,798; aged 50-64 y) provided information about diet and established risk factors for breast cancer in the cohort "Diet, Cancer and Health." During follow-up, 425 cases were diagnosed with breast cancer. Associations between intake of fruits and vegetables and the breast cancer rate were analyzed using Cox's regression model. The association for all breast cancers was an incidence rate ratio (IRR) of 1.02 (95% CI, 0.98-1.06) per 100 g/d increment of total intake of fruits, vegetables and juice. For estrogen receptor-positive (ER(+)) breast cancer, a borderline significant increase in the rate was seen, IRR: 1.05 (95% CI, 1.00-1.10), whereas a preventive effect was seen for estrogen receptor-negative (ER(-)) breast cancers, IRR: 0.90 (95% CI, 0.81-0.99). In conclusion, we did not find the overall breast cancer rate to be associated with the intake of fruits and vegetables, but there seemed to be different effects for ER(+) and ER(-) breast cancer.

  15. Pathogenesis of giant colonic diverticula

    International Nuclear Information System (INIS)

    Muhletaler, C.A.; Berger, J.L.; Robinette, C.L. Jr.

    1981-01-01

    The clinical, radiographic, and pathologic findings of 3 patients with giant colonic diverticula are presented. Although several theories have been proposed for the formation of these diverticula, they have not been fully documented. One of our cases illustrates the evolution of this disorder following typical colonic diverticulitis. The pathogenesis and differential diagnosis of this unusual entity are discussed. (orig.)

  16. Pathogenesis of Candida infections.

    Science.gov (United States)

    Odds, F C

    1994-09-01

    Candida infections of the skin and superficial mucosal sites are the result of an interplay between fungal virulence and host defenses. Epidermal proliferation and T-lymphocyte immune responses are expressed by the host to combat fungal invasion, but inflammatory responses and nonspecific inhibitors also probably play a role. Candida albicans can express at least three types of surface adhesion molecules to colonize epithelial surfaces, plus an aspartyl proteinase enzyme able to facilitate initial penetration of keratinized cells. Deeper penetration of keratinized epithelia is assisted by hypha formation, and C. albicans hyphae may use contact sensing (thigmotropism) as a guiding mechanism. Pathogenesis requires differential expression of virulence factors at each new stage of the process: a propensity for rapid alteration of the expressed phenotype in C. albicans may therefore be a significant factor in establishing the comparatively high pathogenic potential of this species.

  17. Independent Preharvest Applications of Methyl Jasmonate and Chitosan Elicit Differential Upregulation of Defense-Related Genes with Reduced Incidence of Gray Mold Decay during Postharvest Storage of Fragaria chiloensis Fruit

    Directory of Open Access Journals (Sweden)

    Gabriela M. Saavedra

    2017-07-01

    Full Text Available The Chilean strawberry (Fragaria chiloensis fruit has interesting organoleptic properties, but its postharvest life is affected by gray mold decay caused by Botrytis cinerea. The effect of preharvest applications of methyl jasmonate (MeJA or chitosan on the molecular defense-related responses and protection against gray mold decay were investigated in Chilean strawberry fruit during postharvest storage. Specifically, we inoculated harvested fruit with B. cinerea spores and studied the expression of genes encoding for the pathogenesis-related (PR proteins β-1,3-glucanases (FcBG2-1, FcBG2-2 and FcBG2-3 and chitinases (FcCHI2-2 and FcCHI3-1, and for polygalacturonase inhibiting proteins (FcPGIP1 and FcPGIP2 at 0, 2, 24, 48, and 72 h post inoculation (hpi. Remarkably, MeJA- and chitosan-treated fruit exhibited a lower incidence of B. cinerea infection than the control-treated at 48 and 72 hpi. At the molecular level, both are efficient elicitors for priming in F. chiloensis fruit since we observed an upregulation of the FcBG2-1, FcBG2-3, FcPGIP1, and FcPGIP2 at 0 hpi. Moreover, a chitosan-mediated upregulation of FcPGIPs at early times post inoculation (2–24 hpi and MeJA upregulated FcBGs (24–72 hpi and FcPGIP1 at later times could contribute to reduce B. cinerea incidence by differential upregulation of defense genes. We concluded that preharvest applications of MeJA or chitosan had a long-lasting effect on the reduction of B. cinerea incidence during postharvest as well as an enhancer effect on the induction of PR and PGIP gene expression.

  18. Independent Preharvest Applications of Methyl Jasmonate and Chitosan Elicit Differential Upregulation of Defense-Related Genes with Reduced Incidence of Gray Mold Decay during Postharvest Storage of Fragaria chiloensis Fruit.

    Science.gov (United States)

    Saavedra, Gabriela M; Sanfuentes, Eugenio; Figueroa, Pablo M; Figueroa, Carlos R

    2017-07-03

    The Chilean strawberry ( Fragaria chiloensis ) fruit has interesting organoleptic properties, but its postharvest life is affected by gray mold decay caused by Botrytis cinerea . The effect of preharvest applications of methyl jasmonate (MeJA) or chitosan on the molecular defense-related responses and protection against gray mold decay were investigated in Chilean strawberry fruit during postharvest storage. Specifically, we inoculated harvested fruit with B. cinerea spores and studied the expression of genes encoding for the pathogenesis-related (PR) proteins β-1,3-glucanases ( FcBG2-1 , FcBG2-2 and FcBG2-3 ) and chitinases ( FcCHI2-2 and FcCHI3-1 ), and for polygalacturonase inhibiting proteins ( FcPGIP1 and FcPGIP2 ) at 0, 2, 24, 48, and 72 h post inoculation (hpi). Remarkably, MeJA- and chitosan-treated fruit exhibited a lower incidence of B. cinerea infection than the control-treated at 48 and 72 hpi. At the molecular level, both are efficient elicitors for priming in F. chiloensis fruit since we observed an upregulation of the FcBG2-1 , FcBG2-3 , FcPGIP1, and FcPGIP2 at 0 hpi. Moreover, a chitosan-mediated upregulation of FcPGIP s at early times post inoculation (2-24 hpi) and MeJA upregulated FcBG s (24-72 hpi) and FcPGIP1 at later times could contribute to reduce B. cinerea incidence by differential upregulation of defense genes. We concluded that preharvest applications of MeJA or chitosan had a long-lasting effect on the reduction of B. cinerea incidence during postharvest as well as an enhancer effect on the induction of PR and PGIP gene expression.

  19. Differential host determinants contribute to the pathogenesis of 2009 pandemic H1N1 and human H5N1 influenza A viruses in experimental mouse models.

    Science.gov (United States)

    Otte, Anna; Sauter, Martina; Alleva, Lisa; Baumgarte, Sigrid; Klingel, Karin; Gabriel, Gülsah

    2011-07-01

    Influenza viruses are responsible for high morbidities in humans and may, eventually, cause pandemics. Herein, we compared the pathogenesis and host innate immune responses of a seasonal H1N1, two 2009 pandemic H1N1, and a human H5N1 influenza virus in experimental BALB/c and C57BL/6J mouse models. We found that both 2009 pandemic H1N1 isolates studied (A/Hamburg/05/09 and A/Hamburg/NY1580/09) were low pathogenic in BALB/c mice [log mouse lethal dose 50 (MLD(50)) >6 plaque-forming units (PFU)] but displayed remarkable differences in virulence in C57BL/6J mice. A/Hamburg/NY1580/09 was more virulent (logMLD(50) = 3.5 PFU) than A/Hamburg/05/09 (logMLD(50) = 5.2 PFU) in C57BL/6J mice. In contrast, the H5N1 influenza virus was more virulent in BALB/c mice (logMLD(50) = 0.3 PFU) than in C57BL/6J mice (logMLD(50) = 1.8 PFU). Seasonal H1N1 influenza revealed marginal pathogenicity in BALB/c or C57BL/6J mice (logMLD(50) >6 PFU). Enhanced susceptibility of C57BL/6J mice to pandemic H1N1 correlated with a depressed cytokine response. In contrast, enhanced H5N1 virulence in BALB/c mice correlated with an elevated proinflammatory cytokine response. These findings highlight that host determinants responsible for the pathogenesis of 2009 pandemic H1N1 influenza viruses are different from those contributing to H5N1 pathogenesis. Our results show, for the first time to our knowledge, that the C57BL/6J mouse strain is more appropriate for the evaluation and identification of intrinsic pathogenicity markers of 2009 pandemic H1N1 influenza viruses that are "masked" in BALB/c mice. Copyright © 2011 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  20. Incidence of Nonthyroidal Primary Malignancy and the Association with (131)I Treatment in Patients with Differentiated Thyroid Cancer.

    Science.gov (United States)

    Hirsch, Dania; Shohat, Tzippy; Gorshtein, Alex; Robenshtok, Eyal; Shimon, Ilan; Benbassat, Carlos

    2016-08-01

    The occurrence of nonthyroidal primary malignancy (NTPM) and the potential association of with radioiodine (RAI) treatment are important concerns in patients with differentiated thyroid cancer (DTC), but incidence data are conflicting. The aims of the present study were to investigate the incidence of NTPM and its association with RAI treatment in a cohort of DTC patients treated at a single tertiary medical center. The data of 1943 patients with DTC recorded in the Rabin Medical Center Thyroid Cancer Registry were cross-matched with data from the Israeli National Cancer Registry to identify those diagnosed with an NTPM. Patient medical files were reviewed. Second primary malignancy (SPM) was defined as new malignancy diagnosed at least two years after DTC diagnosis. For 1434 of the 1943 patients (73.8%), the American Joint Committee on Cancer TNM stage was 1-2. The mean follow-up was 9.3 years. Of the 1943 patients, 1574 (81%) were treated with RAI, and 1467 were followed for at least 2 years, and of these, 1145 patients (78%) received a cumulative dose of ≤200 mCi. A total of 409 NTPMs were diagnosed in 368/1943 patients with DTC (18.9%; 265 female, mean age 53.9 ± 15 years), including 173 SPMs (42.3%) in 166/368 patients. The most common NTPM and SPM was breast cancer followed by hematologic malignancies. In patients followed for ≥2 years, SPMs were diagnosed in 9% of RAI-treated patients and 10.5% of non-RAI-treated patients. SPM rates were 10.2% and 7.8% for a cumulative RAI dose of ≤100 mCi and >100 mCi respectively. Hazard ratios for SPM in patients that received/did not receive RAI treatment was 1.27 (95% confidence interval 0.88-1.82; p = 0.1). There was no correlation between first or cumulative RAI dose and diagnosis of SPM. NTPMs are not uncommon in patients with DTC and usually antecede the DTC. In a population of mostly low-risk DTC patients, in whom limited activities of RAI are usually administered, this treatment is apparently not

  1. Primary meningeal Epstein-Barr virus-related leiomyosarcoma in a man infected with human immunodeficiency virus: review of literature, emphasizing the differential diagnosis and pathogenesis.

    Science.gov (United States)

    Zevallos-Giampietri, Eduardo-Alfredo; Yañes, Hugo Heinicke; Orrego Puelles, José; Barrionuevo, Carlos

    2004-12-01

    We describe the clinical, radiologic, surgical, and pathologic findings of a 29-year-old Peruvian human immunodeficiency virus-infected man with a primary parasellar meningeal leiomyosarcoma involving the left lesser esphenoidal wing and the cavernous sinus. Over a period of 13 months, he developed headache, vomiting, insomnia, and diplopia. Magnetic resonance imaging revealed a left parasellar extra-axial mass that was isointense in T1, hypointense in T2, and gadolinium-enhanced. The patient underwent subtotal resection of the tumor. The neoplasm was composed of spindle cells with smooth-muscle features. It showed moderate atypia, inconspicuous nucleoli, and scanty mitosis. No tumor necrosis was detected. The immunohistochemistry revealed strong positivity for vimentin, desmin, and smooth-muscle alpha-actin. A low-grade leiomyosarcoma was diagnosed. The in situ hybridization showed positive nuclear reactivity for Epstein-Barr virus-encoded RNA. The immunohistochemistry was negative for Epstein-Barr virus latent membrane protein 1. The main differential diagnosis of primary meningeal smooth-muscle tumors includes meningioma and peripheral nerve sheath tumors. Epstein-Barr virus has been demonstrated in most smooth-muscle tumors associated with acquired immune deficiency syndrome (AIDS). Primary meningeal smooth-muscle tumors, exceedingly rare neoplasms, remarkably affect young adults with AIDS. Comparatively, most AIDS-related visceral (nonmeningeal) smooth-muscle tumors have been reported in children. The permissiveness and tumorigenesis associated with Epstein-Barr virus may depend on the age of human immunodeficiency virus infection.

  2. Men's and Women's Health Beliefs Differentially Predict Coronary Heart Disease Incidence in a Population-Based Sample

    Science.gov (United States)

    Korin, Maya Rom; Chaplin, William F.; Shaffer, Jonathan A.; Butler, Mark J.; Ojie, Mary-Jane; Davidson, Karina W.

    2013-01-01

    Objective: To examine gender differences in the association between beliefs in heart disease preventability and 10-year incidence of coronary heart disease (CHD) in a population-based sample. Methods: A total of 2,688 Noninstitutionalized Nova Scotians without prior CHD enrolled in the Nova Scotia Health Study (NSHS95) and were followed for 10…

  3. Biology and pathogenesis of Acanthamoeba

    Directory of Open Access Journals (Sweden)

    Siddiqui Ruqaiyyah

    2012-01-01

    Full Text Available Abstract Acanthamoeba is a free-living protist pathogen, capable of causing a blinding keratitis and fatal granulomatous encephalitis. The factors that contribute to Acanthamoeba infections include parasite biology, genetic diversity, environmental spread and host susceptibility, and are highlighted together with potential therapeutic and preventative measures. The use of Acanthamoeba in the study of cellular differentiation mechanisms, motility and phagocytosis, bacterial pathogenesis and evolutionary processes makes it an attractive model organism. There is a significant emphasis on Acanthamoeba as a Trojan horse of other microbes including viral, bacterial, protists and yeast pathogens.

  4. Biology and pathogenesis of Acanthamoeba

    Science.gov (United States)

    2012-01-01

    Acanthamoeba is a free-living protist pathogen, capable of causing a blinding keratitis and fatal granulomatous encephalitis. The factors that contribute to Acanthamoeba infections include parasite biology, genetic diversity, environmental spread and host susceptibility, and are highlighted together with potential therapeutic and preventative measures. The use of Acanthamoeba in the study of cellular differentiation mechanisms, motility and phagocytosis, bacterial pathogenesis and evolutionary processes makes it an attractive model organism. There is a significant emphasis on Acanthamoeba as a Trojan horse of other microbes including viral, bacterial, protists and yeast pathogens. PMID:22229971

  5. Modeling the differential incidence of "child abuse, neglect and exploitation" in poor households in South Africa: Focus on child trafficking

    CSIR Research Space (South Africa)

    Mbecke, P

    2010-06-01

    Full Text Available abuse ignore or underplay integration of multiple variables from different aspects contributing to the incidence of child abuse. Newberger et al (1983) demonstrated the need for further research and the importance of theory for knowledge, prevention... structures in South Africa as resulted from measures put in place by the past apartheid Government. Apartheid forced parents to travel great distances to get to work or to work away from home (migrant labor policies). The ?Group Areas Act? stipulated...

  6. Pathogenesis of Parkinson's disease

    OpenAIRE

    Riederer, Peter; Lange, Klaus W.

    1992-01-01

    The importance of genetic aspects, ageing, environmental factors, head trauma, defective mitochondrial respiration, altered iron metabolism, oxidative stress and glutamatergic overactivity of the basal ganglia in the pathogenesis of Parkinson's disease (PD) are considered in this review.

  7. Viral pathogenesis in diagrams

    National Research Council Canada - National Science Library

    Tremblay, Michel; Berthiaume, Laurent; Ackermann, Hans-Wolfgang

    2001-01-01

    .... The 268 diagrams in Viral Pathogenesis in Diagrams were selected from over 800 diagrams of English and French virological literature, including one derived from a famous drawing by Leonardo da Vinci...

  8. Incidence and characterization of beta-hemolytic Streptococcus milleri and differentiation from S. pyogenes (group A), S. equisimilis (group C), and large-colony group G streptococci.

    Science.gov (United States)

    Lawrence, J; Yajko, D M; Hadley, W K

    1985-01-01

    The biochemical characteristics of 172 clinical isolates of group A, C, F, or G or "nongroupable" beta-hemolytic streptococci were examined. Among these isolates, 91 were identified as beta-hemolytic strains of Streptococcus milleri. The remaining isolates included 20 Streptococcus pyogenes, 21 Streptococcus equisimilis, 37 large-colony group G streptococci, and 3 unidentified nongroupable isolates. A majority (84%) of the S. milleri strains possessed Lancefield group antigen (3 A, 27 C, 41 F, and 5 G), whereas 15 S. milleri strains (16%) were nongroupable. Serological tests did not differentiate S. milleri isolates with group A, C, or G antigen from S. pyogenes (group A), S. equisimilis (group C), or large-colony group G streptococci. Biochemical tests which were found useful for differentiation included the Voges-Proskauer test, hydrolysis of pyroglutamic acid and beta-D-glucuronide, bacitracin susceptibility, and acid production from ribose. S. milleri represented 56% of the group C, 100% of the group F, and 83% of the nongroupable beta-hemolytic streptococci isolated in our clinical laboratory, whereas the incidence of S. milleri among group A and group G streptococci was estimated to be low. The role of beta-hemolytic S. milleri as a cause of human infection remains obscured by the failure to routinely differentiate S. milleri from other beta-hemolytic streptococci. PMID:3902878

  9. Are the poor differentially benefiting from provision of priority public health services? A benefit incidence analysis in Nigeria

    Directory of Open Access Journals (Sweden)

    Onwujekwe Obinna

    2012-11-01

    Full Text Available Abstract Background The paper presents evidence about the distribution of the benefits of public expenditures on a subset of priority public health services that are supposed to be provided free of charge in the public sector, using the framework of benefit incidence analysis. Methods The study took place in 2 rural and 2 urban Local Government Areas from Enugu and Anambra states, southeast Nigeria. A questionnaire was used to collect data on use of the priority public health services by all individuals in the households (n=22,169. The level of use was disaggregated by socio-economic status (SES, rural-urban location and gender. Benefits were valued using the cost of providing the service. Net benefit incidence was calculated by subtracting payments made for services from the value of benefits. Results The results showed that 3,281 (14.8% individuals consumed wholly free services. There was a greater consumption of most free services by rural dwellers, females and those from poorer SES quintiles (but not for insecticide-treated nets and ante-natal care services. High levels of payment were observed for immunisation services, insecticide-treated nets, anti-malarial medicines, antenatal care and childbirth services, all of which are supposed to be provided for free. The net benefits were significantly higher for the rural residents, males and the poor compared to the urban residents, females and better-off quintiles. Conclusion It is concluded that coverage of all of these priority public health services fell well below target levels, but the poorer quintiles and rural residents that are in greater need received more benefits, although not so for females. Payments for services that are supposed to be delivered free of charge suggests that there may have been illegal payments which probably hindered access to the public health services.

  10. Differential distribution of sperm subpopulations and incidence of pleiomorphisms in ejaculates of captive howling monkeys ( Alouatta caraya)

    Science.gov (United States)

    Valle, R. R.; Carvalho, F. M.; Muniz, J. A. P. C.; Leal, C. L. V.; García-Herreros, M.

    2013-10-01

    The aim of this study was to develop an objective method to determine the incidence of pleiomorphisms and its influence on the distribution of sperm morphometric subpopulations in ejaculates of howling monkeys ( Alouatta caraya) by using a combination of computerized analysis system (ASMA) and principal component analysis (PCA) methods. Ejaculates were collected by electroejaculation methods on a regular basis from five individuals maintained under identical captive environmental, nutritional, and management conditions. Each sperm head was measured for dimensional parameters (Area [ A, (square micrometers)], Perimeter [ P, (micrometers)], Length [ L, (micrometers)], and Width [ W, (micrometers)]) and shape-derived parameters (Ellipticity [( L/ W)], Elongation [( L - W)/( L + W)], and Rugosity [(4л A/ P 2)]). PCA revealed two principal components explaining more than the 96 % of the variance. Clustering methods and discriminant analyzes were performed and seven separate subpopulations were identified. There were differences ( P ASMA and PCA is a useful clinical diagnostic resource for detecting deficiencies in sperm morphology and sperm subpopulations in A. caraya ejaculates that could be used in ex situ conservation programs of threatened species in Alouatta genus or even other endangered neotropical primate species.

  11. Pathogenesis of Hepatic Encephalopathy

    Directory of Open Access Journals (Sweden)

    Irena Ciećko-Michalska

    2012-01-01

    Full Text Available Hepatic encephalopathy can be a serious complication of acute liver failure and chronic liver diseases, predominantly liver cirrhosis. Hyperammonemia plays the most important role in the pathogenesis of hepatic encephalopathy. The brain-blood barrier disturbances, changes in neurotransmission, neuroinflammation, oxidative stress, GABA-ergic or benzodiazepine pathway abnormalities, manganese neurotoxicity, brain energetic disturbances, and brain blood flow abnormalities are considered to be involved in the development of hepatic encephalopathy. The influence of small intestine bacterial overgrowth (SIBO on the induction of minimal hepatic encephalopathy is recently emphasized. The aim of this paper is to present the current views on the pathogenesis of hepatic encephalopathy.

  12. Is the incidence of differentiated thyroid cancer increased in patients with thyrotropin-secreting adenomas? Report of three cases from a large consecutive series.

    Science.gov (United States)

    Perticone, Francesca; Pigliaru, Francesca; Mariotti, Stefano; Deiana, Luca; Furlani, Lino; Mortini, Pietro; Losa, Marco

    2015-04-01

    Patients with a thyrotropin-secreting pituitary adenoma (TSHoma) are exposed to unregulated and inappropriately high levels of thyrotropin (TSH). Given the rarity of this condition, it is not known whether this chronic TSH stimulation of the thyroid gland might represent a risk factor for the development of differentiated thyroid cancer (DTC). We analyzed the incidence of DTC in a large cohort of patients with TSHomas. The study population consisted of all consecutive patients who underwent neurosurgery for a TSHoma between 1990 and 2013. Criteria for the diagnosis of TSHoma in patients without previous thyroid ablative procedures included elevated free thyroid hormones and normal/high serum TSH concentrations, presence of a lesion at magnetic resonance imaging (MRI), and abnormal response of TSH to at least one dynamic test. Patients who had received thyroid ablative procedures were required to have a pituitary lesion on MRI and TSH levels not suppressed while on levothyroxine therapy at doses causing elevation of free thyroid hormone levels. Sixty-two patients (32 females, 30 males) underwent surgery for a TSHoma at our center. Among them, 3 patients had a coexistent diagnosis of DTC with an estimated incidence of 4.8%. In 2 patients, DTC was diagnosed during the evaluation for suspected TSH-dependent hyperthyroidism, whereas in the third patient, diagnosis of DTC preceded the detection of the pituitary tumor. The elevated incidence of DTC in patients with TSHoma suggests a possible role of TSH hypersecretion in the development of thyroid tumors. A formal high-resolution ultrasound of the thyroid is recommended in patients diagnosed with a TSHoma, especially if a long history of the pituitary tumor is suspected. Moreover, suspicion about the presence of TSHoma should be raised by the lack of suppression of TSH levels despite adequate doses of levothyroxine after thyroidectomy for DTC.

  13. The Pathogenesis of Nontraumatic Osteonecrosis

    Directory of Open Access Journals (Sweden)

    Jesse Seamon

    2012-01-01

    Full Text Available Nontraumatic osteonecrosis continues to be a challenging problem causing debilitating major joint diseases. The etiology is multifactorial, but steroid- and alcohol-induced osteonecrosis contribute to more than two thirds of all cases with genetic risk factors playing an important role in many other cases, especially when they contribute to hypercoagulable states. While the exact mechanisms remain elusive, many new insights have emerged from research in the last decade that have given us a clearer picture of the pathogenesis of nontraumatic osteonecrosis of the femoral head. Progression to end stage osteonecrosis of the femoral head appears to be related to four main factors: interactions involving the differentiation pathway of osteoprogenitor cells that promote adipogenesis, decreased angiogenesis, direct suppression of osteogenic gene expression and proliferation of bone marrow stem cells, and genetic anomalies or other diseases that promote hypercoagulable states.

  14. The Pathogenesis of Autism

    Directory of Open Access Journals (Sweden)

    Timothy John Watts

    2008-01-01

    Full Text Available Autism is well known as a complex developmental disorder with a seemingly confusing and uncertain pathogenesis. The definitive mechanisms that promote autism are poorly understood and mostly unknown, yet available theories do appear to focus on the disruption of normal cerebral development and its subsequent implications on the functional brain unit. This mini-review aims solely to discuss and evaluate the most prominent current theories regarding the pathogenesis of autism. The main conclusion is that although there is not a clear pathway of mechanisms directed towards a simple pathogenesis and an established link to autism on the symptomatic level; there are however several important theories (neural connectivity, neural migration, excitatory-inhibitory neural activity, dendritic morphology, neuroimmune; calcium signalling and mirror neurone which appear to offer an explanation to how autism develops. It seems probable that autism's neurodevelopmental defect is ‘multi-domain’ in origin (rather than a single anomaly and is hence distributed across numerous levels of study (genetic, immunopathogenic, etc.. A more definitive understanding of the pathogenesis could facilitate the development of better treatments for this complex psychiatric disorder.

  15. Molecular Pathogenesis of Spondyloarthritis

    DEFF Research Database (Denmark)

    Carlsen, Thomas Gelsing

    This dissertation includes a presentation of knowledge on the molecular pathogenesis of spondyloarthritis achieved through a PhD programme at Aalborg University from 1.12.2011 - 1.12.2014. Work was carried out in the Laboratory of Medical Mass Spectrometry, headed by: Professor Svend Birkelund...

  16. Double-differential beryllium neutron cross sections at incident neutron energies of 5. 9, 10. 1, and 14. 2 MeV. [5. 9 to 14. 2 MeV, differential cross sections, ENDF/B-IV

    Energy Technology Data Exchange (ETDEWEB)

    Drake, D.M.; Auchampaugh, G.F.; Arthur, E.D.; Ragan, C.E.; Young, P.G.

    1976-08-01

    Beryllium neutron-production cross sections were measured using the time-of-flight technique at incident neutron energies of 5.9, 10.1, and 14.2 MeV, and at laboratory angles of 25, 27.5, 30, 35, 45, 60, 80, 100, 110, 125, and 145/sup 0/. The differential elastic and inelastic cross sections are presented. Inelastic is defined here as those reactions that proceed through the states at 1.69-, 2.43-, 2.8-, and 3.06-MeV excitation energy in /sup 9/Be. Comparison of emission energy spectra with calculations using the ENDF/B-IV beryllium cross sections shows that the ENDF/B cross sections strongly overemphasize the low lying states in /sup 9/Be.

  17. Complement and Viral Pathogenesis

    Science.gov (United States)

    Stoermer, Kristina A.; Morrison, Thomas E.

    2011-01-01

    The complement system functions as an immune surveillance system that rapidly responds to infection. Activation of the complement system by specific recognition pathways triggers a protease cascade, generating cleavage products that function to eliminate pathogens, regulate inflammatory responses, and shape adaptive immune responses. However, when dysregulated, these powerful functions can become destructive and the complement system has been implicated as a pathogenic effector in numerous diseases, including infectious diseases. This review highlights recent discoveries that have identified critical roles for the complement system in the pathogenesis of viral infection. PMID:21292294

  18. Pathogenesis of microbial keratitis.

    Science.gov (United States)

    Lakhundi, Sahreena; Siddiqui, Ruqaiyyah; Khan, Naveed Ahmed

    2017-03-01

    Microbial keratitis is a sight-threatening ocular infection caused by bacteria, fungi, and protist pathogens. Epithelial defects and injuries are key predisposing factors making the eye susceptible to corneal pathogens. Among bacterial pathogens, the most common agents responsible for keratitis include Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pneumonia and Serratia species. Fungal agents of corneal infections include both filamentous as well as yeast, including Fusarium, Aspergillus, Phaeohyphomycetes, Curvularia, Paecilomyces, Scedosporium and Candida species, while in protists, Acanthamoeba spp. are responsible for causing ocular disease. Clinical features include redness, pain, tearing, blur vision and inflammation but symptoms vary depending on the causative agent. The underlying molecular mechanisms associated with microbial pathogenesis include virulence factors as well as the host factors that aid in the progression of keratitis, resulting in damage to the ocular tissue. The treatment therefore should focus not only on the elimination of the culprit but also on the neutralization of virulence factors to minimize the damage, in addition to repairing the damaged tissue. A complete understanding of the pathogenesis of microbial keratitis will lead to the rational development of therapeutic interventions. This is a timely review of our current understanding of the advances made in this field in a comprehensible manner. Coupled with the recently available genome sequence information and high throughput genomics technology, and the availability of innovative approaches, this will stimulate interest in this field. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Deletion of genes implicated in protecting the integrity of male germ cells has differential effects on the incidence of DNA breaks and germ cell loss.

    Directory of Open Access Journals (Sweden)

    Catriona Paul

    2007-10-01

    Full Text Available Infertility affects approximately 20% of couples in Europe and in 50% of cases the problem lies with the male partner. The impact of damaged DNA originating in the male germ line on infertility is poorly understood but may increase miscarriage. Mouse models allow us to investigate how deficiencies in DNA repair/damage response pathways impact on formation and function of male germ cells. We have investigated mice with deletions of ERCC1 (excision repair cross-complementing gene 1, MSH2 (MutS homolog 2, involved in mismatch repair pathway, and p53 (tumour suppressor gene implicated in elimination of germ cells with DNA damage.We demonstrate for the first time that depletion of ERCC1 or p53 from germ cells results in an increased incidence of unrepaired DNA breaks in pachytene spermatocytes and increased numbers of caspase-3 positive (apoptotic germ cells. Sertoli cell-only tubules were detected in testes from mice lacking expression of ERCC1 or MSH2 but not p53. The number of sperm recovered from epididymes was significantly reduced in mice lacking testicular ERCC1 and 40% of sperm contained DNA breaks whereas the numbers of sperm were not different to controls in adult Msh2 -/- or p53 -/- mice nor did they have significantly compromised DNA.These data have demonstrated that deletion of Ercc1, Msh2 and p53 can have differential but overlapping affects on germ cell function and sperm production. These findings increase our understanding of the ways in which gene mutations can have an impact on male fertility.

  20. Molecular Pathogenesis of NASH

    Directory of Open Access Journals (Sweden)

    Alessandra Caligiuri

    2016-09-01

    Full Text Available Nonalcoholic steatohepatitis (NASH is the main cause of chronic liver disease in the Western world and a major health problem, owing to its close association with obesity, diabetes, and the metabolic syndrome. NASH progression results from numerous events originating within the liver, as well as from signals derived from the adipose tissue and the gastrointestinal tract. In a fraction of NASH patients, disease may progress, eventually leading to advanced fibrosis, cirrhosis and hepatocellular carcinoma. Understanding the mechanisms leading to NASH and its evolution to cirrhosis is critical to identifying effective approaches for the treatment of this condition. In this review, we focus on some of the most recent data reported on the pathogenesis of NASH and its fibrogenic progression, highlighting potential targets for treatment or identification of biomarkers of disease progression.

  1. Pathogenesis of Takotsubo syndrome

    Directory of Open Access Journals (Sweden)

    Daniele Masarone

    2017-01-01

    Full Text Available Takotsubo syndrome (TTS is an enigmatic disease with a multifactorial and still unresolved pathogenesis. Postulated mechanisms include catecholamine excess, coronary artery spasm, and microvascular dysfunction, however catecholamines seem to play a central role in the pathophysiology of TTS. In facts catecholamines have relevant effects on the vasculature and myocardium. Toxic direct effects of catecholamine on myocardium are mediated by multiple pathway including functional hypoxia, metabolic changes and changes in membrane permeability leading to various electrolytic imbalances. Recently report of familial cases has suggested a genetic component. Further research is required to help clarify the proposed hypotheses and to increase our understanding of the cardiovascular responses to acute stress and the pathophysiology underpinning TTS.

  2. The roles of environmental pollutants in the pathogenesis and ...

    African Journals Online (AJOL)

    ... rise worldwide with a growing suspicion of association between environmental pollutants and diabetes. This paper reviewed the roles of environmental pollutants in the pathogenesis and increasing incidence of diabetes. Relevant information was retrieved from reliable sources in the internet using Google search engine.

  3. Pathogenesis of Mucormycosis

    Science.gov (United States)

    Spellberg, Brad; Walsh, Thomas J.; Kontoyiannis, Dimitrios P.

    2012-01-01

    Mucormycosis is a life-threatening infection that occurs in patients who are immunocompromised because of diabetic ketoacidosis, neutropenia, organ transplantation, and/or increased serum levels of available iron. Because of the increasing prevalence of diabetes mellitus, cancer, and organ transplantation, the number of patients at risk for this deadly infection is increasing. Despite aggressive therapy, which includes disfiguring surgical debridement and frequently adjunctive toxic antifungal therapy, the overall mortality rate is high. New strategies to prevent and treat mucormycosis are urgently needed. Understanding the pathogenesis of mucormycosis and the host response to invading hyphae ultimately will provide targets for novel therapeutic interventions. In this supplement, we review the current knowledge about the virulence traits used by the most common etiologic agent of mucormycosis, Rhizopus oryzae. Because patients with elevated serum levels of available iron are uniquely susceptible to mucormycosis and these infections are highly angioinvasive, emphasis is placed on the ability of the organism to acquire iron from the host and on its interactions with endothelial cells lining blood vessels. Several promising therapeutic strategies in preclinical stages are identified. PMID:22247441

  4. Kaposi sarcoma herpesvirus pathogenesis.

    Science.gov (United States)

    Mariggiò, Giuseppe; Koch, Sandra; Schulz, Thomas F

    2017-10-19

    Kaposi sarcoma herpesvirus (KSHV), taxonomical name human gammaherpesvirus 8, is a phylogenetically old human virus that co-evolved with human populations, but is now only common (seroprevalence greater than 10%) in sub-Saharan Africa, around the Mediterranean Sea, parts of South America and in a few ethnic communities. KSHV causes three human malignancies, Kaposi sarcoma, primary effusion lymphoma, and many cases of the plasmablastic form of multicentric Castleman's disease (MCD) as well as occasional cases of plasmablastic lymphoma arising from MCD; it has also been linked to rare cases of bone marrow failure and hepatitis. As it has colonized humans physiologically for many thousand years, cofactors are needed to allow it to unfold its pathogenic potential. In most cases, these include immune defects of genetic, iatrogenic or infectious origin, and inflammation appears to play an important role in disease development. Our much improved understanding of its life cycle and its role in pathogenesis should now allow us to develop new therapeutic strategies directed against key viral proteins or intracellular pathways that are crucial for virus replication or persistence. Likewise, its limited (for a herpesvirus) distribution and transmission should offer an opportunity for the development and use of a vaccine to prevent transmission.This article is part of the themed issue 'Human oncogenic viruses'. © 2017 The Authors.

  5. Pathogenesis and biology.

    Science.gov (United States)

    Winkler, Frank

    2018-01-01

    Metastasis to the brain is an increasing complication of solid cancers. Fortunately, our understanding of its pathogenesis has greatly increased in the last decade, with crucial insights into the molecular and cellular determinants of successful brain colonization; some aspects remain less well understood. The latter include the exact features of brain metastasis-initiating cancer cells, and a potential premetastatic niche. It is clear that a brain-arrested cancer cell has to master a sequence of steps to eventually grow to a clinically relevant brain metastasis. Various brain-specific cell types and molecular niches promote or hinder brain colonization in a dynamic and reciprocal manner. After mandatory extravasation and colonization of a brain-specific perivascular niche, the cancer cell can stay dormant, or further grow by dynamic interactions with cerebral blood vessels. In addition, the activation of certain molecular pathways on site of the cancer cell which are related to growth, motility, survival, and adaptation to the brain environment appears also important, given their characteristic modification in brain metastases of patients. A deeper understanding of the most vulnerable steps of the brain metastatic cascade may foster the development of novel preventive approaches, and that of core biologic mechanisms for macrometastatic growth and persistence will help to develop better therapeutics. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Pathogenesis of rhinitis.

    Science.gov (United States)

    Eifan, A O; Durham, S R

    2016-09-01

    Rhinitis is a heterogeneous condition that has been associated with inflammatory responses as in allergic rhinitis but can also occur in the absence of inflammation such as in so-called idiopathic (previously 'vasomotor') rhinitis. Allergic rhinitis affects approximately one in four of the population of westernized countries and is characterized by typical symptoms of nasal itching, sneezing, watery discharge and congestion. The intention of this review is to illustrate key concepts of the pathogenesis of rhinitis. Imbalance in innate and adaptive immunity together with environmental factors is likely to play major roles. In allergic rhinitis, initial allergen exposure and sensitization involves antigen-presenting cells, T and B lymphocytes and results in the generation of allergen-specific T cells and allergen-specific IgE antibodies. On re-exposure to relevant allergens, cross-linking of IgE on mast cells results in the release of mediators of hypersensitivity such as histamine and immediate nasal symptoms. Within hours, there is an infiltration by inflammatory cells, particularly Th2 T lymphocytes, eosinophils and basophils into nasal mucosal tissue that results in the late-phase allergic response. Evidence for nasal priming and whether or not remodelling may be a feature of allergic rhinitis will be reviewed. The occurrence of so-called local allergic rhinitis in the absence of systemic IgE will be discussed. Non-allergic (non-IgE-mediated) rhinitis will be considered in the context of inflammatory and non-inflammatory disorders. © 2016 John Wiley & Sons Ltd.

  7. Pathogenesis of bovine neosporosis.

    Science.gov (United States)

    Dubey, J P; Buxton, D; Wouda, W

    2006-05-01

    The protozoan parasite Neospora caninum is a major pathogen of cattle and dogs, being a significant cause of abortion in cattle in many countries. It is one of the most efficiently transmitted parasites, with up to 90% of cattle infected in some herds. The pathogenesis of abortion due to Neospora is complex and only partially understood. Losses occur after a primary infection during pregnancy but more commonly as the result of recrudescence of a persistent infection during pregnancy. Parasitaemia is followed by invasion of the placenta and fetus. It is suggested that abortion occurs when primary parasite-induced placental damage jeopardises fetal survival directly or causes release of maternal prostaglandins that in turn cause luteolysis and abortion. Fetal damage may also occur due to primary tissue damage caused by the multiplication of N. caninum in the fetus or due to insufficient oxygen/nutrition, secondary to placental damage. In addition, maternal immune expulsion of the fetus may occur associated with maternal placental inflammation and the release of maternal pro-inflammatory cytokines in the placenta. Thus N. caninum is a primary pathogen capable of causing abortion either through maternal placental inflammation, maternal and fetal placental necrosis, fetal damage, or a combination of all three. The question of how N. caninum kills the fetus exposes the complex and finely balanced biological processes that have evolved to permit bovine and other mammalian pregnancies to occur. Defining these immunological mechanisms will shed light on potential methods of control of bovine neosporosis and enrich our understanding of the continuity of mammalian and protozoal survival.

  8. Pathogenesis of Acanthamoeba Keratitis

    Science.gov (United States)

    Panjwani, Noorjahan

    2010-01-01

    Acanthamoeba keratitis (AK) is a serious infection of the cornea. At present, diagnosis of the disease is not straightforward and treatment is very demanding. While contact lens wear is the leading risk factor for AK, Acanthamoeba parasites are increasingly recognized as an important cause of keratitis in non-contact lens wearers. The first critical step in the pathogenesis of infection is the adhesion of the microbe to the surface of the host tissues. Acanthamoebae express a major virulence protein, the mannose-binding protein (MBP), which mediates the adhesion of amoebae to the surface of the cornea. The MBP is a transmembrane protein with characteristics of a typical cell surface receptor. Subsequent to the MBP-mediated adhesion to host cells, the amoebae produce a contact-dependent metalloproteinase and several contact-independent serine proteinases. These proteinases work in concert to produce a potent cytopathic effect (CPE) involving killing of the host cells, degradation of epithelial basement membrane and underlying stromal matrix, and penetration into the deeper layers of the cornea. In the hamster animal model, oral immunization with the recombinant MBP protects against AK, and this protection is associated with an increased level of anti-MBP IgA in tears of protected animals. Normal human tear fluid contains IgA antibodies against Acanthamoeba MBP that is likely to provide protection by inhibiting the adhesion of parasites to host cells. Indeed, in in vitro CPE assays, even a low concentration of tears (10 [MU]μL of undiluted tears per milliliter of media) almost completely inhibits Acanthamoeba-induced CPE. In addition to adherence-inhibiting, IgA-mediated protection, human tears also contain IgA-independent factors that provide protection against Acanthamoeba-induced CPE by inhibiting the activity of cytotoxic proteinases. Characterization of the CPE-inhibitory factors of human tears should lead to a better understanding of the mechanism by which the

  9. Molecular mechanisms of rosacea pathogenesis

    Directory of Open Access Journals (Sweden)

    Davydova A.M.

    2013-09-01

    Full Text Available The article presents possible molecular mechanisms for rosacea pathogenesis from current domestic and foreign clinical observations and laboratory research: regulation and expression defects of antimicrobial peptides, vascular endothelial growth factor, the effect of serine proteases, oxidative stress, reactive oxygen species and ferritin on the occurrence and course of rosacea. New developments in molecular biology and genetics are advanced for researching the interaction of multiple factors involved in rosacea pathogenesis, as well as providing the bases for potentially new therapies.

  10. Immunomodulatory role of vitamin D in the pathogenesis of preeclampsia.

    Science.gov (United States)

    Smith, Tyler A; Kirkpatrick, Daniel R; Kovilam, Oormila; Agrawal, Devendra K

    2015-01-01

    Worldwide, preeclampsia is a significant health risk to both pregnant women and their unborn children. Despite scientific advances, the exact pathogenesis of preeclampsia is not yet fully understood. Meanwhile, the incidence of preeclampsia is expected to increase. A series of potential etiologies for preeclampsia has been identified, including endothelial dysfunction, immunological dysregulation and trophoblastic invasion. In this literature review, we have critically reviewed existing literature regarding the research findings that link the role of vitamin D to the pathogenesis and immunoregulation of preeclampsia. The relationship of vitamin D with the suspected etiologies of preeclampsia underscores its clinical potential in the diagnosis and treatment of preeclampsia.

  11. Review: pathogenesis of gallstones.

    Science.gov (United States)

    Dowling, R H

    2000-05-01

    The aim of this article is to review selected aspects of the pathogenesis of cholesterol-rich, gall-bladder stones (GBS)--with emphasis on recent developments in biliary cholesterol saturation, cholesterol microcrystal nucleation, statis within the gall-bladder and, particularly, on the roles of intestinal transit and altered deoxycholic acid (DCA) metabolism, in GBS development. In biliary cholesterol secretion, transport and saturation, recent developments include evidence in humans and animals, that bile lipid secretion is under genetic control. Thus in mice the md-2 gene, and in humans the MDR-3 gene, encodes for a canalicular protein that acts as a 'flippase' transporting phospholipids from the inner to the outer hemi-leaflet of the canalicular membrane. In the absence of this gene, there is virtually no phospholipid or cholesterol secretion into bile. Furthermore, when inbred strains of mice that have 'lith genes' are fed a lithogenic diet, they become susceptible to high rates of GBS formation. The precipitation/nucleation of cholesterol microcrystals from supersaturated bile remains a critical step in gallstone formation. methods of studying this phenomenon have now been refined from the original 'nucleation time' to measurement of cholesterol appearance/detection times, and crystal growth assays. Furthermore, the results of recent studies indicate that, in addition to classical Rhomboid-shape monohydrate crystals, cholesterol can also crystallize, transiently, as needle-, spiral- and tubule-shaped crystals of anhydrous cholesterol. A lengthy list of promoters, and a shorter list of inhibitors, has now been defined. There are many situations where GB stasis in humans is associated with an increased risk of gallstone formation--including iatrogenic stone formation in acromegalic patients treated chronically with octreotide (OT). As well as GB stasis, however, OT-treated patients all have 'bad' bile which is supersaturated with cholesterol, has excess

  12. Ubiquitination in melanoma pathogenesis and treatment.

    Science.gov (United States)

    Ma, Jinyuan; Guo, Weinan; Li, Chunying

    2017-06-01

    Melanoma is one of the most aggressive skin cancers with fiercely increasing incidence and mortality. Since the progressive understanding of the mutational landscape and immunologic pathogenic factors in melanoma, the targeted therapy and immunotherapy have been recently established and gained unprecedented improvements for melanoma treatment. However, the prognosis of melanoma patients remains unoptimistic mainly due to the resistance and nonresponse to current available drugs. Ubiquitination is a posttranslational modification which plays crucial roles in diverse cellular biological activities and participates in the pathogenesis of various cancers, including melanoma. Through the regulation of multiple tumor promoters and suppressors, ubiquitination is emerging as the key contributor and therefore a potential therapeutic target for melanoma. Herein, we summarize the current understanding of ubiquitination in melanoma, from mechanistic insights to clinical progress, and discuss the prospect of ubiquitination modification in melanoma treatment. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  13. Monoclonal antibodies that bind to common epitopes on the dengue virus type 2 nonstructural-1 and envelope glycoproteins display weak neutralizing activity and differentiated responses to virulent strains: implications for pathogenesis and vaccines.

    Science.gov (United States)

    Falconar, Andrew K I

    2008-03-01

    The abilities of monoclonal antibodies (MAbs) that bind to defined sequential epitopes on the dengue virus (DENV) nonstructural-1 (NS1) glycoproteins to cross-react with epitopes on the DENV envelope (E) glycoproteins were investigated. In this study, some of these MAbs cross-reacted with the DENV type 2 (DENV-2) E glycoprotein and with synthetic peptides representing X-ray crystallographically confirmed surface-exposed regions on this glycoprotein. MAb 1G5.3 cross-reacted with the flavivirus-conserved 101-WGNGCGLFG-109 fusion sequence, the 273-SSGNL-277 DENV-2 hinge region sequence, and the 156-GKHGKEIKIT-165 sequence of virulent DENV-2 strains. MAb 1G5.4-A1-C3 cross-reacted with the 67-NTTTESRCPT-76 and 156-GKHGKEIKIT-165 sequences of virulent DENV-2 strains, the 338-EIMDLDNRHV-347 sequence from a highly virulent DENV-2 (M2) strain, and two epitopes on a virulent DENV-3 strain (288-KMDKLELKG-296 and 323-RVEYRGEDAP-332), which all contained target ELK/KLE-type motifs (underlined). These MAbs showed reduced cross-reactions with the corresponding sequences from weakly pathogenic strains of all four DENV serotypes and had either no (MAb 1G5.4-A1-C3) or weak (MAb 1G5.3) neutralizing activity against them. MAb 1G5.3 more strongly neutralized DENV-2 strains with higher pathogenic capacities, while MAb 1G5.4-A1-C3 showed increasing neutralizing titers against the virulent DENV-3 strain and the moderately virulent and highly virulent (M2) DENV-2 strains. These cross-reactions with the E glycoprotein accord with the observation that MAb 1G5.3 caused dramatic and lethal antibody-enhanced replication (AER) of a DENV-2 strain in vivo. Together with in vivo AER studies of these DENV strains using MAb 1G5.4-A1-C3, these results may account for the increased pathogenic capacities of such strains, which is likely to have important implications for pathogenesis and vaccines.

  14. Genes contributing to prion pathogenesis

    DEFF Research Database (Denmark)

    Tamgüney, Gültekin; Giles, Kurt; Glidden, David V

    2008-01-01

    incubation times, indicating that the conversion reaction may be influenced by other gene products. To identify genes that contribute to prion pathogenesis, we analysed incubation times of prions in mice in which the gene product was inactivated, knocked out or overexpressed. We tested 20 candidate genes...... show that many genes previously implicated in prion replication have no discernible effect on the pathogenesis of prion disease. While most genes tested did not significantly affect survival times, ablation of the amyloid beta (A4) precursor protein (App) or interleukin-1 receptor, type I (Il1r1...

  15. Huntington disease: pathogenesis and treatment.

    Science.gov (United States)

    Dayalu, Praveen; Albin, Roger L

    2015-02-01

    Huntington disease (HD) is an autosomal dominant inherited neurodegenerative disease characterized by progressive motor, behavioral, and cognitive decline, culminating in death. It is caused by an expanded CAG repeat in the huntingtin gene. Even years before symptoms become overt, mutation carriers show subtle but progressive striatal and cerebral white matter atrophy by volumetric MRI. Although there is currently no direct treatment of HD, management options are available for several symptoms. A better understanding of HD pathogenesis, and more sophisticated clinical trials using newer biomarkers, may lead to meaningful treatments. This article reviews the current knowledge of HD pathogenesis and treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Immunomodulatory Role of Vitamin D in the Pathogenesis of Preeclampsia

    OpenAIRE

    Smith, Tyler A.; Kirkpatrick, Daniel R.; Kovilam, Oormila; Agrawal, Devendra K.

    2015-01-01

    Worldwide, preeclampsia is a significant health risk to both pregnant women and their unborn children. Despite scientific advances, the exact pathogenesis of preeclampsia is not yet fully understood. Meanwhile, the incidence of preeclampsia is expected to increase. A series of potential etiologies for preeclampsia have been identified, including endothelial dysfunction, immunological dysregulation, and trophoblastic invasion. In this literature review, we have critically reviewed existing lit...

  17. Major but differential decline in the incidence of Staphylococcus aureus bacteraemia in HIV-infected individuals from 1995 to 2007: a nationwide cohort study(*)

    DEFF Research Database (Denmark)

    Larsen, Mv; Harboe, Zb; Ladelund, S

    2012-01-01

    OBJECTIVES: Incidence rates (IRs) of Staphylococcus aureus bacteraemia (SAB) are known to be higher in HIV-infected individuals than in the general population, but have not been assessed in the era of highly active antiretroviral therapy. METHODS: From 1 January 1995 to 31 December 2007, all Dani...... and the smallest decline in IR, while men who have sex with men (MSM) had the largest decline over time. Among HIV-infected individuals, a latest CD4 count MSM). Low CD4 cell count and IDU were strong predictors of SAB among HIV-infected individuals....

  18. Neutron and gamma-ray emission double differential cross sections for the nuclear reaction by 1.5 GeV {pi}{sup +} incidence

    Energy Technology Data Exchange (ETDEWEB)

    Iga, Kiminori; Ishibashi, Kenji; Shigyo, Nobuhiro [Kyushu Univ., Fukuoka (Japan)] [and others

    1998-03-01

    Neutron and gamma-ray production double differential cross sections were measured for iron by the use of 1.5 GeV {pi}{sup +} mesons. The measured cross sections were compared with the calculated values by HETC-KFA2. For the neutrons, the calculated results deviate from the experimental data in the neutron energy region below 30 MeV. The calculated values of gamma-ray production agree with the experimental data at gamma-ray energies from 1 to 7 MeV within a factor of three. (author)

  19. Wheelchair incidents

    NARCIS (Netherlands)

    Drongelen AW van; Roszek B; Hilbers-Modderman ESM; Kallewaard M; Wassenaar C; LGM

    2002-01-01

    This RIVM study was performed to gain insight into wheelchair-related incidents with powered and manual wheelchairs reported to the USA FDA, the British MDA and the Dutch Center for Quality and Usability Research of Technical Aids (KBOH). The data in the databases do not indicate that incidents with

  20. Epigenetics and Colorectal Cancer Pathogenesis

    International Nuclear Information System (INIS)

    Bardhan, Kankana; Liu, Kebin

    2013-01-01

    Colorectal cancer (CRC) develops through a multistage process that results from the progressive accumulation of genetic mutations, and frequently as a result of mutations in the Wnt signaling pathway. However, it has become evident over the past two decades that epigenetic alterations of the chromatin, particularly the chromatin components in the promoter regions of tumor suppressors and oncogenes, play key roles in CRC pathogenesis. Epigenetic regulation is organized at multiple levels, involving primarily DNA methylation and selective histone modifications in cancer cells. Assessment of the CRC epigenome has revealed that virtually all CRCs have aberrantly methylated genes and that the average CRC methylome has thousands of abnormally methylated genes. Although relatively less is known about the patterns of specific histone modifications in CRC, selective histone modifications and resultant chromatin conformation have been shown to act, in concert with DNA methylation, to regulate gene expression to mediate CRC pathogenesis. Moreover, it is now clear that not only DNA methylation but also histone modifications are reversible processes. The increased understanding of epigenetic regulation of gene expression in the context of CRC pathogenesis has led to development of epigenetic biomarkers for CRC diagnosis and epigenetic drugs for CRC therapy

  1. Epigenetics and Colorectal Cancer Pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Bardhan, Kankana; Liu, Kebin, E-mail: Kliu@gru.edu [Department of Biochemistry and Molecular Biology, Medical College of Georgia, and Cancer Center, Georgia Regents University, Augusta, GA 30912 (United States)

    2013-06-05

    Colorectal cancer (CRC) develops through a multistage process that results from the progressive accumulation of genetic mutations, and frequently as a result of mutations in the Wnt signaling pathway. However, it has become evident over the past two decades that epigenetic alterations of the chromatin, particularly the chromatin components in the promoter regions of tumor suppressors and oncogenes, play key roles in CRC pathogenesis. Epigenetic regulation is organized at multiple levels, involving primarily DNA methylation and selective histone modifications in cancer cells. Assessment of the CRC epigenome has revealed that virtually all CRCs have aberrantly methylated genes and that the average CRC methylome has thousands of abnormally methylated genes. Although relatively less is known about the patterns of specific histone modifications in CRC, selective histone modifications and resultant chromatin conformation have been shown to act, in concert with DNA methylation, to regulate gene expression to mediate CRC pathogenesis. Moreover, it is now clear that not only DNA methylation but also histone modifications are reversible processes. The increased understanding of epigenetic regulation of gene expression in the context of CRC pathogenesis has led to development of epigenetic biomarkers for CRC diagnosis and epigenetic drugs for CRC therapy.

  2. [New knowledge of the pathogenesis of Crohn's disease].

    Science.gov (United States)

    Ambrůzová, B; Rédová, M; Michálek, J; Sachlová, M; Slabý, O

    2012-04-01

    Crohns disease is a complex chronic inflammatory disease of the gastrointestinal tract with multifactorial pathogenesis. Over the recent years, there has been rather a sharp increase in the incidence of Crohn's disease and, even though this disease had been known for some time, the cause remains unknown. Studies exploring genetic basis of Crohn's disease have provided new knowledge of the pathogenesis of this disease, suggesting that this may be associated with a failure of mechanisms behind symbiosis of gut microflora and intestinal mucosal immune system. Crohn's disease seems to be caused by inadequate immune response to intestinal flora in genetically predisposed individuals. Crohn's disease has been linked to a number of genes. Many of them are related to the modulation of non-specific immune response, defects of which are considered to be key in Crohn's disease pathogenesis. The aim of this review paper is to summarize the new knowledge on the pathogenesis of Crohn's disease at the level of polymorphisms of the NOD2, ATG16L1 genes and the IL23-Th17-lymfocytes signalling pathway genes and to consider further research directions in this disease.

  3. Measurement of neutron-production double-differential cross sections for 8 and 15 GeV proton incidence in the most-forward directions

    CERN Document Server

    Shigyo, N; Iwamoto, Y; Ishimoto, S; Kawasaki, Y; Takayama, Y; Tenzou, H; Ishibashi, K; Nakamoto, T; Numajiri, M; Meigo, S

    2002-01-01

    Neutron-production double-differential cross sections in the most- forward directions were measured for proton-induced reactions on Fe and Pb targets at 0.8 and 1.5 GeV. The experiment was performed at the pi 2 beam line of the 12 GeV proton synchrotron in High Energy Accelerator Research Organization (KEK). Neutrons were measured by time-of-flight technique with two different flight path lengths, i.e. 3.5 and 5.0 in at 0.8 and 1.5 GeV, respectively. NE213 liquid organic scintillators 12.7 cm in diameter and 12.7 cm in thickness were set at 0 degrees and 5 degrees as neutron detectors. For the improvement of the energy resolution, the scintillator at 0 degrees was connected with three Hamamatsu H2431 photomultipliers 5.1 cm in diameter. The neutron detection efficiencies were obtained by the SCINFUL-QMD code. The experimental data were compared with the calculation results of the intranuclear-cascade-evaporation and QMD models. (15 refs).

  4. Pathogenesis of oral FIV infection

    Science.gov (United States)

    Miller, Craig; Boegler, Karen; Carver, Scott; MacMillan, Martha; Bielefeldt-Ohmann, Helle

    2017-01-01

    Feline immunodeficiency virus (FIV) is the feline analogue of human immunodeficiency virus (HIV) and features many hallmarks of HIV infection and pathogenesis, including the development of concurrent oral lesions. While HIV is typically transmitted via parenteral transmucosal contact, recent studies prove that oral transmission can occur, and that saliva from infected individuals contains significant amounts of HIV RNA and DNA. While it is accepted that FIV is primarily transmitted by biting, few studies have evaluated FIV oral infection kinetics and transmission mechanisms over the last 20 years. Modern quantitative analyses applied to natural FIV oral infection could significantly further our understanding of lentiviral oral disease and transmission. We therefore characterized FIV salivary viral kinetics and antibody secretions to more fully document oral viral pathogenesis. Our results demonstrate that: (i) saliva of FIV-infected cats contains infectious virus particles, FIV viral RNA at levels equivalent to circulation, and lower but significant amounts of FIV proviral DNA; (ii) the ratio of FIV RNA to DNA is significantly higher in saliva than in circulation; (iii) FIV viral load in oral lymphoid tissues (tonsil, lymph nodes) is significantly higher than mucosal tissues (buccal mucosa, salivary gland, tongue); (iv) salivary IgG antibodies increase significantly over time in FIV-infected cats, while salivary IgA levels remain static; and, (v) saliva from naïve Specific Pathogen Free cats inhibits FIV growth in vitro. Collectively, these results suggest that oral lymphoid tissues serve as a site for enhanced FIV replication, resulting in accumulation of FIV particles and FIV-infected cells in saliva. Failure to induce a virus-specific oral mucosal antibody response, and/or viral capability to overcome inhibitory components in saliva may perpetuate chronic oral cavity infection. Based upon these findings, we propose a model of oral FIV pathogenesis and suggest

  5. Pathogenesis of oral FIV infection.

    Directory of Open Access Journals (Sweden)

    Craig Miller

    Full Text Available Feline immunodeficiency virus (FIV is the feline analogue of human immunodeficiency virus (HIV and features many hallmarks of HIV infection and pathogenesis, including the development of concurrent oral lesions. While HIV is typically transmitted via parenteral transmucosal contact, recent studies prove that oral transmission can occur, and that saliva from infected individuals contains significant amounts of HIV RNA and DNA. While it is accepted that FIV is primarily transmitted by biting, few studies have evaluated FIV oral infection kinetics and transmission mechanisms over the last 20 years. Modern quantitative analyses applied to natural FIV oral infection could significantly further our understanding of lentiviral oral disease and transmission. We therefore characterized FIV salivary viral kinetics and antibody secretions to more fully document oral viral pathogenesis. Our results demonstrate that: (i saliva of FIV-infected cats contains infectious virus particles, FIV viral RNA at levels equivalent to circulation, and lower but significant amounts of FIV proviral DNA; (ii the ratio of FIV RNA to DNA is significantly higher in saliva than in circulation; (iii FIV viral load in oral lymphoid tissues (tonsil, lymph nodes is significantly higher than mucosal tissues (buccal mucosa, salivary gland, tongue; (iv salivary IgG antibodies increase significantly over time in FIV-infected cats, while salivary IgA levels remain static; and, (v saliva from naïve Specific Pathogen Free cats inhibits FIV growth in vitro. Collectively, these results suggest that oral lymphoid tissues serve as a site for enhanced FIV replication, resulting in accumulation of FIV particles and FIV-infected cells in saliva. Failure to induce a virus-specific oral mucosal antibody response, and/or viral capability to overcome inhibitory components in saliva may perpetuate chronic oral cavity infection. Based upon these findings, we propose a model of oral FIV pathogenesis

  6. Incidents analysis

    International Nuclear Information System (INIS)

    Francois, P.

    1996-01-01

    We undertook a study programme at the end of 1991. To start with, we performed some exploratory studies aimed at learning some preliminary lessons on this type of analysis: Assessment of the interest of probabilistic incident analysis; possibility of using PSA scenarios; skills and resources required. At the same time, EPN created a working group whose assignment was to define a new approach for analysis of incidents on NPPs. This working group gave thought to both aspects of Operating Feedback that EPN wished to improve: Analysis of significant incidents; analysis of potential consequences. We took part in the work of this group, and for the second aspects, we proposed a method based on an adaptation of the event-tree method in order to establish a link between existing PSA models and actual incidents. Since PSA provides an exhaustive database of accident scenarios applicable to the two most common types of units in France, they are obviously of interest for this sort of analysis. With this method we performed some incident analyses, and at the same time explores some methods employed abroad, particularly ASP (Accident Sequence Precursor, a method used by the NRC). Early in 1994 EDF began a systematic analysis programme. The first, transient phase will set up methods and an organizational structure. 7 figs

  7. Differential Dengue Tropism & Neutralization: Potential Mechanisms of Pathogenesis

    Science.gov (United States)

    2006-01-04

    the bite of infected Aedes mosquitoes. The primary vectors of dengue virus transmission include Aedes aegypti, A. albopictus , and A. polynesiensis...have found that the antibody response to candidate live dengue virus vaccines was enhanced in subjects previously immunized with a yellow fever virus...growth in Vero and C6/36 ( Aedes albopictus ) cells. The altered cell tropism correlated with a difference in entry kinetics, increased dependence on

  8. Nail psoriasis: clinical features, pathogenesis, differential diagnoses, and management

    Directory of Open Access Journals (Sweden)

    Haneke E

    2017-10-01

    Full Text Available Eckart Haneke1–4 1Department of Dermatology, Inselspital, University of Bern, Bern, Switzerland; 2Dermatology Practice Dermaticum, Freiburg, Germany; 3Centro de Dermatología Epidermis, Instituto CUF, Porto, Portugal; 4Department of Dermatology, University Hospital, Gent, Belgium Abstract: Psoriasis is the skin disease that most frequently affects the nails. Depending on the very nail structure involved, different clinical nail alterations can be observed. Irritation of the apical matrix results in psoriatic pits, mid-matrix involvement may cause leukonychia, whole matrix affection may lead to red lunulae or severe nail dystrophy, nail bed involvement may cause salmon spots, subungual hyperkeratosis, and splinter hemorrhages, and psoriasis of the distal nail bed and hyponychium causes onycholysis whereas that of the proximal nail fold causes psoriatic paronychia. The more extensive the involvement, the more severe is the nail destruction. Pustular psoriasis may be seen as yellow spots under the nail or, in case of acrodermatitis continua suppurativa, as an insidious progressive loss of the nail organ. Nail psoriasis has a severe impact on quality of life and may interfere with professional and other activities. Management includes patient counseling, avoidance of stress and strain to the nail apparatus, and different types of treatment. Topical therapy may be tried but is rarely sufficiently efficient. Perilesional injections with corticosteroids and methotrexate are often beneficial but may be painful and cannot be applied to many nails. All systemic treatments clearing widespread skin lesions usually also clear the nail lesions. Recently, biologicals were introduced into nail psoriasis treatment and found to be very effective. However, their use is restricted to severe cases due to high cost and potential systemic adverse effects. Keywords: nail psoriasis, etiology, pathology, quality of life, impact, treatment

  9. Epigenetic mechanisms in the pathogenesis of diabetic retinopathy.

    Science.gov (United States)

    Zeng, Jun; Chen, Baihua

    2014-01-01

    Diabetic retinopathy (DR), which arises as a result of an increasing incidence of diabetes mellitus, has gradually become a common disease. Due to its complex pathogenesis, the treatment means of DR are very limited. The findings of several studies have shown that instituting tight glycemic control in diabetic patients does not immediately benefit the progression of retinopathy, and the benefits of good control persist beyond the period of good glycemic control. This has led to the concept of persistent epigenetic changes. Epigenetics has now become an increasingly important area of biomedical research. Recently, important roles of various epigenetic mechanisms have been identified in the pathogenesis of diabetes and its complications. The aim of this review is to provide an overview of the epigenetics and epigenetic mechanisms in diabetes and diabetes complications, and the focus is on the emerging evidence for aberrant epigenetic mechanisms in DR. © 2014 S. Karger AG, Basel.

  10. Premature ovarian insufficiency: Pathogenesis and management

    Directory of Open Access Journals (Sweden)

    Anna J Fenton

    2015-01-01

    Full Text Available The term premature ovarian insufficiency (POI describes a continuum of declining ovarian function in a young woman, resulting in an earlier than average menopause. It is a term that reflects the variable nature of the condition and is substantially less emotive than the formerly used "premature ovarian failure" which signaled a single event in time. Contrary to the decline in the age of menarche seen over the last 3-4 decades there has been no similar change in the age of menopause. In developed nations, the average age for cessation of menstrual cycles is 50-52 years. The age is younger among women from developing nations. Much has been written about POI despite a lack of good data on the incidence of this condition. It is believed that 1% of women under the age of 40 years and 0.1% under the age of 30 years will develop POI. Research is increasingly providing information about the pathogenesis and treatments are being developed to better preserve ovarian function during cancer treatment and to improve fertility options. This narrative review summarizes the current literature to provide an approach to best practice management of POI.

  11. Molecular Pathogenesis of Neuromyelitis Optica

    Directory of Open Access Journals (Sweden)

    Simon A Broadley

    2012-10-01

    Full Text Available Neuromyelitis optica (NMO is a rare autoimmune disorder, distinct from multiple sclerosis, causing inflammatory lesions in the optic nerves and spinal cord. An autoantibody (NMO IgG against aquaporin-4 (AQP4, a water channel expressed on astrocytes is thought to be causative. Peripheral production of the antibody is triggered by an unknown process in genetically susceptible individuals. Anti-AQP4 antibody enters the central nervous system (CNS when the blood brain barrier is made permeable and has high affinity for orthogonal array particles of AQP4. Like other autoimmune diseases, Th17 cells and their effector cytokines (such as interleukin 6 have been implicated in pathogenesis. AQP4 expressing peripheral organs are not affected by NMO IgG, but the antibody causes extensive astrocytic loss in specific regions of the CNS through complement mediated cytotoxicity. Demyelination occurs during the inflammatory process and is probably secondary to oligodendrocyte apoptosis subsequent to loss of trophic support from astrocytes. Ultimately, extensive axonal injury leads to severe disability. Despite rapid advances in the understanding of NMO pathogenesis, unanswered questions remain, particularly with regards to disease mechanisms in NMO IgG seronegative cases. Increasing knowledge of the molecular pathology is leading to improved treatment strategies.

  12. Ion channelopathies and migraine pathogenesis.

    Science.gov (United States)

    Albury, Cassie L; Stuart, Shani; Haupt, Larisa M; Griffiths, Lyn R

    2017-08-01

    Migraine is a common neurological disorder that affects approximately 12-20% of the general adult population. Migraine pathogenesis is complex and not wholly understood. Molecular genetic investigations, imaging and biochemical studies, have unveiled a number of interconnected neurological pathways which seem to have a cause and effect component integral to its cause. Much weight of migraine attack initiation can be placed on the initial trigger and the pathways involved in its neuronal counter reaction. Ion channels play a large role in the generation, portrayal and mitigation of the brains response to external triggers. Several genetic studies have identified and implicated a number of ion channelopathy genes which may contribute to this generalised process. This review will focus on the genetics of migraine with particular emphasis placed on the potentially important role genes HEPH (responsible for iron transport and homeostasis) and KCNK18 (important for the transport and homeostasis of potassium) play in migraine cause.

  13. The pathogenesis of cardiac fibrosis.

    Science.gov (United States)

    Kong, Ping; Christia, Panagiota; Frangogiannis, Nikolaos G

    2014-02-01

    Cardiac fibrosis is characterized by net accumulation of extracellular matrix proteins in the cardiac interstitium, and contributes to both systolic and diastolic dysfunction in many cardiac pathophysiologic conditions. This review discusses the cellular effectors and molecular pathways implicated in the pathogenesis of cardiac fibrosis. Although activated myofibroblasts are the main effector cells in the fibrotic heart, monocytes/macrophages, lymphocytes, mast cells, vascular cells and cardiomyocytes may also contribute to the fibrotic response by secreting key fibrogenic mediators. Inflammatory cytokines and chemokines, reactive oxygen species, mast cell-derived proteases, endothelin-1, the renin/angiotensin/aldosterone system, matricellular proteins, and growth factors (such as TGF-β and PDGF) are some of the best-studied mediators implicated in cardiac fibrosis. Both experimental and clinical evidence suggests that cardiac fibrotic alterations may be reversible. Understanding the mechanisms responsible for initiation, progression, and resolution of cardiac fibrosis is crucial to design anti-fibrotic treatment strategies for patients with heart disease.

  14. Rosacea: Epidemiology, pathogenesis, and treatment

    Science.gov (United States)

    Rainer, Barbara M.; Kang, Sewon; Chien, Anna L.

    2017-01-01

    ABSTRACT Rosacea is a chronic relapsing inflammatory skin disease with a high prevalence among adults of Northern European heritage with fair skin. Symptoms present in various combinations and severity, often fluctuating between periods of exacerbation and remission. Based on morphological characteristics, rosacea is generally classified into four major subtypes: erythematotelangiectatic, papulopustular, phymatous, and ocular. Diverse environmental and endogenous factors have been shown to stimulate an augmented innate immune response and neurovascular dysregulation; however, rosacea's exact pathogenesis is still unclear. An evidence-based approach is essential in delineating differences between the many available treatments. Because of the diverse presentations of rosacea, approaches to treatment must be individualized based on the disease severity, quality-of-life implications, comorbidities, trigger factors, and the patient's commitment to therapy. PMID:29484096

  15. Pathogenesis of Idiopathic Pulmonary Fibrosis

    Science.gov (United States)

    Wolters, Paul J.; Collard, Harold R.; Jones, Kirk D.

    2014-01-01

    Idiopathic pulmonary fibrosis (IPF) is a fibrosing interstitial lung disease associated with aging that is characterized by the histopathological pattern of usual interstitial pneumonia. Although an understanding of the pathogenesis of IPF is incomplete, recent advances delineating specific clinical and pathologic features of IPF have led to better definition of the molecular pathways that are pathologically activated in the disease. In this review we highlight several of these advances, with a focus on genetic predisposition to IPF and how genetic changes, which occur primarily in epithelial cells, lead to activation of profibrotic pathways in epithelial cells. We then discuss the pathologic changes within IPF fibroblasts and the extracellular matrix, and we conclude with a summary of how these profibrotic pathways may be interrelated. PMID:24050627

  16. Etiology and Pathogenesis of Psoriasis.

    Science.gov (United States)

    Boehncke, Wolf-Henning

    2015-11-01

    Psoriasis is a common, chronic inflammatory skin disease most often appearing in the form of well-demarcated, scaly plaques. These lesions highlight the fundamental processes underlying its pathogenesis, namely, inflammation and epidermal hyperproliferation. Both phenomena are considered consequences of an intimate interplay between the innate and the adaptive immune system. This concept is supported by results of genetic studies, pointing toward the signaling pathways of nuclear factor-κB, interferon-γ, and interleukin (IL)-23 as well as antigen presentation as central axes of the psoriatic inflammation. Efficacy of biologics targeting tumor necrosis factor-α, IL-23, or IL-17 provides further evidence in favor of this model. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. The dynamics and pathogenesis of traumatic subdural hygromas

    International Nuclear Information System (INIS)

    Kopp, W.

    1988-01-01

    Of 2005 patients, who had suffered blunt skull trauma, 108 developed post-traumatic subdural hygromas (TSH). CT was used to observe the course of subdural hygromas not treated surgically, with particular reference to the time of their appearance and regression. The relative incidence of TSH, and of the severity of head trauma quanitified on a 5-grade scale was determined in different age groups. From the traumatic changes demonstrated on CT, some conclusions could be drawn regarding the pathogenesis. A hypothetical model has been developed which explains TSH as a result of shearing forces. (orig.) [de

  18. The role of adenoidal obstruction in the pathogenesis of Otitis media ...

    African Journals Online (AJOL)

    Background: Although adenoidectomy is generally applied in the treatment of otitis media with effusion (OME), there is still much debate about the role of adenoid in the pathogenesis of OME. The purpose of this study is to determine the incidence of OME in children with obstructive adenoid disease in comparison with ...

  19. Molecular Pathogenesis of MALT Lymphoma

    Directory of Open Access Journals (Sweden)

    Katharina Troppan

    2015-01-01

    Full Text Available Approximately 8% of all non-Hodgkin lymphomas are extranodal marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT, also known as MALT lymphoma, which was first described in 1983 by Isaacson and Wright. MALT lymphomas arise at a wide range of different extranodal sites, with the highest frequency in the stomach, followed by lung, ocular adnexa, and thyroid, and with a low percentage in the small intestine. Interestingly, at least 3 different, apparently site-specific, chromosomal translocations and missense and frameshift mutations, all pathway-related genes affecting the NF-κB signal, have been implicated in the development and progression of MALT lymphoma. However, these genetic abnormalities alone are not sufficient for malignant transformation. There is now increasing evidence suggesting that the oncogenic product of translocation cooperates with immunological stimulation in oncogenesis, that is, the association with chronic bacterial infection or autoaggressive process. This review mainly discusses MALT lymphomas in terms of their genetic aberration and association with chronic infections and summarizes recent advances in their molecular pathogenesis.

  20. Achondroplasia: Development, pathogenesis, and therapy.

    Science.gov (United States)

    Ornitz, David M; Legeai-Mallet, Laurence

    2017-04-01

    Autosomal dominant mutations in fibroblast growth factor receptor 3 (FGFR3) cause achondroplasia (Ach), the most common form of dwarfism in humans, and related chondrodysplasia syndromes that include hypochondroplasia (Hch), severe achondroplasia with developmental delay and acanthosis nigricans (SADDAN), and thanatophoric dysplasia (TD). FGFR3 is expressed in chondrocytes and mature osteoblasts where it functions to regulate bone growth. Analysis of the mutations in FGFR3 revealed increased signaling through a combination of mechanisms that include stabilization of the receptor, enhanced dimerization, and enhanced tyrosine kinase activity. Paradoxically, increased FGFR3 signaling profoundly suppresses proliferation and maturation of growth plate chondrocytes resulting in decreased growth plate size, reduced trabecular bone volume, and resulting decreased bone elongation. In this review, we discuss the molecular mechanisms that regulate growth plate chondrocytes, the pathogenesis of Ach, and therapeutic approaches that are being evaluated to improve endochondral bone growth in people with Ach and related conditions. Developmental Dynamics 246:291-309, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  1. Molecular Pathogenesis of MALT Lymphoma

    Science.gov (United States)

    Troppan, Katharina; Wenzl, Kerstin; Neumeister, Peter; Deutsch, Alexander

    2015-01-01

    Approximately 8% of all non-Hodgkin lymphomas are extranodal marginal zone B cell lymphoma of mucosa associated lymphoid tissue (MALT), also known as MALT lymphoma, which was first described in 1983 by Isaacson and Wright. MALT lymphomas arise at a wide range of different extranodal sites, with the highest frequency in the stomach, followed by lung, ocular adnexa, and thyroid, and with a low percentage in the small intestine. Interestingly, at least 3 different, apparently site-specific, chromosomal translocations and missense and frameshift mutations, all pathway-related genes affecting the NF-κB signal, have been implicated in the development and progression of MALT lymphoma. However, these genetic abnormalities alone are not sufficient for malignant transformation. There is now increasing evidence suggesting that the oncogenic product of translocation cooperates with immunological stimulation in oncogenesis, that is, the association with chronic bacterial infection or autoaggressive process. This review mainly discusses MALT lymphomas in terms of their genetic aberration and association with chronic infections and summarizes recent advances in their molecular pathogenesis. PMID:25922601

  2. The Pathogenesis of Lupus Nephritis

    Science.gov (United States)

    Lech, Maciej

    2013-01-01

    Lupus nephritis is an immune complex GN that develops as a frequent complication of SLE. The pathogenesis of lupus nephritis involves a variety of pathogenic mechanisms. The extrarenal etiology of systemic lupus is based on multiple combinations of genetic variants that compromise those mechanisms normally assuring immune tolerance to nuclear autoantigens. This loss of tolerance becomes clinically detectable by the presence of antinuclear antibodies. In addition, nucleic acids released from netting or apoptotic neutrophils activate innate and adaptive immunity via viral nucleic acid-specific Toll-like receptors. Therefore, many clinical manifestations of systemic lupus resemble those of viral infection. In lupus, endogenous nuclear particles trigger IFN-α signaling just like viral particles during viral infection. As such, dendritic cells, T helper cells, B cells, and plasma cells all contribute to the aberrant polyclonal autoimmunity. The intrarenal etiology of lupus nephritis involves antibody binding to multiple intrarenal autoantigens rather than the deposition of circulating immune complexes. Tertiary lymphoid tissue formation and local antibody production add to intrarenal complement activation as renal immunopathology progresses. Here we provide an update on the pathogenic mechanisms that lead to lupus nephritis and provide the rationale for the latest and novel treatment strategies. PMID:23929771

  3. Pathogenesis of ovarian cancer: current perspectives | Chesang ...

    African Journals Online (AJOL)

    Objective: To present a review of current knowledge of the pathogenesis of ovarian cancer and its clinical implications. Data Source: Extensive literature search was conducted to identify relevant studies. Study Selection: Studies in the English language about or related to pathogenesis of ovarian cancer were selected.

  4. Significance of Inactivated Genes in Leukemia: Pathogenesis and Prognosis

    Science.gov (United States)

    Heidari, Nazanin; Abroun, Saeid; Bertacchini, Jessika; Vosoughi, Tina; Rahim, Fakher; Saki, Najmaldin

    2017-01-01

    Epigenetic and genetic alterations are two mechanisms participating in leukemia, which can inactivate genes involved in leukemia pathogenesis or progression. The purpose of this review was to introduce various inactivated genes and evaluate their possible role in leukemia pathogenesis and prognosis. By searching the mesh words “Gene, Silencing AND Leukemia” in PubMed website, relevant English articles dealt with human subjects as of 2000 were included in this study. Gene inactivation in leukemia is largely mediated by promoter’s hypermethylation of gene involving in cellular functions such as cell cycle, apoptosis, and gene transcription. Inactivated genes, such as ASPP1, TP53, IKZF1 and P15, may correlate with poor prognosis in acute lymphoid leukemia (ALL), chronic lymphoid leukemia (CLL), chronic myelogenous leukemia (CML) and acute myeloid leukemia (AML), respectively. Gene inactivation may play a considerable role in leukemia pathogenesis and prognosis, which can be considered as complementary diagnostic tests to differentiate different leukemia types, determine leukemia prognosis, and also detect response to therapy. In general, this review showed some genes inactivated only in leukemia (with differences between B-ALL, T-ALL, CLL, AML and CML). These differences could be of interest as an additional tool to better categorize leukemia types. Furthermore; based on inactivated genes, a diverse classification of Leukemias could represent a powerful method to address a targeted therapy of the patients, in order to minimize side effects of conventional therapies and to enhance new drug strategies. PMID:28580304

  5. An Odyssey to Viral Pathogenesis.

    Science.gov (United States)

    Oldstone, Michael B A

    2016-05-23

    polishing by Karl Habel (a superb senior virologist who left the National Institutes of Health and came to Scripps), and the gifted postdoctoral fellows who joined my laboratory over four decades form the log of my scientific voyage. The strong friendships and collaborations developed with other young but growing experimentalists like Bernie Fields and Abner Notkins are the fabric of the tale I will weave and were pivotal in the establishment of viral pathogenesis as a discipline.

  6. Abnormal epidermal barrier in the pathogenesis of psoriasis.

    Science.gov (United States)

    Wolf, Ronni; Orion, Edith; Ruocco, Eleonora; Ruocco, Vincenzo

    2012-01-01

    Almost 2 decades ago, Williams and Elias suggested a unifying concept for the pathogenesis of disorders of cornification, according to which the integrity of the epidermal barrier and its effective function is an important factor in the regulation of epidermal DNA synthesis. Interference with the barrier integrity or function will result in epidermal hyperplasia and may be the primary event leading to hyperproliferative skin diseases, such as psoriasis. We have analyzed alterations to several structures of the epidermal barrier that might be responsible for barrier dysfunction and thus lead to hyperproliferation of the epidermis in an attempt to repair the barrier and, as a result, might be inducers of psoriasis. There are several convincing reports indicating that inhibiting of epidermal transglutaminase may lead to epidermal hyperproliferation and that this stimulus might trigger psoriasis among genetically predisposed patients. Disturbance of epidermal barrier function caused by derangement of lipid or cholesterol or ceramide synthesis leads to increased DNA synthesis and epidermal hyperplasia and as a result might be an inducer of psoriasis. We could find little evidence to show that defective defense of the epidermis or an abnormal response of it to bacteria plays a role in the pathogenesis of psoriasis. Accumulating data indicate that there is an association of psoriasis and mutations of genes within the epidermal differentiation complex, which are crucial for the development, maturation, cornification, cross-linking, and terminal differentiation of the epidermis, called psoriasis susceptibility locus 4. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Microbial pathogenesis and biofilm development

    DEFF Research Database (Denmark)

    Reisner, A.; Høiby, N.; Tolker-Nielsen, Tim

    2004-01-01

    cycles of different microorganisms will eventually lead to improved treatments. Several bacteria have evolved specific strategies for virulent colonization of humans in addition to their otherwise harmless establishment as environmental inhabitants. In many such cases biofilm development seems to play...... been termed 'maturation', which is thought to be mediated by a differentiation process. Maturation into late stages of biofilm development resulting in stable and robust structures may require the formation of a matrix of extracellular polymeric substances (EPS), which are most often assumed to consist...... permit bacterial growth to occur. In laboratory model systems the growth of the surface-associated bacteria is supported by the nutrient supply in the moving or standing liquid. A benchmark of biofilm formation by several organisms in vitro is the development of three-dimensional structures that have...

  8. Current understanding in pathogenesis of atopic dermatitis

    Directory of Open Access Journals (Sweden)

    Tess McPherson

    2016-01-01

    Full Text Available There have been advances in our understanding of the complex pathogenesis of atopic eczema over the past few decades. This article examines the multiple factors which are implicated in this process.

  9. How can macroscopically normal peritoneum contribute to the pathogenesis of endometriosis?

    Science.gov (United States)

    Fassbender, Amelie; Overbergh, Lut; Verdrengh, Eefje; Kyama, Cleophas M; Vodolazakaia, Alexandra; Bokor, Attila; Meuleman, Christel; Peeraer, Karen; Tomassetti, Carla; Waelkens, Etienne; Mathieu, Chantal; D'Hooghe, Thomas

    2011-09-01

    This study indicates that the immunobiology of macroscopically normal peritoneum is relevant to understand the pathogenesis of endometriosis. Peritoneal interleukin 6, interleukin 12, and ferritin were differentially expressed in women with and without endometriosis. Copyright © 2011 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  10. Toll-like receptors in the pathogenesis of human B cell malignancies

    NARCIS (Netherlands)

    Isaza-Correa, Johana M.; Liang, Zheng; van den Berg, Anke; Diepstra, Arjan; Visser, Lydia

    2014-01-01

    Toll-like receptors (TLRs) are important players in B-cell activation, maturation and memory and may be involved in the pathogenesis of B-cell lymphomas. Accumulating studies show differential expression in this heterogeneous group of cancers. Stimulation with TLR specific ligands, or agonists of

  11. Autophagy in lung disease pathogenesis and therapeutics

    Directory of Open Access Journals (Sweden)

    Stefan W. Ryter

    2015-04-01

    Full Text Available Autophagy, a cellular pathway for the degradation of damaged organelles and proteins, has gained increasing importance in human pulmonary diseases, both as a modulator of pathogenesis and as a potential therapeutic target. In this pathway, cytosolic cargos are sequestered into autophagosomes, which are delivered to the lysosomes where they are enzymatically degraded and then recycled as metabolic precursors. Autophagy exerts an important effector function in the regulation of inflammation, and immune system functions. Selective pathways for autophagic degradation of cargoes may have variable significance in disease pathogenesis. Among these, the autophagic clearance of bacteria (xenophagy may represent a crucial host defense mechanism in the pathogenesis of sepsis and inflammatory diseases. Our recent studies indicate that the autophagic clearance of mitochondria, a potentially protective program, may aggravate the pathogenesis of chronic obstructive pulmonary disease by activating cell death programs. We report similar findings with respect to the autophagic clearance of cilia components, which can contribute to airways dysfunction in chronic lung disease. In certain diseases such as pulmonary hypertension, autophagy may confer protection by modulating proliferation and cell death. In other disorders, such as idiopathic pulmonary fibrosis and cystic fibrosis, impaired autophagy may contribute to pathogenesis. In lung cancer, autophagy has multiple consequences by limiting carcinogenesis, modulating therapeutic effectiveness, and promoting tumor cell survival. In this review we highlight the multiple functions of autophagy and its selective autophagy subtypes that may be of significance to the pathogenesis of human disease, with an emphasis on lung disease and therapeutics.

  12. Onychomycosis: Pathogenesis, Diagnosis, and Management

    Science.gov (United States)

    Elewski, Boni E.

    1998-01-01

    Although not life-threatening, onychomycosis (a fungal infection of the nail, usually caused by a dermatophyte) constitutes an important public health problem because of its high prevalence (about 10% of the U.S. population) and associated morbidity. The disease can have certain negative consequences for patients, such as pain, and can potentially undermine work and social lives. This review discusses the etiology, classification, diagnosis, and treatment of onychomycosis. Four types of onychomycosis are recognized based on the site and pattern of fungal invasion. Dermatophyte fungi are the predominant pathogens, but yeasts (especially Candida albicans) and nondermatophyte molds may also be implicated. Accurate diagnosis requires direct microscopy and fungal culture. The differential diagnosis includes psoriasis, lichen planus, onychogryphosis, and nail trauma. Onychomycosis is more difficult to treat than most dermatophytoses because of the inherent slow growth of the nail. Older antifungal agents (ketoconazole and griseofulvin) are unsuitable for onychomycosis because of their relatively poor efficacy and potential adverse effects. Three recently developed antimycotic agents (fluconazole, itraconazole, and terbinafine) offer high cure rates and good safety profiles. In addition, the short treatment times (<3 months) and intermittent dosing schedules are likely to enhance compliance and reduce the costs of therapy. PMID:9665975

  13. Animal models of papillomavirus pathogenesis.

    Science.gov (United States)

    Campo, M Saveria

    2002-11-01

    Tumorigenesis due to papillomavirus (PV) infection was first demonstrated in rabbits and cattle early last century. Despite the evidence obtained in animals, the role of viruses in human cancer was dismissed as irrelevant. It took a paradigm shift in the late 1970s for some viruses to be recognised as 'tumour viruses' in humans, and in 1995, more than 60 years after Rous's first demonstration of CRPV oncogenicity, WHO officially declared that 'HPV-16 and HPV-18 are carcinogenic to humans'. Experimental studies with animal PVs have been a determining factor in this decision. Animal PVs have been studied both as agents of disease in animals and as models of human PV infection. In addition to the study of PV infection in whole animals, in vitro studies with animal PV proteins have contributed greatly to the understanding of the mechanisms of cell transformation. Animal PVs cause distressing diseases in both farm and companion animals, such as teat papillomatosis in cattle, equine sarcoids and canine oral papillomatosis and there is an urgent need to understand the pathogenesis of these problematic infections. Persistent and florid teat papillomatosis in cows can lead to mastitis, prevent the suckling of calves and make milking impossible; heavily affected animals are culled and so occasionally are whole herds. Equine sarcoids are often recurrent and untreatable and lead to loss of valuable animals. Canine oral papillomatosis can be very extensive and persistent and lead to great distress. Thus the continuing research in the biology of animal PVs is amply justified. BPVs and CRPV have been for many years the model systems with which to study the biology of HPV. Induction of papillomas and their neoplastic progression has been experimentally demonstrated and reproduced in cattle and rabbits, and virus-cofactor interactions have been elucidated in these systems. With the advancements in molecular and cell culture techniques, the direct study of HPV has become less

  14. Diet, gut microbes, and the pathogenesis of inflammatory bowel diseases.

    Science.gov (United States)

    Dolan, Kyle T; Chang, Eugene B

    2017-01-01

    The rising incidence of inflammatory bowel diseases in recent decades has notably paralleled changing lifestyle habits in Western nations, which are now making their way into more traditional societies. Diet plays a key role in IBD pathogenesis, and there is a growing appreciation that the interaction between diet and microbes in a susceptible person contributes significantly to the onset of disease. In this review, we examine what is known about dietary and microbial factors that promote IBD. We summarize recent findings regarding the effects of diet in IBD epidemiology from prospective population cohort studies, as well as new insights into IBD-associated dysbiosis. Microbial metabolism of dietary components can influence the epithelial barrier and the mucosal immune system, and understanding how these interactions generate or suppress inflammation will be a significant focus of IBD research. Our knowledge of dietary and microbial risk factors for IBD provides important considerations for developing therapeutic approaches through dietary modification or re-shaping the microbiota. We conclude by calling for increased sophistication in designing studies on the role of diet and microbes in IBD pathogenesis and disease resolution in order to accelerate progress in response to the growing challenge posed by these complex disorders. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  15. MicroRNAs in the pathogenesis of malignant melanoma

    DEFF Research Database (Denmark)

    Glud, M; Gniadecki, R

    2013-01-01

    Cutaneous malignant melanoma is the most aggressive and lethal form of skin cancer. Over the past decades, its incidence has been increasing by 3-8% per year in western countries while mortality has stabilized. Melanoma is a heterogenous disease and can be subclassified based on distinct clinical...... to play a crucial role in cell homeostasis and carcinogenesis. MiRNAs might prove to be powerful cancer biomarkers and future therapeutic targets. In this review, we focused on the miRNA involvement in four molecular pathways known to be deregulated in malignant melanoma, including the RAS...... characteristics, histopathological features and mutation patterns within NRAS and BRAF genes. Recent data indicate that microRNAs (miRNAs) are involved in the pathogenesis of malignant melanoma. MiRNAs are small, non-coding, regulatory RNA molecules expressed in a tissue and cell specific manner and are known...

  16. Trichomonas vaginalis Pathogenesis: a Narrative Review

    Directory of Open Access Journals (Sweden)

    Zahra Arab-Mazar

    2015-07-01

    Full Text Available In the latest articles which were published during 2013-2014, Trichomonas vaginalis (T. vaginalis was mentioned as a neglected sexual transmission disease (STD, while the exact mechanism of its pathogenesis has not been cleared yet. Although trichomonasiasis is easy curable, there is concern that resistance to drug are increasing. This common infection as concerning the important public health implications needs more research to be done for understanding the diagnosis, treatment, immunology and pathogenesis. In this review we searched all valuable and relevant information considering the pathogenesis of T. vaginalis. We referred to the information databases of Medline, PubMed, Scopus and Google scholar. The used keywords were the combinations of T. vaginalis and words associated with pathogenicity. This review discusses the host-parasite interaction and pathogenicity of this parasite.

  17. Bordetella pertussis pathogenesis: current and future challenges

    Science.gov (United States)

    Melvin, Jeffrey A.; Scheller, Erich V.; Miller, Jeff F.; Cotter, Peggy A.

    2014-01-01

    Pertussis, or whooping cough, has recently reemerged as a major public health threat despite high levels of vaccination against the etiological agent, Bordetella pertussis. In this Review, we describe the pathogenesis of this disease, with a focus on recent mechanistic insights into virulence factor function. We also discuss the changing epidemiology of pertussis and the challenges of vaccine development. Despite decades of research, many aspects of B. pertussis physiology and pathogenesis remain poorly understood. We highlight knowledge gaps that must be addressed to develop improved vaccines and therapeutic strategies. PMID:24608338

  18. Incidents malignant neoplasias maxillofacial area.

    Science.gov (United States)

    Goiato, Marcelo Coelho; Haddad, Marcela Filié; dos Santos, Daniela Micheline; Pesqueira, Aldiéres Alves; Filho, Humberto Gennari; Pellizzer, Eduardo Piza

    2009-07-01

    Cancer is regarded as abnormal cellular multiplication; it is not controlled by the organism, and its cells present a differentiated DNA. Initially, the disease does not show clinical signs, but it can be diagnosed by laboratory examinations. When tumors are present in the maxillofacial area, the carrier can lose structures in this area, resulting to the carrier's social environment exclusion. This article aims to show incidences and causes of malignant neoplasias in the maxillofacial area.

  19. Pathogenesis of thyroid autoimmune disease: the role of cellular mechanisms.

    Science.gov (United States)

    Ramos-Leví, Ana Maria; Marazuela, Mónica

    2016-10-01

    Hashimoto's thyroiditis (HT) and Graves' disease (GD) are two very common organ-specific autoimmune diseases which are characterized by circulating antibodies and lymphocyte infiltration. Although humoral and cellular mechanisms have been classically considered separately in the pathogenesis of autoimmune thyroid diseases (AITD), recent research suggests a close reciprocal relationship between these two immune pathways. Several B- and T-cell activation pathways through antigen-presenting cells (APCs) and cytokine production lead to specific differentiation of T helper (Th) and T regulatory (Treg) cells. This review will focus on the cellular mechanisms involved in the pathogenesis of AITD. Specifically, it will provide reasons for discarding the traditional simplistic dichotomous view of the T helper type 1 and 2 pathways (Th1/Th2) and will focus on the role of the recently characterized T cells, Treg and Th17 lymphocytes, as well as B lymphocytes and APCs, especially dendritic cells (DCs). Copyright © 2016 SEEN. Publicado por Elsevier España, S.L.U. All rights reserved.

  20. Salivary proteomics in lichen planus: A relationship with pathogenesis?

    Science.gov (United States)

    Souza, M M; Florezi, G P; Nico, Mms; de Paula, F; Paula, F M; Lourenço, S V

    2018-01-30

    Oral lichen planus is a chronic, T-cell-mediated, inflammatory disease that affects the oral cavity. The oral lichen planus pathogenesis is still unclear, however, the main evidence is that the mechanisms of activation of different T lymphocyte pathway induce apoptosis with an increase in Th1 and Th17 subtypes cells, triggered by the release of cytokines. This study analysed saliva proteomics to identify protein markers that might be involved in the pathogenesis and development of the disease. Proteins differentially expressed by oral lichen planus and healthy controls were screened using mass spectrometry; the proteins found in oral lichen planus were subjected to bioinformatics analysis, including gene ontology and string networks analysis. The multiplex analysis validation allowed the correlation between the proteins identified and the involved cytokines in Th17 response. One hundred and eight proteins were identified in oral lichen planus, of which 17 proteins showed a high interaction between them and indicated an association with the disease. Expression of these proteins was correlated with the triggering of cytokines, more specifically the Th17 cells. Proteins, such as S100A8, S100A9, haptoglobin, can trigger cytokines and might be associated with a pathological function and antioxidant activities in oral lichen planus. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd. All rights reserved.

  1. Comparative genomics reveals multistep pathogenesis of E2A-PBX1 acute lymphoblastic leukemia

    OpenAIRE

    Duque-Afonso, Jesús; Feng, Jue; Scherer, Florian; Lin, Chiou-Hong; Wong, Stephen H.K.; Wang, Zhong; Iwasaki, Masayuki; Cleary, Michael L.

    2015-01-01

    Acute lymphoblastic leukemia (ALL) is the most common childhood cancer; however, its genetic diversity limits investigation into the molecular pathogenesis of disease and development of therapeutic strategies. Here, we engineered mice that conditionally express the E2A-PBX1 fusion oncogene, which results from chromosomal translocation t(1;19) and is present in 5% to 7% of pediatric ALL cases. The incidence of leukemia in these mice varied from 5% to 50%, dependent on the Cre-driving promoter ...

  2. Influenza A virus-induced polymorphonuclear leukocyte dysfunction in the pathogenesis of experimental pneumococcal otitis media.

    OpenAIRE

    Abramson, J S; Giebink, G S; Quie, P G

    1982-01-01

    The role of influenza A virus-induced polymorphonuclear leukocyte and eustachian tube dysfunction in the pathogenesis of acute purulent otitis media was studied in chinchillas. Polymorphonuclear leukocyte function, middle ear pressure, and the incidence of pneumococcal otitis media were observed after intranasal inoculation with influenza A virus, Streptococcus pneumoniae, or both. Results showed that depressed negative middle ear pressure and polymorphonuclear leukocyte chemiluminescence and...

  3. Comparative genomics reveals multistep pathogenesis of E2A-PBX1 acute lymphoblastic leukemia.

    Science.gov (United States)

    Duque-Afonso, Jesús; Feng, Jue; Scherer, Florian; Lin, Chiou-Hong; Wong, Stephen H K; Wang, Zhong; Iwasaki, Masayuki; Cleary, Michael L

    2015-09-01

    Acute lymphoblastic leukemia (ALL) is the most common childhood cancer; however, its genetic diversity limits investigation into the molecular pathogenesis of disease and development of therapeutic strategies. Here, we engineered mice that conditionally express the E2A-PBX1 fusion oncogene, which results from chromosomal translocation t(1;19) and is present in 5% to 7% of pediatric ALL cases. The incidence of leukemia in these mice varied from 5% to 50%, dependent on the Cre-driving promoter (Cd19, Mb1, or Mx1) used to induce E2A-PBX1 expression. Two distinct but highly similar subtypes of B cell precursor ALLs that differed by their pre-B cell receptor (pre-BCR) status were induced and displayed maturation arrest at the pro-B/large pre-B II stages of differentiation, similar to human E2A-PBX1 ALL. Somatic activation of E2A-PBX1 in B cell progenitors enhanced self-renewal and led to acquisition of multiple secondary genomic aberrations, including prominent spontaneous loss of Pax5. In preleukemic mice, conditional Pax5 deletion cooperated with E2A-PBX1 to expand progenitor B cell subpopulations, increasing penetrance and shortening leukemia latency. Recurrent secondary activating mutations were detected in key signaling pathways, most notably JAK/STAT, that leukemia cells require for proliferation. These data support conditional E2A-PBX1 mice as a model of human ALL and suggest targeting pre-BCR signaling and JAK kinases as potential therapeutic strategies.

  4. [Pathogenesis of lipodystrophy and metabolic syndromes associated with HIV infection].

    Science.gov (United States)

    Muñoz-Sanz, Agustín; Rodríguez-Vidigal, Francisco F; Domingo, Pere

    2006-09-30

    Lipodystrophy, and the metabolic alterations (dislipemia, insulin-resistance) associated with human immunodeficiency virus (HIV) infection, is a multifactorial syndrome due to the interaction of host related factors (cellular immune status, diet, gene mutations), viral factors (cytokine synthesis, polyunsaturated fatty acid or PUFA depletion), and pharmacological effects (mitochondrial DNA-polymerase inhibition, lipolysis inhibition, adiponectin synthesis reduction). HIV probably modifies the adipocyte differentiation and the lipid metabolism. This retroviral effect is mediated by proinflammatory cytokines (tumor necrosis factor) and the participation of other factors (drugs, diet), all in the context of a particular host genetic setting. The adipocyte (and several cellular receptors, fatty acids, membrane proteins, and cytokines) plays a central role in the pathogenesis of HIV-associated lipodystrophy.

  5. Pathogenesis of helicobacter pylori infection involves interaction ...

    African Journals Online (AJOL)

    It is now clear that both bacterial virulence factors and host susceptibility play key roles in disease pathogenesis. The nature and levels of these interactions between these major factors has been found to determine the spectrum of clinical outcomes of the infection with this important bacterium. Virulence factors include the ...

  6. Immunological pathogenesis of inflammatory bowel disease

    Directory of Open Access Journals (Sweden)

    Seung Hoon Lee

    2018-01-01

    Full Text Available Inflammatory bowel disease (IBD is a chronic inflammatory state of the gastrointestinal tract and can be classified into 2 main clinical phenomena: Crohn's disease (CD and ulcerative colitis (UC. The pathogenesis of IBD, including CD and UC, involves the presence of pathogenic factors such as abnormal gut microbiota, immune response dysregulation, environmental changes, and gene variants. Although many investigations have tried to identify novel pathogenic factors associated with IBD that are related to environmental, genetic, microbial, and immune response factors, a full understanding of IBD pathogenesis is unclear. Thus, IBD treatment is far from optimal, and patient outcomes can be unsatisfactory. As result of massive studying on IBD, T helper 17 (Th17 cells and innate lymphoid cells (ILCs are investigated on their effects on IBD. A recent study of the plasticity of Th17 cells focused primarily on colitis. ILCs also emerging as novel cell family, which play a role in the pathogenesis of IBD. IBD immunopathogenesis is key to understanding the causes of IBD and can lead to the development of IBD therapies. The aim of this review is to explain the pathogenesis of IBD, with a focus on immunological factors and therapies.

  7. Pathogenesis of nosocomial infections with Enterococcus faecalis

    NARCIS (Netherlands)

    Waar, Karola

    2004-01-01

    In this thesis, we analyzed the role of the different virulence factors of E. faecalis known in literature in the pathogenesis of infections. We investigated the prevalence of virulence factors in E. faecalis isolates from different hosts as well as their role in biomaterial related infections. The

  8. Frontoethmoidal encephaloceles, a study of their pathogenesis

    NARCIS (Netherlands)

    Hoving, Eelco; Vermeij-Keers, C

    1997-01-01

    A prospective clinical study of 30 patients with frontoethmoidal encephaloceles was performed in order to find support for a proposed theory concerning its pathogenesis, based on a previously performed embryological study and relevant findings in the literature. According to this proposed theory the

  9. Fungal Plant Pathogenesis Mediated by Effectors

    NARCIS (Netherlands)

    Wit, de P.J.G.M.; Testa, A.; Oliver, R.

    2016-01-01

    The interactions between fungi and plants encompass a spectrum of ecologies ranging from saprotrophy (growth on dead plant material) through pathogenesis (growth of the fungus accompanied by disease on the plant) to symbiosis (growth of the fungus with growth enhancement of the plant). We consider

  10. Pathogenesis of bovine spongiform encephalopathy in sheep

    NARCIS (Netherlands)

    Keulen, van L.J.M.; Vromans, M.E.W.; Dolstra, C.H.; Bossers, A.; Zijderveld, van F.G.

    2008-01-01

    The pathogenesis of bovine spongiform encephalopathy (BSE) in sheep was studied by immunohistochemical detection of scrapie-associated prion protein (PrPSc) in the gastrointestinal, lymphoid and neural tissues following oral inoculation with BSE brain homogenate. First accumulation of PrPSc was

  11. [Purulent corneal ulcers: etiology, pathogenesis, classification].

    Science.gov (United States)

    Kasparova, Evg A; Kasparova, Evg A

    2015-01-01

    Advanced purulent corneal ulcer, as well as abscess, is a serious vision-threatening condition notable for its fulminant course and possible loss of the eye due to endophthalmitis. Its leading causes, pathogenesis, and classifications are described and analyzed in this paper.

  12. Cavitating pulmonary tuberculosis in children: correlating radiology with pathogenesis

    International Nuclear Information System (INIS)

    Griffith-Richards, S.B.; Andronikou, Savvas; Przybojewski, Stefan J.; Strachan, Melanie; Vadachia, Yousuf; Kathan, David L.; Goussard, Pierre; Gie, Robert P.

    2007-01-01

    Cavitating pulmonary tuberculosis (PTB) is generally known as a disease of adults, with children typically having features of primary PTB. To group children with PTB and cavities according to possible pathogenesis by evaluating the clinical and radiological findings. The clinical and radiological findings in ten randomly selected children with PTB and cavitations on chest radiographs were retrospectively reviewed and evaluated. Three groups emerged: group 1 (four children) had cavities, usually single and unilateral in the classic upper lobe distribution of postprimary PTB; group 2 (three children) developed progressive primary spread of disease with extensive and bilateral pulmonary cavities; and group 3 (three children) developed cavities secondary to airway obstruction by mediastinal lymph nodes with consequent distal collapse and consolidation. Children in group 1 responded well to treatment and had unremarkable recoveries. Children in group 2 were all below 2 years of age with complicated recoveries. Children in group 3 had frequent complications resulting in one fatality. Cavities in PTB in children may arise by one of three possible mechanisms with a relatively equal incidence. A study is underway to determine the incidence of cavity formation associated with mediastinal lymphadenopathy and airway obstruction. (orig.)

  13. Evaluating the role of the hepatitis C virus in the pathogenesis of Hodgkin's lymphoma in Egyptian patients

    Directory of Open Access Journals (Sweden)

    Aml S. Nasr

    2012-01-01

    Conclusion In Conclusion , the Results of our study show that there is a higher incidence of HCV infection in B-NHL patients compared with apparently healthy individuals. This supports the suspected role of HCV in the pathogenesis and etiology of B-NHL.

  14. [Pathogenesis and therapy of hydronephrosis after hematopoietic stem cell transplantation].

    Science.gov (United States)

    Yu, Lu-ping; Xu, Tao; Huang, Xiao-bo; Wang, Xiao-feng

    2014-08-18

    To investigate the pathogenesis and therapy of hydronephrosis after hematopoietic stem cell transplantation (HSCT). From March 2004 to March 2014, 23 patients with hydronephrosis after HSCT were identified. With these data, the pathogenesis of hydronephrosis after HSCT were analyzed. According to the surgical intervention of hydronephrosis and ureteral dialation of ureteral stricture, the patients were divided into two groups, rank-sum test and exact probability test were used to evaluate whether there were significant differences in the time of hemorrhagic cystitis (HC) occurred, ureteritis and viremia. HC, ureteritis, ureteral stenosis were all the causes of hydronephrosis after HSCT. In this study, 69.6% (16/23) of the patients suffered from HSCT were cured by conservative treatment, 30.4% (7/23) by surgical intervention, and 13.0% (3/23) by insertion DJ stent or nephrostomy.Of the patients [17.4% (4/23)] who suffered ureteral stenosis, 2 were cured after the balloon dialation of ureter, 1 needed DJ tube long-term insertion, and 1 was still followed-up. rank-sum test and exact probability test results showed that the patients who needed surgical intervention might suffer from HC later than other patients, and their incidences of viremia and ureteritis were higher, but the differences between the two groups were not statistically significant (P = 0.524, P = 0.169, and P = 0.124, respectively). The results also showed that the ureteritis incidences of the patients who suffered from ureteral stricture and needed ureteral dialation were higher than that of the other patients, and the difference between the two groups was statistically significant (P = 0.024). The patients who needed ureteral dialation suffered from HC later and their incidences of viremia was higher, but the differences between the two groups were not statistically significant (P = 0.73 and P = 0.27). HC, ureteritis and ureteral stenosis may cause hydronephrosis after HSCT. Patients may treated by

  15. Differential SPR immunosensing

    NARCIS (Netherlands)

    Berger, Charles E.H.; Berger, C.E.H.; Greve, Jan

    2000-01-01

    In this work we describe a surface plasmon resonance (SPR) sensor with a differential detection of the SPR angle, and demonstrate it. The angle of incidence is modulated by a simple piezo-electric actuator, and the reflectance signal is measured with a lockin-amplifier. When the conditions for SPR

  16. [The etiology and pathogenesis of Sprengel's disease].

    Science.gov (United States)

    Skopichenko, D N

    1999-01-01

    Basing on the analysis of clinico-radiological and functional signs, electromyographic and histological changes in the shoulder girdle (SG) upper extremities muscles, macro- and microscopic investigations of omovertebral formations in the patients with Sprengel disease, and the literature data there was formulated the scheme of etiology and pathogenesis of the inborn high position of shoulder blade. The leading role in the Sprengel disease etiology plays teratogenic exo- or endogenous harmful agent, affecting mesenchymal tissue in the moment of the vertebral column and SG inlay on the 4-5th week of embryogenesis. Underdevelopment and degeneration of the SG muscles, creation of fibrous, fibrous-cartilaginous and osteal tissues due to the embryogenesis disorder occurrence, are playing essential role in pathogenesis of anatomic-functional disorders, causing occurrence of the inborn high position of shoulder blade.

  17. Theories on the Pathogenesis of Endometriosis

    Directory of Open Access Journals (Sweden)

    Samer Sourial

    2014-01-01

    Full Text Available Endometriosis is a common, chronic inflammatory disease defined by the presence of extrauterine endometrial tissue. The aetiology of endometriosis is complex and multifactorial, where several not fully confirmed theories describe its pathogenesis. This review examines existing theories on the initiation and propagation of different types of endometriotic lesions, as well as critically appraises the myriad of biologically relevant evidence that support or oppose each of the proposed theories. The current literature suggests that stem cells, dysfunctional immune response, genetic predisposition, and aberrant peritoneal environment may all be involved in the establishment and propagation of endometriotic lesions. An orchestrated scientific and clinical effort is needed to consider all factors involved in the pathogenesis of this multifaceted disease and to propose novel therapeutic targets to reach effective treatments for this distressing condition.

  18. The epigenetic paradigm in periodontitis pathogenesis

    Directory of Open Access Journals (Sweden)

    Vamsi Lavu

    2015-01-01

    Full Text Available Epigenome refers to "epi" meaning outside the "genome." Epigenetics is the field of study of the epigenome. Epigenetic modifications include changes in the promoter CpG Islands, modifications of histone protein structure, posttranslational repression by micro-RNA which contributes to the alteration of gene expression. Epigenetics provides an understanding of the role of gene-environment interactions on disease phenotype especially in complex multifactorial diseases. Periodontitis is a chronic inflammatory disorder that affects the supporting structures of the tooth. The role of the genome (in terms of genetic polymorphisms in periodontitis pathogenesis has been examined in numerous studies, and chronic periodontitis has been established as a polygenic disorder. The potential role of epigenetic modifications in the various facets of pathogenesis of periodontitis is discussed in this paper based on the available literature.

  19. [The pathogenesis of small-plaque parapsoriasis].

    Science.gov (United States)

    Olisova, O Iu; Kop'eva, T N

    1994-01-01

    The paper deals with the origin of parapsoriasis nodularis, which in its micronodular variant belongs to chronic dermatosis and has a clear-cut clinical and histological appearance. The disease arises most frequently after stress and occurs for the most part in middle-aged males. The leading role in pathogenesis of parapsoriasis nodularis is played by cellular immunity as indicated by reduced count of T-lymphocytes, active T-lymphocytes as well as the emergence of delayed hypersensitivity.

  20. Osmotin, a Pathogenesis-Related Protein

    Czech Academy of Sciences Publication Activity Database

    Viktorová, J.; Krásný, Lukáš; Kamlar, M.; Nováková, M.; Macková, M.; Macek, T.

    2012-01-01

    Roč. 13, č. 7 (2012), s. 672-681 ISSN 1389-2037 Grant - others:GA ČR(CZ) GAP501/11/1654; GA ČR(CZ) GA522/09/1693 Program:GA; GA Institutional support: RVO:61388971 Keywords : osmotin * pathogenesis-related proteins * antifungal activity Subject RIV: CE - Biochemistry Impact factor: 2.326, year: 2012

  1. Acute pancreatitis: Etiology and common pathogenesis

    OpenAIRE

    Wang, Guo-Jun; Gao, Chun-Fang; Wei, Dong; Wang, Cun; Ding, Si-Qin

    2009-01-01

    Acute pancreatitis is an inflammatory disease of the pancreas. The etiology and pathogenesis of acute pancreatitis have been intensively investigated for centuries worldwide. Many causes of acute pancreatitis have been discovered, but the pathogenetic theories are controversial. The most common cause of acute pancreatitis is gallstone impacting the distal common bile-pancreatic duct. The majority of investigators accept that the main factors for acute billiary pancreatitis are pancreatic hype...

  2. [Anatomy and pathogenesis of diverticular disease].

    Science.gov (United States)

    Wedel, T; Böttner, M

    2014-04-01

    Although diverticular disease is one of the most frequent gastrointestinal disorders the pathogenesis is not yet sufficiently clarified. The aim is to define the anatomy and pathogenesis of diverticular disease considering the risk factors and description of structural and functional alterations of the bowel wall. This article gives an appraisal of the literature, presentation and evaluation of classical etiological factors, analysis and discussion of novel pathogenetic concepts. Colonic diverticulosis is defined as an acquired out-pouching of multiple and initially asymptomatic pseudodiverticula through muscular gaps in the colon wall. Diverticular disease is characterized by diverticular bleeding and/or inflammatory processes (diverticulitis) with corresponding complications (e.g. abscess formation, fistula, covered and open perforation, peritonitis and stenosis). Risk factors for diverticular disease include increasing age, genetic predisposition, congenital connective tissue diseases, low fiber diet, high meat consumption and pronounced overweight. Alterations of connective tissue cause a weakening of preformed exit sites of diverticula and rigidity of the bowel wall with reduced flexibility. It is assumed that intestinal innervation disorders and structural alterations of the musculature induce abnormal contractile patterns with increased intraluminal pressure, thereby promoting the development of diverticula. Moreover, an increased release of pain-mediating neurotransmitters is considered to be responsible for persistent pain in chronic diverticular disease. According to the present data the pathogenesis of diverticular disease cannot be attributed to a single factor but should be considered as a multifactorial event.

  3. The role of free-radical processes in the pathogenesis of age-related macular degeneration. Review

    Directory of Open Access Journals (Sweden)

    A. V. Kolesnikov

    2012-01-01

    Full Text Available the modern ideas of the role of free radical processes in the pathogenesis of age-related macular degeneration (AMD are consid- ered. Data of large randomized clinical trials on application of antioxidants for prevention and therapy AMD are provided. Possibility of the differential application of antioxidants depending on the genetic status of patients is discussed.

  4. MCFRS Incidents by Station

    Data.gov (United States)

    Montgomery County of Maryland — This dataset contains the monthly summary data indicating incident occurred in each fire station response area. The summary data is the incident count broken down by...

  5. Police Incident Reports Written

    Data.gov (United States)

    Town of Chapel Hill, North Carolina — This table contains incident reports filed with the Chapel Hill Police Department. Multiple incidents may have been reported at the same time. The most serious...

  6. Pathogenesis of Acute Respiratory Distress Syndrome

    Directory of Open Access Journals (Sweden)

    A. M. Golubev

    2012-01-01

    Full Text Available Acute respiratory distress syndrome (ARDS is a common complication of many diseases. Its polyetiological pattern determines the specific features of lung morphological changes and the clinical course of ARDS. Objective: to analyze the pathogenesis of ARDS in the context of the general pathological processes underlying its development. Material and methods. More than 200 lungs from the people who had died from severe concomitant injury or ARDS-complicated pneumonia were investigated. More than 150 rat experiments simulated various types of lung injury: ventilator-induced lung injury with different ventilation parameters; reperfusion injuries (systemic circulation blockade due to 12-minute vascular fascicle ligation, followed by the recovery of cardiac performance and breathing; microcirculatory disorder (injection of a thromboplastin solution into the jugular vein; blood loss; betaine-pepsin aspiration; and closed chest injury. Different parts of the right and left lungs were histologically examined 1 and 3 hours and 1 and 3 days after initiation of the experiment. Lung pieces were fixed in 10% neutral formalin solution and embedded in paraffin. Histological sections were stained with hematoxylin and eosin and using the van Gieson and Weigert procedures; the Schiff test was used. Results. The influence of aggression factors (trauma, blood loss, aspiration, infection, etc. results in damage to the lung and particularly air-blood barrier structures (endothelium, alveolar epithelium, their basement membrane. In turn the alteration of cellular and extracellular structures is followed by the increased permeability of hemomicrocirculatory bed vessels, leading to the development of non-cardiogenic (interstitial, alveolar pulmonary edema that is a central component in the pathogenesis of ARDS. Conclusion. The diagnosis of the early manifestations of ARDS must account for the nature of an aggression factor, the signs confirming the alteration of the lung

  7. The pathogenesis of progressive multifocal leukoencephalopathy.

    Science.gov (United States)

    Berger, Joseph R; Khalili, Kamel

    2011-12-01

    Interest in pathogenesis of progressive multifocal leukoencephalopathy (PML) followed the observation of the high risk for the disease in HIV infection and the recent observation of an association with a variety of newer therapeutic modalities, e.g., natalizumab, an α4β1 integrin inhibitor, and efalizumab, an anti-CD11a monoclonal antibody. Any hypothesis of PML pathogenesis must account for a number of facts. Firstly, the causative agent JC virus is ubiquitously present, yet only a vanishingly small number of infected persons develop the disease. Secondly, disorders of cell-mediated immunity increase the risk of the disease, particularly HIV infection. Impaired innate immunity is not a risk for PML, and antibodies against JC virus are not protective. Thirdly, a latent period of several months appears necessary following the administration of natalizumab and efalizumab before PML develops. Fourthly, restoration of the immune system can arrest the PML. It is possible that infection with JC virus occurs with a form of the virus shed in the urine of as many as 40% of all adults and present in sewage worldwide. Once acquired, perhaps through an oropharyngeal route, it may replicate and disseminate. A neurotropic form of JC virus that replicates in glial tissues causes PML when immunosurveillance is impaired. There are many unanswered questions with respect to PML pathogenesis. How is virus acquired? What tissues are infected? What is the origin of the neurotropic form? When does virus enter brain? What is the role of central nervous system immunosurveillance? The lack of an animal model has made answering these questions challenging. © Discovery Medicine

  8. Inflammatory Bowel Disease: Genetics, Epigenetics and Pathogenesis

    Directory of Open Access Journals (Sweden)

    Italia eLoddo

    2015-11-01

    Full Text Available Inflammatory Bowel Diseases (IBDs are complex, multifactorial disorders characterized by chronic relapsing intestinal inflammation. Although aetiology remains largely unknown, recent research has suggested that genetic factors, environment, microbiota and immune response are involved in the pathogenesis.Epidemiological evidence for a genetic contribution is defined: 15% of patients with Crohn’s Disease (CD have an affected family member with IBD, and twin studies for CD have shown 50% concordance in monozygotic twins compared to less than 10% in dizygotics. The most recent and largest genetic association studies, which employed genome-wide association data for over 75,000 patients and controls, identified 163 susceptibility loci for IBD. More recently, a trans-ethnic analysis, including over 20,000 individuals, identified an additional 38 new IBD loci.Although most cases are correlated with polygenic contribution toward genetic susceptibility, there is a spectrum of rare genetic disorders that can contribute to early onset IBD (before 5 years or very early IBD (before 2 years. Genetic variants that cause these disorders have a wide effect on gene function. These variants are so rare in allele frequency that the genetic signals are not detected in genome-wide association studies of patients with IBD. With recent advances in sequencing techniques, approximately 50 genetic disorders have been identified and associated with IBD-like immunopathology. Monogenic defects have been found to alter intestinal immune homeostasis through many mechanisms. Candidate gene resequencing should be carried out in early-onset patients in clinical practice.The evidence that genetic factors contribute in small part to disease pathogenesis confirms the important role of microbial and environmental factors. Epigenetic factors can mediate interactions between environment and genome. Epigenetic mechanisms could affect development and progression of IBD. Epigenomics is

  9. Urinary tract infection pathogenesis: host factors.

    Science.gov (United States)

    Stapleton, Ann E

    2014-03-01

    Clinically, host factors in the pathogenesis of urinary tract infection (UTI) may be considered as modifiable (eg, behaviors associated with increased risk of UTI, anatomic and functional problems of the urinary tract) and thus potentially amenable to a change in patient behavior or treatment approach, or as intrinsic and nonmodifiable host factors that neither the patient nor the clinician can influence (eg, gender and genetic influences associated with UTI). Although considering nonmodifiable host factors may be discouraging to patients and clinicians at present, some genetic associations have the potential for future predictive value and may interface with future treatments. Copyright © 2014 Elsevier Inc. All rights reserved.

  10. Treacher Collins syndrome: etiology, pathogenesis and prevention

    Science.gov (United States)

    Trainor, Paul A; Dixon, Jill; Dixon, Michael J

    2009-01-01

    Treacher Collins syndrome (TCS) is a rare congenital disorder of craniofacial development that arises as the result of mutations in the TCOF1 gene, which encodes a nucleolar phosphoprotein known as Treacle. Individuals diagnosed with TCS frequently undergo multiple reconstructive surgeries, which are rarely fully corrective. Identifying potential avenues for rescue and/or repair of TCS depends on a profound appreciation of the etiology and pathogenesis of the syndrome. Recent research using animal models has not only determined the cellular basis of TCS but also, more importantly, unveiled a successful avenue for therapeutic intervention and prevention of the craniofacial anomalies observed in TCS. PMID:19107148

  11. Urinary Tract Infection: Pathogenesis and Outlook.

    Science.gov (United States)

    McLellan, Lisa K; Hunstad, David A

    2016-11-01

    The clinical syndromes comprising urinary tract infection (UTI) continue to exert significant impact on millions of patients worldwide, most of whom are otherwise healthy women. Antibiotic therapy for acute cystitis does not prevent recurrences, which plague up to one fourth of women after an initial UTI. Rising antimicrobial resistance among uropathogenic bacteria further complicates therapeutic decisions, necessitating new approaches based on fundamental biological investigation. In this review, we highlight contemporary advances in the field of UTI pathogenesis and how these might inform both our clinical perspective and future scientific priorities. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Pathogenesis and treatment of diabetic glomerulopathy

    International Nuclear Information System (INIS)

    Marre, M.; Le Jeune, J.J.

    1995-01-01

    Diabetic glomerulopathy is the consequence, at the glomerular level, of diabetes. Diagnosis is based on the association of proteinuria, arterial hypertension and an early reduction of glomerular filtration in a diabetic patient, generally insulin-dependent. Diabetic glomerulopathy is a complication of type I diabetes, which begins in childhood or adolescence, but can also be discovered in type II diabetes. A definite diagnosis requires histological evidences ; glomerular clearance measurements ( 125 I-iodothalamate or 51 Cr-EDTA) yield important information concerning glomerular filtration. The authors subsequently address pathogenesis and therapeutic regimens, and they report on the particularities of this condition in type II diabetes. (authors). 30 refs., 2 tabs

  13. Biology and pathogenesis of Naegleria fowleri.

    Science.gov (United States)

    Siddiqui, Ruqaiyyah; Ali, Ibne Karim M; Cope, Jennifer R; Khan, Naveed Ahmed

    2016-12-01

    Naegleria fowleri is a protist pathogen that can cause lethal brain infection. Despite decades of research, the mortality rate related with primary amoebic meningoencephalitis owing to N. fowleri remains more than 90%. The amoebae pass through the nose to enter the central nervous system killing the host within days, making it one of the deadliest opportunistic parasites. Accordingly, we present an up to date review of the biology and pathogenesis of N. fowleri and discuss needs for future research against this fatal infection. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Etiology and pathogenesis of periodontal diseases.

    Science.gov (United States)

    Tatakis, Dimitris N; Kumar, Purnima S

    2005-07-01

    The two most prevalent and most investigated periodontal diseases are dental plaque-induced gingivitis and chronic periodontitis. The last 10 to 15 years have seen the emergence of several important new findings and concepts regarding the etiopathogenesis of periodontal diseases. These findings include the recognition of dental bacterial plaque as a biofilm, identification and characterization of genetic defects that predispose individuals to periodontitis, host-defense mechanisms implicated in periodontal tissue destruction, and the interaction of risk factors with host defenses and bacterial plaque. This article reviews current aspects of the etiology and pathogenesis of periodontal diseases.

  15. The fascinating germ theories on cancer pathogenesis.

    Science.gov (United States)

    Tsoucalas, G; Laios, K; Karamanou, M; Gennimata, V; Androutsos, G

    2014-01-01

    For more than 100 years, the germ theory of cancer, proposing that microorganisms were at the origin of the disease, dominated medicine. Several eminent scientists like Etienne Burnet, Mikhail Stepanovich Voronin, Charles-Louis Malassez, and Francis-Peyton Rous argued on the pathogenesis presenting their theories that implicated cocci, fungi and parasites. The impact of these theories was culminated by the Nobel Prize in 1926 that was attributed to the Danish scientist Johannes Fibiger for his work on the nematode Spiroptera as a causative agent in cancer. Even if those theories were the result of fantasy and misinterpretation, they paved the way for the scientific research in oncology.

  16. Molecular pathogenesis and mechanisms of thyroid cancer

    Science.gov (United States)

    Xing, Mingzhao

    2013-01-01

    Thyroid cancer is a common endocrine malignancy. There has been exciting progress in understanding its molecular pathogenesis in recent years, as best exemplified by the elucidation of the fundamental role of several major signalling pathways and related molecular derangements. Central to these mechanisms are the genetic and epigenetic alterations in these pathways, such as mutation, gene copy-number gain and aberrant gene methylation. Many of these molecular alterations represent novel diagnostic and prognostic molecular markers and therapeutic targets for thyroid cancer, which provide unprecedented opportunities for further research and clinical development of novel treatment strategies for this cancer. PMID:23429735

  17. Incident Information Management Tool

    CERN Document Server

    Pejovic, Vladimir

    2015-01-01

    Flaws of\tcurrent incident information management at CMS and CERN\tare discussed. A new data\tmodel for future incident database is\tproposed and briefly described. Recently developed draft version of GIS-­‐based tool for incident tracking is presented.

  18. Circular differential microscopy

    International Nuclear Information System (INIS)

    Maestre, M.F.; Bustamante, C.; Keller, D.

    1985-01-01

    The authors describe the historical development of the theory of differential imaging and the invention of the circular differential imaging microscope. The technique is shown to be a logical extension of the research on the interaction of circularly polarized light with stuctures whose dimensions are arbitrary with respect to the wavelength of light. Shown is the circular dichroism spectra in arbitrary units of E. cirrhosa sperm heads, measured by techniques with different collection angles of scattered light. Also presented is a scanning electron micrograph of a freexe-dried sperm head from E. cirrhosa. It was shown that circular differential scattering is specially sensitive to the dimensions of the structure close to the wavelength of the incident light, and application of circular intensity differential scattering theory to images extend these results

  19. CREB Signaling Is Involved in Rett Syndrome Pathogenesis.

    Science.gov (United States)

    Bu, Qian; Wang, Anxin; Hamzah, Hamdi; Waldman, Alex; Jiang, Keer; Dong, Qiping; Li, Ronghui; Kim, Jason; Turner, Daniel; Chang, Qiang

    2017-03-29

    Rett syndrome (RTT) is a debilitating neurodevelopmental disorder caused by mutations in the MECP2 gene. To facilitate the study of cellular mechanisms in human cells, we established several human stem cell lines: human embryonic stem cell (hESC) line carrying the common T158M mutation ( MECP2 T158M/T158M ), hESC line expressing no MECP2 ( MECP2-KO ), congenic pair of wild-type and mutant RTT patient-specific induced pluripotent stem cell (iPSC) line carrying the V247fs mutation (V247fs-WT and V247fs-MT), and iPSC line in which the V247fs mutation was corrected by CRISPR/Cas9-based genome editing (V247fs-MT-correction). Detailed analyses of forebrain neurons differentiated from these human stem cell lines revealed genotype-dependent quantitative phenotypes in neurite growth, dendritic complexity, and mitochondrial function. At the molecular level, we found a significant reduction in the level of CREB and phosphorylated CREB in forebrain neurons differentiated from MECP2 T158M/T158M , MECP2-KO , and V247fs-MT stem cell lines. Importantly, overexpression of CREB or pharmacological activation of CREB signaling in those forebrain neurons rescued the phenotypes in neurite growth, dendritic complexity, and mitochondrial function. Finally, pharmacological activation of CREB in the female Mecp2 heterozygous mice rescued several behavioral defects. Together, our study establishes a robust in vitro platform for consistent quantitative evaluation of genotype-dependent RTT phenotypes, reveals a previously unappreciated role of CREB signaling in RTT pathogenesis, and identifies a potential therapeutic target for RTT. SIGNIFICANCE STATEMENT Our study establishes a robust human stem cell-based platform for consistent quantitative evaluation of genotype-dependent Rett syndrome (RTT) phenotypes at the cellular level. By providing the first evidence that enhancing cAMP response element binding protein signaling can alleviate RTT phenotypes both in vitro and in vivo , we reveal a

  20. Epidemiology and pathogenesis of osteonecrosis of the jaw.

    Science.gov (United States)

    Reid, Ian R; Cornish, Jillian

    2011-11-29

    Osteonecrosis of the jaw (ONJ) is defined as exposed bone in the oral cavity that persists despite appropriate therapy. Over the past decade, ONJ has been reported in about 5% of patients with cancer receiving high-dose intravenous bisphosphonates, and more recently in similar patients treated with denosumab, another potent inhibitor of osteoclastic bone resorption. The condition has also been described in patients treated with bisphosphonates for benign diseases, such as osteoporosis, but whether bisphosphonates or denosumab increase the incidence above that seen in untreated patients of comparable age and frailty is yet to be established. The pathogenesis of ONJ is uncertain: the toxic effects of bisphosphonates in a wide variety of cells could increase susceptibility to infections in the oral cavity or impair mucosal healing, and denosumab might interfere with monocyte and macrophage function. Local osteolysis is an important defense against infection on bone surfaces that is blocked by both bisphosphonates and denosumab. Preventive dentistry prior to high-dose antiresorptive therapy is a critical measure in cancer patients, but is not usually justified in patients with osteoporosis. The management of established ONJ lesions is problematic: the greatest success seems to come from vigorous antimicrobial therapy with judicious use of surgical debridement.

  1. Advances in the cellular immunological pathogenesis of type 1 diabetes.

    Science.gov (United States)

    Li, Min; Song, Lu-Jun; Qin, Xin-Yu

    2014-05-01

    Type 1 diabetes is an autoimmune disease caused by the immune-mediated destruction of insulin-producing pancreatic β cells. In recent years, the incidence of type 1 diabetes continues to increase. It is supposed that genetic, environmental and immune factors participate in the damage of pancreatic β cells. Both the immune regulation and the immune response are involved in the pathogenesis of type 1 diabetes, in which cellular immunity plays a significant role. For the infiltration of CD4(+) and CD8(+) T lymphocyte, B lymphocytes, natural killer cells, dendritic cells and other immune cells take part in the damage of pancreatic β cells, which ultimately lead to type 1 diabetes. This review outlines the cellular immunological mechanism of type 1 diabetes, with a particular emphasis to T lymphocyte and natural killer cells, and provides the effective immune therapy in T1D, which is approached at three stages. However, future studies will be directed at searching for an effective, safe and long-lasting strategy to enhance the regulation of a diabetogenic immune system with limited toxicity and without global immunosuppression. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  2. Oligodendrocyte Injury and Pathogenesis of HIV-1-Associated Neurocognitive Disorders

    Directory of Open Access Journals (Sweden)

    Han Liu

    2016-07-01

    Full Text Available Oligodendrocytes wrap neuronal axons to form myelin, an insulating sheath which is essential for nervous impulse conduction along axons. Axonal myelination is highly regulated by neuronal and astrocytic signals and the maintenance of myelin sheaths is a very complex process. Oligodendrocyte damage can cause axonal demyelination and neuronal injury, leading to neurological disorders. Demyelination in the cerebrum may produce cognitive impairment in a variety of neurological disorders, including human immunodeficiency virus type one (HIV-1-associated neurocognitive disorders (HAND. Although the combined antiretroviral therapy has markedly reduced the incidence of HIV-1-associated dementia, a severe form of HAND, milder forms of HAND remain prevalent even when the peripheral viral load is well controlled. HAND manifests as a subcortical dementia with damage in the brain white matter (e.g., corpus callosum, which consists of myelinated axonal fibers. How HIV-1 brain infection causes myelin injury and resultant white matter damage is an interesting area of current HIV research. In this review, we tentatively address recent progress on oligodendrocyte dysregulation and HAND pathogenesis.

  3. Pathogenesis and Laboratory Diagnosis of Childhood Urinary Tract Infection

    Directory of Open Access Journals (Sweden)

    Jharna Mandal

    2016-04-01

    Full Text Available Urinary tract infection (UTI is one of the most common infections of childhood. The clinical presentations are mostly non-specific or mild. As any episode of UTI can potentially damage the kidneys, timely diagnosis and treatment are necessary to prevent renal damage. Incidence of UTI varies depending on the age, gender, and race of the child. UTIs in children are commonly caused by bacteria, though viruses, fungi, and parasites are also occasionally involved. The pathogenesis of UTI is complex where several host and pathogen factors influence the course of the disease and its outcome. Urine culture is still considered the gold standard method for the diagnosis of UTI. The means of obtaining urine samples from children for culture involves urethral catheterisation and suprapubic aspiration. The conventional methods of antibiotic susceptibility testing are labour intensive and time exhaustive. With the advent of technology, many automated platforms are available which are rapid, involve less volume of the culture or the sample, and have high accuracy.

  4. Penile cancer: epidemiology, pathogenesis and prevention.

    Science.gov (United States)

    Bleeker, M C G; Heideman, D A M; Snijders, P J F; Horenblas, S; Dillner, J; Meijer, C J L M

    2009-04-01

    Penile cancer is a disease with a high morbidity and mortality. Its prevalence is relatively rare, but the highest in some developing countries. Insight into its precursor lesions, pathogenesis and risk factors offers options to prevent this potentially mutilating disease. This review presents an overview of the different histologically and clinically identified precursor lesions of penile cancer and discusses the molecular pathogenesis, including the role of HPV in penile cancer development. A systematic review of the literature evaluating penile carcinogenesis, risk factors and molecular mechanisms involved. Careful monitoring of men with lichen sclerosis, genital Bowen's disease, erythroplasia of Queyrat and bowenoid papulosis seems useful, thereby offering early recognition of penile cancer and, subsequently, conservative therapeutic options. Special attention is given to flat penile lesions, which contain high numbers of HPV. Their role in HPV transmission to sexual partners is highlighted, but their potential to transform as a precursor lesion into penile cancer has been unsatisfactorily explored. Further research should not only focus on HPV mediated pathogenic pathways but also on the non-HPV related molecular and genetic factors that play a role in penile cancer development. Options for prevention of penile cancer include (neonatal) circumcision, limitation of penile HPV infections (either by prophylactic vaccination or condom use), prevention of phimosis, treatment of chronic inflammatory conditions, limiting PUVA treatment, smoking cessation and hygienic measures.

  5. Non Melanoma Skin Cancer Pathogenesis Overview.

    Science.gov (United States)

    Didona, Dario; Paolino, Giovanni; Bottoni, Ugo; Cantisani, Carmen

    2018-01-02

    (1) Background: Non-melanoma skin cancer is the most frequently diagnosed cancer in humans. The process of skin carcinogenesis is still not fully understood. However, several studies have been conducted to better explain the mechanisms that lead to malignancy; (2) Methods: We reviewed the more recent literature about the pathogenesis of non-melanoma skin cancer focusing on basal cell carcinomas, squamous cell carcinoma and actinic keratosis; (3) Results: Several papers reported genetic and molecular alterations leading to non-melanoma skin cancer. Plenty of risk factors are involved in non-melanoma skin cancer pathogenesis, including genetic and molecular alterations, immunosuppression, and ultraviolet radiation; (4) Conclusion: Although skin carcinogenesis is still not fully understood, several papers demonstrated that genetic and molecular alterations are involved in this process. In addition, plenty of non-melanoma skin cancer risk factors are now known, allowing for an effective prevention of non-melanoma skin cancer development. Compared to other papers on the same topic, our review focused on molecular and genetic factors and analyzed in detail several factors involved in non-melanoma skin cancer.

  6. Pathogenesis of Apical Periodontitis: a Literature Review

    Directory of Open Access Journals (Sweden)

    Indre Graunaite

    2011-09-01

    Full Text Available Objectives: This review article discusses the host response in apical periodontitis with the main focus on cytokines, produced under this pathological condition and contributing to the degradation of periradicular tissues. The pace of research in this field has greatly accelerated in the last decade. Here we provide an analysis of studies published in this area during this period.Material and methods: Literature was selected through a search of PubMed electronic database. The keywords used for search were pathogenesis of apical periodontitis cytokines, periapical granuloma cytokines, inflammatory infiltrate apical periodontitis. The search was restricted to English language articles, published from 1999 to December 2010. Additionally, a manual search in the cytokine production, cytokine functions and periapical tissue destruction in the journals and books was performed.Results: In total, 97 literature sources were obtained and reviewed. The topics covered in this article include cellular composition of an inflammatory infiltrate in the periapical lesions, mechanisms of the formation of the innate and specific immune response. Studies which investigated cytokine secretion and functions were identified and cellular and molecular interactions in the course of apical periodontitis described.Conclusions: The abundance and interactions of various inflammatory and anti-inflammatory molecules can influence and alter the state and progression of the disease. Therefore, periapical inflammatory response offers a model, suited for the study of many facets of pathogenesis, biocompatibility of different materials to periapical tissues and development of novel treatment methods, based on the regulation of cytokines expression.

  7. Pathogenesis of apical periodontitis: a literature review.

    Science.gov (United States)

    Graunaite, Indre; Lodiene, Greta; Maciulskiene, Vita

    2012-01-01

    This review article discusses the host response in apical periodontitis with the main focus on cytokines, produced under this pathological condition and contributing to the degradation of periradicular tissues. The pace of research in this field has greatly accelerated in the last decade. Here we provide an analysis of studies published in this area during this period. Literature was selected through a search of PubMed electronic database. The keywords used for search were pathogenesis of apical periodontitis cytokines, periapical granuloma cytokines, inflammatory infiltrate apical periodontitis. The search was restricted to English language articles, published from 1999 to December 2010. Additionally, a manual search in the cytokine production, cytokine functions and periapical tissue destruction in the journals and books was performed. In total, 97 literature sources were obtained and reviewed. The topics covered in this article include cellular composition of an inflammatory infiltrate in the periapical lesions, mechanisms of the formation of the innate and specific immune response. Studies which investigated cytokine secretion and functions were identified and cellular and molecular interactions in the course of apical periodontitis described. The abundance and interactions of various inflammatory and anti-inflammatory molecules can influence and alter the state and progression of the disease. Therefore, periapical inflammatory response offers a model, suited for the study of many facets of pathogenesis, biocompatibility of different materials to periapical tissues and development of novel treatment methods, based on the regulation of cytokines expression.

  8. Channelopathy Pathogenesis in Autism Spectrum Disorders

    Directory of Open Access Journals (Sweden)

    Galina eSchmunk

    2013-11-01

    Full Text Available Autism spectrum disorder (ASD is a syndrome that affects normal brain development and is characterized by impaired social interaction as well as verbal and non-verbal communication and by repetitive, stereotypic behavior. ASD is a complex disorder arising from a combination of multiple genetic and environmental factors that are independent from racial, ethnic and socioeconomical status. The high heritability of ASD suggests a strong genetic basis for the disorder. Furthermore, a mounting body of evidence implies a role of various ion channel gene defects (channelopathies in the pathogenesis of autism. Indeed, recent genome-wide association, and whole exome- and whole- genome resequencing studies linked polymorphisms and rare variants in calcium, sodium and potassium channels and their subunits with susceptibility to ASD, much as they do with bipolar disorder, schizophrenia and other neuropsychiatric disorders, and animal models with these genetic variations recapitulate endophenotypes considered to be correlates of autistic behavior seen in patients. An ion flux across the membrane regulates a variety of cell functions, from generation of action potentials to gene expression and cell morphology, thus it is not surprising that channelopathies have profound effects on brain functions. In the present work, we summarize existing evidence for the role of ion channel gene defects in the pathogenesis of autism with a focus on calcium signaling and its downstream effects.

  9. Transport proteins promoting Escherichia coli pathogenesis

    Science.gov (United States)

    Tang, Fengyi; Saier, Milton H.

    2014-01-01

    Escherichia coli is a genetically diverse species infecting hundreds of millions of people worldwide annually. We examined seven well-characterized E. coli pathogens causing urinary tract infections, gastroenteritis, pyelonephritis and haemorrhagic colitis. Their transport proteins were identified and compared with each other and a non-pathogenic E. coli K12 strain to identify transport proteins related to pathogenesis. Each pathogen possesses a unique set of protein secretion systems for export to the cell surface or for injecting effector proteins into host cells. Pathogens have increased numbers of iron siderophore receptors and ABC iron uptake transporters, but the numbers and types of low-affinity secondary iron carriers were uniform in all strains. The presence of outer membrane iron complex receptors and high-affinity ABC iron uptake systems correlated, suggesting co-evolution. Each pathovar encodes a different set of pore-forming toxins and virulence-related outer membrane proteins lacking in K12. Intracellular pathogens proved to have a characteristically distinctive set of nutrient uptake porters, different from those of extracellular pathogens. The results presented in this report provide information about transport systems relevant to various types of E. coli pathogenesis that can be exploited in future basic and applied studies. PMID:24747185

  10. Transport proteins promoting Escherichia coli pathogenesis.

    Science.gov (United States)

    Tang, Fengyi; Saier, Milton H

    2014-01-01

    Escherichia coli is a genetically diverse species infecting hundreds of millions of people worldwide annually. We examined seven well-characterized E. coli pathogens causing urinary tract infections, gastroenteritis, pyelonephritis and haemorrhagic colitis. Their transport proteins were identified and compared with each other and a non-pathogenic E. coli K12 strain to identify transport proteins related to pathogenesis. Each pathogen possesses a unique set of protein secretion systems for export to the cell surface or for injecting effector proteins into host cells. Pathogens have increased numbers of iron siderophore receptors and ABC iron uptake transporters, but the numbers and types of low-affinity secondary iron carriers were uniform in all strains. The presence of outer membrane iron complex receptors and high-affinity ABC iron uptake systems correlated, suggesting co-evolution. Each pathovar encodes a different set of pore-forming toxins and virulence-related outer membrane proteins lacking in K12. Intracellular pathogens proved to have a characteristically distinctive set of nutrient uptake porters, different from those of extracellular pathogens. The results presented in this report provide information about transport systems relevant to various types of E. coli pathogenesis that can be exploited in future basic and applied studies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. Irritable bowel syndrome: Diagnosis and pathogenesis

    Science.gov (United States)

    El-Salhy, Magdy

    2012-01-01

    Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder that considerably reduces the quality of life. It further represents an economic burden on society due to the high consumption of healthcare resources and the non-productivity of IBS patients. The diagnosis of IBS is based on symptom assessment and the Rome III criteria. A combination of the Rome III criteria, a physical examination, blood tests, gastroscopy and colonoscopy with biopsies is believed to be necessary for diagnosis. Duodenal chromogranin A cell density is a promising biomarker for the diagnosis of IBS. The pathogenesis of IBS seems to be multifactorial, with the following factors playing a central role in the pathogenesis of IBS: heritability and genetics, dietary/intestinal microbiota, low-grade inflammation, and disturbances in the neuroendocrine system (NES) of the gut. One hypothesis proposes that the cause of IBS is an altered NES, which would cause abnormal GI motility, secretions and sensation. All of these abnormalities are characteristic of IBS. Alterations in the NES could be the result of one or more of the following: genetic factors, dietary intake, intestinal flora, or low-grade inflammation. Post-infectious IBS (PI-IBS) and inflammatory bowel disease-associated IBS (IBD-IBS) represent a considerable subset of IBS cases. Patients with PI- and IBD-IBS exhibit low-grade mucosal inflammation, as well as abnormalities in the NES of the gut. PMID:23066308

  12. Generalized anxiety disorder: Differential diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    Tatyana Gratsiyevna Voznesenskaya

    2013-01-01

    Full Text Available Generalized anxiety disorder (GAD is poorly diagnosed and inadequately treated by general practitioners. The paper considers the major diagnostic signs of GAD, its differential diagnosis, prevalence, etiology, and pathogenesis. Antidepressants from a group of selective serotonin reuptake inhibitors in combination with psychotherapy are the drugs of first choice.

  13. Foodborne Campylobacter: Infections, Metabolism, Pathogenesis and Reservoirs

    Science.gov (United States)

    Epps, Sharon V. R.; Harvey, Roger B.; Hume, Michael E.; Phillips, Timothy D.; Anderson, Robin C.; Nisbet, David J.

    2013-01-01

    Campylobacter species are a leading cause of bacterial-derived foodborne illnesses worldwide. The emergence of this bacterial group as a significant causative agent of human disease and their propensity to carry antibiotic resistance elements that allows them to resist antibacterial therapy make them a serious public health threat. Campylobacter jejuni and Campylobacter coli are considered to be the most important enteropathogens of this genus and their ability to colonize and survive in a wide variety of animal species and habitats make them extremely difficult to control. This article reviews the historical and emerging importance of this bacterial group and addresses aspects of the human infections they cause, their metabolism and pathogenesis, and their natural reservoirs in order to address the need for appropriate food safety regulations and interventions. PMID:24287853

  14. Origin and pathogenesis of antiphospholipid antibodies

    Directory of Open Access Journals (Sweden)

    C.M. Celli

    1998-06-01

    Full Text Available Antiphospholipid antibodies (aPL are a heterogeneous group of antibodies that are detected in the serum of patients with a variety of conditions, including autoimmune (systemic lupus erythematosus, infectious (syphilis, AIDS and lymphoproliferative disorders (paraproteinemia, myeloma, lymphocytic leukemias. Thrombosis, thrombocytopenia, recurrent fetal loss and other clinical complications are currently associated with a subgroup of aPL designating the antiphospholipid syndrome. In contrast, aPL from patients with infectious disorders are not associated with any clinical manifestation. These findings led to increased interest in the origin and pathogenesis of aPL. Here we present the clinical features of the antiphospholipid syndrome and review the origin of aPL, the characteristics of experimentally induced aPL and their historical background. Within this context, we discuss the most probable pathogenic mechanisms induced by these antibodies.

  15. Ovarian Cancer Pathogenesis: A Model in Evolution

    Directory of Open Access Journals (Sweden)

    Alison M. Karst

    2010-01-01

    Full Text Available Ovarian cancer is a deadly disease for which there is no effective means of early detection. Ovarian carcinomas comprise a diverse group of neoplasms, exhibiting a wide range of morphological characteristics, clinical manifestations, genetic alterations, and tumor behaviors. This high degree of heterogeneity presents a major clinical challenge in both diagnosing and treating ovarian cancer. Furthermore, the early events leading to ovarian carcinoma development are poorly understood, thus complicating efforts to develop screening modalities for this disease. Here, we provide an overview of the current models of ovarian cancer pathogenesis, highlighting recent findings implicating the fallopian tube fimbria as a possible site of origin of ovarian carcinomas. The ovarian cancer model will continue to evolve as we learn more about the genetics and etiology of this disease.

  16. Update on bacterial pathogenesis in BRD.

    Science.gov (United States)

    Confer, Anthony W

    2009-12-01

    Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, Mycoplasma bovis and Arcanobacterium pyogenes are all frequently implicated in bovine respiratory disease (BRD). M. haemolytica is considered the most important of the group. These bacteria are commensals in the nasopharynx and establish infection in the lungs of cattle that are subjected to a variety of stresses. Factors that permit adherence to and proliferation in the lungs and factors that cause tissue destruction and inflammation have been identified as having major roles in pathogenesis. These virulence factors include protein adhesins, capsular polysaccharide, outer membrane proteins, iron-binding proteins, lipopolysacharide or lipooligosaccharide, enzymes and toxins. These bacterial products function to evade the immune system, damage the immune system and induce a severe inflammatory response.

  17. Vibrio cholerae Biofilms and Cholera Pathogenesis.

    Directory of Open Access Journals (Sweden)

    Anisia J Silva

    2016-02-01

    Full Text Available Vibrio cholerae can switch between motile and biofilm lifestyles. The last decades have been marked by a remarkable increase in our knowledge of the structure, regulation, and function of biofilms formed under laboratory conditions. Evidence has grown suggesting that V. cholerae can form biofilm-like aggregates during infection that could play a critical role in pathogenesis and disease transmission. However, the structure and regulation of biofilms formed during infection, as well as their role in intestinal colonization and virulence, remains poorly understood. Here, we review (i the evidence for biofilm formation during infection, (ii the coordinate regulation of biofilm and virulence gene expression, and (iii the host signals that favor V. cholerae transitions between alternative lifestyles during intestinal colonization, and (iv we discuss a model for the role of V. cholerae biofilms in pathogenicity.

  18. Apnea of prematurity: pathogenesis and management strategies.

    Science.gov (United States)

    Mathew, O P

    2011-05-01

    Apnea of prematurity (AOP) is a significant clinical problem manifested by an unstable respiratory rhythm reflecting the immaturity of respiratory control systems. This review will address the pathogenesis of and treatment strategies for AOP. Although the neuronal mechanisms leading to apnea are still not well understood, recent decades have provided better insight into the generation of the respiratory rhythm and its modulation in the neonate. Ventilatory responses to hypoxia and hypercarbia are impaired and inhibitory reflexes are exaggerated in the neonate. These unique vulnerabilities predispose the neonate to the development of apnea. Treatment strategies attempt to stabilize the respiratory rhythm. Caffeine remains the primary pharmacological treatment modality and is presumed to work through blockade of adenosine receptors A(1) and A(2). Recent evidences suggest that A(2A) receptors may have a greater role than previously thought. AOP typically resolves with maturation suggesting increased myelination of the brainstem.

  19. Pathogenesis of Staphylococcus aureus Bloodstream Infections

    Science.gov (United States)

    Thomer, Lena; Schneewind, Olaf; Missiakas, Dominique

    2016-01-01

    Staphylococcus aureus , a Gram-positive bacterium colonizing nares, skin, and the gastrointestinal tract, frequently invades the skin, soft tissues, and bloodstreams of humans. Even with surgical and antibiotic therapy, bloodstream infections are associated with significant mortality. The secretion of coagulases, proteins that associate with and activate the host hemostatic factor prothrombin, and the bacterial surface display of agglutinins, proteins that bind polymerized fibrin, are key virulence strategies for the pathogenesis of S. aureus bloodstream infections, which culminate in the establishment of abscess lesions. Pathogen-controlled processes, involving a wide spectrum of secreted factors, are responsible for the recruitment and destruction of immune cells, transforming abscess lesions into purulent exudate, with which staphylococci disseminate to produce new infectious lesions or to infect new hosts. Research on S. aureus bloodstream infections is a frontier for the characterization of protective vaccine antigens and the development of immune therapeutics aiming to prevent disease or improve outcomes. PMID:26925499

  20. Vibrio cholerae Biofilms and Cholera Pathogenesis

    Science.gov (United States)

    Silva, Anisia J.; Benitez, Jorge A.

    2016-01-01

    Vibrio cholerae can switch between motile and biofilm lifestyles. The last decades have been marked by a remarkable increase in our knowledge of the structure, regulation, and function of biofilms formed under laboratory conditions. Evidence has grown suggesting that V. cholerae can form biofilm-like aggregates during infection that could play a critical role in pathogenesis and disease transmission. However, the structure and regulation of biofilms formed during infection, as well as their role in intestinal colonization and virulence, remains poorly understood. Here, we review (i) the evidence for biofilm formation during infection, (ii) the coordinate regulation of biofilm and virulence gene expression, and (iii) the host signals that favor V. cholerae transitions between alternative lifestyles during intestinal colonization, and (iv) we discuss a model for the role of V. cholerae biofilms in pathogenicity. PMID:26845681

  1. [Etiology and pathogenesis of overactive bladder].

    Science.gov (United States)

    Bschleipfer, T; Wagenlehner, F; Weidner, W

    2011-04-01

    The symptom complex"overactive bladder" (OAB) affects more than 10% of adult individuals. The etiopathology is complex and multifactorial. Foremost, urinary tract infection, bladder cancer, foreign bodies, and history of radiation or intravesical instillation of chemotherapeutics must be excluded. In many cases, OAB is caused by neurogenic disorders that activate involuntary detrusor contractions (detrusor overactivity, DO). Also, non-neurogenic disorders such as bladder outlet obstruction or dysfunctions of the female pelvic floor/slack ligaments that affect the urothelium, suburothelium, detrusor and bladder afferents are substantially involved in the pathogenesis of OAB. Until now, circulatory disorders have not been adequately taken into consideration but seem to be another etiological factor that causes OAB. Henceforth, molecular changes of bladder afferents and circulatory disorders in patients suffering from OAB have to be investigated in more detail.

  2. Pathogenesis of Insulin Resistance in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Muhammad A. Abdul-Ghani

    2010-01-01

    Full Text Available Insulin resistance in skeletal muscle is manifested by decreased insulin-stimulated glucose uptake and results from impaired insulin signaling and multiple post-receptor intracellular defects including impaired glucose transport, glucose phosphorylation, and reduced glucose oxidation and glycogen synthesis. Insulin resistance is a core defect in type 2 diabetes, it is also associated with obesity and the metabolic syndrome. Dysregulation of fatty acid metabolism plays a pivotal role in the pathogenesis of insulin resistance in skeletal muscle. Recent studies have reported a mitochondrial defect in oxidative phosphorylation in skeletal muscle in variety of insulin resistant states. In this review, we summarize the cellular and molecular defects that contribute to the development of insulin resistance in skeletal muscle.

  3. Cellular and molecular mechanisms of chikungunya pathogenesis.

    Science.gov (United States)

    Lum, Fok-Moon; Ng, Lisa F P

    2015-08-01

    Chikungunya virus (CHIKV) is an arthropod-borne virus that causes chikungunya fever, a disease characterized by the onset of fever and rashes, with arthralgia as its hallmark symptom. CHIKV has re-emerged over the past decade, causing numerous outbreaks around the world. Since late 2013, CHIKV has reached the shores of the Americas, causing more than a million cases of infection. Despite concentrated efforts to understand the pathogenesis of the disease, further outbreaks remain a threat. This review highlights important findings regarding CHIKV-associated immunopathogenesis and offers important insights into future directions. This article forms part of a symposium in Antiviral Research on "Chikungunya discovers the New World." Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Oxidative stress in the pathogenesis of psoriasis.

    Science.gov (United States)

    Zhou, Qiang; Mrowietz, Ulrich; Rostami-Yazdi, Martin

    2009-10-01

    Psoriasis is a chronic immune-mediated hyperproliferative inflammatory skin disease in which a cytokine network concept is well established. Skin is a major target of oxidative stress mainly due to reactive oxygen species (ROS) originating from the environment and skin metabolism itself. Although endogenous antioxidants attenuate the harmful effects of ROS, increased or prolonged presence of free radicals can override ROS defense mechanisms and mediate numerous cellular responses that contribute to the development of a variety of skin disorders, including psoriasis. Regarding psoriasis, antioxidant strategies have proven to be beneficial therapeutics. The cellular signaling pathways such as mitogen-activated protein kinase/activator protein 1, nuclear factor kappaB, and Janus kinase-signal transducers and activators of transcription are known to be redox sensitive and proven to be involved in the progress of psoriasis. This review summarizes the current knowledge of the role of the redox system in regulating these signaling pathways related to the pathogenesis of psoriasis.

  5. Psoriatic arthritis: from pathogenesis to therapy.

    LENUS (Irish Health Repository)

    Fitzgerald, Oliver

    2012-02-01

    Psoriatic arthritis is a multigenic autoimmune disease that involves synovial tissue, entheseal sites and skin, and that may result in significant joint damage. Although there are no diagnostic tests for psoriatic arthritis, research has identified consistent features that help to distinguish the condition from other common rheumatic diseases. Comparison of HLA-B and HLA-C regions in psoriatic arthritis with those in psoriasis without joint involvement demonstrates significant differences, such that psoriatic arthritis cannot be viewed simply as a subset of genetically homogeneous psoriasis. T-cell receptor phenotypic studies have failed to identify antigen-driven clones, and an alternative hypothesis for CD8 stimulation involving innate immune signals is proposed. Finally, imaging studies have highlighted entheseal involvement in psoriatic arthritis, and it is possible that entheseal-derived antigens may trigger an immune response that is critically involved in disease pathogenesis.

  6. Mathematical models of HIV replication and pathogenesis.

    Science.gov (United States)

    Wodarz, Dominik

    2014-01-01

    This review outlines how mathematical models have been helpful, and continue to be so, for obtaining insights into the in vivo dynamics of HIV infection. The review starts with a discussion of a basic mathematical model that has been frequently used to study HIV dynamics. Some crucial results are described, including the estimation of key parameters that characterize the infection, and the generation of influential theories which argued that in vivo virus evolution is a key player in HIV pathogenesis. Subsequently, more recent concepts are reviewed that have relevance for disease progression, including the multiple infection of cells and the direct cell-to-cell transmission of the virus through the formation of virological synapses. These are important mechanisms that can influence the rate at which HIV spreads through its target cell population, which is tightly linked to the rate at which the disease progresses towards AIDS.

  7. Innate immunity in the pathogenesis of psoriasis.

    LENUS (Irish Health Repository)

    Sweeney, Cheryl M

    2011-12-01

    Psoriasis is a common, immune-mediated inflammatory skin disorder. T helper(h)1 and Th17 lymphocytes contribute to the pathogenesis of psoriasis through the release of inflammatory cytokines that promote further recruitment of immune cells, keratinocyte proliferation and sustained inflammation. The innate immune system is the first line of defence against infection and plays a crucial role in the initiation of the adaptive immune response. The presence of innate immune cells and their products in psoriatic skin plaques suggests a role for innate immunity in this disease. In addition, the innate immune system can direct the development of pathogenic Th cells in psoriasis. In this article, we will summarise the role of the innate immune system in psoriasis with particular emphasis on the role of cytokines, signalling pathways and cells of the innate immune system.

  8. Pilonidal sinus disease - Etiological factors, pathogenesis and clinical features

    Directory of Open Access Journals (Sweden)

    Kazim Duman

    2016-12-01

    Full Text Available and lsquo;Pilonidal sinus' disease, which is most commonly seen in reproductive populations, such as young adults - mostly in males who are in their twenties - is actually a controversial disease in that there is no consensus on its many facets. It is sometimes seen as an infected abscess draining from an opening or a lesion extending to the perineum. It may also present as a draining fistula opening to skin. In terms of etiological factors, various theories (main theories being congenital and acquired have been established since it was first described, no universal understanding achieved. A long and significant post-operative care period with different lengths of recovery depending on the type of operation are quite prevalent with regards to recurrence and complication status. In order to prevent recurrence and improve the quality of life, etiological and predisposing factors as well as clinical features of sacrococcygeal pilonidal disease should be well known, a detailed differential diagnosis should be made, and a suitable and timely intervention should be performed. It was aimed here to explain the etiological factors, pathogenesis and clinical features of the disease that may present with various clinical symptoms. [Arch Clin Exp Surg 2016; 5(4.000: 228-232

  9. Thrombotic thrombocytopenic purpura: pathogenesis, diagnosis and potential novel therapeutics.

    Science.gov (United States)

    Saha, M; McDaniel, J K; Zheng, X L

    2017-10-01

    Thrombotic thrombocytopenic purpura (TTP), a potentially fatal clinical syndrome, is primarily caused by autoantibodies against the von Willebrand factor (VWF)-cleaving metalloprotease ADAMTS-13. In general, severe deficiency of plasma ADAMTS-13 activity ( 10 IU dL -1 ) in a similar clinical context supports an alternative diagnosis such as atypical hemolytic uremic syndrome (aHUS) or other types of TMA. Prompt differentiation of TTP from other causes of TMA is crucial for the initiation of an appropriate therapy to reduce morbidity and mortality. Although plasma infusion is often sufficient for prophylaxis or treatment of hereditary TTP due to ADAMTS-13 mutations, daily therapeutic plasma exchange remains the initial treatment of choice for acquired TTP with demonstrable autoantibodies. Immunomodulatory therapies, including corticosteroids, rituximab, vincristine, cyclosporine, cyclophosphamide and splenectomy, etc., should be considered to eliminate autoantibodies for a sustained remission. Other emerging therapeutic modalities, including recombinant ADAMTS-13, adeno-associated virus (AAV) 8-mediated gene therapy, platelet-delivered ADAMTS-13, and antagonists targeting the interaction between platelet glycoprotein 1b and VWF are under investigation. This review highlights the recent progress in our understanding of the pathogenesis and diagnosis of, and current and potential novel therapies for, hereditary and acquired TTP. © 2017 International Society on Thrombosis and Haemostasis.

  10. Traumatic ulcerative granuloma with stromal eosinophilia - Mystery of pathogenesis revisited.

    Science.gov (United States)

    Sarangarajan, R; Vaishnavi Vedam, V K; Sivadas, G; Sarangarajan, Anuradha; Meera, S

    2015-08-01

    Oral ulcers are a common symptom in clinical practice. Among various causative factors, different types of ulcers in oral cavity exist. Among this, traumatic ulcerative granuloma with stromal eosinophilia (TUGSE) appears to be quite neglected by the clinicians due to the limited knowledge and awareness. On reviewing with a detailed approach to titles and abstracts of articles eliminating duplicates, 40 relevant articles were considered. Randomized studies, review articles, case reports and abstracts were included while conference papers and posters were excluded. Of importance, TUGSE cases been reported only to a minimal extent in the literature. Lack of its awareness tends to lead clinicians to a misconception of cancer. Thus, this particular lesion needs to be differentiated from other malignant lesions to provide a proper mode of treatment. The present article reviews various aspects of the TUGSE with emphasis on the clinical manifestation, pathogenesis, histological, and immunohistochemical study. This study provides the clinician contemporaries, a humble expansion to their knowledge of the disease, based on the searched literature, enabling a more comprehensive management of this rare occurrence.

  11. Pathogenesis of Chagas' Disease: Parasite Persistence and Autoimmunity

    Science.gov (United States)

    Teixeira, Antonio R. L.; Hecht, Mariana M.; Guimaro, Maria C.; Sousa, Alessandro O.; Nitz, Nadjar

    2011-01-01

    Summary: Acute Trypanosoma cruzi infections can be asymptomatic, but chronically infected individuals can die of Chagas' disease. The transfer of the parasite mitochondrial kinetoplast DNA (kDNA) minicircle to the genome of chagasic patients can explain the pathogenesis of the disease; in cases of Chagas' disease with evident cardiomyopathy, the kDNA minicircles integrate mainly into retrotransposons at several chromosomes, but the minicircles are also detected in coding regions of genes that regulate cell growth, differentiation, and immune responses. An accurate evaluation of the role played by the genotype alterations in the autoimmune rejection of self-tissues in Chagas' disease is achieved with the cross-kingdom chicken model system, which is refractory to T. cruzi infections. The inoculation of T. cruzi into embryonated eggs prior to incubation generates parasite-free chicks, which retain the kDNA minicircle sequence mainly in the macrochromosome coding genes. Crossbreeding transfers the kDNA mutations to the chicken progeny. The kDNA-mutated chickens develop severe cardiomyopathy in adult life and die of heart failure. The phenotyping of the lesions revealed that cytotoxic CD45, CD8+ γδ, and CD8α+ T lymphocytes carry out the rejection of the chicken heart. These results suggest that the inflammatory cardiomyopathy of Chagas' disease is a genetically driven autoimmune disease. PMID:21734249

  12. Increasing incidence of premature thelarche in the Central Region of Denmark - Challenges in differentiating girls less than 7 years of age with premature thelarche from girls with precocious puberty in real-life practice

    DEFF Research Database (Denmark)

    Sømod, Mia Elbek; Vestergaard, Esben Thyssen; Kristensen, Kurt

    2016-01-01

    was the variable which best discriminated PT from PP. Third, stimulated LH in 1-3 years old girls with PT is similar to stimulated LH in 5-7 years old girls with PP. Age, BMISDS, ethnicity, bone age, stimulated gonadotropins and LH/FSH and SHBG are all useful variables for differentiating PP from PT. However....... Diagnoses were validated and the girls were categorized to the groups PP (n = 27) and PT (n = 164). Anthropometry, Tanner stages, ethnicity, bone age, and biochemistry, were recorded. Conventional variables for diagnosing PP were compared between the groups at time of referral to identify parameters...... predictive for the diagnosis. RESULTS: The referral rate of PT increased from 1998-2013. Girls with PT and PP differed with regards to age at referral, body mass index standard deviation scores (BMISDS), ethnicity, bone age advancement, basal luteinizing hormone (LH), gonadotropin releasing hormone (Gn...

  13. Some aspects of periodontitis pathogenesis in children

    Directory of Open Access Journals (Sweden)

    Shcherbina I.N.

    2013-12-01

    Full Text Available Inflammatory processes in the tissues surrounding tooth root are frequent enough and develop as the direct complication of caries. As acute periodontitis is manifested with grinding toothache and violation of ph¬y¬sio¬logical act of chewing, symptoms of general intoxication, the continuous sluggish chronic periodontitis is harmful and dangerous to the organism as well. It forms the state of chronic оdontogenetic intoxication and chroneosepsis with wrong functioning of some internal organs and body systems. The like complications can cause significant disturbance to the function of kidneys, liver, heart, joints and their treatment without ablating focus of inflammation is often in- effective; this must be taken into account by doctors-interns. However, scanning of the oral cavity by conservative means has its difficulties mostly because of ignoring pathogenesis of such inflammation. That is why activity of ferments of blood dehydrogenases from the periapical tissues of the teeth affected with the chronic periodontitis was studied. The level of succinate dehydrogenase and alpha-glycerophosphate degydrogenase of lymphocytes of 110 schoolchildren aged 13-17 years old was studied. The main group of examined individuals included those of infected with tuber¬culousis – 50 individuals, and the control group (60 individuals – clinically healthy ones without tuberculousis desease. All schoolchildren had 1 or 2 teeth affected with chronic periodontitis of the apical localization. The researchers found that a significant inhibition of activity of succinate dehydrogenase and alpha-glycerophosphate degydrogenase ferments occurs in the inflammatory periodontal tissues, which indicates to local immunity decline, and as a consequence, pathogenic bacteria activation. In people infected with tuberculousis these violations were more developed. Such features of periodontitis pathogenesis must be taken into account when providing a combined treatment.

  14. Multi-platform ’Omics Analysis of Human Ebola Virus Disease Pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Eisfeld, Amie J.; Halfmann, Peter J.; Wendler, Jason P.; Kyle, Jennifer E.; Burnum-Johnson, Kristin E.; Peralta, Zuleyma; Maemura, Tadashi; Walters, Kevin B.; Watanabe, Tokiko; Fukuyama, Satoshi; Yamashita, Makoto; Jacobs, Jon M.; Kim, Young-Mo; Casey, Cameron P.; Stratton, Kelly G.; Webb-Robertson, Bobbie-Jo M.; Gritsenko, Marina A.; Monroe, Matthew E.; Weitz, Karl K.; Shukla, Anil K.; Tian, Mingyuan; Neumann, Gabriele; Reed, Jennifer L.; van Bakel, Harm; Metz, Thomas O.; Smith, Richard D.; Waters, Katrina M.; N' jai, Alhaji; Sahr, Foday; Kawaoka, Yoshihiro

    2017-12-01

    The pathogenesis of human Ebola virus disease (EVD) is complex. EVD is characterized by high levels of virus replication and dissemination, dysregulated immune responses, extensive virus- and host-mediated tissue damage, and disordered coagulation. To clarify how host responses contribute to EVD pathophysiology, we performed multi-platform ’omics analysis of peripheral blood mononuclear cells and plasma from EVD patients. Our results indicate that EVD molecular signatures overlap with those of sepsis, imply that pancreatic enzymes contribute to tissue damage in fatal EVD, and suggest that Ebola virus infection may induce aberrant neutrophils whose activity could explain hallmarks of fatal EVD. Moreover, integrated biomarker prediction identified putative biomarkers from different data platforms that differentiated survivors and fatalities early after infection. This work reveals insight into EVD pathogenesis, suggests an effective approach for biomarker identification, and provides an important community resource for further analysis of human EVD severity.

  15. Selective IgA Deficiency: Epidemiology, Pathogenesis, Clinical Phenotype, Diagnosis, Prognosis and Management.

    Science.gov (United States)

    Yazdani, R; Azizi, G; Abolhassani, H; Aghamohammadi, A

    2017-01-01

    Selective immunoglobulin A deficiency (SIgAD) is the most common primary antibody deficiency. Although more patients with SIgAD are asymptomatic, selected patients suffer from different clinical complications such as pulmonary infections, allergies, autoimmune diseases, gastrointestinal disorders and malignancy. Pathogenesis of SIgAD is still unknown; however, a defective terminal differentiation of B cells and defect in switching to IgA-producing plasma cells are presumed to be responsible. Furthermore, some cytogenic defects and monogenic mutations are associated with SIgAD. There is no specific treatment for patients with symptomatic IgA deficiency, although prophylactic antibiotic therapy along with circumstantial immunoglobulin replacement with justification and supportive care (using a product that contains minimal IgA) could be helpful for patients with a severe phenotype. The epidemiology, pathogenesis, clinical phenotype, diagnosis, prognosis, management and treatment in patients with SIgAD have been reviewed. © 2016 The Foundation for the Scandinavian Journal of Immunology.

  16. Research advances in the pathogenesis of nonalcoholic fatty liver disease

    Directory of Open Access Journals (Sweden)

    WANG Hu

    2017-04-01

    Full Text Available Nonalcoholic fatty liver disease (NAFLD has been developing rapidly in recent years and has become one of the most common liver diseases. However, its pathogenesis remains unclear, and there are no widely accepted therapeutic regimens. NAFLD has a complex pathogenesis with multiple factors involved, including insulin resistance, oxidative stress, bile acid metabolic disorders, and autophagy. This article reviews the pathogenesis of NAFLD in order to provide a reference for further research and clinical treatment in the future.

  17. Functional modeling of the craniospinal system for in-vitro parameter studies on the pathogenesis of NPH

    Directory of Open Access Journals (Sweden)

    Benninghaus Anne

    2017-09-01

    Full Text Available Normal Pressure Hydrocephalus (NPH has become a common disease in the elderly coming along with typical symptoms of dementia, gait ataxia and urinary incontinence, which make the differential diagnosis with other forms of dementia difficult. Furthermore the pathogenesis of NPH is still not understood. About 10% of all demented patients might be suffering from NPH [1]. Many hypotheses suggest that modified biomechanical boundary conditions affect the craniospinal dynamics inducing the pathogenesis of NPH. We present a novel approach for an in-vitro model of the craniospinal system to investigate important hydrodynamic influences on the system such as (dynamic compliance of the vascular system and especially the spinal subarachnoid space (SAS as well as reabsorption and hydrostatics. The experimental set-up enables the individual adjustment of relevant parameters for sensitivity analyses regarding the impact of resulting CSF dynamics on the pathogenesis of NPH.

  18. Pathogenesis of Arterial Hypertension in the Pregnant Females

    Directory of Open Access Journals (Sweden)

    N. V. Kabanova

    2007-01-01

    system (elevated T4 was common in the pathogenesis of AH in the pregnant females. The knowledge of the pathogenetic mechanisms underlying the development of AH in pregnant females serves as the basis for working out a differential intensive care program. 

  19. Molecular detection, distribution and Pathogenesis of cowpea ...

    African Journals Online (AJOL)

    user

    2012-09-25

    Sep 25, 2012 ... heating at 95°C for 2 min followed by 35 cycles of 95°C for 30 s, 53 to 55°C ... rubbed with carborundum to induce injury to the plant cells to ease virus entry ... The figures in brackets () are percentage virus incidences in seed samples per district and number seed samples that tested positive for particular ...

  20. Pathogenesis and prevention of stomach cancer.

    OpenAIRE

    Youn, H. S.; Ko, G. H.; Chung, M. H.; Lee, W. K.; Cho, M. J.; Rhee, K. H.

    1996-01-01

    In many Western developed countries, the incidence of stomach cancer has declined dramatically. This decrease was an extraordinary, "unplanned triumph", especially when compared to other cancers. Stomach cancer is still the most prevalent malignant tumor in Korea. Most Koreans carry Helicobacter pylori in their stomach. Thus, a new hypothesis, based on the relationship between the host and Helicobacter pylori, is presented as the carcinogenesis of human stomach cancer. The reasons for why the...

  1. Acute incidents during anaesthesia

    African Journals Online (AJOL)

    Incidents can occur during induction, maintenance and emergence from anaesthesia. The following acute critical incidents are discussed in this article: • Anaphylaxis. • Aspiration ..... Already used in South Africa and Malawi, a scale-up of the technique is under way in Tanzania, Rwanda and Ghana. The report found that.

  2. Radiological incidents in radiotherapy

    International Nuclear Information System (INIS)

    Hobzova, L.; Novotny, J.

    2008-01-01

    In many countries a reporting system of radiological incidents to national regulatory body exists and providers of radiotherapy treatment are obliged to report all major and/or in some countries all incidents occurring in institution. State Office for Nuclear Safety (SONS) is providing a systematic guidance for radiotherapy departments from 1997 by requiring inclusion of radiation safety problems into Quality assurance manual, which is the basic document for obtaining a license of SONS for handling with sources of ionizing radiation. For that purpose SONS also issued the recommendation 'Introduction of QA system for important sources in radiotherapy-radiological incidents' in which the radiological incidents are defined and the basic guidance for their classification (category A, B, C, D), investigation and reporting are given. At regular periods the SONS in co-operation with radiotherapy centers is making a survey of all radiological incidents occurring in institutions and it is presenting obtained information in synoptic communication (2003 Motolske dny, 2005 Novy Jicin). This presentation is another summary report of radiological incidents that occurred in our radiotherapy institutions during last 3 years. Emphasis is given not only to survey and statistics, but also to analysis of reasons of the radiological incidents and to their detection and prevention. Analyses of incidents in radiotherapy have led to a much broader understanding of incident causation. Information about the error should be shared as early as possible during or after investigation by all radiotherapy centers. Learning from incidents, errors and near misses should be a part of improvement of the QA system in institutions. Generally, it is recommended that all radiotherapy facilities should participate in the reporting, analyzing and learning system to facilitate the dissemination of knowledge throughout the whole country to prevent errors in radiotherapy.(authors)

  3. [The incidence of Frey syndrome following parotidectomy: results of a survey and follow-up].

    Science.gov (United States)

    Neumann, A; Rosenberger, D; Vorsprach, O; Dazert, S

    2011-02-01

    Frey's syndrome (FS) is defined as facial sweating due to gustatory stimuli following surgery or trauma of the parotid gland. Concomitant symptoms may occur in the area of the auriculotemporal nerve: swelling, facial flushing, and paresthesia. A misguided re-innervation of perspiratory glands by secretory parasympathetic fibres is likely responsible in the pathogenesis. The reported incidence in the literature varies considerably from 1.7% to 97.6%. The present study aims to clarify the incidence of FS. A questionnaire was sent to 221 consecutive patients who underwent parotidectomy between 07/2005 and 07/2008. No selection for type of parotidectomy or histological result was made. Patients were invited to undergo a follow-up examination including Minor's iodine starch test. A total of 135 of 221 (61%) questionnaires were available for evaluation. In all, 82 patients took part in the follow-up, with a follow-up period of 2.8 years (15-51 months). According to the questionnaire, 54% of patients claimed to be free of symptoms. Sweating following gustatory stimuli was reported by 23% of patients. Of the 82 Minor's tests performed, 62.2% were positive. All patients with subjective presence of FS had a positive Minor's test. In 27%, Minor's test was positive although patients did not suffer from facial sweating subjectively ("subclinical FS"). In all, 39% had no subjective complaints and Minor's test was also negative. Cases with a positive Minor's test showed no statistically significant relation to the patients' age, gender or to the histological diagnosis or type of parotidectomy. The clinical incidence of FS in our study is 23%, although a positive Minor's iodine starch test was observed in 62% of cases. Therefore, it seems justifiable to differentiate between a symptomatic or clinical FS and a merely asymptomatic or subclinical FS. No correlation was observed between epidemiological factors and the occurrence of FS. © Springer-Verlag 2010

  4. The role of human papillomavirus in the pathogenesis of head & neck squamous cell carcinoma: an overview

    Directory of Open Access Journals (Sweden)

    Lo Muzio Lorenzo

    2011-03-01

    Full Text Available Abstract Cancer statistics report an increased incidence of OSCC and OPSCC around the world. Though improvements in screening and early diagnosis have dramatically reduced the incidence of this neoplasm in recent years, the 5-year-disease-free survival, is still poor, specially for oropharyngeal cancer, despite the great scientific and financial efforts. Recently, several papers showed that HPV may be involved at least in the pathogenesis of a subgroup of oral and cervical SCC, leading to distinct molecular characteristics compared with HPV-negative ones. Nevertheless, OPSCCs associated with HPV infection seem to show a better prognosis and affect younger patients ( Comparing findings reported in the recent literature, the data of this state of the art about HPV might add useful informations concerning oropharyngeal carcinogenesis. Moreover, our review would be useful in order to define novel perspectives of treatment choice for Head & Neck cancer patients, by combining well known chemotherapeutical drugs with new molecular "target" therapy.

  5. Retinoids, race and the pathogenesis of dengue hemorrhagic fever.

    Science.gov (United States)

    Mawson, Anthony R

    2013-12-01

    Dengue hemorrhagic fever (DHF) is the most significant mosquito-borne viral disease worldwide in terms of illness, mortality and economic cost, but the pathogenesis of DHF is not well understood and there is no specific treatment or vaccine. Based on evidence of liver involvement, it is proposed that dengue virus and retinoids interact to cause cholestatic liver damage, resulting in the spillage of stored retinoids into the circulation and in an endogenous form of hypervitaminosisis A manifested by the signs and symptoms of the disease, including: fever, severe joint and bone pain, capillary leakage, thrombocytopenia, headache, and gastrointestinal symptoms. While retinoids in low concentration are essential for numerous biological functions, they are prooxidant, cytotoxic, mutagenic and teratogenic in higher concentration, especially when unbound to protein, and an endogenous form of vitamin A intoxication is recognized in cholestasis. The model tentatively explains the observations that 1) repeat infections are more severe than initial dengue virus infections; 2) the incidence of denue has increased dramatically worldwide in recent decades; 3) DHF is less prevalent in people of African ancestry than those of other racial backgrounds; and 4) infants are protected from dengue. The retinoid toxicity hypothesis of DHF predicts the co-existence of low serum concentrations of retinol coupled with high concentrations of retinoic acid and an increased percentage of retinyl esters to total vitamin A. Subject to such tests, it may be possible to treat DHF effectively using drugs that target the metabolism and expression of retinoids. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. [Testicular and epididymal appendages. Contribution about it's embryology and pathogenesis].

    Science.gov (United States)

    Blesa, E; Moreno, C; Blesa, A; Rodríguez, L; Núñez, R; Cabrera, R

    2003-04-01

    The testicular appendages are structures with biologic activity and with the possibility to become ischaemic or to degenerate before determined stimulus. Laterly, we have seen an apparent increase in our cases of torsion of testicular appendages. The said, together with the questions about embriology and pathogenesis of this structures, encourage us to do this work. 1- Retrospective clinical study of patients operated of torsion of testicular appendages, from January 1984 to December 2001. We asses age, year of operation and clinical features. 2- Prospective clinical study of patients operated of torsion of testicular appendages, between March 1999 and March 2000. We asses age, time of evolution, degree of ischaemia, nutritional status, sexual maturity stage and testicular volume. 3- Inmunocytochemical study of testicular and epididymal appendages. We identified the oestrogen receptors. There is a meaningful increase in the yearly incidence of ischaemia of testicular appendages. The mean age of the patients was 9.3 +/- 2.5 years, similar alone of the study. In the patients of group 2, the mean time of evolution was 49.2 +/- 46.6 hours. The appendages showed oedema and several degrees of ischaemia in the absence of torsion (14/21). The body mass index was 19.5 +/- 3.7, and 90% of patients had stages I and II of Tanner. The mean of testicular volume was 2.1 +/- 1.6 ml. By means of inmunocytochemical study we identified oestrogen receptors in 7 of all testicular appendages studied and absence of oestrogen receptors in all epididymal appendages. The clinical syndrome of the acute scrotum in the majority of cases is due to oedema and ischemia of the appendages, in absence of torsion, probably related to its enlargement in response to hormonal stimulation, at least in some grade, in prepubertal boys. The difference found, related to oestrogen receptors, suggest a different origin for testicular and epididymal appendages.

  7. Defining cerebral palsy: pathogenesis, pathophysiology and new intervention.

    Science.gov (United States)

    Longo, M; Hankins, G D V

    2009-10-01

    Cerebral palsy (CP) affects 2/1 000 live-born children. There are several antenatal factors, including preterm delivery, low birth weight, infection/inflammation, multiple gestations, and other pregnancy complications, that have been associated with CP in both the preterm and term infant, with birth asphyxia playing a minor role. Due to the increasing survival of the very preterm and very low birth weight infant secondary to improvements in neonatal and obstetric care, the incidence of CP may be increasing. The topics of neonatal encephalopathy and CP, as well as hypoxic-ischemic encephalopathy, are of vital importance to anyone who ventures to deliver infants. Criteria sufficient to define an acute intrapartum hypoxic event as sufficient to cause CP have been advanced previously by both the American College of Obstetricians and Gynecologists and the International Cerebral Palsy Task Force. This review will cover the progression toward defining the pathogenesis and pathophysiology of cerebral palsy. Four essential criteria were advanced as prerequisites if one is to propose that an intrapartum hypoxic-ischemic insult has caused a moderate to severe neonatal encephalopathy that subsequently results in CP. Importantly, all four criteria must be met: 1) evidence of metabolic acidosis (pH <7.0 and base deficit of 12 mmol/L or more); 2) early onset of severe or moderate neonatal encephalopathy in infants born at 34 or more weeks' gestation; 3) CP of the spastic quadriplegic or dyskinetic type, and 4) exclusion of other identifiable etiologies, such as trauma, coagulation disorders, infectious conditions, or genetic disorders. Other criteria that together suggest intrapartum timing are also discussed. The focus of this paper is to explore antenatal antecedents as etiologies of CP and the impact of obstetric care on the prevention of CP.

  8. Preeclampsia: Updates in Pathogenesis, Definitions, and Guidelines.

    Science.gov (United States)

    Phipps, Elizabeth; Prasanna, Devika; Brima, Wunnie; Jim, Belinda

    2016-06-06

    Preeclampsia is becoming an increasingly common diagnosis in the developed world and remains a high cause of maternal and fetal morbidity and mortality in the developing world. Delay in childbearing in the developed world feeds into the risk factors associated with preeclampsia, which include older maternal age, obesity, and/or vascular diseases. Inadequate prenatal care partially explains the persistent high prevalence in the developing world. In this review, we begin by presenting the most recent concepts in the pathogenesis of preeclampsia. Upstream triggers of the well described angiogenic pathways, such as the heme oxygenase and hydrogen sulfide pathways, as well as the roles of autoantibodies, misfolded proteins, nitric oxide, and oxidative stress will be described. We also detail updated definitions, classification schema, and treatment targets of hypertensive disorders of pregnancy put forth by obstetric and hypertensive societies throughout the world. The shift has been made to view preeclampsia as a systemic disease with widespread endothelial damage and the potential to affect future cardiovascular diseases rather than a self-limited occurrence. At the very least, we now know that preeclampsia does not end with delivery of the placenta. We conclude by summarizing the latest strategies for prevention and treatment of preeclampsia. A better understanding of this entity will help in the care of at-risk women before delivery and for decades after. Copyright © 2016 by the American Society of Nephrology.

  9. Recent advances in understanding ichthyosis pathogenesis

    Science.gov (United States)

    Marukian, Nareh V.; Choate, Keith A.

    2016-01-01

    The ichthyoses, also known as disorders of keratinization (DOK), encompass a heterogeneous group of skin diseases linked by the common finding of abnormal barrier function, which initiates a default compensatory pathway of hyperproliferation, resulting in the characteristic clinical manifestation of localized and/or generalized scaling. Additional cutaneous findings frequently seen in ichthyoses include generalized xerosis, erythroderma, palmoplantar keratoderma, hypohydrosis, and recurrent infections. In 2009, the Ichthyosis Consensus Conference established a classification consensus for DOK based on pathophysiology, clinical manifestations, and mode of inheritance. This nomenclature system divides DOK into two main groups: nonsyndromic forms, with clinical findings limited to the skin, and syndromic forms, with involvement of additional organ systems. Advances in next-generation sequencing technology have allowed for more rapid and cost-effective genetic analysis, leading to the identification of novel, rare mutations that cause DOK, many of which represent phenotypic expansion. This review focuses on new findings in syndromic and nonsyndromic ichthyoses, with emphasis on novel genetic discoveries that provide insight into disease pathogenesis. PMID:27408699

  10. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Nandy, Debashis; Mukhopadhyay, Debabrata, E-mail: mukhopadhyay.debabrata@mayo.edu [Department of Biochemistry and Molecular Biology, College of Medicine, Mayo Clinic, 200 First Street SW, Guggenheim 1321C, Rochester, MN 55905 (United States)

    2011-02-24

    Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed.

  11. New Insights into the Pathogenesis of Pancreatitis

    Science.gov (United States)

    Sah, Raghuwansh P.; Dawra, Rajinder K.; Saluja, Ashok K.

    2014-01-01

    Purpose of review In this article, we review important advances in our understanding of the mechanisms of pancreatitis. Recent Findings The relative contribution of intra-pancreatic trypsinogen activation and NFκB activation, the two major early independent cellular events in the etiology of pancreatitis, have been investigated using novel genetic models. Trypsinogen activation has traditionally held the spotlight for many decades as it is believed to be the central pathogenic event of pancreatitis However, recent experimental evidence points to the role of trypsin activation in early acinar cell damage but not in the inflammatory response of acute pancreatitis through NFκB activation. Further, chronic pancreatitis in the caerulein model develops independently of typsinogen activation. Sustained activation of the NFκB pathway, but not persistent intra-acinar expression of active trypsin, was shown to result in chronic pancreatitis. Calcineurin-NFAT signaling was shown to mediate downstream effects of pathologic rise in intracellular calcium. IL-6 was identified as a key cytokine mediating pancreatitis-associated lung injury. Summary Recent advances challenge the long-believed trypsin-centered understanding of pancreatitis. It is becoming increasingly clear that activation of intense inflammatory signaling mechanisms in acinar cells is crucial to the pathogenesis of pancreatitis, which may explain the strong systemic inflammatory response in pancreatitis. PMID:23892538

  12. Pain and the pathogenesis of biceps tendinopathy

    Science.gov (United States)

    Raney, Elise B; Thankam, Finosh G; Dilisio, Matthew F; Agrawal, Devendra K

    2017-01-01

    Biceps tendinopathy is a relatively common ailment that typically presents as pain, tenderness, and weakness in the tendon of the long head of the biceps brachii. Though it is often associated with degenerative processes of the rotator cuff and the joint, this is not always the case, thus, the etiology remains considerably unknown. There has been recent interest in elucidating the pathogenesis of tendinopathy, since it can be an agent of chronic pain, and is difficult to manage. The purpose of this article is to critically evaluate relevant published research that reflects the current understanding of pain and how it relates to biceps tendinopathy. A review of the literature was conducted to create an organized picture of how pain arises and manifests itself, and how the mechanism behind biceps tendinopathy possibly results in pain. Chronic pain is thought to arise from neurogenic inflammation, central pain sensitization, excitatory nerve augmentation, inhibitory nerve loss, and/or dysregulation of supraspinal structures; thus, the connections of these theories to the ones regarding the generation of biceps tendinopathy, particularly the neural theory, are discussed. Pain mediators such as tachykinins, CGRP, and alarmins, in addition to nervous system ion channels, are highlighted as possible avenues for research in tendinopathy pain. Recognition of the nociceptive mechanisms and molecular of biceps tendinopathy might aid in the development of novel treatment strategies for managing anterior shoulder pain due to a symptomatic biceps tendon. PMID:28670360

  13. Pathogenesis of trypanosome infections in cattle

    International Nuclear Information System (INIS)

    Murray, M.; Morrison, W.I.; Emery, D.L.; Akol, G.W.O.; Masake, R.A.; Moloo, S.K.

    1980-01-01

    The potential application of radioisotopes are not discussed in this review of trypanosome pathogenesis in cattle. Initially, structural changes in the lymphoid system are characterized by marked proliferation and germinal centre formation, whereas in long-standing infections the lymphoid organs become depleted. These changes appear associated with immunodepression. Anaemia dominates the clinical disease syndrome in bovine trypanosomiasis. It develops with the onset of parasitaemia and is largely haemolytic, resulting from increased red blood cell destruction by phagocytosis. Several factors may be involved in this process including haemolysins produced by the trypanosome, immunological mechanisms, fever, disseminated intravascular coagulation and an expanded and active mononuclear phagocytic system. During this phase of the disease, cattle respond well to chemotherapy. However, in later phases of the disease, when trypanosomes cannot be detected, the anaemia sometimes persists and animals do not respond to treatment. Concerning the underlying mechanisms responsible for the anaemia, continued red cell destruction combined with some dyshaemopoiesis, associated with a defect in iron metabolism, appears responsible. Widespread tissue degeneration occurs. Organs particularly severely affected include the heart. Death in bovine trypanosomiasis is presumably due to a combination of anaemia, microcirculatory disturbances and myocardial damage. The factors incriminated in tissue damage probably vary with the species of trypanosome involved, although under natural field conditions it is common to find T. congolense, T. vivax and T. brucei in one animal. Likely pathogenic mechanisms in bovine include anoxia as a result of anaemia, microcirculatory disorders and hypersensitivity reactions

  14. Achondroplasia: pathogenesis and implications for future treatment.

    Science.gov (United States)

    Laederich, Melanie B; Horton, William A

    2010-08-01

    Although the genetic defect underlying achondroplasia has been known for over a decade, no effective therapies to stimulate bone growth have emerged. Here we review the recent literature and summarize the molecular mechanisms underlying disease pathology and examine their potential as therapeutic targets. Currently used preclinical models are discussed in the context of recent advances with a special focus on C-type natriuretic peptide. Research on the mutation in Fibroblast Growth Factor Receptor 3 (FGFR3) that causes achondroplasia suggests that disease results from increased signal transduction from the mutant receptor. Thus, current therapeutic strategies have focused on reducing signals emanating from FGFR3. First-generation therapies directly targeting FGFR3, such as kinase inhibitors and neutralizing antibodies, designed for targeting FGFR3 in cancer, are still in the preclinical phase and have yet to translate into the management of achondroplasia. Counteracting signal transduction pathways downstream of FGFR3 holds promise with the discovery that administration of C-type natriuretic peptide to achondroplastic mice ameliorates their clinical phenotype. However, more research into long-term effectiveness and safety of this strategy is needed. Direct targeting of therapeutic agents to growth plate cartilage may enhance efficacy and minimize side effects of these and future therapies. Current research into the pathogenesis of achondroplasia has expanded our understanding of the mechanisms of FGFR3-induced disease and has increased the number of approaches that we may use to potentially correct it. Further research is needed to validate these approaches in preclinical models of achondroplasia.

  15. Apoptosis in cancer: from pathogenesis to treatment

    Directory of Open Access Journals (Sweden)

    Wong Rebecca SY

    2011-09-01

    Full Text Available Abstract Apoptosis is an ordered and orchestrated cellular process that occurs in physiological and pathological conditions. It is also one of the most studied topics among cell biologists. An understanding of the underlying mechanism of apoptosis is important as it plays a pivotal role in the pathogenesis of many diseases. In some, the problem is due to too much apoptosis, such as in the case of degenerative diseases while in others, too little apoptosis is the culprit. Cancer is one of the scenarios where too little apoptosis occurs, resulting in malignant cells that will not die. The mechanism of apoptosis is complex and involves many pathways. Defects can occur at any point along these pathways, leading to malignant transformation of the affected cells, tumour metastasis and resistance to anticancer drugs. Despite being the cause of problem, apoptosis plays an important role in the treatment of cancer as it is a popular target of many treatment strategies. The abundance of literature suggests that targeting apoptosis in cancer is feasible. However, many troubling questions arise with the use of new drugs or treatment strategies that are designed to enhance apoptosis and critical tests must be passed before they can be used safely in human subjects.

  16. Fibromyalgia Pathogenesis and Treatment Options Update.

    Science.gov (United States)

    Chinn, Steven; Caldwell, William; Gritsenko, Karina

    2016-04-01

    This review article presents and summarizes up-to-date literature on the clinical manifestations, diagnosis, pathophysiological mechanisms, and treatment options for fibromyalgia patients. First, the most recent diagnostic criteria for fibromyalgia, as put forth by the American College of Rheumatology will be summarized. Clinical features, including chronic widespread pain, hyperalgesia, mood disorders, anxiety, and disturbed sleep patterns will be explored in-depth. The pathogenesis and pathophysiology of fibromyalgia involves alterations in multiple ascending and descending central nervous system pathways, as well as peripheral pathways, leading to heightened pain sensitivity. Risk factors have been studied extensively, and the most recent research focuses on various genetic influences and the contributions of stress and poor sleep. Lastly, the discussion in this article focuses on treatment options for fibromyalgia; some have been mainstay options for many years. Pharmacological agents include tricyclic antidepressants, anti-epileptic drugs, selective serotonin reuptake inhibitors, norepinephrine/serotonin reuptake inhibitors, as well as some investigational agents. The evidence behind non-pharmacologic treatments, including massage therapy, exercise, and acupuncture, are discussed.

  17. [Transthyretin: it's miracle function and pathogenesis].

    Science.gov (United States)

    Ando, Yukio

    2009-03-01

    Transthyretin (TTR) was previously called prealbumin because the band it formed on agarose gel electrophoresis at pH 8.6 was at the prealbumin position. However, it has been well documented that TTR of rodents does not show a prealbumin position on electrophoresis. Now, its name describes its function, binding to retinol binding protein (RBP) and T4. The serum concentration of the protein is 20-40 mg/dl, and TTR forms a tetramer. The plasma half life of the protein is 1.9 days. TTR is synthesized by the liver, retina, pancreas, and choroid plexus. In cerebro-spinal fluid (CSF), it is the second most abundant protein, and is considered as an important protein in the pathogenesis of Alzheimer's disease, depression, and lead intoxication. In addition, TTR is a tryptophan-rich protein, it is used as one of the nutrition assessment proteins, it acts as an anti acute phase protein, and its plasma concentration decreases during inflammation and bacterial infection. Since TTR is a highly amyloidogenic protein because it contains a beta-sheet structure, it becomes a precursor protein in familial amyloidotic polyneuropathy(FAP). Moreover, TTR plays important roles in various CNS disorders, diabetes melitus, and lipid metabolism.

  18. Zika virus genome biology and molecular pathogenesis.

    Science.gov (United States)

    Wang, Anyou; Thurmond, Stephanie; Islas, Leonel; Hui, Kingyung; Hai, Rong

    2017-03-22

    Zika virus (ZIKV) is an emerging RNA virus in the widespread Flavivirus genus. Recently, ZIKV has rapidly spread around the world and has been implicated in human disease, including neurological disorders, triggering public and scientific attention. Understanding how ZIKV causes disease is the highest priority, yet little is known about this virus. Here we examine the currently published data from ZIKV studies to provide the latest understanding of ZIKV genome biology and molecular pathogenesis. The ZIKV genome evolved rapidly from the Flavivirus genus and diverged from the members of this genus, even within the dengue virus cluster to which ZIKV belongs. Genome variations and divergences also exist among ZIKV strains/isolates. These genome divergences might account for the uniqueness of Zika disease. ZIKV infection activates not only the antiviral immune response but also the pro-inflammatory responses associated with disease symptoms. Strikingly, ZIKV activates protein complexes that are functionally associated with disease process, such as glial cell activation and proliferation (for example, Toll-like receptors), apoptosis and cell death, and inflammation. The activation of these complexes may critically contribute to Zika disease. The novel insights into ZIKV genome divergence and disease mechanisms summarized in this review will help accelerate the development of anti-ZIKV strategies.

  19. Naegleria fowleri: pathogenesis, diagnosis, and treatment options.

    Science.gov (United States)

    Grace, Eddie; Asbill, Scott; Virga, Kris

    2015-11-01

    Naegleria fowleri has generated tremendous media attention over the last 5 years due to several high-profile cases. Several of these cases were followed very closely by the general public. N. fowleri is a eukaryotic, free-living amoeba belonging to the phylum Percolozoa. Naegleria amoebae are ubiquitous in the environment, being found in soil and bodies of freshwater, and feed on bacteria found in those locations. While N. fowleri infection appears to be quite rare compared to other diseases, the clinical manifestations of primary amoebic meningoencephalitis are devastating and nearly always fatal. Due to the rarity of N. fowleri infections in humans, there are no clinical trials to date that assess the efficacy of one treatment regimen over another. Most of the information regarding medication efficacy is based on either case reports or in vitro studies. This review will discuss the pathogenesis, diagnosis, pharmacotherapy, and prevention of N. fowleri infections in humans, including a brief review of all survivor cases in North America. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  20. UPDATED MOLECULAR GENETICS AND PATHOGENESIS OF ICHTHYOSES

    Science.gov (United States)

    AKIYAMA, MASASHI

    2011-01-01

    ABSTRACT Research into the molecular genetics and pathomechanisms of ichthyoses have advanced considerably, resulting in the identification of several causative genes and molecules underlying the disease. In 2009, the First Ichthyosis Consensus Conference was held to establish a consensus for the nomenclature and classification of inherited ichthyoses, by which an international consensus for the classification of inherited ichthyosis was achieved. In this review, the pathogeneses of various ichthyoses are summarized based on their revised classification and terminology. Skin barrier defects are involved in the pathogenesis of various types of ichthyosis. The known causative molecules underlying ichthyosis include ABCA12, lipoxygenase-3, 12R-lipoxygenase, CYP4F22, ichthyin and steroid sulfatase, all of which are thought to be related to the intercellular lipid layers. ABCA12 is a known keratinocyte lipid transporter associated with lipid transport in lamellar granules and a loss of ABCA12 function leads to defective lipid transport in the keratinocytes, resulting in the most severe, harlequin ichthyosis phenotype. Other causative molecules for ichthyoses are transglutaminase 1, keratins and filaggrin. Transglutaminase 1 plays a role in cornified cell envelope formation. Keratins 1, 10 and 2 are involved in the keratin network of suprabasal keratinocytes and filaggrin is essential for the formation of keratohyalin granules. It is important to obtain information concerning genetic defects and to elucidate ichthyotic disease pathomechanisms for the establishment of an effective therapy and beneficial genetic counseling, including a prenatal diagnosis for families affected by ichthyotic disease. PMID:21928690

  1. Preeclampsia: Updates in Pathogenesis, Definitions, and Guidelines

    Science.gov (United States)

    Phipps, Elizabeth; Prasanna, Devika; Brima, Wunnie

    2016-01-01

    Preeclampsia is becoming an increasingly common diagnosis in the developed world and remains a high cause of maternal and fetal morbidity and mortality in the developing world. Delay in childbearing in the developed world feeds into the risk factors associated with preeclampsia, which include older maternal age, obesity, and/or vascular diseases. Inadequate prenatal care partially explains the persistent high prevalence in the developing world. In this review, we begin by presenting the most recent concepts in the pathogenesis of preeclampsia. Upstream triggers of the well described angiogenic pathways, such as the heme oxygenase and hydrogen sulfide pathways, as well as the roles of autoantibodies, misfolded proteins, nitric oxide, and oxidative stress will be described. We also detail updated definitions, classification schema, and treatment targets of hypertensive disorders of pregnancy put forth by obstetric and hypertensive societies throughout the world. The shift has been made to view preeclampsia as a systemic disease with widespread endothelial damage and the potential to affect future cardiovascular diseases rather than a self-limited occurrence. At the very least, we now know that preeclampsia does not end with delivery of the placenta. We conclude by summarizing the latest strategies for prevention and treatment of preeclampsia. A better understanding of this entity will help in the care of at-risk women before delivery and for decades after. PMID:27094609

  2. Coronary heart disease: dietary links and pathogenesis.

    Science.gov (United States)

    Renaud, S; Lanzmann-Petithory, D

    2001-04-01

    For decades it has been postulated that the main environmental factor for coronary heart disease (CHD) was the intake of saturated fatty acids (SFA). Nevertheless, confirmation of the role of SFA in CHD through intervention trials has been disappointing. It was only when the diet was enriched in n-3 fatty acids that CHD was significantly prevented, especially cardiac death. In addition to n-3 fatty acids, many other foodstuffs or nutrients such as fibers, antioxidants, folic acid, calcium and even alcohol contribute to prevent CHD. Thus the relationship between diet and CHD morbidity and mortality appears to be much more complex than formerly suspected considering as key factors only SFA, linoleic acid, cholesterol and atherosclerosis. Some of the mechanisms are briefly described, but many additional nutrients (or non nutrients) may also play an important role in the pathogenesis of CHD. Finally, as a result of the most recent epidemiologic studies the ideal diet may comprise: 8% energy from SFA, 5% from polyunsaturated fatty acids with a ratio 5/1 of linoleic/alpha-linolenic acid+longer chains n-3, oleic acid as desired, large intake of cereals, vegetables, legumes and fruits, fish twice a week, cheese and yogurt as dairy products, rapeseed and olive oils as edible fat. Without side effects, such a diet can be highly palatable, easily enjoyed by many populations and may prevent effectively and rapidly (within a few weeks or months) CHD.

  3. Canine neosporosis: perspectives on pathogenesis and management

    Directory of Open Access Journals (Sweden)

    Silva RC

    2016-04-01

    Full Text Available Rodrigo C Silva,1 Gustavo P Machado2 1Department of Pathobiology and Population Medicine, College of Veterinary Medicine, Mississippi State University, Starkville, MS, USA; 2Department of Internal Medicine and Surgery of Small Animals, Dr Munhoz Veterinary Hospital, Itápolis, Brazil Abstract: Canine neosporosis is a worldwide disease caused by the obligate intracellular parasite protozoan Neospora caninum, manifesting mainly neurological symptoms. N. caninum has a heteroxenous life cycle and affects a wide range of warm-blooded animals. The domestic and wild canids are the definitive host of the parasite. They shed oocysts after ingestion of tissue cysts from infected intermediate hosts (ovine, equine, bovine, canine, and many other species, containing bradyzoites, or oocyst-contaminated water and food. The presence of dogs in farms is considered a risk factor for production animals. A wide range of diagnostic methods are currently available, but the most used is serology, ie, indirect fluorescent antibody test specific to the antibody detection in blood serum samples. No vaccine is available, but control strategies should be focused on the vertical and horizontal transmission of the parasite, ie, avoid feeding dogs with raw or undercooked meat, and taking care with water for human and animal consumption. No medicines to control the transplacental transmission are available yet. Keywords: neosporosis, Neospora caninum, pathogenesis, management, dogs

  4. Infantile hemangiomas: from pathogenesis to clinical features

    Directory of Open Access Journals (Sweden)

    Rosenblatt A

    2012-06-01

    Full Text Available Adena Rosenblatt,1 Erin F Mathes,2 Kristina W Rosbe31Department of Pediatrics, University of California, San Francisco, 2Division of Pediatric Dermatology, Departments of Dermatology and Pediatrics, University of California, San Francisco, 3Division of Pediatric Otolaryngology, Department of Otolaryngology – Head and Neck Surgery, University of California, San Francisco, CA, USAAbstract: Infantile hemangiomas (IH are benign vascular tumors consisting of a collection of immature cells, including progenitor stem cells and disorganized blood vessels. They are the most common benign tumors in childhood. Recently, there have been significant, exciting advancements in the understanding of the pathogenesis and treatment of infantile hemangiomas, which are discussed in this review. The decision to initiate treatment for IH is based on many factors, including size and location, functional compromise, psychosocial implications, and risks and benefits of the proposed therapy. For most families of children with hemangiomas, education about the natural history of IH and reassurance are often the only "treatment" required. A minority of patients with large, complex lesions or lesions that cause functional compromise require early intervention. These patients and families benefit from a multidisciplinary approach to care in vascular birthmark centers. Ongoing multi-institutional clinical trials will provide further important data on the efficacy and safety of hemangioma treatments.Keywords: progenitor stem cell, glucose transporter 1, PHACES, LUMBAR, infantile hemangioma

  5. The Pathogenesis of Ebola Virus Disease.

    Science.gov (United States)

    Baseler, Laura; Chertow, Daniel S; Johnson, Karl M; Feldmann, Heinz; Morens, David M

    2017-01-24

    For almost 50 years, ebolaviruses and related filoviruses have been repeatedly reemerging across the vast equatorial belt of the African continent to cause epidemics of highly fatal hemorrhagic fever. The 2013-2015 West African epidemic, by far the most geographically extensive, most fatal, and longest lasting epidemic in Ebola's history, presented an enormous international public health challenge, but it also provided insights into Ebola's pathogenesis and natural history, clinical expression, treatment, prevention, and control. Growing understanding of ebolavirus pathogenetic mechanisms and important new clinical observations of the disease course provide fresh clues about prevention and treatment approaches. Although viral cytopathology and immune-mediated cell damage in ebolavirus disease often result in severe compromise of multiple organs, tissue repair and organ function recovery can be expected if patients receive supportive care with fluids and electrolytes; maintenance of oxygenation and tissue perfusion; and respiratory, renal, and cardiovascular support. Major challenges for managing future Ebola epidemics include establishment of early and aggressive epidemic control and earlier and better patient care and treatment in remote, resource-poor areas where Ebola typically reemerges. In addition, it will be important to further develop Ebola vaccines and to adopt policies for their use in epidemic and pre-epidemic situations.

  6. Psychological Stress in Pathogenesis of Essential Hypertension.

    Science.gov (United States)

    Ushakov, Alexey V; Ivanchenko, Vera S; Gagarina, Alina A

    2016-01-01

    The article represents literature review and provides evidence for psychological stress to play essential role in the development of arterial hypertension. The pathogenesis of hypertension is complex with a significant diversity and variability of the mechanisms involved in individual patient. In this regard, the determination of specific pathogenic pathways underlying sustained blood pressure elevation in each patient would substantially individualize therapeutic approaches, and hence increase the effectiveness of treatment. Psychological stress is proposed as a significant factor contributing to the development of hypertension. Global urbanization, sedentary lifestyle, daily stress at workplace, lack of physical activity and social support lead to increased anxiety, uncertainty, and finally to chronic mental and emotional stress. This review provides information about alterations in neuroendocrine and immune systems as the main pathogenic pathways linking psychological stress and hypertension. Endothelial dysfunction is considered not only as a consequence but also a primary factor causing prohypertensive state. Moreover, physical inactivity is discussed as one of the plausible mechanisms playing a key role in the development of hypertension in modern lifestyle conditions. Particularly the loss of connection between psychosocial strain and physical activity may underlie the deleterious effect of stress on cardiovascular and metabolic health. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Growth Factor Mediated Signaling in Pancreatic Pathogenesis

    International Nuclear Information System (INIS)

    Nandy, Debashis; Mukhopadhyay, Debabrata

    2011-01-01

    Functionally, the pancreas consists of two types of tissues: exocrine and endocrine. Exocrine pancreatic disorders mainly involve acute and chronic pancreatitis. Acute pancreatitis typically is benign, while chronic pancreatitis is considered a risk factor for developing pancreatic cancer. Pancreatic carcinoma is the fourth leading cause of cancer related deaths worldwide. Most pancreatic cancers develop in the exocrine tissues. Endocrine pancreatic tumors are more uncommon, and typically are less aggressive than exocrine tumors. However, the endocrine pancreatic disorder, diabetes, is a dominant cause of morbidity and mortality. Importantly, different growth factors and their receptors play critical roles in pancreatic pathogenesis. Hence, an improved understanding of how various growth factors affect pancreatitis and pancreatic carcinoma is necessary to determine appropriate treatment. This chapter describes the role of different growth factors such as vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF), platelet derived growth factor (PDGF), fibroblast growth factor (FGF), epidermal growth factor (EGF), and transforming growth factor (TGF) in various pancreatic pathophysiologies. Finally, the crosstalk between different growth factor axes and their respective signaling mechanisms, which are involved in pancreatitis and pancreatic carcinoma, are also discussed

  8. Pathogenesis of odontogenic cysts: an update.

    Science.gov (United States)

    Chindia, M L

    1991-04-01

    This article briefly reviews the origin, classification and pathogenesis of the various odontogenic cysts. Keratocysts and follicular cysts are said to be developmental lesions arising from the remnants of the dental lamina and the cell rests of the dental follicle respectively. The radicular cysts are the most commonly occurring lesions associated with the apices of non-vital teeth. They are said to arise from proliferation of the cell rests of Malassez in chronically inflamed granulomata. It is noted that bone resorption is the major requirement for any bony lesion to expand; hence the interest in the role of diverse cellular and chemical mediators of bone resorption in disease. The current concepts of the role, in cyst initiation and growth, of enzymes including cellular metabolites and cytokines are presented. Evidence on the activities of collagenase, arachidonic acid metabolites, leukotrienes, hydroxyeicosatetraenoic acids, interleukin--1 and prostaglandins is cited. It is observed that the understanding of these cellular and molecular biological behaviour patterns may yield more appropriate information necessary for the development of more effective management modalities for such tissue degrading lesions as odontogenic cysts.

  9. Tryptophan-induced pathogenesis of breast cancer | Cao | African ...

    African Journals Online (AJOL)

    Background: The pathogenesis of breast cancer remains unclear. Aims: To investigate the pathogenesis of breast cancer through targeted metabolomics of amino acids components in serum of patients with breast cancer. Methods: Patients with breast cancers were enrolled in our hospital between year January 1st, 2013 ...

  10. Aetio-pathogenesis of breast cancer | Abdulkareem | Nigerian ...

    African Journals Online (AJOL)

    This is a literature review on the aetiology and pathogenesis of breast cancer, which is the most common cancer worldwide, and the second leading cause of cancer death, especially in Western countries. Several aetiological factors have been implicated in its pathogenesis, and include age, genetics, family history, diet, ...

  11. Necrotizing enterocolitis. New thoughts about pathogenesis and potential treatments.

    Science.gov (United States)

    MacKendrick, W; Caplan, M

    1993-10-01

    Necrotizing enterocolitis (NEC) remains a major cause of morbidity and mortality in premature infants. An incomplete understanding of its pathogenesis has hampered efforts to devise an effective preventative strategy. New insights into the pathogenesis of NEC, particularly at the cellular and biochemical level, however, offer a rational basis for the development of new approaches to this disease.

  12. Role of Endogenous Peptides and Enzymes in the Pathogenesis of ...

    African Journals Online (AJOL)

    pathogenesis mechanism of acute pancreatitis that are related to various inflammatory and pro- inflammatory mediators. Keywords: Acute ... cytokines which are released by neutrophils and macrophages during acute pancreatitis, ... platelet activating factor have been shown to play significant roles in the pathogenesis of ...

  13. Cytokines in Gaucher disease: Role in the pathogenesis of bone ...

    African Journals Online (AJOL)

    Azza A.G. Tantawy

    2015-03-03

    Mar 3, 2015 ... Cytokines in Gaucher disease: Role in the pathogenesis of bone and pulmonary ... Studies are increasingly recognizing the role of immune dysregulation and inflammation in the pathogenesis of Gaucher disease. ..... by various other cells of the immune system [11]. Recent work in a murine model of ...

  14. Demonstrating concepts of pathogenesis using effectors of Phytophthora infestans

    Science.gov (United States)

    Pathogenesis, or how pathogens cause disease, is an important concept in plant pathology. The study of pathogenesis in plant pathology has rapidly expanded and is now a significant portion of plant pathology research (especially research at the molecular level of host-pathogen interaction). With the...

  15. Insights into the pathogenesis and clinicopathological spectrum of oral vegetable granuloma. Case series with literature review

    Directory of Open Access Journals (Sweden)

    Shankargouda Patil

    2017-10-01

    Full Text Available Oral vegetable granuloma represents an inflammatory lesion of foreign body origin resulting from the implantation of vegetable matter. Controversy regarding its pathogenesis is reflected by the various terminologies used to describe the lesion. Its diverse clinical presentations are due to variations in the antigenic potential of the vegetable material and the host response. As the diagnosis is solely histopathological, it is critical to differentiate vegetable granuloma from other oral granulomatous lesions like tuberculosis, sarcoidosis and Wegner’s granulomatosis. Here, we report six cases with the varied clinicopathological presentation of hyaline ring granulomas in association with different pathological lesions.

  16. Pathogenesis and treatment of gastric carcinoma: "An up-date with brief review"

    Directory of Open Access Journals (Sweden)

    Khan Farhat

    2006-01-01

    Full Text Available Gastric cancer is one of the most common cancers and most frequent causes of cancer-related deaths in the world. The overall survival rate is 15-20%. Although the incidence is declining, its prognosis remains poor. The etiological factors and pathogenesis of gastric cancer are not yet fully understood. The integrated research in molecular pathology clarified the details of genetic and epigenetic abnormalities of cancer-related genes in the course of development and progression of gastric cancer. Although epidemiological evidences indicate that environmental factors play a major role in the carcinogenesis, the role of immunological, genetic and immunogenetic factors are thought to contribute to etiopathogenesis of gastric carcinoma. In addition to better understanding of pathogenesis of gastric cancer, the incidence, diagnostic studies and the therapeutic options have also undergone important changes in the last decade. There is ongoing debate regarding the role of adjuvant treatment. In advanced disease, palliation of symptoms, rather than cure, is the primary goal of patient management. Several combination therapies have been developed and have been examined in phase III trials; however, in most cases, they have failed to demonstrate a survival advantage over the reference arm. This review summarizes the newer concepts of molecular biology on gastric carcinogenesis and the new important recommendations for the management of patient with gastric carcinoma.

  17. The Role of Genetic and Immune Factors for the Pathogenesis of Primary Sclerosing Cholangitis in Childhood

    Directory of Open Access Journals (Sweden)

    Priscila Menezes Ferri

    2016-01-01

    Full Text Available Primary sclerosing cholangitis (PSC is a rare cholestatic liver disease characterized by chronic inflammation of the biliary tree resulting in liver fibrosis. PSC is more common in male less than 40 years of age. The diagnosis of PSC is based on clinical, laboratory, image, and histological findings. A biochemical profile of mild to severe chronic cholestasis can be observed. Endoscopic retrograde cholangiography is the golden standard method for diagnosis, but magnetic resonance cholangiography is currently also considered a first-line method of investigation. Differences in clinical and laboratory findings were observed in young patients, including higher incidence of overlap syndromes, mostly with autoimmune hepatitis, higher serum levels of aminotransferases and gamma-glutamyl transferase, and lower incidence of serious complications as cholangiocarcinoma. In spite of the detection of several HLA variants as associated factors in large multicenter cohorts of adult patients, the exact role and pathways of these susceptibility genes remain to be determined in pediatric population. In addition, the literature supports a role for an altered immune response to pathogens in the pathogenesis of PSC. This phenomenon contributes to abnormal immune system activation and perpetuation of the inflammatory process. In this article, we review the role of immune and genetic factors in the pathogenesis of PSC in pediatric patients.

  18. Sexually transmitted papillomavirus infections: epidemiology pathogenesis, clinic, morphology, important differential diagnostic aspects, current diagnostic and treatment options Infecções por papilomavírus sexualmente transmitida: epidemiologia, patogênese, clínica, morfologia, aspectos importantes do diagnóstico diferencial, diagnóstico atual e opções de tratamento

    Directory of Open Access Journals (Sweden)

    Georgi Tchernev

    2009-08-01

    Full Text Available The family of human papilloma viruses (HPV comprises more than 100 genotypes. Approximately 30 of the genotypes are responsible for infections in the human anogenital area. A precisely defined algorithm with the goal of diagnosing and removing HPV for a prolonged or indefinite length of time, as well as to protect the patient from any malignant ransformation, does not currently exist. The identification of HPV strains by PCR or DNA hybridization in lesional tissue provides higher security for the patients. In high-risk patients additional colposcopy, rectoscopy, and rethroscopy/cystoscopy increase the probability of proper diagnosis and the application of a reliable therapeutic strategy. Removal of lesions by means of invasive methods, such as electrodessication, cryosurgery, and/or laser therapy, may be successful and could be combined pre- and postoperatively with the local application of podophyllotoxin, Trichloroacetic acid, 5-fluorouracil epinephrine gel, imiquimod, cidofovir or interferon. The administration of vaccine to young patients prevents to a significant extent the clinical manifestation of the most frequent viral strains, being HPV-6,-11 and -18. The different therapeutic methods must be applied in accordance with the clinical picture, taking into account the patient's general status, the presence of concomitant diseases, as well as the local and systematic compatibility of the side effects of each remedy. The review focuses on the diagnosis and treatment options of sexually transmitted HPV-infections and includes synopsis of the most recent literature regarding new data of epidemiology, pathogenesis, ifferential diagnosis and morphology of HPV infections in humans.A família de papiloma vírus humano (HPV compreende mais de 100 genótipos. Aproximadamente 30 dos genótipos são responsáveis pelas infecções na área anogenital em humanos. Não dispomos no momento de um algoritmo precisamente definido tendo como meta o diagn

  19. Critical incident stress management.

    Science.gov (United States)

    Lim, J J; Childs, J; Gonsalves, K

    2000-10-01

    Recent studies have indicated implementation of the CISM Program has impacted and reduced the cost of workers' compensation claims for stress related conditions and the number of lost work days (Ott, 1997; Western Management Consultants, 1996). Occupational health professionals need to be ready to develop and implement a comprehensive critical incident stress management process in anticipation of a major event. The ability to organize, lead, or administer critical incident stress debriefings for affected employees is a key role for the occupational health professional. Familiarity with these concepts and the ability to identify a critical incident enhances value to the business by mitigating the stress and impact to the workplace. Critical Incident Stress Management Systems have the potential for decreasing stress and restoring employees to normal life function--a win/win situation for both the employees and the organization.

  20. Marine Animal Incident Database

    Data.gov (United States)

    National Oceanic and Atmospheric Administration, Department of Commerce — Large whale stranding, death, ship strike and entanglement incidents are all recorded to monitor the health of each population and track anthropogenic factors that...

  1. Police Incident Blotter (Archive)

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — The Police Blotter Archive contains crime incident data after it has been validated and processed to meet Uniform Crime Reporting (UCR) standards, published on a...

  2. Prediction of Safety Incidents

    Data.gov (United States)

    National Aeronautics and Space Administration — Safety incidents, including injuries, property damage and mission failures, cost NASA and contractors thousands of dollars in direct and indirect costs. This project...

  3. 2011 Japanese Nuclear Incident

    Science.gov (United States)

    EPA’s RadNet system monitored the environmental radiation levels in the United States and parts of the Pacific following the Japanese Nuclear Incident. Learn about EPA’s response and view historical laboratory data and news releases.

  4. Osteoarthritis: Control of human cartilage hypertrophic differentiation. Research highlight van: Gremlin1, frizzled-related protein, and Dkk-1 are key regulators of human articular cartilage homeostasis

    NARCIS (Netherlands)

    Buckland, J.; Leijten, Jeroen Christianus Hermanus; van Blitterswijk, Clemens; Karperien, Hermanus Bernardus Johannes

    2012-01-01

    Disruption of articular cartilage homeostasis is important in osteoarthritis (OA) pathogenesis, key to which is activation of articular chondrocyte hypertrophic differentiation. Healthy articular cartilage is resistant to hypertrophic differentiation, whereas growth-plate cartilage is destined to

  5. Pathogenesis of Noroviruses, Emerging RNA Viruses

    Directory of Open Access Journals (Sweden)

    Stephanie M. Karst

    2010-03-01

    Full Text Available Human noroviruses in the family Caliciviridae are a major cause of epidemic gastroenteritis. They are responsible for at least 95% of viral outbreaks and over 50% of all outbreaks worldwide. Transmission of these highly infectious plus-stranded RNA viruses occurs primarily through contaminated food or water, but also through person-to-person contact and exposure to fomites. Norovirus infections are typically acute and self-limited. However, disease can be much more severe and prolonged in infants, elderly, and immunocompromised individuals. Norovirus outbreaks frequently occur in semi-closed communities such as nursing homes, military settings, schools, hospitals, cruise ships, and disaster relief situations. Noroviruses are classified as Category B biodefense agents because they are highly contagious, extremely stable in the environment, resistant to common disinfectants, and associated with debilitating illness. The number of reported norovirus outbreaks has risen sharply since 2002 suggesting the emergence of more infectious strains. There has also been increased recognition that noroviruses are important causes of childhood hospitalization. Moreover, noroviruses have recently been associated with multiple clinical outcomes other than gastroenteritis. It is unclear whether these new observations are due to improved norovirus diagnostics or to the emergence of more virulent norovirus strains. Regardless, it is clear that human noroviruses cause considerable morbidity worldwide, have significant economic impact, and are clinically important emerging pathogens. Despite the impact of human norovirus-induced disease and the potential for emergence of highly virulent strains, the pathogenic features of infection are not well understood due to the lack of a cell culture system and previous lack of animal models. This review summarizes the current understanding of norovirus pathogenesis from the histological to the molecular level, including

  6. [Evolution of pathogenesis of atherosclerosis in phylogenesis].

    Science.gov (United States)

    Titov, V N

    2014-01-01

    The first atherosclerosis pandemics developed in phylogenesis when animals went out of the ocean, the second coincided with mutations of proteins that transferred zero-cholesterol esters, the third (present-day pandemics) results from disturbed biological function of trophology, abnormally high content of saturated fatty acids and their trans-forms in food, and blockade of bioavailability of polyenic FA (PNFA) for cells. The blood pool of ligand-free lipoproteins, phylogenetically early macrophages are only partly utilized in intima giving rise to atheromatosis. When active absorption of w-3 and w-6 PNFA is blocked, the cells synthesize by way of compensation non-physiological w-9 eicosanoids which creates the basis of pathogenesis of atherosclerosis, pathology ofautocrine regulation, and paracrine humoral regulation of cell communities and the body. A rise in the frequency of non-infectious diseases above 5-7% is regarded as pathology of biological functions and reactions. Non-physiological environmental effects should be neutralized by normalization of tropholgy function, exotrophic biological reaction. Metabolic pandemics may have two outcomes. First: (a) effective reduction to a minimum of infavourable environmental effects, i.e. normalization of the nutritive function, (b) matching it with possibilities of lipoproteins, (c) reduction of morbidity and mortality from atherosclerosis. Second: man continues to develop as in phylogenesis and adapts himself to nonphysiological nutrition. Mortality from infarction and stroke will remain high during the next 40-50 thousand years. Increased content of w-3 PNFA in food without reduction of NAF with blockade of bioavailability will further facilitate atheromatosis. Man should rely on physiological nutrition, there is no reason to rely on hypolipidemic agents. Otherwise, the second outcome awaits the mankind. Tertium non datum.

  7. Pathogenesis of reduced or increased bladder sensation.

    Science.gov (United States)

    Tsunoyama, Kuniko; Sakakibara, Ryuji; Yamaguchi, Chiharu; Uchiyama, Tomoyuki; Yamamoto, Tatsuya; Yamanishi, Tomonori; Takahashi, Osamu; Sugiyama, Megumi; Kishi, Masahiko; Ogawa, Emina

    2011-03-01

    Pathogenesis of reduced or increased bladder sensation is not well known. Hence, we systematically investigated the frequency of reduced or increased bladder sensation in neurologic/mental diseases. We analyzed 911 patients who were referred from within our hospital. Data registries included a diagnosis, a lower urinary tract symptom questionnaire, a urodynamic study, and neurological examinations. Reduced bladder sensation is defined as bladder volume at the first sensation >300 ml. Increased bladder sensation is defined as bladder volume at the first sensation sensation (33.3-43.8% in diabetic neuropathy, etc.). Myelopathies are the second most common cause (17.4-25.0% in multiple sclerosis, etc.). Less common is brain diseases (9.6% in multiple system atrophy, etc.). In contrast, myelopathies are the most common cause of increased bladder sensation without DO (25.0-40.0% in spinal forms of systemic lupus erythematosus, Sjogren's syndrome, etc.). Neuropathies are the second most common (17.3-22.2% in post-pelvic organ surgery, diabetic neuropathy, etc.). Less common is brain/mental diseases (20.0% in psychogenic bladder dysfunction, 8.1% in Parkinson's disease, etc.). The present study revealed that neuropathies are the most common cause of reduced bladder sensation in neurologic/mental diseases. Increased bladder sensation without DO occurs mainly in peripheral and central sensory pathway lesions, as well as in basal ganglia lesions and psychogenic bladder dysfunction. Reduced and increased bladder sensation should be a major treatment target for maximizing patients' quality of life. Copyright © 2011 Wiley-Liss, Inc.

  8. Pathogenesis of diverticulosis and diverticular disease.

    Science.gov (United States)

    Walker, Marjorie M; Harris, Angela K

    2017-06-01

    Diverticulosis is defined by the presence of diverticula due to herniation of mucosa and muscularis mucosa through the muscularis propria at sites of vascular penetration in the colon and is asymptomatic in the vast majority affected. There are global differences of distribution, in Western industrialized societies, the most common site is in the left colon, but in Asia right sided diverticulosis predominates. Whilst present in 17.5% of a general population and 42% of all comers at endoscopy it is seen in 71% of those aged ≥80 years. Diverticular disease is defined as clinically significant and symptomatic diverticulosis, which may have an absence of macroscopically overt colitis and in true diverticulitis there is macroscopic inflammation of diverticula with related acute or chronic complications. Whilst overall, diverticulitis affects only 4% of those with diverticulosis, in younger patients (aged 40-49 years) this peaks at 11%. Diverticulosis is one of the most common chronic diseases, yet research in this field on pathogenesis has lagged behind other common conditions such as diabetes mellitus. However, in the last decade there have been major advances in taxonomy that can be used to relate to patients' outcome and treatment in both medicine and surgery. It has been shown there is an association with age, diet, drugs and smoking. Genetic studies have shown a familial association and a specific gene, TNFSF 15 may predict severity of disease. The role of the microbiome has been explored and microbial and metabolomic signatures are also important in predicting disease severity. That diverticulosis is a chronic disease is shown by mucosal pathology with subtle chronic inflammation present in those with asymptomatic diverticulosis and inflammation may lead to muscular hypertrophy, enteric nerve remodeling with disordered motility. The diverticulitis quality of life instrument shows that this condition impacts markedly on patients' well-being and prevention and

  9. Obesity Pathogenesis: An Endocrine Society Scientific Statement.

    Science.gov (United States)

    Schwartz, Michael W; Seeley, Randy J; Zeltser, Lori M; Drewnowski, Adam; Ravussin, Eric; Redman, Leanne M; Leibel, Rudolph L

    2017-08-01

    Obesity is among the most common and costly chronic disorders worldwide. Estimates suggest that in the United States obesity affects one-third of adults, accounts for up to one-third of total mortality, is concentrated among lower income groups, and increasingly affects children as well as adults. A lack of effective options for long-term weight reduction magnifies the enormity of this problem; individuals who successfully complete behavioral and dietary weight-loss programs eventually regain most of the lost weight. We included evidence from basic science, clinical, and epidemiological literature to assess current knowledge regarding mechanisms underlying excess body-fat accumulation, the biological defense of excess fat mass, and the tendency for lost weight to be regained. A major area of emphasis is the science of energy homeostasis, the biological process that maintains weight stability by actively matching energy intake to energy expenditure over time. Growing evidence suggests that obesity is a disorder of the energy homeostasis system, rather than simply arising from the passive accumulation of excess weight. We need to elucidate the mechanisms underlying this "upward setting" or "resetting" of the defended level of body-fat mass, whether inherited or acquired. The ongoing study of how genetic, developmental, and environmental forces affect the energy homeostasis system will help us better understand these mechanisms and are therefore a major focus of this statement. The scientific goal is to elucidate obesity pathogenesis so as to better inform treatment, public policy, advocacy, and awareness of obesity in ways that ultimately diminish its public health and economic consequences. Copyright © 2017 Endocrine Society.

  10. Constraint Differentiation

    DEFF Research Database (Denmark)

    Mödersheim, Sebastian Alexander; Basin, David; Viganò, Luca

    2010-01-01

    We introduce constraint differentiation, a powerful technique for reducing search when model-checking security protocols using constraint-based methods. Constraint differentiation works by eliminating certain kinds of redundancies that arise in the search space when using constraints to represent...... results show that constraint differentiation substantially reduces search and considerably improves the performance of OFMC, enabling its application to a wider class of problems....

  11. Information Security Incident Management

    Directory of Open Access Journals (Sweden)

    D. I. Persanov

    2010-03-01

    Full Text Available The present report highlights the points of information security incident management in an enterprise. Some aspects of the incident and event classification are given. The author presents his view of the process scheme over the monitoring and processing information security events. Also, the report determines a few critical points of the listed process and gives the practical recommendations over its development and optimization.

  12. PATHOGENESIS AND TREATMENT OF THROMBOHEMORRHAGIC DIATHESIS IN ACUTE PROMYELOCYTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Anna Falanga

    2011-12-01

    Full Text Available Acute promyelocytic leukemia (APL is a distinct subtype of myeloid leukemia characterized by t(15;17 chromosomal translocation, which involves the retinoic acid receptor-alpha (RAR-alpha. APL typically presents with a life-threatening hemorrhagic diathesis. Before the introduction of all-trans retinoic acid (ATRA for the cure of APL, fatal hemorrhages due, at least in part, to the APL-associated coagulopathy, were a major cause of induction remission failure. The laboratory abnormalities of blood coagulation found in these patients are compatible with a syndrome of disseminated intravascular coagulation (DIC. Major determinants of the coagulopathy of APL are endogenous factors expressed by the leukemic cells, including procoagulant factors, fibrinolytic proteins, and non-specific proteolytic enzymes. In addition, these cells have an increased capacity to adhere to the vascular endothelium, and to secrete inflammatory cytokines [i.e. interleukin-1beta (IL-1beta and tumor necrosis factor (TNF-alpha], which in turn stimulate the expression of prothrombotic activities by endothelial cells and leukocytes. ATRA can interfere with each of the principal hemostatic properties of the leukemic cell, thus reducing the APL cell procoagulant potential, in parallel to the induction of cellular differentiation. This effect occurs in vivo, in the bone marrow of APL patients receiving ATRA, and is associated with the improvement of the bleeding symptoms. Therapy with arsenic trioxide (ATO also beneficially affects coagulation in APL. However, early deaths from bleeding still remain a major problem in APL and further research is required in this field. In this review, we will summarize our current knowledge of the pathogenesis of the APL-associated coagulopathy and will overview the therapeutic approaches for the management of this complication.

  13. Differential manifolds

    CERN Document Server

    Kosinski, Antoni A

    2007-01-01

    The concepts of differential topology form the center of many mathematical disciplines such as differential geometry and Lie group theory. Differential Manifolds presents to advanced undergraduates and graduate students the systematic study of the topological structure of smooth manifolds. Author Antoni A. Kosinski, Professor Emeritus of Mathematics at Rutgers University, offers an accessible approach to both the h-cobordism theorem and the classification of differential structures on spheres.""How useful it is,"" noted the Bulletin of the American Mathematical Society, ""to have a single, sho

  14. Differential games.

    Science.gov (United States)

    Varaiya, P. P.

    1972-01-01

    General discussion of the theory of differential games with two players and zero sum. Games starting at a fixed initial state and ending at a fixed final time are analyzed. Strategies for the games are defined. The existence of saddle values and saddle points is considered. A stochastic version of a differential game is used to examine the synthesis problem.

  15. Genomic Heterogeneity of Breast Tumor Pathogenesis

    Science.gov (United States)

    Ellsworth, Rachel E.; Hooke, Jeffrey A.; Shriver, Craig D.; Ellsworth, Darrell L.

    2009-01-01

    Pathological grade is a useful prognostic factor for stratifying breast cancer patients into favorable (low-grade, well-differentiated tumors) and less favorable (high-grade, poorly-differentiated tumors) outcome groups. Under the current system of tumor grading, however, a large proportion of tumors are characterized as intermediate-grade, making determination of optimal treatments difficult. In an effort to increase objectivity in the pathological assessment of tumor grade, differences in chromosomal alterations and gene expression patterns have been characterized in low-grade, intermediate-grade, and high-grade disease. In this review, we outline molecular data supporting a linear model of progression from low-grade to high-grade carcinomas, as well as contradicting genetic data suggesting that low-grade and high-grade tumors develop independently. While debate regarding specific pathways of development continues, molecular data suggest that intermediate-grade tumors do not comprise an independent disease subtype, but represent clinical and molecular hybrids between low-grade and high-grade tumors. Finally, we discuss the clinical implications associated with different pathways of development, including a new clinical test to assign grade and guide treatment options. PMID:20689613

  16. Nuclear matrix - structure, function and pathogenesis.

    Science.gov (United States)

    Wasąg, Piotr; Lenartowski, Robert

    2016-12-20

    The nuclear matrix (NM), or nuclear skeleton, is the non-chromatin, ribonucleoproteinaceous framework that is resistant to high ionic strength buffers, nonionic detergents, and nucleolytic enzymes. The NM fulfills a structural role in eukaryotic cells and is responsible for maintaining the shape of the nucleus and the spatial organization of chromatin. Moreover, the NM participates in several cellular processes, such as DNA replication/repair, gene expression, RNA transport, cell signaling and differentiation, cell cycle regulation, apoptosis and carcinogenesis. Short nucleotide sequences called scaffold/matrix attachment regions (S/MAR) anchor the chromatin loops to the NM proteins (NMP). The NMP composition is dynamic and depends on the cell type and differentiation stage or metabolic activity. Alterations in the NMP composition affect anchoring of the S/MARs and thus alter gene expression. This review aims to systematize information about the skeletal structure of the nucleus, with particular emphasis on the organization of the NM and its role in selected cellular processes. We also discuss several diseases that are caused by aberrant NM structure or dysfunction of individual NM elements.

  17. Pathogenesis of glucose intolerance in uremia.

    Science.gov (United States)

    DeFronzo, R A

    1978-12-01

    The pathogenesis of glucose intolerance in uremia was examined with the glucose clamp technique. Hyperglycemic clamp (n = 8): The plasma glucose concentration is acutely raised and maintained at 125 mg/dl above basal levels. Under these steady state conditions the glucose infusion rate, M, equals the amount of glucose metabolized: Predialysis M averaged 4.23 +/- 0.36 mg/kg/min and increased to 7.71 +/- 0.43 postdialysis (p less than 0.001). The plasma insulin response predialysis was 90 +/- 20 microU/ml and decreased to 80 +/- 23 microU/ml following dialysis. Consequently the M/l ratio, a measure of tissue sensitivity to insulin, increased by 80% +/- 25% (p less than 0.001) but still remained less than controls (p less than 0.01). Euglycemic insulin clamp (n = 10): The plasma insulin concentration is acutely raised by 100 microU/ml and the plasma glucose concentration is held constant at the basal level. Predialysis both M (3.37 +/- 0.36 mg/kg/min) and M/l (3.56 +/- 0.33 mg/kg/min per microU/ml X 100) were significantly less than controls (p less than 0.01). Postdialysis both M and M/l increased significantly (p less than 0.01) to a mean that was not significantly different from controls. Basal hepatic glucose production (n = 6), 2.15 +/- 0.09 mg/kg/min, was similar to controls and fell (87% +/- 4%) normally during the insulin clamp. In five uremic subjects in wom insulin binding to monocytes was measured, there was no correlation with tissue sensitivity to insulin (M/l). Significant abnormalities in both growth hormone and glucagon physiology were present in uremic individuals, but no correlation with either the presence or degree of glucose intolerance was demonstrable. In conclusion, glucose intolerance is universally present in uremic subjects and results primarily from peripheral tissue insensitivity to insulin. Insulin secretion is usually enhanced in an attempt to compensate for this insulin resistance but in occasional subjects uremia also inhibits beta

  18. Modifier genes: Moving from pathogenesis to therapy.

    Science.gov (United States)

    McCabe, Edward R B

    2017-09-01

    This commentary will focus on how we can use our knowledge about the complexity of human disease and its pathogenesis to identify novel approaches to therapy. We know that even for single gene Mendelian disorders, patients with identical mutations often have different presentations and outcomes. This lack of genotype-phenotype correlation led us and others to examine the roles of modifier genes in the context of biological networks. These investigations have utilized vertebrate and invertebrate model organisms. Since one of the goals of research on modifier genes and networks is to identify novel therapeutic targets, the challenges to patient access and compliance because of the high costs of medications for rare genetic diseases must be recognized. A recent article explored protective modifiers, including plastin 3 (PLS3) and coronin 1C (CORO1C), in spinal muscular atrophy (SMA). SMA is an autosomal recessive deficit of survival motor neuron protein (SMN) caused by mutations in SMN1. However, the severity of SMA is determined primarily by the number of SMN2 copies, and this results in significant phenotypic variability. PLS3 was upregulated in siblings who were asymptomatic compared with those who had SMA2 or SMA3, but identical homozygous SMN1 deletions and equal numbers of SMN2 copies. CORO1C was identified by interrogation of the PLS3 interactome. Overexpression of these proteins rescued endocytosis in SMA models. In addition, antisense RNA for upregulation of SMN2 protein expression is being developed as another way of modifying the SMA phenotype. These investigations suggest the practical application of protective modifiers to rescue SMA phenotypes. Other examples of the potential therapeutic value of novel protective modifiers will be discussed, including in Duchenne muscular dystrophy and glycerol kinase deficiency. This work shows that while we live in an exciting era of genomic sequencing, a functional understanding of biology, the impact of its

  19. Role of perfumes in pathogenesis of autism.

    Science.gov (United States)

    Bagasra, Omar; Golkar, Zhabiz; Garcia, Miranda; Rice, Lakya N; Pace, Donald Gene

    2013-06-01

    Autism spectrum disorders (ASDs) are developmental conditions characterized by deficits in social interaction, verbal and nonverbal communication, and obsessive/stereotyped patterns of behavior. Although there is no reliable neurophysiological marker associated with ASDs, dysfunction of the parieto-frontal mirror neuron system and underdeveloped olfactory bulb (OB) has been associated with the disorder. It has been reported that the number of children who have ASD has increased considerably since the early 1990 s. In developed countries, it is now reported that 1-1.5% of children have ASD, and in the US it is estimated that one in 88 children suffer from ASD. Currently, there is no known cause for ASD. During the last three decades, the most commonly accepted paradigm about autism is that it is a genetically inherited disease. The recent trio analyses, in which both biological parents and the autistic child's exomes are sequenced, do not support this paradigm. On the other hand, the environmental factors that may induce genetic mutations in vitro have not been clearly identified, and there is little irrefutable evidence that pesticides, water born chemicals, or food preservatives play critical roles in inducing the genetic mutations associated with known intellectual deficiencies that have been linked to autism spectrum disorder (ASD). Here, we hypothesize and provide scientific evidence that ASD is the result of exposure to perfumes and cosmetics. The highly mutagenic, neurotoxic, and neuromodulatory chemicals found in perfumes are often overlooked and ignored as a result of a giant loophole in the Federal Fair Packaging and Labeling Act of 1973, which explicitly exempts fragrance producers from having to disclose perfume ingredients on product labels. We hypothesize that perfumes and cosmetics may be important factors in the pathogenesis of ASD. Synthetic perfumes have gained global utility not only as perfumes but also as essential chemicals in detergents

  20. Radiation incidents in dentistry

    International Nuclear Information System (INIS)

    Lovelock, D.J.

    1996-01-01

    Most dental practitioners act as their own radiographer and radiologist, unlike their medical colleagues. Virtually all dental surgeons have a dental X-ray machine for intraoral radiography available to them and 40% of dental practices have equipment for dental panoramic tomography. Because of the low energy of X-ray equipment used in dentistry, radiation incidents tend to be less serious than those associated with other aspects of patient care. Details of 47 known incidents are given. The advent of the 1985 and 1988 Ionising Radiation Regulations has made dental surgeons more aware of the hazards of radiation. These regulations, and general health and safety legislation, have led to a few dental surgeons facing legal action. Because of the publicity associated with these court cases, it is expected that there will be a decrease in radiation incidents arising from the practice of dentistry. (author)

  1. Hepatitis E virus incidence in patients with non-identified acute viral hepatitis in Mexico

    Directory of Open Access Journals (Sweden)

    R. Berebichez-Fridman

    2016-07-01

    Conclusions: The incidence of HEV infection is probably underdiagnosed, and there is a marked lack of knowledge regarding its epidemiology in Mexico. Further studies should be performed in order to understand the epidemiology, risks factors, pathogenesis and prevention of this disease.

  2. Water hardness influences Flavobacterium columnare pathogenesis in channel catfish

    Science.gov (United States)

    Studies were conducted to determine aspects of water chemistry responsible for large differences in pathogenesis and mortality rates in challenges of channel catfish Ictalurus punctatus with Flavobacterium columnare; challenges were conducted in water supplying the Stuttgart National Aquaculture Res...

  3. Oral candidiasis: pathogenesis, clinical presentation, diagnosis and treatment strategies.

    Science.gov (United States)

    Lalla, Rajesh V; Patton, Lauren L; Dongari-Bagtzoglou, Anna

    2013-04-01

    Oral candidiasis is a clinical fungal infection that is the most common opportunistic infection affecting the human oral cavity. This article reviews the pathogenesis, clinical presentations, diagnosis and treatmentstrategies for oral candidiasis.

  4. Current insights in sepsis: from pathogenesis to new treatment targets

    NARCIS (Netherlands)

    Wiersinga, W. Joost

    2011-01-01

    Sepsis continues to be a leading cause of ICU death. This review summarizes current knowledge on sepsis pathogenesis and new therapeutical strategies. Although systemic inflammatory response syndrome predominates in early sepsis, the compensatory anti-inflammatory response syndrome causes

  5. Multiparametric Bioinformatics Distinguish the CD4/CD8 Ratio as a Suitable Laboratory Predictor of Combined T Cell Pathogenesis in HIV Infection

    DEFF Research Database (Denmark)

    Buggert, Marcus; Frederiksen, Juliet Wairimu; Noyan, Kajsa

    2014-01-01

    -DR), exhaustion (PD-1, Tim-3), senescence (CD28, CD57), and memory differentiation (CD45RO, CD27) in a cohort of 47 untreated HIV-infected individuals. Using bioinformatical methods, we identified 139 unique populations, representing the “combined T cell pathogenesis,” which significantly differed between the HIV...

  6. Signaling Pathways in Pathogenesis of Diamond Blackfan Anemia

    Science.gov (United States)

    2015-12-01

    AWARD NUMBER: W81XWH-12-1-0590 TITLE: SIGNALING PATHWAYS IN PATHOGENESIS OF DIAMOND BLACKFAN ANEMIA PRINCIPAL INVESTIGATOR: KATHLEEN M...SUBTITLE 5a. CONTRACT NUMBER W81XWH-12-1-0590 SIGNALING PATHWAYS IN PATHOGENESIS OF DIAMOND BLACKFAN ANEMIA 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER...Unlimited 13. SUPPLEMENTARY NOTES None 14. ABSTRACT: Diamond Blackfan Anemia (DBA) is a disorder that results in pure red cell aplasia, congenital

  7. Differential games

    CERN Document Server

    Friedman, Avner

    2006-01-01

    This volume lays the mathematical foundations for the theory of differential games, developing a rigorous mathematical framework with existence theorems. It begins with a precise definition of a differential game and advances to considerations of games of fixed duration, games of pursuit and evasion, the computation of saddle points, games of survival, and games with restricted phase coordinates. Final chapters cover selected topics (including capturability and games with delayed information) and N-person games.Geared toward graduate students, Differential Games will be of particular interest

  8. Pathogenesis of radiation-induced osteosarcomas

    International Nuclear Information System (INIS)

    Luz, A.

    1980-07-01

    Results backed by experiments are presented here for the osteosarcoma induction in mice after incorporation of radium-224 or thorium-227. The dose-response relationship for osteosarcoma induction by short-lived alpha radiation is very much influenced by the time distribution of the applied activity and is thus influenced by the dose rate in the skeleton. In the total dose range investigated the decrease of the dose rate leads to an increase of the ontogenetic effect to a tumour incidence of nearly 100%. If the internal exposure starts after the period of rapid skeletal growth the osteosarcoma risk is not reduced compared with the young animals and the tumour latency period is even shorter. This reducing of the latency period is dependent on the expected osteosarcoma risk. In the case of a lower exogenic risk the date for the clinical tumour manifestations seems to be determined by the date of the manifestation of spontaneous osteosarcomas whereas, in the case of a great exogenic risk, the agent obviously determines when the tumour appears. A spontaneous osteodysplasia in the skeleton of old female mice certainly cannot be defined as the co-factor of osteosarcomagenesis. The non-neoplastic proliferated cells which are morphologically similar to the osteodysplastia are found to a larger extent in the skeleton of female mice with but also in male mice. It is not clear whether this is a real preneoplasia or a parallel phenomenon of the osteosarcomagenesis. (orig./MG) [de

  9. Cardiac syndrome X. Diagnosis, pathogenesis and management.

    Science.gov (United States)

    Kaski, Juan Carlos; Aldama, Guillermo; Cosín-Sales, Juan

    2004-01-01

    Patients with cardiac syndrome X (typical chest pain and normal coronary arteriograms) represent a heterogeneous syndrome, which encompasses different pathogenic mechanisms. Although symptoms in most patients with cardiac syndrome X are non-cardiac, a sizable proportion of them have angina pectoris due to transient myocardial ischemia. Thus radionuclide myocardial perfusion defects, coronary sinus oxygen saturation abnormalities and pH changes, myocardial lactate production and stress-induced alterations of cardiac high energy phosphate suggest an ischemic origin of symptoms in at least a proportion of patients with cardiac syndrome X. Microvascular abnormalities, caused by endothelial dysfunction, appear to be responsible for myocardial ischemia in patients with cardiac syndrome X. Endothelial dysfunction is likely to be multifactorial in these patients and it is conceivable that risk factors such as hypertension, hypercholesterolemia, diabetes mellitus and smoking can contribute to its development. Most patients with cardiac syndrome X are postmenopausal women and estrogen deficiency has been therefore proposed as a pathogenic factor in female patients. Additional factors such as abnormal pain perception may contribute to the pathogenesis of chest pain in patients with angina pectoris and normal coronary angiograms. Although prognosis is good regarding survival, patients with cardiac syndrome X have an impaired quality of life. Management of this syndrome represents a major challenge to the treating physician. Understanding the mechanism underlying the condition is of vital importance for patient management. Thus diagnostic tests should aim at identifying the cause of the symptoms in the individual patient, i.e. myocardial ischemia, increased pain perception, abnormalities of adrenergic tone, non-cardiac mechanisms, etc. Moreover, it is important to bear in mind that treatment of cardiac syndrome X should be mainly directed towards improving quality of life, as

  10. Pyomyositis - a differential diagnosis of malignant soft tissue tumours

    International Nuclear Information System (INIS)

    Ahrens, P.; Gross-Fengels, W.; Bovelet, K.

    1991-01-01

    The case of a seven-year-old boy with an enlarging woody-hard mass in the upper thigh is described and the related literature is reviewed. In absence of conclusive sings of inflammatory on both clinical and radiological findings a malignant soft tissue tumour was initially suspected. On operation the mass was found to contain multiple loculated abscesses, and turned out to be a subacute staphylococcal myositis (pyomyositis). Such lesions are quite common in subtropical and tropical climates, and a review of the literature indicates that the incidence of this formerly rare entity is increasing in temperature climates. A variety of factors play a role in pathogenesis, and a history of previous aspectic trauma can be found in about 50% of all cases. The most frequent location is the proximal lower limb or buttock. The clinical history and physical findings are often non-specific. Plain radiographs are non-diagnostic; ultrasound, CT and/or MRI may in some cases be equivocal and angiography sometimes is even misleading. It is important to keep this differential diagnosis in mind, especially in children. (orig.) [de

  11. Incidents in nuclear installations

    International Nuclear Information System (INIS)

    Franzen, L.F.; Wienhold, W.

    1976-09-01

    With reference to the incident list of the Ministry for the period 1971-74, Prof. Bechert has expressed a lot of questions and statements in a letter to the Government. The letter is quoted in full. Inadequate conclusions drawn by Prof. Bechert in connection with quotations from daily newspapers and other documents are put right. (HP) [de

  12. Lightning incidents in Mongolia

    Directory of Open Access Journals (Sweden)

    Myagmar Doljinsuren

    2015-11-01

    Full Text Available This is one of the first studies that has been conducted in Mongolia on the distribution of lightning incidents. The study covers a 10-year period from 2004 to 2013. The country records a human death rate of 15.4 deaths per 10 million people per year, which is much higher than that of many countries with similar isokeraunic level. The reason may be the low-grown vegetation observed in most rural areas of Mongolia, a surface topography, typical to steppe climate. We suggest modifications to Gomes–Kadir equation for such countries, as it predicts a much lower annual death rate for Mongolia. The lightning incidents spread over the period from May to August with the peak of the number of incidents occurring in July. The worst lightning affected region in the country is the central part. Compared with impacts of other convective disasters such as squalls, thunderstorms and hail, lightning stands as the second highest in the number of incidents, human deaths and animal deaths. Economic losses due to lightning is only about 1% of the total losses due to the four extreme weather phenomena. However, unless precautionary measures are not promoted among the public, this figure of losses may significantly increase with time as the country is undergoing rapid industrialization at present.

  13. Fire Incident Reporting Manual

    Science.gov (United States)

    1984-02-01

    the result of an incident that requires (or should require) treatment by a practitioner of medicine , a registered emergency medical technician, or a...UNANNOUNCED AIRCRAFT EMERGENCYS ~~PRIOR TO TAKE OFF OR AFTERLADN 5 FUEL OPERATIONS REQUIRING 1AREING G A FIRE10 ARRESTING GEAR’BARRIER FR . ENGAGEMENTS AND

  14. Differential Geometry

    CERN Document Server

    Stoker, J J

    2011-01-01

    This classic work is now available in an unabridged paperback edition. Stoker makes this fertile branch of mathematics accessible to the nonspecialist by the use of three different notations: vector algebra and calculus, tensor calculus, and the notation devised by Cartan, which employs invariant differential forms as elements in an algebra due to Grassman, combined with an operation called exterior differentiation. Assumed are a passing acquaintance with linear algebra and the basic elements of analysis.

  15. Fibromyalgia Syndrome: Etiology, Pathogenesis, Diagnosis, and Treatment

    Directory of Open Access Journals (Sweden)

    Enrico Bellato

    2012-01-01

    Full Text Available Fibromyalgia syndrome is mainly characterized by pain, fatigue, and sleep disruption. The etiology of fibromyalgia is still unclear: if central sensitization is considered to be the main mechanism involved, then many other factors, genetic, immunological, and hormonal, may play an important role. The diagnosis is typically clinical (there are no laboratory abnormalities and the physician must concentrate on pain and on its features. Additional symptoms (e.g., Raynaud’s phenomenon, irritable bowel disease, and heat and cold intolerance can be associated with this condition. A careful differential diagnosis is mandatory: fibromyalgia is not a diagnosis of exclusion. Since 1990, diagnosis has been principally based on the two major diagnostic criteria defined by the ACR. Recently, new criteria have been proposed. The main goals of the treatment are to alleviate pain, increase restorative sleep, and improve physical function. A multidisciplinary approach is optimal. While most nonsteroidal anti-inflammatory drugs and opioids have limited benefit, an important role is played by antidepressants and neuromodulating antiepileptics: currently duloxetine (NNT for a 30% pain reduction 7.2, milnacipran (NNT 19, and pregabalin (NNT 8.6 are the only drugs approved by the US Food and Drug Administration for the treatment of fibromyalgia. In addition, nonpharmacological treatments should be associated with drug therapy.

  16. Fibromyalgia Syndrome: Etiology, Pathogenesis, Diagnosis, and Treatment

    Science.gov (United States)

    Bellato, Enrico; Marini, Eleonora; Castoldi, Filippo; Barbasetti, Nicola; Mattei, Lorenzo; Bonasia, Davide Edoardo; Blonna, Davide

    2012-01-01

    Fibromyalgia syndrome is mainly characterized by pain, fatigue, and sleep disruption. The etiology of fibromyalgia is still unclear: if central sensitization is considered to be the main mechanism involved, then many other factors, genetic, immunological, and hormonal, may play an important role. The diagnosis is typically clinical (there are no laboratory abnormalities) and the physician must concentrate on pain and on its features. Additional symptoms (e.g., Raynaud's phenomenon, irritable bowel disease, and heat and cold intolerance) can be associated with this condition. A careful differential diagnosis is mandatory: fibromyalgia is not a diagnosis of exclusion. Since 1990, diagnosis has been principally based on the two major diagnostic criteria defined by the ACR. Recently, new criteria have been proposed. The main goals of the treatment are to alleviate pain, increase restorative sleep, and improve physical function. A multidisciplinary approach is optimal. While most nonsteroidal anti-inflammatory drugs and opioids have limited benefit, an important role is played by antidepressants and neuromodulating antiepileptics: currently duloxetine (NNT for a 30% pain reduction 7.2), milnacipran (NNT 19), and pregabalin (NNT 8.6) are the only drugs approved by the US Food and Drug Administration for the treatment of fibromyalgia. In addition, nonpharmacological treatments should be associated with drug therapy. PMID:23213512

  17. Cervicogenic headache: Differential diagnosis and treatment

    Directory of Open Access Journals (Sweden)

    Aleksey Nikolayevich Barinov

    2012-01-01

    Full Text Available The paper discusses the issues of differential diagnosis of cervicocranialgia with tension headache and migraine with concomitant cervical myofascial syndrome. It considers the basic mechanisms of the pathogenesis of these nosological entities and common approaches to their treatment. The mechanisms of pathogenetic action of myorelaxants are shown in cervicocranialgia and myofascial pain syndromes. Methods for mini-invasive therapy for cervicogenic headache and other musculoskeletal disorders are presented.

  18. Comparative Incidence of Conformational, Neurodegenerative Disorders.

    Directory of Open Access Journals (Sweden)

    Jesús de Pedro-Cuesta

    Full Text Available The purpose of this study was to identify incidence and survival patterns in conformational neurodegenerative disorders (CNDDs.We identified 2563 reports on the incidence of eight conditions representing sporadic, acquired and genetic, protein-associated, i.e., conformational, NDD groups and age-related macular degeneration (AMD. We selected 245 papers for full-text examination and application of quality criteria. Additionally, data-collection was completed with detailed information from British, Swedish, and Spanish registries on Creutzfeldt-Jakob disease (CJD forms, amyotrophic lateral sclerosis (ALS, and sporadic rapidly progressing neurodegenerative dementia (sRPNDd. For each condition, age-specific incidence curves, age-adjusted figures, and reported or calculated median survival were plotted and examined.Based on 51 valid reported and seven new incidence data sets, nine out of eleven conditions shared specific features. Age-adjusted incidence per million person-years increased from ≤1.5 for sRPNDd, different CJD forms and Huntington's disease (HD, to 1589 and 2589 for AMD and Alzheimer's disease (AD respectively. Age-specific profiles varied from (a symmetrical, inverted V-shaped curves for low incidences to (b those increasing with age for late-life sporadic CNDDs and for sRPNDd, with (c a suggested, intermediate, non-symmetrical inverted V-shape for fronto-temporal dementia and Parkinson's disease. Frequently, peak age-specific incidences from 20-24 to ≥90 years increased with age at onset and survival. Distinct patterns were seen: for HD, with a low incidence, levelling off at middle age, and long median survival, 20 years; and for sRPNDd which displayed the lowest incidence, increasing with age, and a short median disease duration.These results call for a unified population view of NDDs, with an age-at-onset-related pattern for acquired and sporadic CNDDs. The pattern linking age at onset to incidence magnitude and survival might

  19. Zebrafish Functional Genetics Approach to the Pathogenesis of Well-Differentiated Liposarcoma

    Science.gov (United States)

    2015-12-01

    Committee World Child Cancer Foundation 2013- Affiliated Faculty of Advisors, Academy of Investigation Boston Combined Residency Program in...from World Child Cancer foundation in the UK. Report of Scholarship Publications Peer reviewed publications in print or other media... Hunger SP, Sallan SE, Look AT. High Frequency of PTEN, PI3K and AKT abnormalities in T cell acute lymphoblastic leukemia. Blood. 2009;114:647. 7

  20. Constipation and Incident CKD.

    Science.gov (United States)

    Sumida, Keiichi; Molnar, Miklos Z; Potukuchi, Praveen K; Thomas, Fridtjof; Lu, Jun Ling; Matsushita, Kunihiro; Yamagata, Kunihiro; Kalantar-Zadeh, Kamyar; Kovesdy, Csaba P

    2017-04-01

    Constipation is one of the most prevalent conditions in primary care settings and increases the risk of cardiovascular disease, potentially through processes mediated by altered gut microbiota. However, little is known about the association of constipation with CKD. In a nationwide cohort of 3,504,732 United States veterans with an eGFR ≥60 ml/min per 1.73 m 2 , we examined the association of constipation status and severity (absent, mild, or moderate/severe), defined using diagnostic codes and laxative use, with incident CKD, incident ESRD, and change in eGFR in Cox models (for time-to-event analyses) and multinomial logistic regression models (for change in eGFR). Among patients, the mean (SD) age was 60.0 (14.1) years old; 93.2% of patients were men, and 24.7% were diabetic. After multivariable adjustments, compared with patients without constipation, patients with constipation had higher incidence rates of CKD (hazard ratio, 1.13; 95% confidence interval [95% CI], 1.11 to 1.14) and ESRD (hazard ratio, 1.09; 95% CI, 1.01 to 1.18) and faster eGFR decline (multinomial odds ratios for eGFR slope constipation associated with an incrementally higher risk for each renal outcome. In conclusion, constipation status and severity associate with higher risk of incident CKD and ESRD and with progressive eGFR decline, independent of known risk factors. Further studies should elucidate the underlying mechanisms. Copyright © 2017 by the American Society of Nephrology.

  1. Cancer incidence among firefighters

    DEFF Research Database (Denmark)

    Pukkala, Eero; Martinsen, Jan Ivar; Weiderpass, Elisabete

    2014-01-01

    .51), adenocarcinoma of the lung (SIR=1.90, 95% CI 1.34 to 2.62), and mesothelioma (SIR=2.59, 95% CI 1.24 to 4.77). By contrast with earlier studies, the incidence of testicular cancer was decreased (SIR=0.51, 95% CI 0.23 to 0.98). CONCLUSIONS: Some of these associations have been observed previously, and potential...

  2. Cancer incidence among waiters

    DEFF Research Database (Denmark)

    Reijula, Jere; Kjaerheim, Kristina; Lynge, Elsebeth

    2015-01-01

    AIMS: To study cancer risk patterns among waiters in the Nordic countries. METHODS: We identified a cohort of 16,134 male and 81,838 female waiters from Denmark, Finland, Iceland, Norway and Sweden. During the follow-up period from 1961 to 2005, we found that 19,388 incident cancer cases were...... diagnosed. Standardised incidence ratio (SIR) was defined as the observed number of cancer cases divided by the expected number, based on national age, time period and gender-specific cancer incidence rates in the general population. RESULTS: The SIR of all cancers in waiters, in the five countries combined......, was 1.46 (95% CI 1.41-1.51) in men and 1.09 (1.07-1.11) in women. In male waiters, the SIR decreased from 1.79 (1.63-1.96) in 1961-1975, to 1.33 (1.26-1.40) in 1991-2005, but remained stable among women. The SIR among male waiters was highest for cancers in the pharynx (6.11; 95% CI 5.02-7.37), oral...

  3. Contaminated Mexican steel incident

    International Nuclear Information System (INIS)

    1985-01-01

    This report documents the circumstances contributing to the inadvertent melting of cobalt 60 (Co-60) contaminated scrap metal in two Mexican steel foundries and the subsequent distribution of contaminated steel products into the United States. The report addresses mainly those actions taken by US Federal and state agencies to protect the US population from radiation risks associated with the incident. Mexico had much more serious radiation exposure and contamination problems to manage. The United States Government maintained a standing offer to provide technical and medical assistance to the Mexican Government. The report covers the tracing of the source to its origin, response actions to recover radioactive steel in the United States, and return of the contaminated materials to Mexico. The incident resulted in significant radiation exposures within Mexico, but no known significant exposure within the United States. Response to the incident required the combined efforts of the Nuclear Regulatory Commission (NRC), Department of Energy, Department of Transportation, Department of State, and US Customs Service (Department of Treasury) personnel at the Federal level and representatives of all 50 State Radiation Control Programs and, in some instances, local and county government personnel. The response also required a diplomatic interface with the Mexican Government and cooperation of numerous commercial establishments and members of the general public. The report describes the factual information associated with the event and may serve as information for subsequent recommendations and actions by the NRC. 8 figures

  4. Hypertension in the African American population: A succinct look at its epidemiology, pathogenesis, and therapy

    Directory of Open Access Journals (Sweden)

    Luis M. Ortega

    2015-03-01

    Full Text Available Arterial hypertension is prevalent in the black population in the United States. It is directly related to cardiovascular and kidney damage. Its pathogenesis is complex and includes the high incidence of obesity, salt sensitivity and the activation of the renin-angiotensinaldosterone system. This complexity requires a therapeutic combination that includes changes in dietary habits and appropriate antihypertensive regimes. The International Society of Hypertension in Blacks recommends initiating dietary intervention for values of systolic/diastolic arterial blood pressure above 115/75 mmHg and maintaining arterial blood pressure below 135/85 mmHg using appropiate antihypertensive medication. The most adequate antihypertensive drug for this population has yet to be determined.

  5. Hypertension in the African American population: A succinct look at its epidemiology, pathogenesis, and therapy

    Directory of Open Access Journals (Sweden)

    Luis M Ortega

    2015-03-01

    Full Text Available Arterial hypertension is prevalent in the black population in the United States. It is directly related to cardiovascular and kidney damage. Its pathogenesis is complex and includes the high incidence of obesity, salt sensitivity and the activation of the renin-angiotensinaldosterone system. This complexity requires a therapeutic combination that includes changes in dietary habits and appropriate antihypertensive regimes. The International Society of Hypertension in Blacks recommends initiating dietary intervention for values of systolic/ diastolic arterial blood pressure above 115/75 mmHg and maintaining arterial blood pressure below 135/85 mmHg using appropiate antihypertensive medication. The most adequate antihypertensive drug for this population has yet to be determined.

  6. The evolution of diabetic ketoacidosis: An update of its etiology, pathogenesis and management.

    Science.gov (United States)

    Nyenwe, Ebenezer A; Kitabchi, Abbas E

    2016-04-01

    The prognosis of diabetic ketoacidosis has undergone incredibly remarkable evolution since the discovery of insulin nearly a century ago. The incidence and economic burden of diabetic ketoacidosis have continued to rise but its mortality has decreased to less than 1% in good centers. Improved outcome is attributable to a better understanding of the pathophysiology of the disease and widespread application of treatment guidelines. In this review, we present the changes that have occurred over the years, highlighting the evidence behind the recommendations that have improved outcome. We begin with a discussion of the precipitants and pathogenesis of DKA as a prelude to understanding the rationale for the recommendations. A brief review of ketosis-prone type 2 diabetes, an update relating to the diagnosis of DKA and a future perspective are also provided. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Cardiac Hemodynamics in the Pathogenesis of Congenital Heart Disease and Aortic Valve Calcification

    Science.gov (United States)

    Nigam, Vishal

    2011-11-01

    An improved understanding of the roles of hemodynamic forces play in cardiac development and the pathogenesis of cardiac disease will have significant scientific and clinical impact. I will focus on the role of fluid dynamics in congenital heart disease and aortic valve calcification. Congenital heart defects are the most common form of birth defect. Aortic valve calcification/stenosis is the third leading cause of adult heart disease and the most common form of acquired valvular disease in developed countries. Given the high incidence of these diseases and their associated morbidity and mortality, the potential translational impact of an improved understanding of cardiac hemodynamic forces is very large. Division of Pediatric Cardiology, Rady Children's Hospital, San Diego

  8. Refractory fallopian tube carcinoma – current perspectives in pathogenesis and management

    Directory of Open Access Journals (Sweden)

    Sama AR

    2014-01-01

    Full Text Available Ashwin R Sama, Russell J SchilderDepartment of Medical Oncology, Thomas Jefferson University, Philadelphia, PA, USAAbstract: Fallopian tube carcinoma (FTC is considered a rare malignancy, but recent evidence shows that its incidence may have been underestimated. Risk-reducing salpingo-oophorectomy (RRSO in breast cancer susceptibility gene (BRCA-positive women has provided a unique opportunity to study the pathogenesis of FTC and ovarian carcinomas. Newer data now suggest that most high-grade serous cancers of the ovary originate in the fimbrial end of the fallopian tube. Due to the presumed rarity of FTC, most current and more recent ovarian cancer clinical trials have now included patients with FTC. The treatment guidelines recommend similar overall management and that the same chemotherapy regimens be used for epithelial ovarian cancers and FTC.Keywords: high grade serous cancers, serous tubal intraepithelial carcinomas, fallopian tube carcinoma

  9. The peculiarities of pathogenesis of NSAID-induced gastrointestinal injuries and current prevention strategies

    Directory of Open Access Journals (Sweden)

    Anatol Święcicki

    2014-07-01

    Full Text Available Nonsteroidal anti-inflammatory drugs (NSAIDs are among the most widely used medications. However, NSAID intake is accompanied by an increased risk of gastroduodenal side effects. These adverse events are largely attributed to the ability of these drugs to suppress prostaglandin synthesis, penetrate the mucosal layer in the acid media of the stomach and damage epithelial cells. However, it is becoming clear that such mediators as prostaglandins, NO and lipoxins can protect the stomach from injury. This injury can largely be prevented through suppression of gastric acid secretion (mainly with proton pump inhibitors. In contrast, the pathogenesis of intestinal injury induced by NSAIDs is less well understood. There is no evidence that suppression of gastric acid secretion will reduce the incidence or severity of NSAID enteropathy. In this review the results of recent studies are described, which will help to clarify some mechanisms of development of NSAID gastropathies and NSAID enteropathies and to improve the treatment of these patients.

  10. Latest developments in our understanding of the pathogenesis of mesothelioma and the design of targeted therapies.

    Science.gov (United States)

    Bononi, Angela; Napolitano, Andrea; Pass, Harvey I; Yang, Haining; Carbone, Michele

    2015-10-01

    Malignant mesothelioma is an aggressive cancer whose pathogenesis is causally linked to occupational exposure to asbestos. Familial clusters of mesotheliomas have been observed in settings of genetic predisposition. Mesothelioma incidence is anticipated to increase worldwide in the next two decades. Novel treatments are needed, as current treatment modalities may improve the quality of life, but have shown modest effects in improving overall survival. Increasing knowledge on the molecular characteristics of mesothelioma has led to the development of novel potential therapeutic strategies, including: molecular targeted approaches, that is the inhibition of vascular endothelial growth factor with bevacizumab; immunotherapy with chimeric monoclonal antibody, immunotoxin, antibody drug conjugate, vaccine and viruses; inhibition of asbestos-induced inflammation, that is aspirin inhibition of HMGB1 activity may decrease or delay mesothelioma onset and/or growth. We elaborate on the rationale behind new therapeutic strategies, and summarize available preclinical and clinical results, as well as efforts still ongoing.

  11. [Advances in Pathogenesis and Related Clinical Research of Thromboembolism in Patients with Thalassemia after Splenectomy].

    Science.gov (United States)

    Sun, Na; Cheng, Peng; Deng, Dong-Hong

    2016-06-01

    Thalassemia is the most common human hereditary hemolytic anemia. Due to splenomegaly and hypersp-lenism, splenectomy can be used as a means of treatment for thalassemia. Various complications following splenectomy, however, especially thromboembolic complications are remarkable. This review summarizes the incidence, clinical manifestations and development time of thromboembolism. The pathogenesis of thromboembolism after splenectomy in thalassemia, such as abnormal platelet number and function, changes in red cell membrane, endothelial cell damage, dysfunction of other procoagulant and anticoagulant factors, and local factors associated with splenectomy are elaborated and the trategies to prevent and treat the thromboembolic events in thalassemia after splenectomy, including the attention to risk factors associated with splenectomy, a reassessment of splenectomy, regular blood transfusion to reduce the ratio of abnormal red blood cells, treatment with anticoagulant and antiplatelet drugs, application of hydroxyurea and stem cell transplantation are discussed.

  12. Pathogenesis of hypercalciuria in spontaneously hypertensive rats.

    Science.gov (United States)

    Hsu, C H; Chen, P S; Smith, D E; Yang, C S

    1986-01-01

    The etiology of hypercalciuria remains unknown in spontaneously hypertensive rats (SHR). In order to differentiate absorptive versus renal hypercalciuria, serial measurements of urinary calcium (UCaV) excretion were made weekly under fasting (3-hour urine collection) and after oral administration of CaCl2 (50 mg/100 g; 4-hour urine collection) from age 8 to 14 weeks in SHR (n = 14) and normotensive Wistar Kyoto rats (WKY; n = 14). Fasting UCaV was significantly greater in WKY than in SHR throughout the periods of observation. In contrast, after oral Ca loading UCaV was greater in SHR after 13 weeks of age (13 weeks: SHR UCaV = 954 micrograms/mg creatinine, WKY UCaV = 541 p less than 0.01; 14 weeks: SHR UCaV = 988 micrograms/mg creatinine, WKY UCaV = 534, p less than 0.01). Fasting urinary cyclic adenosine monophosphate (AMP) excretion was not different between WKY and SHR. However, cyclic AMP excretion of SHR, but not WKY, was decreased after calcium loading when compared to the fasting values. The cyclic AMP was also significantly lower in SHR than in WKY rats after calcium loading. Calcium handling by the kidney was not different between SHR and WKY with or without parathyroidectomy. Calcium disposition kinetic studies were performed on these animals at age 15 and 16 weeks. No significant difference of intravenous 45Ca was observed between WKY (n = 6) and SHR (n = 6) in total plasma clearance, nonrenal clearance, biologic half-life, and elimination rate constant from the central compartment. However, the WKY had a significantly greater renal clearance of 45Ca than the SHR (0.48 +/- 0.04 vs. 0.24 +/- 0.02 ml/n, p less than 0.001). Since tissue disposition of intravenous 45Ca was not different between WKY and SHR, the increased renal excretion of calcium after oral administration in SHR, therefore, reflects increased intestinal absorption of calcium. Correction of established hypertension did not abolish the hypercalciuria. We believe that increased

  13. Rheumatic fever pathogenesis: Approach in research needs change

    Directory of Open Access Journals (Sweden)

    Rajendra Tandon

    2012-01-01

    Full Text Available Despite identifying that rheumatic fever (RF is the result of an immunological reaction following group-A beta-hemolytic streptococcal infection, the pathogenesis remains elusive. RF has been incorrectly designated as causing pancarditis, since it does not cause myocarditis. Research directed toward myocarditis, targeting myosin to unravel the pathogenesis has not succeeded in more than 60 years. RF causes permanent damage to cardiac valves. The mitral valve (MV, derived from the wall of the left ventricle, is composed of a central core of connective tissue, covered on both sides by endothelium. The left ventricle does not have either myocardial or intermyocardial connective tissue involvement in RF. By exclusion, therefore, the primary site of RF damage appears to be the endothelium. Evaluation of the histopathology and immunopathology indicates that RF is a disease of the valvular and vascular endothelium. It is not a connective tissue disorder. Research to identify pathogenesis needs to be focused toward valvular endothelium.

  14. The Role of Caveolin 1 in HIV Infection and Pathogenesis.

    Science.gov (United States)

    Mergia, Ayalew

    2017-05-26

    Caveolin 1 (Cav-1) is a major component of the caveolae structure and is expressed in a variety of cell types including macrophages, which are susceptible to human immunodeficiency virus (HIV) infection. Caveolae structures are present in abundance in mechanically stressed cells such as endothelial cells and adipocytes. HIV infection induces dysfunction of these cells and promotes pathogenesis. Cav-1 and the caveolae structure are believed to be involved in multiple cellular processes that include signal transduction, lipid regulation, endocytosis, transcytosis, and mechanoprotection. Such a broad biological role of Cav-1/caveolae is bound to have functional cross relationships with several molecular pathways including HIV replication and viral-induced pathogenesis. The current review covers the relationship of Cav-1 and HIV in respect to viral replication, persistence, and the potential role in pathogenesis.

  15. Differential belongings

    DEFF Research Database (Denmark)

    Oldrup, Helene

    2014-01-01

    This paper explores suburban middle-class residents’ narratives about housing choice, everyday life and belonging in residential areas of Greater Copenhagen, Denmark, to understand how residential processes of social differentiation are constituted. Using Savage et al.’s concepts of discursive...

  16. Medication incidents reported to an online incident reporting system.

    LENUS (Irish Health Repository)

    Alrwisan, Adel

    2011-01-15

    AIMS: Approximately 20% of deaths from adverse events are related to medication incidents, costing the NHS an additional £500 million annually. Less than 5% of adverse events are reported. This study aims to assess the reporting rate of medication incidents in NHS facilities in the north east of Scotland, and to describe the types and outcomes of reported incidents among different services. Furthermore, we wished to quantify the proportion of reported incidents according to the reporters\\' profession. METHODS: A retrospective description was made of medication incidents reported to an online reporting system (DATIX) over a 46-month-period (July 2005 to April 2009). Reports originated from acute and community hospitals, mental health, and primary care facilities. RESULTS: Over the study period there were 2,666 incidents reported with a mean monthly reporting rate of 78.2\\/month (SD±16.9). 6.1% of all incidents resulted in harm, with insulin being the most commonly implicated medication. Nearly three-quarters (74.2%, n=1,978) of total incidents originated from acute hospitals. Administration incidents were implicated in the majority of the reported medication incidents (59%), followed by prescribing (10.8%) and dispensing (9.9%), while the nondescript "other medication incidents" accounted for 20.3% of total incidents. The majority of reports were made by nursing and midwifery staff (80%), with medical and dental professionals reporting the lowest number of incidents (n=56, 2%). CONCLUSIONS: The majority of medication incidents in this study were reported by nursing and midwifery staff, and were due to administration incidents. There is a clear need to elucidate the reasons for the limited contribution of the medical and dental professionals to reporting medication incidents.

  17. Potential Biomarkers Found by Protein Profiling May Provide Insight for the Macrovascular Pathogenesis of Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    William C. S. Cho

    2006-01-01

    Full Text Available Diabetes mellitus (DM is an alarming threat to health of mankind, yet its pathogenesis is unclear. The purpose of this study was to find potential biomarkers to serve as indicators for the pathogenesis of DM in a time course manner. Based on our previous findings that oxidative stress occurred at week 8, aorta lysate and sera of 102 streptozotocin (STZ-induced diabetic and 85 control male Sprague-Dawley rats were obtained at the 4th, 8th and 12th week after STZ injection. The protein profiles were studied employing surface-enhanced laser desorption/ionization time-of-flight mass spectrometry technology in attomole sensitivity range. In the aorta, a multiple biomarker panel was discovered at the 4th week. At the 8th week, 4 biomarkers were found, while at the 12th week, 3 biomarkers were identified. In the sera, a triplet of 3 peaks and 2 biomarkers were all discovered to have 100% classification accuracy rate to differentiate the DM and control groups at all time intervals. Besides, 2 biomarkers were also found to have high classification value at week 12. Comparing the aorta and sera from DM and non-DM rats, a bundle of potential biomarkers with significant changes in peak intensities and high classification values were found. Two of the serum biomarkers matched with islet amyloid polypeptide and resistin in the SWISS-PROT knowledgebase. Validation has been conducted using immunoassay kits. These potential biomarkers may provide valuable insight on the pathogenesis of DM and macrovascular complications.

  18. MicroRNAs in inflammatory bowel disease - pathogenesis, diagnostics and therapeutics

    Science.gov (United States)

    Coskun, Mehmet; Bjerrum, Jacob Tveiten; Seidelin, Jakob Benedict; Nielsen, Ole Haagen

    2012-01-01

    The pathogenesis of inflammatory bowel disease (IBD) is complex and largely unknown. Until recently, research has focused on the study of protein regulators in inflammation to reveal the cellular and molecular networks in the pathogenesis of IBD. However, in the last few years, new and promising insights have been generated from studies describing an association between an altered expression of a specific class of non-coding RNAs, called microRNAs (miRs or miRNAs) and IBD. The short (approximately 22 nucleotides), endogenous, single-stranded RNAs are evolutionary conserved in animals and plants, and regulate specific target mRNAs at the post-transcriptional level. MiRNAs are involved in several biological processes, including development, cell differentiation, proliferation and apoptosis. Furthermore, it is estimated that miRNAs may be responsible for regulating the expression of nearly one-third of the genes in the human genome. Thus, miRNA deregulation often results in an impaired cellular function, and a disturbance of downstream gene regulation and signaling cascades, suggesting their implication in disease etiology. Despite the identification of more than 1900 mature human miRNAs, very little is known about their biological functions and functional targets. Recent studies have identified dysregulated miRNAs in tissue samples of IBD patients and have demonstrated similar differences in circulating miRNAs in the serum of IBD patients. Thus, there is great promise that miRNAs will aid in the early diagnosis of IBD, and in the development of personalized therapies. Here, we provide a short review of the current state-of-the-art of miRNAs in IBD pathogenesis, diagnostics and therapeutics. PMID:23002331

  19. From the microbiome to the central nervous system, an update on the epidemiology and pathogenesis of bacterial meningitis in childhood

    Science.gov (United States)

    Janowski, Andrew B; Newland, Jason G

    2017-01-01

    In the past century, advances in antibiotics and vaccination have dramatically altered the incidence and clinical outcomes of bacterial meningitis. We review the shifting epidemiology of meningitis in children, including after the implementation of vaccines that target common meningitic pathogens and the introduction of intrapartum antibiotic prophylaxis offered to mothers colonized with Streptococcus agalactiae. We also discuss what is currently known about the pathogenesis of meningitis. Recent studies of the human microbiome have illustrated dynamic relationships of bacterial and viral populations with the host, which may potentiate the risk of bacterial meningitis. PMID:28184287

  20. [A comparison of proteomic analysis of Helicobacter pylori in patients with gastritis and gastric cancer between areas of high and low incidence of gastric cancer].

    Science.gov (United States)

    Liu, Lin-na; Zhang, Jing; Ding, Shi-gang; Zhong, Li Jun; Li, Guang-chuan; Shi, Yan-yan; Wang, Ye

    2011-12-18

    To identify the differentially expressed proteins of Helicobacter pylori (Hp) in patients with gastritis and gastric cancer from areas of high and low incidence of gastric cancer by 2-dimensional electrophoresis (2-DE), and to discuss the role of bacterial factor in pathogenesis. Hp in the endoscopic biopsy specimens of gastric mucosa of patients with gastritis and gastric cancer from areas of high (Xining) and low (Beijing) incidence of gastric cancer, were separated, cultured and saved at -80°C. The bacteria were recovered. Then the whole-cell protein of the Hp were extracted and characterized by 2-DE. The different protein spots were analyzed by PDQuest analysis software and identified by electrospray ionization quadruple time-of-flight mass spectrometry (ESI-Q-TOF-MS), and searched by the Mascot database. Nine differentially expressed proteins were identified, and four protein spots were over expressed in the protein maps from gastric cancer in both areas, which were: Urease subunit alpha, chaperone protein dnaK, superoxide dismutase, DNA-directed RNA polymerase subunit alpha; two protein spots were over expressed in the protein maps from gastritis in both areas, which were: Probablethiol peroxidase, nucleoside diphosphate kinase; 60×10(3) chaperonin, and inorganic pyrophosphatase were over expressed only in the protein map from gastric cancer in Xining; S-ribosyl homocysteinelyase was over expressed only in the protein map from gastric cancer in Beijing. There are differences between proteomic analyses of Hp in patients with gastritis and gastric cancer in areas of high and low incidents of gastric cancer, but 2/3 of the protein spots over expressed in the areas are consistent. The protein spots over expressed from gastric cancer in the area with high incidence of gastric cancer are more than in the area with low incidence of gastric cancer. For the Hp extracted from patients with gastric cancer, the mechanism of gastric cancer may be similar, but the role

  1. The epidemiology, pathogenesis and histopathology of fatty liver disease.

    Science.gov (United States)

    Levene, Adam P; Goldin, Robert D

    2012-08-01

    Fatty liver disease includes non-alcoholic fatty liver disease (NAFLD) and alcoholic liver disease (ALD), each of which is increasing in prevalence. Each represents a histological spectrum that extends from isolated steatosis to steatohepatitis and cirrhosis. NAFLD is associated with obesity, diabetes, and insulin resistance, and is considered to be the liver manifestation of the metabolic syndrome. The pathogenesis of NAFLD and ALD involves cytokines, adipokines, oxidative stress, and apoptosis. Histopathology is the gold standard for assessing the severity of liver damage in NAFLD and ALD. We have reviewed the literature, and described and compared the epidemiology, natural disease history, pathogenesis and histopathology of NAFLD and ALD. © 2012 Blackwell Publishing Ltd.

  2. Modern views on the epidemiology, etiology and pathogenesis of gynecomastia

    Directory of Open Access Journals (Sweden)

    Yu. N. Yashina

    2014-01-01

    Full Text Available The review deals with one of the pressing andrological issues – gynecomastia, its etiology and pathogenesis. Based on the current epidemiological and experimental data, most common etiological factors of gynecomastia were investigated. A multiple-valued role of various causes of gynecomastia in several age-groups was revealed. Literature data show that gynecomastia may be a manifestation of various diseases: endocrine, genetic, systematic. As well as that, gynecomastia may occur in patients with oncological diseases. However, gynecomastia can be an iatrogenic complication. Currently, we continue to make insights to the problem of gynecomastia in order to be able to classify its etiological factors and determine its basic pathogenesis pathways.

  3. The role of EPCR in the pathogenesis of severe malaria

    DEFF Research Database (Denmark)

    Mosnier, Laurent O; Lavstsen, Thomas

    2016-01-01

    malaria syndromes and that these PfEMP1 variants contain EPCR binding domains provides new opportunities to improve our understanding of the molecular mechanisms responsible for the pathogenesis of severe malaria. EPCR is known for its essential role in the protein C (PC) system and for its ability...... the new paradigm that EPCR plays a central role in the pathogenesis of severe malaria. Thus, targeting of the PfEMP1-EPCR interaction and restoring the functionality of the PC system may provide new strategies for the development of novel adjuvant therapies for severe malaria....

  4. ROLE OF UBIQUITIN PROTEASOME SYSTEM IN GASTRIC CANCER PATHOGENESIS

    Directory of Open Access Journals (Sweden)

    E. V. Ivanova

    2014-01-01

    Full Text Available The review presents data on the ubiquitin-proteasome system participation in pathogenesis of gastric cancer. The role of proteasome system in regulation of cell cycle, angiogenesis and tumor metastasis has been shown. The aspects of the participation of ubiquitin-proteasome proteolytic system in the pathogenesis of intensive muscle protein degradation in cancer cachexia are analyzed. The role of proteasome system in the development of H. Pylori-induced gastric cancer is discussed. The clinical assessment of selective proteasome inhibitor (bortezomib is a promising area of research for metastatic gastric cancer.

  5. Recent advances in dengue pathogenesis and clinical management.

    Science.gov (United States)

    Simmons, Cameron P; McPherson, Kirsty; Van Vinh Chau, Nguyen; Hoai Tam, D T; Young, Paul; Mackenzie, Jason; Wills, Bridget

    2015-12-10

    This review describes and commentates on recent advances in the understanding of dengue pathogenesis and immunity, plus clinical research on vaccines and therapeutics. We expand specifically on the role of the dermis in dengue virus infection, the contribution of cellular and humoral immune responses to pathogenesis and immunity, NS1 and mechanisms of virus immune evasion. Additionally we review a series of therapeutic intervention trials for dengue, as well as recent clinical research aimed at improving clinical diagnosis, risk prediction and disease classification. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. (ALPHA)2(BETA)1 Integrin-Induced Breast Cancer Differentiation

    National Research Council Canada - National Science Library

    Kamata, Tetsuji

    1998-01-01

    .... The integrin alpha 2 beta 1 functions as a collagen and/or laminin receptor. Previous reports suggest that alpha 2 beta 1 plays a critical role in normal mammary cell differentiation as well as in the pathogenesis of breast cancer...

  7. Incident users of antipsychotics

    DEFF Research Database (Denmark)

    Baandrup, Lone; Kruse, Marie

    2016-01-01

    PURPOSE: In Denmark, as well as in many other countries, consumption of antipsychotics is on the rise, partly due to increasing off-label use. The aim of this study was to analyze and quantify the extent of off-label use and polypharmacy in incident users of antipsychotic medication, and to examine...... initial antipsychotic prescribing patterns and associated use of mental health care services. METHOD: Population-based cohort study linking the following Danish national registers: the Central Psychiatric Research Register, the Register of Medicinal Product Statistics, and Statistics Denmark. RESULTS...

  8. Egg introduction: differential allergic responses

    Directory of Open Access Journals (Sweden)

    Dosanjh A

    2017-04-01

    Full Text Available Amrita Dosanjh Medical Center, Rady Childrens Hospital, San Diego, CA, USA Abstract: The use of egg protein preparations in clinical trials to reduce the incidence of egg allergy among infants includes a number of preparations of egg. These include whole egg, egg white protein, and egg yolk preparations. The study of the differential immune responses to these allergenic proteins in comparison is suggested as a future research area of investigation. Keywords: food allergy, egg allergy, clinical trial, atopy

  9. Egg introduction: differential allergic responses

    OpenAIRE

    Dosanjh,Amrita

    2017-01-01

    Amrita Dosanjh Medical Center, Rady Childrens Hospital, San Diego, CA, USA Abstract: The use of egg protein preparations in clinical trials to reduce the incidence of egg allergy among infants includes a number of preparations of egg. These include whole egg, egg white protein, and egg yolk preparations. The study of the differential immune responses to these allergenic proteins in comparison is suggested as a future research area of investigation. Keywords: food allergy, egg allergy, clinica...

  10. Improving freight crash incident management.

    Science.gov (United States)

    2015-06-01

    The objective of this study was to determine the most effective way to mitigate the effect of freight : crash incidents on Louisiana freeways. Candidate incident management strategies were reviewed from : practice in other states and from those publi...

  11. Common Causes of Pesticide Incidents

    Science.gov (United States)

    There are many types of pesticide incidents. EPA staff analyze pesticide incident reports involving people (including children and farm workers), pets, domestic animals, wildlife including bees and other pollinators, and the environment.

  12. A role for Apolipoprotein A-I in the pathogenesis of multiple sclerosis.

    Science.gov (United States)

    Meyers, Lindsay; Groover, Chassidy J; Douglas, Joshua; Lee, Sangmin; Brand, David; Levin, Michael C; Gardner, Lidia A

    2014-12-15

    Apolipoprotein A1 (Apo A-I), the most abundant component of high-density lipoprotein (HDL), is an anti-inflammatory molecule, yet its potential role in the pathogenesis of multiple sclerosis (MS) has not been fully investigated. In this study, Western blot analyses of human plasma showed differential Apo A-I expression in healthy controls compared to MS patients. Further, primary progressive MS patients had less plasma Apo A-I than other forms of MS. Using experimental allergic encephalomyelitis (EAE) as a model for MS, Apo A-I deficient mice exhibited worse clinical disease and more neurodegeneration concurrent with increased levels of pro-inflammatory cytokines compared to wild-type animals. These data suggest that Apo A-I plays a role in the pathogenesis of EAE, a model for MS, creating the possibility for agents that increase Apo A-I levels as potential therapies for MS. Copyright © 2014 Elsevier B.V. All rights reserved.

  13. The pathogenesis shared between abdominal aortic aneurysms and intracranial aneurysms: a microarray analysis.

    Science.gov (United States)

    Wang, Wen; Li, Hao; Zhao, Zheng; Wang, Haoyuan; Zhang, Dong; Zhang, Yan; Lan, Qing; Wang, Jiangfei; Cao, Yong; Zhao, Jizong

    2018-04-01

    Abdominal aortic aneurysms (AAAs) and intracranial saccular aneurysms (IAs) are the most common types of aneurysms. This study was to investigate the common pathogenesis shared between these two kinds of aneurysms. We collected 12 IAs samples and 12 control arteries from the Beijing Tiantan Hospital and performed microarray analysis. In addition, we utilized the microarray datasets of IAs and AAAs from the Gene Expression Omnibus (GEO), in combination with our microarray results, to generate messenger RNA expression profiles for both AAAs and IAs in our study. Functional exploration and protein-protein interaction (PPI) analysis were performed. A total of 727 common genes were differentially expressed (404 was upregulated; 323 was downregulated) for both AAAs and IAs. The GO and pathway analyses showed that the common dysregulated genes were mainly enriched in vascular smooth muscle contraction, muscle contraction, immune response, defense response, cell activation, IL-6 signaling and chemokine signaling pathways, etc. The further protein-protein analysis identified 35 hub nodes, including TNF, IL6, MAPK13, and CCL5. These hub node genes were enriched in inflammatory response, positive regulation of IL-6 production, chemokine signaling pathway, and T/B cell receptor signaling pathway. Our study will gain new insight into the molecular mechanisms for the pathogenesis of both types of aneurysms and provide new therapeutic targets for the patients harboring AAAs and IAs.

  14. Metabolic reprogramming in the pathogenesis of chronic lung diseases including BPD, COPD, and pulmonary fibrosis.

    Science.gov (United States)

    Zhao, Haifeng; Dennery, Phyllis A; Yao, Hongwei

    2018-01-04

    The metabolism of nutrient substrates including glucose, glutamine and fatty acids provides acetyl-CoA for the tricarboxylic acid cycle to generate energy, and metabolites for the biosynthesis of biomolecules including nucleotides, proteins, and lipids. It has been shown that metabolism of glucose, fatty acid, and glutamine plays important roles in modulating cellular proliferation, differentiation, apoptosis, autophagy, senescence, and inflammatory responses. All these cellular processes contribute to the pathogenesis of chronic lung diseases, including bronchopulmonary dysplasia, chronic obstructive pulmonary disease, and pulmonary fibrosis. Recent studies demonstrate that metabolic reprogramming occurs in patients with and animal models of chronic lung diseases, suggesting that metabolic dysregulation may participate in the pathogenesis and progression of these diseases. In this review, we briefly discuss the catabolic pathways for glucose, glutamine and fatty acids, and focus on how metabolic reprogramming of these pathways impacts cellular functions and leads to the development of these chronic lung diseases. We also highlight how targeting metabolic pathways can be utilized in the prevention and treatment of these diseases.

  15. Psychological risk factors for HIV pathogenesis: mediation by the autonomic nervous system.

    Science.gov (United States)

    Cole, Steve W; Kemeny, Margaret E; Fahey, John L; Zack, Jerome A; Naliboff, Bruce D

    2003-12-15

    Epidemiologic studies have identified psychological risk factors for specific physical diseases, but the biological mechanisms mediating these relationships remain poorly defined. Social inhibition and autonomic nervous system (ANS) activity were assessed on multiple occasions in 54 gay men with asymptomatic human immunodeficiency virus (HIV) infection. Following baseline ANS assessment, plasma HIV-1 viral load and CD4+ T cell levels were monitored for 12-18 months to assess relationships between ANS activity and HIV pathogenesis. We confirmed the previously reported relationship between socially inhibited temperament and vulnerability to viral pathology. Plasma viral load set-point was elevated eight-fold in socially inhibited individuals, and these individuals showed poorer virologic and immunologic response to initiation of highly active antiretroviral therapy (HAART). Effects were independent of duration of infection, HAART regimen, demographic characteristics, and health-relevant behavior. Neurophysiologic assessments documented elevated ANS activity in socially inhibited individuals, and mediational analyses showed that such differences could account for 64%-92% of the covariance between social inhibition and virologic parameters. These data provide the first clinical evidence that differential neural activity mediates relationships between psychological risk factors and infectious disease pathogenesis. Such findings also suggest novel targets for adjunctive therapy in long-term control of HIV-1 disease.

  16. Increasing incidence of pyogenic spondylodiscitis

    DEFF Research Database (Denmark)

    Kehrer, Michala; Pedersen, Court; Jensen, Thøger G

    2014-01-01

    Smaller studies indicate that the incidence of pyogenic spondylodiscitis is increasing, possible related to a growing elderly population. Data supporting this is sparse, and we therefore studied patient characteristics and changes in spondylodiscitis incidence 1995-2008.......Smaller studies indicate that the incidence of pyogenic spondylodiscitis is increasing, possible related to a growing elderly population. Data supporting this is sparse, and we therefore studied patient characteristics and changes in spondylodiscitis incidence 1995-2008....

  17. Incident Management: Process into Practice

    Science.gov (United States)

    Isaac, Gayle; Moore, Brian

    2011-01-01

    Tornados, shootings, fires--these are emergencies that require fast action by school district personnel, but they are not the only incidents that require risk management. The authors have introduced the National Incident Management System (NIMS) and the Incident Command System (ICS) and assured that these systems can help educators plan for and…

  18. Differential discriminator

    International Nuclear Information System (INIS)

    Dukhanov, V.I.; Mazurov, I.B.

    1981-01-01

    A principal flowsheet of a differential discriminator intended for operation in a spectrometric circuit with statistical time distribution of pulses is described. The differential discriminator includes four integrated discriminators and a channel of piled-up signal rejection. The presence of the rejection channel enables the discriminator to operate effectively at loads of 14x10 3 pulse/s. The temperature instability of the discrimination thresholds equals 250 μV/ 0 C. The discrimination level changes within 0.1-5 V, the level shift constitutes 0.5% for the filling ratio of 1:10. The rejection coefficient is not less than 90%. Alpha spectrum of the 228 Th source is presented to evaluate the discriminator operation with the rejector. The rejector provides 50 ns time resolution

  19. Differential topology

    CERN Document Server

    Margalef-Roig, J

    1992-01-01

    ...there are reasons enough to warrant a coherent treatment of the main body of differential topology in the realm of Banach manifolds, which is at the same time correct and complete. This book fills the gap: whenever possible the manifolds treated are Banach manifolds with corners. Corners add to the complications and the authors have carefully fathomed the validity of all main results at corners. Even in finite dimensions some results at corners are more complete and better thought out here than elsewhere in the literature. The proofs are correct and with all details. I see this book as a reliable monograph of a well-defined subject; the possibility to fall back to it adds to the feeling of security when climbing in the more dangerous realms of infinite dimensional differential geometry. Peter W. Michor

  20. [Understanding and treatment strategy of the pathogenesis of periodontal disease based on chronic inflammation].

    Science.gov (United States)

    Murakami, Tomohiko

    2016-05-01

    Prolonged inflammation continuously promotes the infiltration of macrophages in the organization and chronically induces the production of pro-inflammatory cytokines such as TNF and IL-1. In periodontal tissues, these inflammatory cytokines enhance the differentiation and activity of osteoclasts, which cause destruction of the alveolar bone. Therefore, inhibition of inflammatory cytokine production leads to the prevention or treatment of periodontal disease. IL-1 is a pro-inflammatory cytokine that strongly enhances the bone-resorbing activity of osteoclasts. Elucidation of mechanisms for the production of IL-1 is critical for understanding the pathogenesis of periodontal disease. This paper reviews recent findings of the molecular mechanisms regulating IL-1 production and focuses on inflammasome.

  1. iPS cells in the study of PD molecular pathogenesis.

    Science.gov (United States)

    Cobb, Melanie M; Ravisankar, Abinaya; Skibinski, Gaia; Finkbeiner, Steven

    2017-12-12

    Parkinson's disease (PD) is the second most common neurodegenerative disease and its pathogenic mechanisms are poorly understood. The majority of PD cases are sporadic but a number of genes are associated with familial PD. Sporadic and familial PD have many molecular and cellular features in common, suggesting some shared pathogenic mechanisms. Induced pluripotent stem cells (iPSCs) have been derived from patients harboring a range of different mutations of PD-associated genes. PD patient-derived iPSCs have been differentiated into relevant cell types, in particular dopaminergic neurons and used as a model to study PD. In this review, we describe how iPSCs have been used to improve our understanding of the pathogenesis of PD. We describe what cellular and molecular phenotypes have been observed in neurons derived from iPSCs harboring known PD-associated mutations and what common pathways may be involved.

  2. Potential role of retinoids in ovarian physiology and pathogenesis of polycystic ovary syndrome.

    Science.gov (United States)

    Jiang, Yanwen; Li, Chunjin; Chen, Lu; Wang, Fengge; Zhou, Xu

    2017-06-01

    Retinoids (retinol and its derivatives) are required for maintaining vision, immunity, barrier function, reproduction, embryogenesis, cell proliferation and differentiation. Furthermore, retinoid signaling plays a key role in initiating meiosis of germ cells of the mammalian fetal ovary. Recently, studies indicated that precise retinoid level regulation in the ovary provides a molecular control of ovarian development, steroidogenesis and oocyte maturation. Besides, abnormal retinoid signaling may be involved in the pathogenesis of polycystic ovary syndrome (PCOS), one of the most common ovarian endocrinopathies in reproductive-aged women worldwide. This review primarily summarizes recent advancements made in investigating the action of retinoid signaling in ovarian physiology as well as the abnormal retinoid signaling in PCOS. Copyright © 2017. Published by Elsevier B.V.

  3. Pathogenesis of germ cell neoplasia in testicular dysgenesis and disorders of sex development

    DEFF Research Database (Denmark)

    Jørgensen, Anne; Lindhardt Johansen, Marie; Juul, Anders

    2015-01-01

    reproductive problems within the testicular dysgenesis syndrome (TDS), with large overlap between the syndromes. These disorders carry an increased but variable risk of germ cell neoplasia. In this review, we discuss the pathogenesis of germ cell neoplasia associated with gonadal dysgenesis, especially...... in individuals with 46,XY DSD. We summarise knowledge concerning development and sex differentiation of human gonads, with focus on sex-dimorphic steps of germ cell maturation, including meiosis. We also briefly outline the histopathology of germ cell neoplasia in situ (GCNIS) and gonadoblastoma (GDB), which...... are essentially the same precursor lesion but with different morphological structure dependent upon the masculinisation of the somatic niche. To assess the risk of germ cell neoplasia in different types of DSD, we have performed a PubMed search and provide here a synthesis of the evidence from studies published...

  4. Revealing the potential pathogenesis of glioma by utilizing a glioma associated protein-protein interaction network.

    Science.gov (United States)

    Pan, Weiran; Li, Gang; Yang, Xiaoxiao; Miao, Jinming

    2015-04-01

    This study aims to explore the potential mechanism of glioma through bioinformatic approaches. The gene expression profile (GSE4290) of glioma tumor and non-tumor samples was downloaded from Gene Expression Omnibus database. A total of 180 samples were available, including 23 non-tumor and 157 tumor samples. Then the raw data were preprocessed using robust multiarray analysis, and 8,890 differentially expressed genes (DEGs) were identified by using t-test (false discovery rate What' more, for the top 10 sub-networks, Gene Ontology (GO) enrichment analysis (p value tissue-specific genes were calculated (p value = 1.0, 1.0, and 0.00014, respectively) and visualized by Venn Diagram package in R. About 61% of human tissue-specific genes were DEGs as well. This research shed new light on the pathogenesis of glioma based on DEGs and GAPN, and our findings might provide potential targets for clinical glioma treatment.

  5. Hepatocyte differentiation.

    Science.gov (United States)

    Olsavsky Goyak, Katy M; Laurenzana, Elizabeth M; Omiecinski, Curtis J

    2010-01-01

    Increasingly, research suggests that for certain systems, animal models are insufficient for human toxicology testing. The development of robust, in vitro models of human toxicity is required to decrease our dependence on potentially misleading in vivo animal studies. A critical development in human toxicology testing is the use of human primary hepatocytes to model processes that occur in the intact liver. However, in order to serve as an appropriate model, primary hepatocytes must be maintained in such a way that they persist in their differentiated state. While many hepatocyte culture methods exist, the two-dimensional collagen "sandwich" system combined with a serum-free medium, supplemented with physiological glucocorticoid concentrations, appears to robustly maintain hepatocyte character. Studies in rat and human hepatocytes have shown that when cultured under these conditions, hepatocytes maintain many markers of differentiation including morphology, expression of plasma proteins, hepatic nuclear factors, phase I and II metabolic enzymes. Functionally, these culture conditions also preserve hepatic stress response pathways, such as the SAPK and MAPK pathways, as well as prototypical xenobiotic induction responses. This chapter will briefly review culture methodologies but will primarily focus on hallmark hepatocyte structural, expression and functional markers that characterize the differentiation status of the hepatocyte.

  6. On the Pathogenesis of Alzheimer's Disease: The MAM Hypothesis.

    Science.gov (United States)

    Area-Gomez, Estela; Schon, Eric A

    2017-03-01

    The pathogenesis of Alzheimer's disease (AD) is currently unclear and is the subject of much debate. The most widely accepted hypothesis designed to explain AD pathogenesis is the amyloid cascade, which invokes the accumulation of extracellular plaques and intracellular tangles as playing a fundamental role in the course and progression of the disease. However, besides plaques and tangles, other biochemical and morphological features are also present in AD, often manifesting early in the course of the disease before the accumulation of plaques and tangles. These include altered calcium, cholesterol, and phospholipid metabolism; altered mitochondrial dynamics; and reduced bioenergetic function. Notably, these other features of AD are associated with functions localized to a subdomain of the endoplasmic reticulum (ER), known as mitochondria-associated ER membranes (MAMs). The MAM region of the ER is a lipid raft-like domain closely apposed to mitochondria in such a way that the 2 organelles are able to communicate with each other, both physically and biochemically, thereby facilitating the functions of this region. We have found that MAM-localized functions are increased significantly in cellular and animal models of AD and in cells from patients with AD in a manner consistent with the biochemical findings noted above. Based on these and other observations, we propose that increased ER-mitochondrial apposition and perturbed MAM function lie at the heart of AD pathogenesis.-Area-Gomez, E., Schon, E. A. On the pathogenesis of Alzheimer's disease: the MAM hypothesis. © FASEB.

  7. Role of free radicals in pathogenesis of diabetes nephropathy ...

    African Journals Online (AJOL)

    However, the pathogenesis of diabetes nephropathy remains illusive, notwithstanding, free radicals seem to be the most favorable linkage between all the associated factors suggested. Consequently, free radicals, oxidative stress and antioxidants have become commonly used terms in modern discussions of renal disease ...

  8. Etiology and pathogenesis of anterior open bite: A review | Wanjau ...

    African Journals Online (AJOL)

    Objective: To review the etiology and pathogenesis of anterior open bite malocclusion. Data source: Review of literature was affected through Pubmed, Google scholar and Science direct. References identified from articles found from the primary search were also reviewed. Study selection: Published data on etiology and ...

  9. Tick-borne encephalitis: Pathogenesis and clinical implications

    Czech Academy of Sciences Publication Activity Database

    Růžek, Daniel; Dobler, G.; Mantke, O. D.

    2010-01-01

    Roč. 8, č. 4 (2010), s. 223-232 ISSN 1477-8939 R&D Projects: GA ČR GPP302/10/P438; GA MŠk(CZ) LC06009 Institutional research plan: CEZ:AV0Z60220518 Keywords : Tick-borne encephalitis * Tick-borne encephalitis virus * Pathogenesis * Clinical data Subject RIV: EE - Microbiology, Virology

  10. Deciphering the pathogenesis of tendinopathy: a three-stages process

    Directory of Open Access Journals (Sweden)

    Fu Sai-Chuen

    2010-12-01

    Full Text Available Abstract Our understanding of the pathogenesis of "tendinopathy" is based on fragmented evidences like pieces of a jigsaw puzzle. We propose a "failed healing theory" to knit these fragments together, which can explain previous observations. We also propose that albeit "overuse injury" and other insidious "micro trauma" may well be primary triggers of the process, "tendinopathy" is not an "overuse injury" per se. The typical clinical, histological and biochemical presentation relates to a localized chronic pain condition which may lead to tendon rupture, the latter attributed to mechanical weakness. Characterization of pathological "tendinotic" tissues revealed coexistence of collagenolytic injuries and an active healing process, focal hypervascularity and tissue metaplasia. These observations suggest a failed healing process as response to a triggering injury. The pathogenesis of tendinopathy can be described as a three stage process: injury, failed healing and clinical presentation. It is likely that some of these "initial injuries" heal well and we speculate that predisposing intrinsic or extrinsic factors may be involved. The injury stage involves a progressive collagenolytic tendon injury. The failed healing stage mainly refers to prolonged activation and failed resolution of the normal healing process. Finally, the matrix disturbances, increased focal vascularity and abnormal cytokine profiles contribute to the clinical presentations of chronic tendon pain or rupture. With this integrative pathogenesis theory, we can relate the known manifestations of tendinopathy and point to the "missing links". This model may guide future research on tendinopathy, until we could ultimately decipher the complete pathogenesis process and provide better treatments.

  11. The Roles of Environmental Pollutants in the Pathogenesis and ...

    African Journals Online (AJOL)

    ADOWIE PERE

    researchers have tried to explain the association between pollutants and diabetes using human and animal studies. Evidence from Human Studies: A study from Chile found elevated levels of particulate matter in children that developed type 1 diabetes, suggesting pollutants may play a role in the pathogenesis of diabetes.

  12. Renin-sodium profile and renal prostaglandins in the pathogenesis ...

    African Journals Online (AJOL)

    Renin-sodium profile and renal prostaglandins in the pathogenesis of systemic arterial hypertension in blacks. L. Somova, J. Mufunda. Thirteen black women with systemic (essential) arterial hypertension, age-matched with normotensives, were examined during two protocols inducing sodium depletion and sodium loading ...

  13. Molecular cloning and characterization of pathogenesis-related ...

    African Journals Online (AJOL)

    We described the cloning and characterization of pathogenesis-related protein 5 gene in maize, named ZmPR5 (GenBank Accession Number: HM230665). Molecular and bioinformatic analyses of ZmPR5 revealed an open reading frame (ORF) of 525 bp, encoding a protein of 175 amino acids (aa) and a deduced ...

  14. ALCOHOLIC CARDIOMYOPATHY: BASIC ASPECTS OF EPIDEMIOLOGY, PATHOGENESIS AND PHARMACOTHERAPY

    Directory of Open Access Journals (Sweden)

    A. O. Yusupova

    2014-01-01

    Full Text Available Data on the epidemiology and pathogenesis of alcoholic cardiomyopathy (ACMP are presented. Special aspects of clinical manifestations as well as management of these patients are considered. Psychotropic therapy aimed at reduction in motivation to alcohol consumption in patients with ACMP is discussed separately.

  15. Advances in understanding the pathogenesis of pneumococcal otitis media.

    NARCIS (Netherlands)

    Tonnaer, E.L.G.M.; Graamans, K.; Sanders, E.A.M.; Curfs, J.H.A.J.

    2006-01-01

    In this review, a state of the art on otitis media research is provided with emphasis on the role of Streptococcus pneumoniae in the pathogenesis of this disease. Articles have been selected by MEDLINE search supplemented with a manual crosscheck of bibliographies. Pathogenic mechanisms in middle

  16. A review of the Pathogenesis and Pathology of Bovine Schistosomosis

    African Journals Online (AJOL)

    Keywords: Schistosomosis, zoonosis, cattle, pathology, pathogenesis. Schistosomes are trematodes of separate sex living in blood vessels. They have part of their life cycle in a snail before becoming cercariae, and they reach the final host. Schistosomosis is a zoonosis. Several aspects of schistosomosis and Schistosoma ...

  17. The puzzle of polymorphous light eruption : Patients and pathogenesis

    NARCIS (Netherlands)

    Schornagel, I.J.

    2007-01-01

    Polymorphous light eruption (PLE) is a photosensitivity disorder of which the pathogenesis is not fully understood. Patient history in PLE is important since lesions are transient and often not present at time of consultation. Phototesting is done to reproduce the PLE skin lesions and to obtain

  18. Review: Cytokines in Gaucher disease: Role in the pathogenesis of ...

    African Journals Online (AJOL)

    Review: Cytokines in Gaucher disease: Role in the pathogenesis of bone and pulmonary disease. AAG Tantawy. Abstract. Gaucher disease (GD) is the most frequently encountered lysosomal storage disease caused by inborn defects of themembrane-bound lysosomal enzyme, acid b-glucosidase or glucocerebrosidase.

  19. Role of Endogenous Peptides and Enzymes in the Pathogenesis of ...

    African Journals Online (AJOL)

    Acute pancreatitis is an inflammatory disease with the clinical manifestation of acute abdominal pain. Several factors are involved in the pathogenesis of acute pancreatitis. The exact mechanism(s) by which diverse etiological factors induce an attack are still unclear. However, one of the proposed mechanisms for induction ...

  20. Radiation-induced carcinogenesis: Pathogenesis of bone tumors

    International Nuclear Information System (INIS)

    Goessner, W.

    1984-01-01

    The occurrence of bone tumours after incorporation of bone-seeking radionuclides in humans is reported with special emphasis on the observations after incorporation of the short-lived Radium-224 (Thorium X). In addition some general remarks concerning the pathogenesis of tumour development after internal irradiation are discussed. (orig.) [de

  1. Leprosy and the eye a review of epidemiology, pathogenesis, ocular ...

    African Journals Online (AJOL)

    Objectives: 1. To update knowledge on the current trends in the epidemiology, pathogenesis, and treatment of leprosy 2. To highlight the ocular complications associated with leprosy. Methodology:Current literature on various aspects of leprosy research obtained from the Internet and supplemented by available journals ...

  2. Autoimmune pathogenesis of Chagas heart disease: looking back, looking ahead.

    Science.gov (United States)

    Bonney, Kevin M; Engman, David M

    2015-06-01

    Chagas heart disease is an inflammatory cardiomyopathy that develops in approximately one-third of individuals infected with the protozoan parasite Trypanosoma cruzi. Since the discovery of T. cruzi by Carlos Chagas >100 years ago, much has been learned about Chagas disease pathogenesis; however, the outcome of T. cruzi infection is highly variable and difficult to predict. Many mechanisms have been proposed to promote tissue inflammation, but the determinants and the relative importance of each have yet to be fully elucidated. The notion that some factor other than the parasite significantly contributes to the development of myocarditis was hypothesized by the first physician-scientists who noted the conspicuous absence of parasites in the hearts of those who succumbed to Chagas disease. One of these factors-autoimmunity-has been extensively studied for more than half a century. Although questions regarding the functional role of autoimmunity in the pathogenesis of Chagas disease remain unanswered, the development of autoimmune responses during infection clearly occurs in some individuals, and the implications that this autoimmunity may be pathogenic are significant. In this review, we summarize what is known about the pathogenesis of Chagas heart disease and conclude with a view of the future of Chagas disease diagnosis, pathogenesis, therapy, and prevention, emphasizing recent advances in these areas that aid in the management of Chagas disease. Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  3. Genetic approaches to defining pathogenesis of Toxoplasma gondii

    Science.gov (United States)

    Toxoplasma gondii is a widespread parasite of warm-blooded vertebrates that also causes opportunistic infections in humans. Rodents are a natural host for transmission to cats, which serve as the definitive host for sexual development. The laboratory mouse provides a model to study pathogenesis. Str...

  4. Recovery of active pathogenesis-related enzymes from the apoplast ...

    African Journals Online (AJOL)

    Overall protease activity intensity was higher in the symplast. Maximum symplast contamination of the apoplast was 2% as estimated by glucose 6-phosphate dehydrogenase activity, a biochemical marker for symplast. Accumulation of pathogenesis-related enzymatic activities in the apoplast of M. acuminata leaf tissue was ...

  5. Obesity-associated cardiac pathogenesis in broiler breeder hens: Pathological adaption of cardiac hypertrophy.

    Science.gov (United States)

    Chen, C Y; Lin, H Y; Chen, Y W; Ko, Y J; Liu, Y J; Chen, Y H; Walzem, R L; Chen, S E

    2017-07-01

    Broiler hens consuming feed to appetite (ad libitum; AL) show increased mortality. Feed restriction (R) typically improves reproductive performance and livability of hens. Rapidly growing broilers can exhibit increased mortality due to cardiac insufficiency but it is unknown whether the increased mortality of non-R broiler hens is also due to cardiac compromise. To assess cardiac growth and physiology in fully mature birds, 45-week-old hens were either continued on R rations or assigned to AL feeding for 7 or 21 days. AL hens exhibited increased bodyweight, adiposity, absolute and relative heart weight, ventricular hypertrophy, and cardiac protein/DNA ratio by d 21 (P hens (P Hens allowed AL feeding for 70 d exhibited a higher incidence of mortality (40% vs. 10%) in association with ascites, pericardial effusion, and ventricle dilation. A higher incidence of irregular ECG patterns and rhythmicity consistent with persistently elevated systolic blood pressure and ventricle fibrosis were observed in AL hens (P feeding in broiler hens results in maladaptive cardiac hypertrophy that progresses to overt pathogenesis in contractility and thereby increases mortality. Feed restriction provides clear physiological benefit to heart function of adult broiler hens. © 2017 Poultry Science Association Inc.

  6. Grazing incidence beam expander

    Energy Technology Data Exchange (ETDEWEB)

    Akkapeddi, P.R.; Glenn, P.; Fuschetto, A.; Appert, Q.; Viswanathan, V.K.

    1985-01-01

    A Grazing Incidence Beam Expander (GIBE) telescope is being designed and fabricated to be used as an equivalent end mirror in a long laser resonator cavity. The design requirements for this GIBE flow down from a generic Free Electron Laser (FEL) resonator. The nature of the FEL gain volume (a thin, pencil-like, on-axis region) dictates that the output beam be very small. Such a thin beam with the high power levels characteristic of FELs would have to travel perhaps hundreds of meters or more before expanding enough to allow reflection from cooled mirrors. A GIBE, on the other hand, would allow placing these optics closer to the gain region and thus reduces the cavity lengths substantially. Results are presented relating to optical and mechanical design, alignment sensitivity analysis, radius of curvature analysis, laser cavity stability analysis of a linear stable concentric laser cavity with a GIBE. Fabrication details of the GIBE are also given.

  7. What differentiates a differential psychopharmacology?

    OpenAIRE

    Krüger, Hans-Peter

    2010-01-01

    The methodological implications of a differential psychopharmacology are discussed. It is shown that the technique of stratifying subjects with personality scores depends on one basic assumption: the personality score is not affected by the other experimental factors. Two experiments are reported in which pre- and posttest (after the experiment) scores were measured. The pre-post-differences showed themselves to be affected by the medication. It is argued that in psychopharmacological experim...

  8. Differential geometry

    CERN Document Server

    Ciarlet, Philippe G

    2007-01-01

    This book gives the basic notions of differential geometry, such as the metric tensor, the Riemann curvature tensor, the fundamental forms of a surface, covariant derivatives, and the fundamental theorem of surface theory in a selfcontained and accessible manner. Although the field is often considered a classical one, it has recently been rejuvenated, thanks to the manifold applications where it plays an essential role. The book presents some important applications to shells, such as the theory of linearly and nonlinearly elastic shells, the implementation of numerical methods for shells, and

  9. Differential equations

    CERN Document Server

    Tricomi, FG

    2013-01-01

    Based on his extensive experience as an educator, F. G. Tricomi wrote this practical and concise teaching text to offer a clear idea of the problems and methods of the theory of differential equations. The treatment is geared toward advanced undergraduates and graduate students and addresses only questions that can be resolved with rigor and simplicity.Starting with a consideration of the existence and uniqueness theorem, the text advances to the behavior of the characteristics of a first-order equation, boundary problems for second-order linear equations, asymptotic methods, and diff

  10. Differential topology

    CERN Document Server

    Guillemin, Victor

    2010-01-01

    Differential Topology provides an elementary and intuitive introduction to the study of smooth manifolds. In the years since its first publication, Guillemin and Pollack's book has become a standard text on the subject. It is a jewel of mathematical exposition, judiciously picking exactly the right mixture of detail and generality to display the richness within. The text is mostly self-contained, requiring only undergraduate analysis and linear algebra. By relying on a unifying idea-transversality-the authors are able to avoid the use of big machinery or ad hoc techniques to establish the main

  11. Subclavian Vein Stenosis/Occlusion Following Transvenous Cardiac Pacemaker and Defibrillator Implantation: Incidence, Pathophysiology and Current Management

    Directory of Open Access Journals (Sweden)

    Brian O'Leary

    2015-08-01

    Full Text Available Subclavian vein stenosis is a common, but usually asymptomatic, complication following cardiac device placement. In addition to reviewing the literature on incidence, pathogenesis and management options for this important clinical problem, we describe two cases of symptomatic subclavian vein occlusion following pacemaker/defibrillator placement and successful treatment with venoplasty and stenting.

  12. HIV-1 and recombinant gp120 affect the survival and differentiation of human vessel wall-derived mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Pasquinelli Gianandrea

    2011-05-01

    Full Text Available Abstract Background HIV infection elicits the onset of a progressive immunodeficiency and also damages several other organs and tissues such as the CNS, kidney, heart, blood vessels, adipose tissue and bone. In particular, HIV infection has been related to an increased incidence of cardiovascular diseases and derangement in the structure of blood vessels in the absence of classical risk factors. The recent characterization of multipotent mesenchymal cells in the vascular wall, involved in regulating cellular homeostasis, suggests that these cells may be considered a target of HIV pathogenesis. This paper investigated the interaction between HIV-1 and vascular wall resident human mesenchymal stem cells (MSCs. Results MSCs were challenged with classical R5 and X4 HIV-1 laboratory strains demonstrating that these strains are able to enter and integrate their retro-transcribed proviral DNA in the host cell genome. Subsequent experiments indicated that HIV-1 strains and recombinant gp120 elicited a reliable increase in apoptosis in sub-confluent MSCs. Since vascular wall MSCs are multipotent cells that may be differentiated towards several cell lineages, we challenged HIV-1 strains and gp120 on MSCs differentiated to adipogenesis and endotheliogenesis. Our experiments showed that the adipogenesis is increased especially by upregulated PPARγ activity whereas the endothelial differentiation induced by VEGF treatment was impaired with a downregulation of endothelial markers such as vWF, Flt-1 and KDR expression. These viral effects in MSC survival and adipogenic or endothelial differentiation were tackled by CD4 blockade suggesting an important role of CD4/gp120 interaction in this context. Conclusions The HIV-related derangement of MSC survival and differentiation may suggest a direct role of HIV infection and gp120 in impaired vessel homeostasis and in genesis of vessel damage observed in HIV-infected patients.

  13. The Role of Environmental Factors in the Pathogenesis of Inflammatory Bowel Diseases: A Review.

    Science.gov (United States)

    Shouval, Dror S; Rufo, Paul A

    2017-10-01

    Inflammatory bowel diseases (IBD), such as Crohn disease and ulcerative colitis, are chronic relapsing conditions that affect a growing number of children worldwide. The pathogenesis of these disorders is complex and thought to be mediated by the interplay between genetic susceptibility, microbial dysbiosis, and environmental factors that result in a dysregulated immune system. This dysregulation ultimately mediates intestinal inflammation and clinical symptoms typically observed in patients with IBD including abdominal pain, diarrhea, and poor growth. A dramatic increase in the incidence of IBD has been observed in the past 2 decades, mainly in developed countries but also in developing regions. This increased incidence has paralleled changes in diet, sanitation conditions, and lifestyle habits. The increased incidence of IBD can likely be attributed to more than evolving genetic diversity alone and strongly suggests that environmental factors are playing an increasingly critical role in the development of these disorders and in the modulation of IBD clinical phenotypes over time. Here, we review the data suggesting how different environmental factors may modulate the risk of developing IBD including diets, smoking, lifestyle choices, enteric infections, appendectomy, air pollution, and the use of medications, with an emphasis on antibiotics. We will also discuss how early-life events can influence the subsequent likelihood of developing one of these diseases and suggest directions that can help decrease the risk of IBD in particularly high-risk populations. Dramatic lifestyle changes in the last century have substantially improved the quality of life but are also associated with increased risk of various diseases. Pediatricians should be aware of the changing epidemiology of IBD and environmental factors that modulate the risk of developing these conditions.

  14. Endogenous anticancer mechanism: differentiation.

    Science.gov (United States)

    Werneck, Miriam Bianchi de Frontin

    2012-06-01

    It has been recently shown that within heterogeneous tumor masses a small population of less differentiated transformed cells has the ability to self-renew and regenerate the bulk of the tumor. Their similarities with normal stem cells in terms of gene expression patterns, proliferative capacity and surface markers rendered them the name of cancer stem-like cells (CSC), and these are thought to be the tumor initiating cells (TIC). Their limited susceptibility to classical anti-tumor therapy help explain the high incidence of cancer-treatment relapses observed in selected malignancies. Much effort is being directed towards the understanding of factors that maintain CSC survival and their self-renewal capacity, with the goal that these same signaling pathways can be harnessed for treatments that aim at inducing CSC differentiation. This review will discuss the CSC theory, its implications, potential signaling pathways responsible for maintaining their undifferentiated and pluripotent states, and new venues being explored to target these cells in modern cancer therapy.

  15. Endotoxemia is associated with an increased risk of incident diabetes.

    Science.gov (United States)

    Pussinen, Pirkko J; Havulinna, Aki S; Lehto, Markku; Sundvall, Jouko; Salomaa, Veikko

    2011-02-01

    Diabetes is accompanied with a chronic low-grade inflammation, which may in part be mediated by endotoxins derived from Gram-negative bacteria. We investigated in a population-based cohort whether endotoxemia is associated with clinically incident diabetes. The serum endotoxin activity was measured by limulus assay from the FINRISK97 cohort comprising 7,169 subjects aged 25-74 years and followed up for 10 years. Both the subjects with prevalent diabetes (n = 537) and those with incident diabetes (n = 462) had higher endotoxin activity than the nondiabetic individuals (P endotoxemia with an increased risk of incident diabetes was independent of the metabolic syndrome as defined either by the National Cholesterol Educational Program-Adult Treatment Panel III or the International Diabetes Federation. Endotoxin activity was linearly related (P metabolic syndrome. Both prevalent and incident diabetes were associated with endotoxemia, which may link metabolic disorders to inflammation. The results suggest that microbes play a role in the pathogenesis of diabetes.

  16. Influenza A Virus-Host Protein Interactions Control Viral Pathogenesis.

    Science.gov (United States)

    Zhao, Mengmeng; Wang, Lingyan; Li, Shitao

    2017-08-01

    The influenza A virus (IAV), a member of the Orthomyxoviridae family, is a highly transmissible respiratory pathogen and represents a continued threat to global health with considerable economic and social impact. IAV is a zoonotic virus that comprises a plethora of strains with different pathogenic profiles. The different outcomes of viral pathogenesis are dependent on the engagement between the virus and the host cellular protein interaction network. The interactions may facilitate virus hijacking of host molecular machinery to fulfill the viral life cycle or trigger host immune defense to eliminate the virus. In recent years, much effort has been made to discover the virus-host protein interactions and understand the underlying mechanisms. In this paper, we review the recent advances in our understanding of IAV-host interactions and how these interactions contribute to host defense and viral pathogenesis.

  17. Multiple pathways contribute to the pathogenesis of Huntington disease

    Directory of Open Access Journals (Sweden)

    Li Xiao-Jiang

    2006-12-01

    Full Text Available Abstract Huntington disease (HD is caused by expansion of a polyglutamine (polyQ domain in the protein known as huntingtin (htt, and the disease is characterized by selective neurodegeneration. Expansion of the polyQ domain is not exclusive to HD, but occurs in eight other inherited neurodegenerative disorders that show distinct neuropathology. Yet in spite of the clear genetic defects and associated neurodegeneration seen with all the polyQ diseases, their pathogenesis remains elusive. The present review focuses on HD, outlining the effects of mutant htt in the nucleus and neuronal processes as well as the role of cell-cell interactions in HD pathology. The widespread expression and localization of mutant htt and its interactions with a variety of proteins suggest that mutant htt engages multiple pathogenic pathways. Understanding these pathways will help us to elucidate the pathogenesis of HD and to target therapies effectively.

  18. MODERN IDEA ON THE PATHOGENESIS OF SPONDYLOARTHRITIS: MOLECULAR MECHANISMS

    Directory of Open Access Journals (Sweden)

    E. L. Nasonov

    2015-01-01

    Full Text Available As of now, impaired immune homeostasis of the intestinal mucosa in genetically predisposed individuals is considered to be one of the major components in the pathogenesis of spondyloarthritis (SpA, which leads to systemic chronic inflammation. The results of recent studies may suggest that the interleukin-23/interleukin-17 (IL-23/IL-17 axis plays a leading role in the development of these diseases. The multifactorial components of the pathogenesis of SpA are characterized by not only the hyperproduction of IL-23, but also by the change in cell target susceptibility to this cytokine with aconcurrent increase in their number, resulting in the chronic autoinflammatory process that occurs via a wide spectrum of clinical manifestations of different types of SpA

  19. Comparative Pathogenesis and Systems Biology for Biodefense Virus Vaccine Development

    Directory of Open Access Journals (Sweden)

    Gavin C. Bowick

    2010-01-01

    Full Text Available Developing vaccines to biothreat agents presents a number of challenges for discovery, preclinical development, and licensure. The need for high containment to work with live agents limits the amount and types of research that can be done using complete pathogens, and small markets reduce potential returns for industry. However, a number of tools, from comparative pathogenesis of viral strains at the molecular level to novel computational approaches, are being used to understand the basis of viral attenuation and characterize protective immune responses. As the amount of basic molecular knowledge grows, we will be able to take advantage of these tools not only to rationally attenuate virus strains for candidate vaccines, but also to assess immunogenicity and safety in silico. This review discusses how a basic understanding of pathogenesis, allied with systems biology and machine learning methods, can impact biodefense vaccinology.

  20. New discoveries in the pathogenesis and classification of vitiligo.

    Science.gov (United States)

    Rodrigues, Michelle; Ezzedine, Khaled; Hamzavi, Iltefat; Pandya, Amit G; Harris, John E

    2017-07-01

    Vitiligo is a common autoimmune disease that progressively destroys melanocytes in the skin, resulting in the appearance of patchy depigmentation. This disfiguring condition frequently affects the face and other visible areas of the body, which can be psychologically devastating. The onset of vitiligo often occurs in younger individuals and progresses for life, resulting in a heavy burden of disease and decreased quality of life. Presentation patterns of vitiligo vary, and recognition of these patterns provides both diagnostic and prognostic clues. Recent insights into disease pathogenesis offer a better understanding of the natural history of the disease, its associations, and potential for future treatments. The first article in this continuing medical education series outlines typical and atypical presentations of vitiligo, how they reflect disease activity, prognosis, and response to treatment. Finally, we discuss disease associations, risk factors, and our current understanding of disease pathogenesis. Copyright © 2016 American Academy of Dermatology, Inc. All rights reserved.

  1. Progress towards understanding the pathogenesis of dengue hemorrhagic fever.

    Science.gov (United States)

    Pang, Xiaojing; Zhang, Rudian; Cheng, Gong

    2017-02-01

    Dengue virus (DENV) is a mosquito-borne virus belonging to the Flaviviridae family. There are 4 serotypes of DENV that cause human disease through transmission by mosquito vectors. DENV infection results in a broad spectrum of clinical symptoms, ranging from mild fever to dengue hemorrhagic fever (DHF), the latter of which can progress to dengue shock syndrome (DSS) and death. Researchers have made unremitting efforts over the last half-century to understand DHF pathogenesis. DHF is probably caused by multiple factors, such as virus-specific antibodies, viral antigens and host immune responses. This review summarizes the current progress of studies on DHF pathogenesis, which may provide important information for achieving effective control of dengue in the future.

  2. Peripheral Ulcerative Keratitis Associated with Autoimmune Disease: Pathogenesis and Treatment

    Directory of Open Access Journals (Sweden)

    Yan Cao

    2017-01-01

    Full Text Available Peripheral ulcerative keratitis (PUK is type of crescent-shaped inflammatory damage that occurs in the limbal region of the cornea. PUK is always combined with an epithelial defect and the destruction of the peripheral corneal stroma. PUK may have a connection to systemic conditions, such as long-standing rheumatoid arthritis (RA, systemic lupus erythematosus (SLE, Wegener granulomatosis (WG, relapsing polychondritis, classic polyarteritis nodosa and its variants, microscopic polyangiitis, and Churg-Strauss syndrome. However, the most common connection is with RA, which is also the focus of this review. The pathogenesis of PUK is still unclear. It is thought that circulating immune complexes and cytokines exert an important influence on the progression of this syndrome. Treatment is applied to inhibit certain aspects of PUK pathogenesis.

  3. Peripheral Ulcerative Keratitis Associated with Autoimmune Disease: Pathogenesis and Treatment

    Science.gov (United States)

    Cao, Yan; Zhang, Wensong; Wu, Jie; Zhang, Hong

    2017-01-01

    Peripheral ulcerative keratitis (PUK) is type of crescent-shaped inflammatory damage that occurs in the limbal region of the cornea. PUK is always combined with an epithelial defect and the destruction of the peripheral corneal stroma. PUK may have a connection to systemic conditions, such as long-standing rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), Wegener granulomatosis (WG), relapsing polychondritis, classic polyarteritis nodosa and its variants, microscopic polyangiitis, and Churg-Strauss syndrome. However, the most common connection is with RA, which is also the focus of this review. The pathogenesis of PUK is still unclear. It is thought that circulating immune complexes and cytokines exert an important influence on the progression of this syndrome. Treatment is applied to inhibit certain aspects of PUK pathogenesis. PMID:28785483

  4. Animal Models of Zika Virus Infection, Pathogenesis, and Immunity.

    Science.gov (United States)

    Morrison, Thomas E; Diamond, Michael S

    2017-04-15

    Zika virus (ZIKV) is an emerging mosquito-transmitted flavivirus that now causes epidemics affecting millions of people on multiple continents. The virus has received global attention because of some of its unusual epidemiological and clinical features, including persistent infection in the male reproductive tract and sexual transmission, an ability to cross the placenta during pregnancy and infect the developing fetus to cause congenital malformations, and its association with Guillain-Barré syndrome in adults. This past year has witnessed an intensive effort by the global scientific community to understand the biology of ZIKV and to develop pathogenesis models for the rapid testing of possible countermeasures. Here, we review the recent advances in and utility and limitations of newly developed mouse and nonhuman primate models of ZIKV infection and pathogenesis. Copyright © 2017 American Society for Microbiology.

  5. MicroRNAs in the Cholangiopathies: Pathogenesis, Diagnosis, and Treatment

    Directory of Open Access Journals (Sweden)

    Maria Jose Lorenzo Pisarello

    2015-08-01

    Full Text Available The cholangiopathies are a group of liver diseases resulting from different etiologies but with the cholangiocyte as the primary target. As a group, the cholangiopathies result in significant morbidity and mortality and represent one of the main indications for liver transplant in both children and adults. Contributing to this situation is the absence of a thorough understanding of their pathogenesis and a lack of adequate diagnostic and prognostic biomarkers. MicroRNAs are small non-coding RNAs that modify gene expression post-transcriptionally. They have been implicated in the pathogenesis of many diseases, including the cholangiopathies. Thus, in this review we provide an overview of the literature on miRNAs in the cholangiopathies and discuss future research directions.

  6. HIV Infection of Macrophages: Implications for Pathogenesis and Cure

    Directory of Open Access Journals (Sweden)

    Kiera Leigh Clayton

    2017-05-01

    Full Text Available Although CD4+ T cells represent the major reservoir of persistent HIV and SIV infection, accumulating evidence suggests that macrophages also contribute. However, investigations of the role of macrophages are often underrepresented at HIV pathogenesis and cure meetings. This was the impetus for a scientific workshop dedicated to this area of study, held in Cambridge, MA in January 2017. The workshop brought together experts in the fields of HIV/SIV immunology/virology, macrophage biology and immunology, and animal models of HIV/SIV infection to facilitate discussions regarding the role of macrophages as a physiologically relevant viral reservoir, and the implications of macrophage infection for HIV pathogenesis and cure strategies. An emerging consensus that infected macrophages likely persist in the setting of combination antiretroviral therapy, driving persistent inflammation and contributing to the viral reservoir, indicate the importance of addressing macrophages as well as CD4+ T cells with future therapeutic strategies.

  7. Genes, autoimmunity and pathogenesis of rheumatic heart disease

    International Nuclear Information System (INIS)

    Guilherme, L; Köhler, K F; Postol, E; Kalil, J

    2011-01-01

    Pathogenesis of rheumatic heart disease (RHD) remains incompletely understood. Several genes associated with RHD have been described; most of these are involved with immune responses. Single nucleotide polymorphisms in a number of genes affect patients with RHD compared to controls. Molecular mimicry between streptococcal antigens and human proteins, including cardiac myosin epitopes, vimentin and other intracellular proteins is central to the pathogenesis of RHD. Autoreactive T cells migrate from the peripheral blood to the heart and proliferate in the valves in response to stimulation with specific cytokines. The types of cells involved in the inflammation as well as different cytokine profiles in these patients are being investigated. High TNF alpha, interferon gamma, and low IL4 are found in the rheumatic valve suggesting an imbalance between Th1 and Th2 cytokines and probably contributing to the progressive and permanent valve damage. Animal model of ARF in the Lewis rat may further contribute towards understanding the ARF

  8. Pathogenesis of pulmonary emphysema – cellular and molecular events

    Directory of Open Access Journals (Sweden)

    Antonio Di Petta

    2010-06-01

    Full Text Available Pulmonary emphysema is a chronic obstructive disease, resulting fromimportant alterations in the whole distal structure of terminal bronchioles, either by enlargement of air spaces or by destruction of the alveolar wall, leading to loss of respiratory surface, decreased elastic recoil and lung hyperinflation. For many years, the hypothesis of protease-antiprotease unbalance prevailed as the central theme in the pathogenesis of pulmonary emphysema. According to this hypothesis, the release of active proteolytic enzymes, produced mainly by neutrophils and macrophages, degrades the extracellular matrix, affecting the integrity of its components, especially collagen and elastic fibers. However, new concepts involving cellular and molecular events were proposed, including oxidative stress, cell apoptosis, cellular senescence and failed lung tissue repair. The aim of this review paper was to evaluate the cellular and molecular mechanisms seen in the pathogenesis of pulmonary emphysema.

  9. Propionibacterium acnes in the pathogenesis and immunotherapy of acne vulgaris.

    Science.gov (United States)

    Liu, Pei-Feng; Hsieh, Yao-Dung; Lin, Ya-Ching; Two, Aimee; Shu, Chih-Wen; Huang, Chun-Ming

    2015-01-01

    Acne vulgaris, a multi-factorial disease, is one of the most common skin diseases, affecting an estimated 80% of Americans at some point during their lives. The gram-positive and anaerobic Propionibacterium acnes (P. acnes) bacterium has been implicated in acne inflammation and pathogenesis. Therapies for acne vulgaris using antibiotics generally lack bacterial specificity, promote the generation of antibiotic-resistant bacterial strains, and cause adverse effects. Immunotherapy against P. acnes or its antigens (sialidase and CAMP factor) has been demonstrated to be effective in mice, attenuating P. acnes-induced inflammation; thus, this method may be applied to develop a potential vaccine targeting P. acnes for acne vulgaris treatment. This review summarizes reports describing the role of P. acnes in the pathogenesis of acne and various immunotherapy-based approaches targeting P. acnes, suggesting the potential effectiveness of immunotherapy for acne vulgaris as well as P. acnes-associated diseases.

  10. Understanding Anaplasmataceae pathogenesis using ‘Omics’ approaches

    Directory of Open Access Journals (Sweden)

    Ludovic ePruneau

    2014-07-01

    Full Text Available This paper examines how Omics approaches improve our understanding of Anaplasmataceae pathogenesis, through a global and integrative strategy to identify genes and proteins involved in biochemical pathways key for pathogen-host-vector interactions.The Anaplasmataceae family comprises obligate intracellular bacteria mainly transmitted by arthropods. These bacteria are responsible for major human and animal endemic and emerging infectious diseases with important economic and public health impacts. In order to improve disease control strategies, it is essential to better understand their pathogenesis. Our work focused on four Anaplasmataceae, which cause important animal, human and zoonotic diseases: Anaplasma marginale, A. phagocytophilum, Ehrlichia chaffeensis and E. ruminantium. Wolbachia spp. an endosymbiont of arthropods was also included in this review as a model of a non-pathogenic Anaplasmataceae.A gap analysis on Omics approaches on Anaplasmataceae was performed, which highlighted a lack of studies on the genes and proteins involved in the infection of hosts and vectors. Furthermore, most of the studies have been done on the pathogen itself, mainly on infectious free-living forms and rarely on intracellular forms. In order to perform a transcriptomic analysis of the intracellular stage of development, researchers developed methods to enrich bacterial transcripts from infected cells. These methods are described in this paper. Bacterial genes encoding outer membrane proteins, post-translational modifications, eukaryotic repeated motif proteins, proteins involved in osmotic and oxidative stress and hypothetical proteins have been identified to play a key role in Anaplasmataceae pathogenesis. Further investigations on the function of these outer membrane proteins and hypothetical proteins will be essential to confirm their role in the pathogenesis. Our work underlines the need for further studies in this domain and on host and vector responses

  11. Pathogenesis: common pathways between hidradenitis suppurativa and Crohn disease.

    Science.gov (United States)

    García Martínez, F J; Menchén, L

    2016-09-01

    Both hidradenitis suppurativa and Crohn disease are considered chronic inflammatory diseases due to immune dysregulation. The high prevalence of Crohn disease patients diagnosed with hidradenitis suppurativa suggests the existence of common pathogenic links. The present literature review analyses the similarities and differences in the pathogenesis of the two diseases, in the search for new research and knowledge targets. Copyright © 2016 Elsevier España, S.L.U. y AEDV. All rights reserved.

  12. [Monoamine-hormonal interactions in the pathogenesis of anxious depression].

    Science.gov (United States)

    Uzbekov, M G; Maximova, N M

    2015-01-01

    Biochemical aspects of the relationship between monoaminergic and hormonal systems in the pathogenesis of anxious depression are analyzed on the basis of literature and own results published earlier. Significant alterations in biogenic monoamine metabolism and changes in the hormonal status, that reflects homeostasis disturbance in whole, are inherent to anxious depression. The biochemical mechanisms of imbalance between serotonergic and noradrenergic systems and a role of cortisol in this process are discussed.

  13. [EBOLA HEMORRHAGIC FEVER; ETIOLOGY, EPIDEMIOLOGY, PATHOGENESIS, AND CLINICAL SYMPTOMS].

    Science.gov (United States)

    Zhdanov, K W; Zakharenko, S M; Kovalenko, A N; Semenov, A V; Fusin, A Ya

    2015-01-01

    The data on the prevalence of disease caused by Ebola virus, biological features of its pathogen, character of the epidemiological process, pathogenesis and clinical symptoms are presented. The disease is characterized by suppression of protective immunological mechanisms and systemic inflammatory reaction accounting for the lesions of vascular endothelium, hemostatic and immune systems. It eventually leads to polyorgan insufficiency and severe shock. Lethality amounts to 50%.

  14. The pathogenesis of tendinopathy: balancing the response to loading

    DEFF Research Database (Denmark)

    Magnusson, S Peter; Jørgensen, Henning Langberg; Kjaer, Michael

    2010-01-01

    , such as tendinopathy, which is characterized by pain during activity, localized tenderness upon palpation, swelling and impaired performance. Tendon histological changes include reduced numbers and rounding of fibroblasts, increased content of proteoglycans, glycosaminoglycans and water, hypervascularization......, thus implying that one or more 'weak links' are present in the structure. Understanding how tendon tissue adapts to mechanical loading will help to unravel the pathogenesis of tendinopathy....

  15. Correlation between mitochondrial dysfunction and the pathogenesis of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Xiao-yu LIU

    2014-02-01

    Full Text Available Parkinson's disease (PD is a progressive neurodegenerative disease. A growing number of studies have shown that mitochondrial dysfunction plays an important role in the pathogenesis of PD. Therefore, this review will mainly discuss the research progress on the correlation between PD and abnormal mitochondrial dynamics, mitochondrial autophapy as well as mitochondrial DNA mutations and mitochondrial complex Ⅰ inhibition.doi:10.3969/j.issn.1672-6731.2014.02.012

  16. Therapeutic implications from the pathogenesis of Raynaud's phenomenon

    OpenAIRE

    Herrick, Ariane L

    2017-01-01

    INTRODUCTION: Raynaud's phenomenon (RP) can be either primary (idiopathic) or secondary to a number of different diseases/conditions, when vasopasm can be superimposed upon structural vascular abnormality or a hyperviscosity state and may then lead to severe ischaemia with tissue damage. Treatment must be tailored to the individual. Areas covered: This review discusses how increased understanding of the pathogenesis of RP has driven and is driving new approaches to therapy, and how we are now...

  17. Pathogenesis of apical periodontal cysts: guidelines for diagnosis in palaeopathology

    OpenAIRE

    Dias, G. J.; Prasad, K.; Santos, A. L.

    2007-01-01

    Apical periodontal cysts are benign lesions developing in relation to the apices of non-vital teeth due to inflammatory response from the infective pulp. These are epithelium-lined bony cavities containing fluid. Despite being widely reported in medical/dental literature, this common condition is poorly diagnosed and documented in the archaeological literature. We aim to clarify the correct terminology, demonstrate bony manifestations at different stages of pathogenesis of chronic periapical ...

  18. The fundamental role of endothelial cells in hantavirus pathogenesis

    Directory of Open Access Journals (Sweden)

    Jussi eHepojoki

    2014-12-01

    Full Text Available Hantavirus, a genus of rodent- and insectivore-borne viruses in the family Bunyaviridae, is a group of emerging zoonotic pathogens. Hantaviruses cause hemorrhagic fever with renal syndrome (HFRS and hantavirus cardiopulmonary syndrome (HCPS in man, often with severe consequences. Vascular leakage is evident in severe hantavirus infections, and increased permeability contributes to the pathogenesis. This review summarizes the current knowledge on hantavirus interactions with endothelial cells, and their effects on the increased vascular permeability.

  19. The fundamental role of endothelial cells in hantavirus pathogenesis

    OpenAIRE

    Hepojoki, Jussi; Vaheri, Antti; Strandin, Tomas

    2014-01-01

    Hantavirus, a genus of rodent- and insectivore-borne viruses in the family Bunyaviridae, is a group of emerging zoonotic pathogens. Hantaviruses cause hemorrhagic fever with renal syndrome and hantavirus cardiopulmonary syndrome in man, often with severe consequences. Vascular leakage is evident in severe hantavirus infections, and increased permeability contributes to the pathogenesis. This review summarizes the current knowledge on hantavirus interactions with hematopoietic and endothelial ...

  20. Cellulite: a review of pathogenesis-directed therapy.

    Science.gov (United States)

    Callaghan, Daniel J; Robinson, Deanne Mraz; Kaminer, Michael S

    2017-12-01

    Cellulite is a condition that affects the majority of postpubertal women and can negatively impact quality of life. This review discusses several proposed pathophysiologies of cellulite, and examines treatment options that have been utilized, focusing on the etiologic factor targeted by the therapies. This approach aims to help clarify the pathogenesis of cellulite and provide a road map for developing effective treatment paradigms for patients. ©2017 Frontline Medical Communications.

  1. The role of extracellular vesicles in malaria biology and pathogenesis.

    Science.gov (United States)

    Sampaio, Natalia Guimaraes; Cheng, Lesley; Eriksson, Emily M

    2017-06-09

    In the past decade, research on the functions of extracellular vesicles in malaria has expanded dramatically. Investigations into the various vesicle types, from both host and parasite origin, has revealed important roles for extracellular vesicles in disease pathogenesis and susceptibility, as well as cell-cell communication and immune responses. Here, work relating to extracellular vesicles in malaria is reviewed, and the areas that remain unknown and require further investigations are highlighted.

  2. Molecular mechanisms involved in the pathogenesis of septic shock.

    Science.gov (United States)

    López-Bojórquez, Lucia Nikolaia; Dehesa, Alejandro Zentella; Reyes-Terán, Gustavo

    2004-01-01

    Pathogenesis of the development of sepsis is highly complex and has been the object of study for many years. The inflammatory phenomena underlying septic shock are described in this review, as well as the enzymes and genes involved in the cellular activation that precedes this condition. The most important molecular aspects are discussed, ranging from the cytokines involved and their respective transduction pathways to the cellular mechanisms related to accelerated catabolism and multi-organic failure.

  3. Interferons and Alphavirus Pathogenesis: Implications for Developing Medical Countermeasures

    Science.gov (United States)

    2005-12-01

    ines qui interferent avec la croissance d’un virus. Depuis cette d~couverte, on a trouv6 plusieurs sortes d’INF que lPon a classifid en trois types...Defence Research and Recherche et developpement Development Canada pour la defense Canada DEFENCE •DFFENSE a Interferons and Alphavirus Pathogenesis...majestd la reine, reprdsentde par le ministre de la DMfense nationale, 2005 Abstract Our immune system can launch a quick defence against a large

  4. Inclusion body myositis: diagnosis, pathogenesis, and treatment options.

    Science.gov (United States)

    Solorzano, Guillermo E; Phillips, Lawrence H

    2011-05-01

    Inclusion body myositis (IBM) is the most common acquired myopathy in people older than 50 years. IBM typically presents with distal upper extremity weakness accompanied by proximal lower extremity muscle weakness. Associated clinical findings include asymmetric weakness, foot drop, and dysphagia. The pathogenesis of IBM is not clear. In this article the authors briefly discuss postulated pathogenic mechanisms. Although no proven pharmacotherapy exists, some promising candidates are discussed. Copyright © 2011 Elsevier Inc. All rights reserved.

  5. Understanding rare disease pathogenesis: a grand challenge for model organisms.

    Science.gov (United States)

    Hieter, Philip; Boycott, Kym M

    2014-10-01

    In this commentary, Philip Hieter and Kym Boycott discuss the importance of model organisms for understanding pathogenesis of rare human genetic diseases, and highlight the work of Brooks et al., "Dysfunction of 60S ribosomal protein L10 (RPL10) disrupts neurodevelopment and causes X-linked microcephaly in humans," published in this issue of GENETICS. Copyright © 2014 by the Genetics Society of America.

  6. The pathogenesis, diagnosis and treatment of Raynaud phenomenon.

    Science.gov (United States)

    Herrick, Ariane L

    2012-08-01

    The past 10 years have seen the publication of results from several multicentre clinical trials in primary and systemic sclerosis (SSc)-related Raynaud phenomenon. The publication of these studies has occurred as a result of new insights into the pathogenesis of Raynaud phenomenon, which are directing new treatment approaches, and increased international collaboration between clinicians and scientists. Although the pathogenesis of Raynaud phenomenon is complex, abnormalities of the blood vessel wall, of neural control mechanisms and of intravascular (circulating) factors are known to interact and contribute. Key players relevant in drug development include nitric oxide, endothelin-1, alpha adrenergic receptor activation, abnormal signal transduction in vascular smooth muscle, oxidative stress and platelet activation. The main advances in diagnosis have been a clearer understanding of autoantibodies and of abnormal nailfold capillary patterns as independent predictors of SSc, and widespread use and increased availability of capillaroscopy. The ultimate aim is to translate the advances made in the pathophysiology and early diagnosis into development of treatments to prevent and reverse digital vascular dysfunction and injury. This Review provides an update of the pathogenesis, diagnosis and treatment of Raynaud phenomenon. Current and future treatment approaches are discussed, and some key unanswered questions are highlighted.

  7. Molecular Determinants of Influenza Virus Pathogenesis in Mice

    Science.gov (United States)

    Katz, Jaqueline M.; York, Ian A.

    2015-01-01

    Mice are widely used for studying influenza virus pathogenesis and immunology because of their low cost, the wide availability of mouse-specific reagents, and the large number of mouse strains available, including knockout and transgenic strains. However, mice do not fully recapitulate the signs of influenza infection of humans: transmission of influenza between mice is much less efficient than in humans, and influenza viruses often require adaptation before they are able to efficiently replicate in mice. In the process of mouse adaptation, influenza viruses acquire mutations that enhance their ability to attach to mouse cells, replicate within the cells, and suppress immunity, among other functions. Many such mouse-adaptive mutations have been identified, covering all 8 genomic segments of the virus. Identification and analysis of these mutations have provided insight into the molecular determinants of influenza virulence and pathogenesis, not only in mice but also in humans and other species. In particular, several mouse-adaptive mutations of avian influenza viruses have proved to be general mammalian-adaptive changes that are potential markers of pre-pandemic viruses. As well as evaluating influenza pathogenesis, mice have also been used as models for evaluation of novel vaccines and anti-viral therapies. Mice can be a useful animal model for studying influenza biology as long as differences between human and mice infections are taken into account. PMID:25038937

  8. [The pathogenesis and prevention of urinary tract infection in women].

    Science.gov (United States)

    Shabad, A L; Minakov, N K; Mkrtchan, G G; Zabirov, K I; Vasil'ev, M M; Khodyreva, L A; Tolstova, S S; Kisina, V I

    1995-01-01

    Urinary tract infection (UTI) in females occurs significantly more frequently than in males because of specific anatomical and functional features of female urinary system, sequelae of pregnancy, delivery, gynecological diseases. Much controversy still exists as to pathogenesis of UTI and UTI-induced urinary inflammation. We have examined 233 females of different age with UTI and obtained evidence which shows participation of such factors as early and intensive sex, ignorance of sex hygiene, multiple pregnancies, deliveries, abortions, inflammatory gynecological diseases, anogenital infection in its pathogenesis. These factors were registered 2-4 times more frequently in UTI females than in controls without UTI. Bacteriological urinary and genital findings coincide in 80% of cases in terms of an infective agent. This suggests that it is essential to detect urogenital infection in girls and females as early as possible and to treat it adequately with antibacterial and other drugs. The leading role of an ascending urinogenic route in urinary tract infection from local sources in anogenital zone, sexual factor and the absence of relevant hygienic habits proved most contributing to UTI pathogenesis. This concept serves the basis for UTI prevention in females.

  9. Advances in hepatitis E - I: virology, pathogenesis and diagnosis.

    Science.gov (United States)

    Aggarwal, Rakesh; Goel, Amit

    2016-09-01

    Infection with hepatitis E virus (HEV) is the commonest cause of acute hepatitis worldwide. HEV was discovered in 1980s and is known to have small non-enveloped virions with single-stranded RNA genome of positive polarity. In recent years. In recent years, availability of new information has changed our understanding of this virus and the pathogenesis of the related disease. This article reviews the current knowledge about structure, genomic organization, taxonomy, genetic epidemiology, host specificity and replication of the human HEV and of various closely-related viruses that infect other animals. In addition, the models available for the study of HEV infection, the available information on the pathogenesis of this infection and the techniques available for its diagnosis are also reviewed. Expert commentary: A circulating, enveloped form of the human HEV has been recently recognized. Originally believed to naturally infect only humans and possibly primates, HEV-like viruses are now known to infect several vertebrate animals. Based on this, phylogenetic classification of these viruses has recently been revised. In vitro replicons and infection systems have been developed, which have improved our understanding about the virus and the pathogenesis of infection with it. Recent development of mouse models with chimeric livers that contain human hepatocytes provides another avenue for further advancement of this knowledge.

  10. Eosinophils in vasculitis: characteristics and roles in pathogenesis

    Science.gov (United States)

    Khoury, Paneez; Grayson, Peter C.; Klion, Amy D.

    2016-01-01

    Eosinophils are multifunctional granular leukocytes that are implicated in the pathogenesis of a wide variety of disorders, including asthma, helminth infection, and rare hypereosinophilic syndromes. Although peripheral and tissue eosinophilia can be a feature of many types of small-vessel and medium-vessel vasculitis, the role of eosinophils has been best studied in eosinophilic granulomatosis with polyangiitis (EGPA), where eosinophils are a characteristic finding in all three clinical stages of the disorder. Whereas numerous studies have demonstrated an association between the presence of eosinophils and markers of eosinophil activation in the blood and tissues of patients with EGPA, the precise role of eosinophils in disease pathogenesis has been difficult to ascertain owing to the complexity of the disease process. In this regard, results of clinical trials using novel agents that specifically target eosinophils are providing the first direct evidence of a central role of eosinophils in EGPA. This Review focuses on the aspects of eosinophil biology most relevant to the pathogenesis of vasculitis and provides an update of current knowledge regarding the role of eosinophils in EGPA and other vasculitides. PMID:25003763

  11. Diverticular Disease: An Update on Pathogenesis and Management.

    Science.gov (United States)

    Rezapour, Mona; Ali, Saima; Stollman, Neil

    2018-03-15

    Diverticular disease is one of the most common conditions in the Western world and one of the most common findings identified at colonoscopy. Recently, there has been a significant paradigm shift in our understanding of diverticular disease and its management. The pathogenesis of diverticular disease is thought to be multifactorial and include both environmental and genetic factors in addition to the historically accepted etiology of dietary fiber deficiency. Symptomatic uncomplicated diverticular disease (SUDD) is currently considered a type of chronic diverticulosis that is perhaps akin to irritable bowel syndrome. Mesalamine, rifaximin and probiotics may achieve symptomatic relief in some patients with SUDD, although their role(s) in preventing complications remain unclear. Antibiotic use for acute diverticulitis and elective prophylactic resection surgery are considered more individualized treatment modalities that take into account the clinical status, comorbidities and lifestyle of the patient. Our understanding of the pathogenesis of diverticular disease continues to evolve and is likely to be diverse and multifactorial. Paradigm shifts in several areas of the pathogenesis and management of diverticular disease are explored in this review.

  12. Adherence and pathogenesis of Salmonella enteritidis in mice.

    Science.gov (United States)

    Aslanzadeh, J; Paulissen, L J

    1990-01-01

    Adherence of many pathogenic organisms to the host cells has been associated with the presence of fimbriae. The exact role of these organelles in the adherence and pathogenesis of Salmonella enteritidis is not well established. Utilizing hemagglutination tests, S. enteritidis was shown to possess type 1 and type 3 fimbriae. Polyacrylamide gel electrophoresis of the isolated fimbriae showed that type 1 and 3 fimbriae of S. enteritidis had subunit M.r of 17 and 22 kDa, respectively. In vitro adherence assays suggested that S. enteritidis utilized type 1 fimbriae to adhere to human buccal and mouse small intestine epithelial cells. In addition, antibody produced against type 1 and type 3 fimbriae protected the mice from infection with a lethal dose of S. enteritidis. These results suggest that type 1 and possibly type 3 fimbriae are involved in the adherence and pathogenesis of S. enteritidis. The data further suggest that they may have a role in the adherence and pathogenesis of the other enteric organisms.

  13. Protection against retrovirus pathogenesis by SR protein inhibitors.

    Directory of Open Access Journals (Sweden)

    Anne Keriel

    Full Text Available Indole derivatives compounds (IDC are a new class of splicing inhibitors that have a selective action on exonic splicing enhancers (ESE-dependent activity of individual serine-arginine-rich (SR proteins. Some of these molecules have been shown to compromise assembly of HIV infectious particles in cell cultures by interfering with the activity of the SR protein SF2/ASF and by subsequently suppressing production of splicing-dependent retroviral accessory proteins. For all replication-competent retroviruses, a limiting requirement for infection and pathogenesis is the expression of the envelope glycoprotein which strictly depends on the host splicing machinery. Here, we have evaluated the efficiency of IDC on an animal model of retroviral pathogenesis using a fully replication-competent retrovirus. In this model, all newborn mice infected with a fully replicative murine leukemia virus (MLV develop erythroleukemia within 6 to 8 weeks of age. We tested several IDC for their ability to interfere ex vivo with MLV splicing and virus spreading as well as for their protective effect in vivo. We show here that two of these IDC, IDC13 and IDC78, selectively altered splicing-dependent production of the retroviral envelope gene, thus inhibiting early viral replication in vivo, sufficiently to protect mice from MLV-induced pathogenesis. The apparent specificity and clinical safety observed here for both IDC13 and IDC78 strongly support further assessment of inhibitors of SR protein splicing factors as a new class of antiretroviral therapeutic agents.

  14. T cell-dependence of Lassa fever pathogenesis.

    Directory of Open Access Journals (Sweden)

    Lukas Flatz

    2010-03-01

    Full Text Available Lassa virus (LASV, the causative agent of Lassa fever (LF, is endemic in West Africa, accounting for substantial morbidity and mortality. In spite of ongoing research efforts, LF pathogenesis and mechanisms of LASV immune control remain poorly understood. While normal laboratory mice are resistant to LASV, we report that mice expressing humanized instead of murine MHC class I (MHC-I failed to control LASV infection and develop severe LF. Infection of MHC-I knockout mice confirmed a key role for MHC-I-restricted T cell responses in controlling LASV. Intriguingly we found that T cell depletion in LASV-infected HHD mice prevented disease, irrespective of high-level viremia. Widespread activation of monocyte/macrophage lineage cells, manifest through inducible NO synthase expression, and elevated IL-12p40 serum levels indicated a systemic inflammatory condition. The absence of extensive monocyte/macrophage activation in T cell-depleted mice suggested that T cell responses contribute to deleterious innate inflammatory reactions and LF pathogenesis. Our observations in mice indicate a dual role for T cells, not only protecting from LASV, but also enhancing LF pathogenesis. The possibility of T cell-driven enhancement and immunopathogenesis should be given consideration in future LF vaccine development.

  15. Update of enterovirus 71 infection: epidemiology, pathogenesis and vaccine.

    Science.gov (United States)

    Wang, Shih-Min; Liu, Ching-Chuan

    2014-04-01

    Enterovirus 71 (EV71) is a neurotropic human pathogen that is the causative agent of hand foot and mouth disease (HFMD), herpangina and brain stem encephalitis. Recurrent EV71 epidemics of various scales have occurred in the Asia-Pacific region. Several specific cell surface molecules serve as the receptors for EV71. Identification of the receptors is an important step to understand EV71 disease. Cytokines, lymphocytes and monocytes contribute significantly to EV71 pathogenesis. The interaction of EV71 and receptors may be associated with the cytokines immunopathogenesis. Some animal models have been established and aim to explore the pathogenesis of EV71 infections. EV71 antibodies can neutralize or enhance infection at subneutralizing levels. These results are important for EV71 vaccine and therapeutics design. Several clinical trials of human inactivated EV71 vaccine have recently been completed. The purpose of this review is to summarize recent discoveries about the epidemiology and pathogenesis of EV71 and provide insights into human vaccine development.

  16. Increased incidence and prevalence of psoriasis in multiple sclerosis.

    Science.gov (United States)

    Marrie, Ruth Ann; Patten, Scott B; Tremlett, Helen; Wolfson, Christina; Leung, Stella; Fisk, John D

    2017-04-01

    Psoriasis and multiple sclerosis (MS) share some risk factors, and fumarates are effective disease-modifying therapies for both psoriasis and MS, suggesting a common pathogenesis. However, findings regarding the occurrence of psoriasis in the MS population are inconsistent. We aimed to estimate the incidence and prevalence of psoriasis in the MS population versus a matched cohort from the general population. We used population-based administrative data from the Canadian province of Manitoba to identify 4911 persons with MS and 23,274 age-, sex- and geographically-matched controls aged 20 years and older. We developed case definitions for psoriasis using ICD-9/10 codes and prescription claims. These case definitions were compared to self-reported psoriasis diagnoses. The preferred definition was applied to estimate the incidence and prevalence of psoriasis over the period 1998-2008. We used multivariable Cox regression to estimate the risk of psoriasis in the MS population at the individual level, adjusting for sex, age at the index date, socioeconomic status and physician visits. In 2008, the crude incidence of psoriasis per 100,000 person-years was 466.7 (95%CI: 266.8-758.0) in the MS population, and 221.3 in the matched population (95%CI: 158.1-301.4). The crude prevalence of psoriasis per 100,000 persons was 4666.1 (95%CI: 3985.2-5429.9) in the MS population, and 3313.5 (95%CI: 3057.4-3585.3) in the matched population. The incidence and prevalence of psoriasis rose slightly over time. After adjusting for sex, age at the index date, socioeconomic status and physician visits, the risk of incident psoriasis was 54% higher in the MS population (HR 1.54; 95%CI: 1.07-2.24). Psoriasis incidence and prevalence are higher in the MS population than in the matched population. Copyright © 2017. Published by Elsevier B.V.

  17. DMPD: Role of Toll-like receptor responses for sepsis pathogenesis. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 18086373 Role of Toll-like receptor responses for sepsis pathogenesis. Weighardt H, Holzmann B. Immunobiolog... responses for sepsis pathogenesis. Authors Weighardt H, Holzmann B. Publication Immunobiology

  18. Grazing Incidence Optics Technology

    Science.gov (United States)

    Ramsey, Brian; Smith, W. Scott; Gubarev, Mikhail; McCracken, Jeff

    2015-01-01

    This project is to demonstrate the capability to directly fabricate lightweight, high-resolution, grazing-incidence x-ray optics using a commercially available robotic polishing machine. Typical x-ray optics production at NASA Marshall Space Flight Center (MSFC) uses a replication process in which metal mirrors are electroformed on to figured and polished mandrels from which they are later removed. The attraction of this process is that multiple copies can be made from a single master. The drawback is that the replication process limits the angular resolution that can be attained. By directly fabricating each shell, errors inherent in the replication process are removed. The principal challenge now becomes how to support the mirror shell during all aspects of fabrication, including the necessary metrology to converge on the required mirror performance specifications. This program makes use of a Zeeko seven-axis computer-controlled polishing machine (see fig. 1) and supporting fabrication, metrology, and test equipment at MSFC. The overall development plan calls for proof-of-concept demonstration with relatively thick mirror shells (5-6 mm, fig. 2) which are straightforward to support and then a transition to much thinner shells (2-3 mm), which are an order of magnitude thinner than those used for Chandra. Both glass and metal substrates are being investigated. Currently, a thick glass shell is being figured. This has enabled experience to be gained with programming and operating the polishing machine without worrying about shell distortions or breakage. It has also allowed time for more complex support mechanisms for figuring/ polishing and metrology to be designed for the more challenging thinner shells. These are now in fabrication. Figure 1: Zeeko polishing machine.

  19. Goiania incident case study

    International Nuclear Information System (INIS)

    Petterson, J.S.

    1988-06-01

    The reasons for wanting to document this case study and present the findings are simple. According to USDOE technical risk assessments (and our own initial work on the Hanford socioeconomic study), the likelihood of a major accident involving exposure to radioactive materials in the process of site characterization, construction, operation, and closure of a high-level waste repository is extremely remote. Most would agree, however, that there is a relatively high probability that a minor accident involving radiological contamination will occur sometime during the lifetime of the repository -- for example, during transport, at an MRS site or at the permanent site itself during repacking and deposition. Thus, one of the major concerns of the Yucca Mountain Socioeconomic Study is the potential impact of a relatively minor radiation-related accident. A large number of potential impact of a relatively minor radiation-related accident. A large number of potential accident scenarios have been under consideration (such as a transportation or other surface accident which results in a significant decline in tourism, the number of conventions, or the selection of Nevada as a retirement residence). The results of the work in Goiania make it clear, however, that such a significant shift in established social patterns and trends is not likely to occur as a direct outcome of a single nuclear-related accident (even, perhaps, a relatively major one), but rather, are likely to occur as a result of the enduring social interpretations of such an accident -- that is, as a result of the process of understanding, communicating, and socially sustaining a particular set of associations with respect to the initial incident

  20. Incidence and Risk Factors of Recurrence after Surgery for Pathology-proven Diverticular Disease

    OpenAIRE

    Andeweg, Caroline; Peters, Joost; Bleichrodt, Robert; van Goor, Harry

    2008-01-01

    Background Diverticular disease is a common problem in Western countries. Rationale for elective surgery is to prevent recurrent complicated diverticulitis and to reduce emergency procedures. Recurrent diverticulitis occurs in about 10% after resection. The pathogenesis for recurrence is not completely understood. We studied the incidence and risk factors for recurrence and the overall morbidity and mortality of surgical therapy for diverticular disease. Methods Medical records of 183 consecu...

  1. Only incident depressive episodes after myocardial infarction are associated with new cardiovascular events

    NARCIS (Netherlands)

    de Jonge, Peter; van den Brink, Rob H. S.; Spijkerman, Titia A.; Ormel, Johan

    2006-01-01

    OBJECTIVES The purpose of this research was to study whether incident and non-incident depression after myocardial infarction (MI) are differentially associated with prospective fatal and non-fatal cardiovascular events. BACKGROUND Post-MI depression is defined as the presence of depression after

  2. Pathogenesis of Metastatic Calcification and Acute Pancreatitis in Adult T-Cell Leukemia under Hypercalcemic State

    Directory of Open Access Journals (Sweden)

    Masachika Senba

    2012-01-01

    Full Text Available Human T-cell leukemia virus type-1 (HTLV-1 is the causative agent of adult T-cell leukemia (ATL. Hypercalcemia is common in patients with ATL. These patients rarely develop metastatic calcification and acute pancreatitis. The underlying pathogenesis of this condition is osteoclast hyperactivity with associated overproduction of parathyroid hormone-related protein, which results in hypercalcemia in association with bone demineralization. The discovery of the osteoclast differentiation factor receptor activator of nuclear factor-κB ligand (RANKL, its receptor RANK, and its decoy receptor osteoprotegerin (OPG, enhanced our understanding of the mechanisms of ATL-associated hypercalcemia. Macrophage inflammatory protein-1-α, tumor necrosis factor-α, interleukin-1, and interleukin-6 are important molecules that enhance the migration and differentiation of osteoclasts and the associated enhanced production of RANKL for osteoblast formation. In this paper, we focus on metastatic calcification and acute pancreatitis in ATL, highlighting recent advances in the understanding of the molecular role of the RANKL/RANK/OPG system including its interaction with various cytokines and calciotropic hormones in the regulation of osteoclastogenesis for bone resorption in hypercalcemic ATL patients.

  3. MicroRNAs in human tongue squamous cell carcinoma: From pathogenesis to therapeutic implications.

    Science.gov (United States)

    Karatas, Omer Faruk; Oner, Muhammet; Abay, Alican; Diyapoglu, Ali

    2017-04-01

    Being one of the most aggressive cancers of oral cavity, tongue squamous cell carcinoma (TSCC) constitutes 41% of all oral carcinomas. Despite considerable improvements in multimodal diagnosis and treatment techniques, TSCC still remains to be one of the most lethal cancer types in the head and neck region. MicroRNAs are endogenously synthesized, small, non-coding RNAs, which are responsible for post-transcriptional regulation of mRNA expression. They are involved in regulation of almost all biological processes through their spatial and temporal expression. Their deregulation participates in pathogenesis of various diseases, including human TSCC, where they can act as potent oncogenes or tumor suppressors. Extensive microRNA profiling in TSCC samples and further in vitro and in vivo functional characterization of differentially expressed microRNAs revealed their contribution to the underlying molecular mechanisms of TSCC initiation, development, progression, metastasis, chemo-radioresistance, and recurrence. They are suggested as diagnostic and prognostic biomarkers for TSCC due to their differential expression in tumor tissues and their stability in body fluids like plasma, oral cytology, and saliva. MicroRNAs are, therefore, considered amongst the most promising candidates for development of novel therapeutic approaches against TSCC. In this review, we summarized important findings including our own works on microRNAs as implicated in TSCC and the new insights into the roles of microRNAs in squamous cell carcinoma of tongue. Copyright © 2017 Elsevier Ltd. All rights reserved.

  4. Monocyte Proteomics Reveals Involvement of Phosphorylated HSP27 in the Pathogenesis of Osteoporosis

    Directory of Open Access Journals (Sweden)

    Bhavna Daswani

    2015-01-01

    Full Text Available Peripheral monocytes, precursors of osteoclasts, have emerged as important candidates for identifying proteins relevant to osteoporosis, a condition characterized by low Bone Mineral Density (BMD and increased susceptibility for fractures. We employed 4-plex iTRAQ (isobaric tags for relative and absolute quantification coupled with LC-MS/MS (liquid chromatography coupled with tandem mass spectrometry to identify differentially expressed monocyte proteins from premenopausal and postmenopausal women with low versus high BMD. Of 1801 proteins identified, 45 were differentially abundant in low versus high BMD, with heat shock protein 27 (HSP27 distinctly upregulated in low BMD condition in both premenopausal and postmenopausal categories. Validation in individual samples (n=80 using intracellular ELISA confirmed that total HSP27 (tHSP27 as well as phosphorylated HSP27 (pHSP27 was elevated in low BMD condition in both categories (P<0.05. Further, using transwell assays, pHSP27, when placed in the upper chamber, could increase monocyte migration (P<0.0001 and this was additive in combination with RANKL (receptor activator of NFkB ligand placed in the lower chamber (P=0.05. Effect of pHSP27 in monocyte migration towards bone milieu can result in increased osteoclast formation and thus contribute to pathogenesis of osteoporosis. Overall, this study reveals for the first time a novel link between monocyte HSP27 and BMD.

  5. Differential Expression Profiles of Long Noncoding RNA and mRNA of Osteogenically Differentiated Mesenchymal Stem Cells in Ankylosing Spondylitis.

    Science.gov (United States)

    Xie, Zhongyu; Li, Jinteng; Wang, Peng; Li, Yuxi; Wu, Xiaohua; Wang, Shan; Su, Hongjun; Deng, Wen; Liu, Zhenhua; Cen, Shuizhong; Ouyang, Yi; Wu, Yanfeng; Shen, Huiyong

    2016-08-01

    We previously demonstrated that mesenchymal stem cells (MSC) from patients with ankylosing spondylitis (AS; ASMSC) have a greater osteogenic differentiation capacity than MSC from healthy donors (HDMSC) and that this difference underlies the pathogenesis of pathological osteogenesis in AS. Here we compared expression levels of long noncoding RNA (lncRNA) and mRNA between osteogenically differentiated ASMSC and HDMSC and explored the precise mechanism underlying abnormal osteogenic differentiation in ASMSC. HDMSC and ASMSC were induced with osteogenic differentiation medium for 10 days. Microarray analyses were then performed to identify lncRNA and mRNA differentially expressed between HDMSC and ASMSC, which were then subjected to bioinformatics analysis and confirmed by quantitative real-time PCR (qRT-PCR) assays. In addition, coding-non-coding gene co-expression (CNC) networks were constructed to examine the relationships between the lncRNA and mRNA expression patterns. A total of 520 lncRNA and 665 mRNA were differentially expressed in osteogenically differentiated ASMSC compared with HDMSC. Bioinformatics analysis revealed 64 signaling pathways with significant differences, including transforming growth factor-β signaling. qRT-PCR assays confirmed the reliability of the microarray data. The CNC network indicated that 4 differentially expressed lncRNA, including lnc-ZNF354A-1, lnc-LIN54-1, lnc-FRG2C-3, and lnc-USP50-2 may be involved in the abnormal osteogenic differentiation of ASMSC. Our study characterized the differential lncRNA and mRNA expression profiles of osteogenically differentiated ASMSC and identified 4 lncRNA that may participate in the abnormal osteogenic differentiation of ASMSC. These results provide insight into the pathogenesis of pathological osteogenesis in AS.

  6. Real time freeway incident detection.

    Science.gov (United States)

    2014-04-01

    The US Department of Transportation (US-DOT) estimates that over half of all congestion : events are caused by highway incidents rather than by rush-hour traffic in big cities. Real-time : incident detection on freeways is an important part of any mo...

  7. Soluble CD163 predicts incident chronic lung, kidney and liver disease in HIV infection

    DEFF Research Database (Denmark)

    Kirkegaard-Klitbo, Ditte M; Mejer, Niels; Knudsen, Troels B

    2017-01-01

    .46] and incident chronic kidney disease (aHR, 10.94; 95% CI: 2.32; 51.35), when compared with lowest quartiles. Further, (every 1 mg) increase in plasma sCD163 was positively correlated with incident liver disease (aHR, 1.12; 95% CI: 1.05; 1.19). The sCD163 level was not associated with incident cancer......, cardiovascular disease or diabetes mellitus. CONCLUSION: sCD163 was independently associated with incident chronic kidney disease, chronic lung disease and liver disease in treated HIV-1-infected individuals, suggesting that monocyte/macrophage activation may be involved in the pathogenesis of non...

  8. T cell activation and differentiation is modulated by a CD6 domain 1 antibody Itolizumab.

    Directory of Open Access Journals (Sweden)

    Usha Bughani

    Full Text Available CD6 is associated with T-cell modulation and is implicated in several autoimmune diseases. We previously demonstrated that Itolizumab, a CD6 domain 1 (CD6D1 specific humanized monoclonal antibody, inhibited the proliferation and cytokine production by T lymphocytes stimulated with anti-CD3 antibody or when co-stimulated with ALCAM. Aberrant IL-17 producing CD4+ helper T-cells (Th17 have been identified as pivotal for the pathogenesis of certain inflammatory autoimmune disorders, including psoriasis. Itolizumab has demonstrated efficacy in human diseases known to have an IL-17 driven pathogenesis. Here, in in vitro experiments we show that by day 3 of human PBMC activation using anti-CD3 and anti-CD28 co-stimulation in a Th17 polarizing milieu, 15-35% of CD4+ T-cells overexpress CD6 and there is an establishment of differentiated Th17 cells. Addition of Itolizumab reduces the activation and differentiation of T cells to Th17 cells and decreases production of IL-17. These effects are associated with the reduction of key transcription factors pSTAT3 and RORγT. Further, transcription analysis studies in these conditions indicate that Itolizumab suppressed T cell activation by primarily reducing cell cycle, DNA transcription and translation associated genes. To understand the mechanism of this inhibition, we evaluated the effect of this anti-human CD6D1 mAb on ALCAM-CD6 as well as TCR-mediated T cell activation. We show that Itolizumab but not its F(ab'2 fragment directly inhibits CD6 receptor hyper-phosphorylation and leads to subsequent decrease in associated ZAP70 kinase and docking protein SLP76. Since Itolizumab binds to CD6 expressed only on human and chimpanzee, we developed an antibody binding specifically to mouse CD6D1. This antibody successfully ameliorated the incidence of experimental autoimmune encephalitis in the mice model. These results position CD6 as a key molecule in sustaining the activation and differentiation of T cells and an

  9. Analyses of Brucella pathogenesis, host immunity, and vaccine targets using systems biology and bioinformatics

    Directory of Open Access Journals (Sweden)

    Yongqun eHe

    2012-02-01

    Full Text Available Brucella is a Gram-negative, facultative intracellular bacterium that causes zoonotic brucellosis in humans and various animals. Out of ten classified Brucella species, B. melitensis, B. abortus, B. suis, and B. canis are pathogenic to humans. In the past decade, the mechanisms of Brucella pathogenesis and host immunity have been extensively investigated using the cutting edge systems biology and bioinformatics approaches. This article provides a comprehensive review of the applications of Omics (including genomics, transcriptomics, and proteomics and bioinformatics technologies for the analysis of Brucella pathogenesis, host immune responses, and vaccine targets. Based on more than 30 sequenced Brucella genomes, comparative genomics is able to identify gene variations among Brucella strains that help to explain host specificity and virulence differences among Brucella species. Diverse transcriptomics and proteomics gene expression studies have been conducted to analyze gene expression profiles of wild type Brucella strains and mutants under different laboratory conditions. High throughput Omics analyses of host responses to infections with virulent or attenuated Brucella strains have been focused on responses by mouse and cattle macrophages, bovine trophoblastic cells, mouse and boar splenocytes, and ram buffy coat. Differential serum responses in humans and rams to Brucella infections have been analyzed using high throughput serum antibody screening technology. The Vaxign reverse vaccinology has been used to predict many Brucella vaccine targets. More than 180 Brucella virulence factors and their gene interaction networks have been identified using advanced literature mining methods. The recent development of community-based Vaccine Ontology and Brucellosis Ontology provides an efficient way for Brucella data integration, exchange, and computer-assisted automated reasoning.

  10. Transgenic animal models for study of the pathogenesis of Huntington’s disease and therapy

    Directory of Open Access Journals (Sweden)

    Chang RB

    2015-04-01

    Full Text Available Renbao Chang,1 Xudong Liu,1 Shihua Li,2 Xiao-Jiang Li1,2 1State Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, People’s Republic of China; 2Department of Human Genetics, Emory University School of Medicine, Atlanta, GA, USA Abstract: Huntington’s disease (HD is caused by a genetic mutation that results in polyglutamine expansion in the N-terminal regions of huntingtin. As a result, this polyQ expansion leads to the misfolding and aggregation of mutant huntingtin as well as age-dependent neurodegeneration. The genetic mutation in HD allows for generating a variety of animal models that express different forms of mutant huntingtin and show differential pathology. Studies of these animal models have provided an important insight into the pathogenesis of HD. Mouse models of HD include transgenic mice, which express N-terminal or full-length mutant huntingtin ubiquitously or selectively in different cell types, and knock-in mice that express full-length mutant Htt at the endogenous level. Large animals, such as pig, sheep, and monkeys, have also been used to generate animal HD models. This review focuses on the different features of commonly used transgenic HD mouse models as well as transgenic large animal models of HD, and also discusses how to use them to identify potential therapeutics. Since HD shares many pathological features with other neurodegenerative diseases, identification of therapies for HD would also help to develop effective treatment for different neurodegenerative diseases that are also caused by protein misfolding and occur in an age-dependent manner. Keywords: transgenic animal models, Huntington’s disease, pathogenesis, therapy

  11. Analyses of Brucella Pathogenesis, Host Immunity, and Vaccine Targets using Systems Biology and Bioinformatics

    Science.gov (United States)

    He, Yongqun

    2011-01-01

    Brucella is a Gram-negative, facultative intracellular bacterium that causes zoonotic brucellosis in humans and various animals. Out of 10 classified Brucella species, B. melitensis, B. abortus, B. suis, and B. canis are pathogenic to humans. In the past decade, the mechanisms of Brucella pathogenesis and host immunity have been extensively investigated using the cutting edge systems biology and bioinformatics approaches. This article provides a comprehensive review of the applications of Omics (including genomics, transcriptomics, and proteomics) and bioinformatics technologies for the analysis of Brucella pathogenesis, host immune responses, and vaccine targets. Based on more than 30 sequenced Brucella genomes, comparative genomics is able to identify gene variations among Brucella strains that help to explain host specificity and virulence differences among Brucella species. Diverse transcriptomics and proteomics gene expression studies have been conducted to analyze gene expression profiles of wild type Brucella strains and mutants under different laboratory conditions. High throughput Omics analyses of host responses to infections with virulent or attenuated Brucella strains have been focused on responses by mouse and cattle macrophages, bovine trophoblastic cells, mouse and boar splenocytes, and ram buffy coat. Differential serum responses in humans and rams to Brucella infections have been analyzed using high throughput serum antibody screening technology. The Vaxign reverse vaccinology has been used to predict many Brucella vaccine targets. More than 180 Brucella virulence factors and their gene interaction networks have been identified using advanced literature mining methods. The recent development of community-based Vaccine Ontology and Brucellosis Ontology provides an efficient way for Brucella data integration, exchange, and computer-assisted automated reasoning. PMID:22919594

  12. Acquired Secondary Events in the Pathogenesis of Hereditary Breast Cancer

    National Research Council Canada - National Science Library

    Tomlinson, Gail

    1999-01-01

    The inheritance of a germ-line mutation of the BRCA1 or BRCA2 gene, although associated with a markedly increased incidence of breast cancer, is not solely responsible for the development of breast...

  13. Bone Circulatory Disturbances in the Development of Spontaneous Bacterial Chondronecrosis with Osteomyelitis: A Translational Model for the Pathogenesis of Femoral Head Necrosis

    Directory of Open Access Journals (Sweden)

    Robert F. Wideman

    2013-01-01

    Full Text Available This review provides a comprehensive overview of the vascularization of the avian growth plate and its subsequent role in the pathogenesis of bacterial chondronecrosis with osteomyelitis (BCO, femoral head necrosis. BCO sporadically causes high incidences of lameness in rapidly growing broiler (meat-type chickens. BCO is believed to be initiated by micro-trauma to poorly mineralized columns of cartilage cells in the proximal growth plates of the leg bones, followed by colonization by hematogenously distributed opportunistic bacteria. Inadequate blood flow to the growth plate, vascular occlusion, and structural limitations of the microvasculature all have been implicated in the pathogenesis of BCO. Treatment strategies have been difficult to investigate because under normal conditions the incidence of BCO typically is low and sporadic. Rearing broilers on wire flooring triggers the spontaneous development of high incidences of lameness attributable to pathognomonic BCO lesions. Wire flooring imposes persistent footing instability and is thought to accelerate the development of BCO by amplifying the torque and shear stress imposed on susceptible leg joints. Wire flooring per se also constitutes a significant chronic stressor that promotes bacterial proliferation attributed to stress-mediated immunosuppression. Indeed, dexamethasone-mediated immunosuppression causes broilers to develop lameness primarily associated with avascular necrosis and BCO. Prophylactic probiotic administration consistently reduces the incidence of lameness in broilers reared on wire flooring, presumably by reducing bacterial translocation from the gastrointestinal tract that likely contributes to hematogenous infection of the leg bones. The pathogenesis of BCO in broilers is directly relevant to osteomyelitis in growing children, as well as to avascular femoral head necrosis in adults. Our new model for reliably triggering spontaneous osteomyelitis in large numbers of

  14. Structural studies of human glioma pathogenesis-related protein 1

    Energy Technology Data Exchange (ETDEWEB)

    Asojo, Oluwatoyin A., E-mail: oasojo@unmc.edu [College of Medicine, Nebraska Medical Center, Omaha, NE 68198-6495 (United States); Koski, Raymond A.; Bonafé, Nathalie [L2 Diagnostics LLC, 300 George Street, New Haven, CT 06511 (United States); College of Medicine, Nebraska Medical Center, Omaha, NE 68198-6495 (United States)

    2011-10-01

    Structural analysis of a truncated soluble domain of human glioma pathogenesis-related protein 1, a membrane protein implicated in the proliferation of aggressive brain cancer, is presented. Human glioma pathogenesis-related protein 1 (GLIPR1) is a membrane protein that is highly upregulated in brain cancers but is barely detectable in normal brain tissue. GLIPR1 is composed of a signal peptide that directs its secretion, a conserved cysteine-rich CAP (cysteine-rich secretory proteins, antigen 5 and pathogenesis-related 1 proteins) domain and a transmembrane domain. GLIPR1 is currently being investigated as a candidate for prostate cancer gene therapy and for glioblastoma targeted therapy. Crystal structures of a truncated soluble domain of the human GLIPR1 protein (sGLIPR1) solved by molecular replacement using a truncated polyalanine search model of the CAP domain of stecrisp, a snake-venom cysteine-rich secretory protein (CRISP), are presented. The correct molecular-replacement solution could only be obtained by removing all loops from the search model. The native structure was refined to 1.85 Å resolution and that of a Zn{sup 2+} complex was refined to 2.2 Å resolution. The latter structure revealed that the putative binding cavity coordinates Zn{sup 2+} similarly to snake-venom CRISPs, which are involved in Zn{sup 2+}-dependent mechanisms of inflammatory modulation. Both sGLIPR1 structures have extensive flexible loop/turn regions and unique charge distributions that were not observed in any of the previously reported CAP protein structures. A model is also proposed for the structure of full-length membrane-bound GLIPR1.

  15. Enterobacterial involvement in the pathogenesis of secondary ankylosing spondylitis.

    Science.gov (United States)

    van Bohemen, C G; Weterings, E; Goei The, H S; Grumet, F C; Zanen, H C

    1988-01-01

    Ankylosing spondylitis (AS) is closely associated with the histocompatibility antigen HLA-B27. Pathogenesis of AS is thought to involve interactions between B27 and certain enterobacterial antigens. However, this is uncertain and contested by some. The present paper argues that the presence of statistically raised specific serum IgA to a common enterobacterial heat modifiable major outer membrane protein (h-momp; Mr 35,000) in active AS (N = 25; IgA = 1485 +/- 20) in comparison to controls, most notably hospital patients without known arthropathies or gastrointestinal disease (N = 12; IgA = 548 +/- 59), supports an inductive contribution of enterobacterial antigens to the pathogenesis of secondary AS. Serum IgG and IgM did not statistically differ. Raised specific serum IgA to h-momp might indicate enterobacterial antigenic stimulation from the gastrointestinal tract. It does not necessarily imply direct involvement in the pathogenesis of primary AS. H-momp appears to be a convenient tool for serological studies of AS and at present is likely to be more suitable than other bacterial antigens, notably those with B27-like epitopes. Namely, the confirmed presence in AS of enterobacteria with freely accessible B27-like antigenic epitopes on their cell surface might induce unusual tolerance to these organisms in B27 positive hosts, thus causing chronic inflammation, initially sacroiliitis (and spondylitis) due to the proximity of presacral and para-aortic colon draining lymph nodes, later becoming more generalized (for reasons unclear) to include other lesions (e.g. peripheral arthritis, uveitis, enthesopathies). Thus, antibodies to B27-like antigenic epitopes need not be detectable or may be absent. Also, cellular immune responsiveness to these antigens might be involved.

  16. Ebolavirus: An Overview of Molecular and Clinical Pathogenesis.

    Science.gov (United States)

    Vine, Veronica; Scott, Dana P; Feldmann, Heinz

    2017-01-01

    Ebolaviruses cause severe, often fatal hemorrhagic fever in Central, East, and West Africa. Until recently, they have been viewed as rare but highly pathogenic infections with regional, but limited, global public health impact. This view has changed with the emergence of the first epidemic of Ebola hemorrhagic fever in West Africa. In this chapter we provide an introduction of the pathogenesis of ebolaviruses as well as a description of clinical disease features. We also describe the current animal models used in ebolavirus research, detailing each model's unique strengths and weaknesses. We focus on Ebola virus representing the type species Zaire ebolavirus of the genus Ebolavirus, as most work relates to this pathogen.

  17. Roles of Rack1 Proteins in Fungal Pathogenesis

    Directory of Open Access Journals (Sweden)

    Xue Zhang

    2016-01-01

    Full Text Available Pathogenic fungi cause diseases on various organisms. Despite their differences in life cycles, fungal pathogens use well-conserved proteins and pathways to regulate developmental and infection processes. In this review, we focus on Rack1, a multifaceted scaffolding protein involved in various biological processes. Rack1 is well conserved in eukaryotes and plays important roles in fungi, though limited studies have been conducted. To accelerate the study of Rack1 proteins in fungi, we review the functions of Rack1 proteins in model and pathogenic fungi and summarize recent progress on how Rack1 proteins are involved in fungal pathogenesis.

  18. Review of Critical Issues in the Pathogenesis of Atopic Dermatitis.

    Science.gov (United States)

    Irvine, Alan D; Eichenfield, Lawrence F; Friedlander, Sheila F; Simpson, Eric L

    2016-06-01

    About a decade age, loss-of-function mutations in the filaggrin molecule were first implicated in the pathogenesis of ichthyosis vulgaris and, subsequently, of atopic dermatitis and other atopic diseases. Since then, intensive study of the role of filaggrin null mutations have led to other milestones in understanding the pathologic pathways in these diseases, including the initiation, maintenance, and promotion of the disease processes. The result has been new and emerging clinical and pharmacologic strategies for early identification of and intervention in atopic diseases. Semin Cutan Med Surg 35(supp5):S89-S91. 2016 published by Frontline Medical Communications.

  19. [The pathogenesis of periodontal disease: a paradigm shift].

    Science.gov (United States)

    Ekstein, J; Shapira, L; Van Dyke, T E

    2010-07-01

    Periodontitis is a family of related diseases that differ in etiology, natural history, disease progression and response to therapy, but have a common underlying chain of events, thatareinfluenced by disease modifiers. The clinical manifestations observed are a result of the complex interplay of these factors. The pathogenesis of human periodontitis was placed on a rational footing for the first time by Page & Schroeder in 1976 and the general principles and the overall conclusions reached in that article are still largely acceptable today. Still, an enormous amount has been learned about all aspects of human periodontitis, including its pathogenesis, since 1976. A critical evaluation of the literature regarding the complex relationship between the microbial factor, the host factor and the occurrence of a disease, might be leading us over a surge of a paradigm shift in our understanding the pathogenesis of the disease. It is well acknowledged that while the etiology of periodontitis is bacterial, the pathogenesis is inflammatory. The understanding of regulation of inflammation in periodontitis is far from complete; however, as the understanding of periodontal inflammation increases, the current understanding of the microbiology of periodontitis becomes less clear. While we think we know that bacteria initiate the disease, the role of specific bacteria is still unknown. The current knowledge of the microbiology of periodontitis is based on large cross-sectional and association studies. Periodontitis is seen as the direct consequence of bacterial invasion and is regarded as an infectious disease. It is however, not possible to draw cause and- effect inferences from these studies. One might state that the inflammation precedes the overgrowth of the bacteria. In this scenario, the initiator of the disease might be early, gram-positive colonizers that elicit a profound inflammatory response in the susceptible host. The implication of that paradigm shift outlined above

  20. Molecular Pathogenesis and Current Therapy in Intrahepatic Cholangiocarcinoma

    DEFF Research Database (Denmark)

    Høgdall, Dan Taksony Solyom; O'Rourke, Colm J; Taranta, Andrzej

    2016-01-01

    Intrahepatic cholangiocarcinoma (iCCA) comprises one of the most rapidly evolving cancer types. An underlying chronic inflammatory liver disease that precedes liver cancer development for several decades and creates a pro-oncogenic microenvironment frequently impairs progress in therapeutic...... approaches. Depending on the cellular target of malignant transformation, a large spectrum of molecular and morphological patterns is observed. As such, it is crucial to advance our existing understanding of the molecular pathogenesis of iCCA, particularly its genomic heterogeneity, to improve current...

  1. Rosacea: part I. Introduction, categorization, histology, pathogenesis, and risk factors.

    Science.gov (United States)

    Two, Aimee M; Wu, Wiggin; Gallo, Richard L; Hata, Tissa R

    2015-05-01

    Rosacea is a chronic inflammatory skin condition that affects approximately 16 million Americans. Four distinct subtypes of rosacea have been recognized, with transient and nontransient facial flushing, telangiectasia, and inflammatory papules and pustules being among the more commonly recognized features. Although the exact pathogenesis of rosacea is unknown, dysregulation of the innate immune system, overgrowth of commensal skin organisms, and aberrant neurovascular signaling may all have a role in promoting the clinical features of rosacea. Copyright © 2014 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

  2. Implication of microRNAs in the Pathogenesis of MDS

    Science.gov (United States)

    Fang, Jing; Varney, Melinda; Starczynowski, Daniel T.

    2016-01-01

    MicroRNAs (miRNAs) are significant regulators of human hematopoietic stem cells (HSC), and their deregulation contributes to hematological malignancies. Myelodysplastic syndromes (MDS) represent a spectrum of hematological disorders characterized by dysfunctional HSC, ineffective blood cell production, progressive marrow failure, and an increased risk of developing acute myeloid leukemia (AML). Although miRNAs have been primarily studied in AML, only recently have similar studies been performed on MDS. In this review, we describe the normal function and expression of miRNAs in human HSC, and describe mounting evidence that deregulation of miRNAs contributes to the pathogenesis of MDS. PMID:22571695

  3. The HBZ gene, a key player in HTLV-1 pathogenesis

    Directory of Open Access Journals (Sweden)

    Green Patrick L

    2009-08-01

    Full Text Available Abstract Human T-cell leukemia virus type 1 (HTLV-1 causes adult T-cell leukemia/lymphoma (ATL and is also associated with a variety of lymphocyte-mediated diseases. The HTLV-1 basic leucine zipper (HBZ gene, found to be consistently expressed in ATL, has recently been the subject of intensive research efforts. In this review, we summarize recent findings about HBZ and discuss its roles and functions not only in the virus life cycle, but also in HTLV-1 disease pathogenesis.

  4. CYTOMEGALOVIRUS: A REVIEW OF PATHOGENESIS, EPIDEMIOLOGY AND DIAGNOSIS OF INFECTION

    Directory of Open Access Journals (Sweden)

    Sócrates Bezerra de Matos

    2011-05-01

    Full Text Available The cytomegalovirus (CMV is a human β-herpesvirus ubiquitous and has high worldwide prevalence. The transmission occurs through contact with biological fluids, such as: saliva, semen, vaginal secretions, urine and breast milk, as well as transplacental, blood transfusion or organ transplantation. The most CMV infected individuals remains asymptomatic, however, some patients, especially the immunosuppressed, can develop severe infection with serious clinical signs, like the transplant recipients, HIV positive, leukemic or newborn. This review aims, among other things, discuss the pathogenesis and highlight important sites of immunology and diagnosis of CMV infection.

  5. Cytomegalovirus: a review of pathogenesis, epidemiology and diagnosis of infection

    Directory of Open Access Journals (Sweden)

    Sócrates Bezerra de Matos

    2011-01-01

    Full Text Available The cytomegalovirus (CMV is a human β-herpesvirus ubiquitous and has high worldwide prevalence. The transmission occurs through contact with biological fluids, such as: saliva, semen, vaginal secretions, urine and breast milk, as well as trans placental, blood transfusion or organ transplantation. The most CMV infected individuals remains asymptomatic, however, some patients, especially the immunosuppressed, can develop severe infection with serious clinical signs, like the transplant recipients, HIV positive, leukemic or newborn. This review aims, among other things, discuss the pathogenesis and highlight important sites of immunology and diagnosis of CMV infection.

  6. The role of inflammation in the pathogenesis of glaucoma

    DEFF Research Database (Denmark)

    Vohra, Rupali; Tsai, James C; Kolko, Miriam

    2013-01-01

    Glaucoma is an ocular disorder characterized by the progressive loss of retinal ganglion cells (RGC) and their axons. There are various hypotheses concerning the cause of RGC death. Previously, glaucoma was defined by high intraocular pressure (IOP); during the past decade, however, glaucoma...... specialists have acknowledged that elevated IOP is the most important risk factor for glaucoma, but does not define the disease. Other factors such as genetics, blood flow, and excitotoxicity are suggested as potential causal factors for progressive RGC death observed in glaucoma. We review recent studies...... elucidating a possible role of low-grade inflammation as a causal factor in the pathogenesis of glaucoma....

  7. Pathogenesis and symptomatics of the acute radiation syndrome

    International Nuclear Information System (INIS)

    Fliedner, T.M.; Haen, M.; Carbonell, F.

    1980-01-01

    The pathogenesis and symptomatics of the acute radiation syndrome are discussed. Diagnosis and therapy would be impossible without detailed knowledge in these fields. The concept of acute radiation syndrome is explained, and a pathophysiological analysis of the various forms of radiation syndrome - haematological, intestinal and affecting the central nervous system is attempted. The developments in the diagnosis and therapy of acute radiation syndrome since its first description - 35 years ago - are reviewed. Today, whole-body doses of 100 rd and more can be treated by radiotherapy. (orig./MG) [de

  8. Oral lichen planus: An update on pathogenesis and treatment

    Science.gov (United States)

    Lavanya, N; Jayanthi, P; Rao, Umadevi K; Ranganathan, K

    2011-01-01

    Oral lichen planus (OLP) is a chronic inflammatory disease that affects the mucus membrane of the oral cavity. It is a T-cell mediated autoimmune disease in which the cytotoxic CD8+ T cells trigger apoptosis of the basal cells of the oral epithelium. Several antigen-specific and nonspecific inflammatory mechanisms have been put forward to explain the accumulation and homing of CD8+ T cells subepithelially and the subsequent keratinocyte apoptosis. A wide spectrum of treatment modalities is available, from topical corticosteroids to laser ablation of the lesion. In this review, we discuss the various concepts in the pathogenesis and current treatment modalities of OLP. PMID:22529568

  9. A new direction in the pathogenesis of idiopathic pulmonary fibrosis?

    Directory of Open Access Journals (Sweden)

    Kolb Martin

    2002-01-01

    Full Text Available Abstract A recent review article suggested that idiopathic pulmonary fibrosis (IPF is a disease that is associated more with abnormal wound healing than with inflammation. Data derived from transgenic and gene transfer rodent models suggest that lung inflammation may be a necessary but insufficient component of IPF, and that at some point in the natural history of the disease IPF becomes no longer dependent on the inflammatory response for propagation. Altered microenvironment and involvement of epithelial cell/mesenchymal cell interaction are the most likely contributors to the pathogenesis of this chronic progressive disorder.

  10. Decreasing incidence rates of bacteremia

    DEFF Research Database (Denmark)

    Nielsen, Stig Lønberg; Pedersen, C; Jensen, T G

    2014-01-01

    BACKGROUND: Numerous studies have shown that the incidence rate of bacteremia has been increasing over time. However, few studies have distinguished between community-acquired, healthcare-associated and nosocomial bacteremia. METHODS: We conducted a population-based study among adults with first......-acquired, 50.0 for healthcare-associated and 66.7 for nosocomial bacteremia. During 2000-2008, the overall incidence rate decreased by 23.3% from 254.1 to 198.8 (3.3% annually, p ...) and the incidence rate of nosocomial bacteremia decreased by 28.9% from 82.2 to 56.0 (4.2% annually, p

  11. Leptospirosis: recent incidents and available diagnostics - a review.

    Science.gov (United States)

    Yuszniahyati, Y; Kenneth, F R; Daisy Vanitha, J

    2015-12-01

    The aim of this article was to review published research articles on leptospirosis, in particular the recent incidence of leptospirosis in Malaysia and the currently available diagnostic methods for the detection of leptospirosis. PubMed, Google Scholar and Google Search databases were searched using the key words Leptospira and leptospirosis. A total of seventy-six references were reviewed including sixty-seven research articles, three annual reports from Ministry of Health and six online newspaper articles. This review includes the following five sub-headings: introduction, leptospirosis transmission, leptospirosis incidents, laboratory diagnosis of leptospirosis and treatment and prevention of leptospirosis. An increase in incidents of leptospirosis cases has been seen in recent years in Malaysia. The recent floods have contributed to the rise in the number of reported cases. Current diagnostic approaches such as dark field microscopy, microscopic agglutination test (MAT), Polymerase chain reaction and serological tests are inadequate as the organism is a slow grower. There is an urgent need to develop newer techniques for rapid detection of leptospirosis. The combination of PCR and ELISA are suggested for rapid and accurate diagnosis of leptospirosis. Studies on the mechanism of pathogenesis of Leptospira are needed for the development of vaccines that are safe for human use.

  12. Traffic incident management resource management.

    Science.gov (United States)

    2009-01-01

    The necessity of a multi-disciplinary approach involving law enforcement, fire and rescue, transportation, towing and recovery, and others has been well-recognized and integrated into incident management operations. This same multidisciplinar...

  13. Police Incident Blotter (30 Day)

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — The 30 Day Police Blotter contains the most recent initial crime incident data, updated on a nightly basis. All data is reported at the block/intersection level,...

  14. Regional comparison of cancer incidence

    International Nuclear Information System (INIS)

    Obralic, N.; Gavrankapetanovic, F.; Dizdarevic, Z.; Duric, O.; Sisic, F.; Selak, I.; Balta, S.; Nakas, B.

    2004-01-01

    Background. Due to specific war and post-war situation in Balkan region, differences in the number, type, development, biological course, treatment of malignant tumours and its outcome are possible. In order to perceive the situation realistically, it is necessary to gather continuously exact data about malignant tumours and compare them with the data from other European and world countries.The aim of the study was to collect and analyse the data on cancer incidence in the region of Sarajevo city, which represents a symbol of difficult times in the recent past, and to compare it to the incidence in the neighbouring countries. Patients and methods. Data on all newly diagnosed cancer cases, permanent residents of Sarajevo Canton, in the years 1999 and 2000 were collected. Crude incidence rate has been calculated according to the years observed, gender and localizations of the disease The data were compared to the cancer registries of Slovenia and Croatia and were observed in the light of specific local situation. Results. The crude cancer incidence of all sites but skin was the highest in both years and by both genders in Croatia. The incidence of the most common tumours (lung and breast cancer) was similar in all three countries. The differences in the incidence between both genders in the Sarajevo canton were registered in laryngeal and urinary bladder cancer, as well as in bone and cartilage sarcoma. Cervical cancer had extremely high incidence and was high up on the incidence list in the Sarajevo canton, which correlates with the data in developing countries. The incidence of other tumours in the post-war period is reaching expected numbers. Conclusions. It is difficult to identify whether the war and post-war stress, irregular and insufficient nutrition during and after the siege of the city of Sarajevo or some other factor influenced the cancer incidence among exposed population. The prevalence of smoking in the whole region is extremely high, in Bosnia and

  15. The role of the neuroendocrine and immune systems in the pathogenesis of depression.

    Science.gov (United States)

    Ogłodek, Ewa; Szota, Anna; Just, Marek; Moś, Danuta; Araszkiewicz, Aleksander

    2014-10-01

    Development of depression is associated with the body's response to prolonged stress, which adversely affects the functioning of the nervous, endocrine and immune systems. Prolonged stress can lead to the development of a so-called allostatic load and reduction of concentration of brain-derived neurotrophic factor. These changes result in impairment of neurogenesis and synaptic remodeling process. This article illustrates the involvement of key mediators of allostasis such as the neuroendocrine and immune systems, in the pathogenesis of depression. The literature concerning the contribution of the neuroendocrine and immune systems to depression incidence was reviewed. Development of depression is associated with disturbance of the body's allostasis and inflammatory activation of the immune system. It leads to a chronic increase in the concentration of cortisol and proinflammatory cytokines, which results in an allostatic load. This load leads to neurodegeneration, eventually causing irreversible cognitive impairment and permanent disability. Determination of the concentration of chemokines and their receptors is an important indicator of activation of the immune and neuroendocrine systems. The activity of these systems reflects the severity of the disease and provides important information for effective antidepressant treatment. Copyright © 2014 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  16. [A pathogenesis study of tic disorder in children based on pathogen incubation theory].

    Science.gov (United States)

    Zhou, Ya-bing; Wu, Min

    2007-11-01

    Pathogen incubation theory includes "no manifestation after infection" and "manifestation after incubation". Clinical data showed that the incidence and recurrence of tic disorders in children had a strong relevance to six exogenous factors. The pathogenesis is similar to the pathogenic mechanism based on incubation of pathogen theory, so we proposed a theory of "tic disorder induced by incubation of pathogen". Pathogenic wind can be classified into exterior wind and endogenous wind. Pathogenic wind is more apt to move, rise and migrate. The characteristics of pathogenic wind, especially easy mobility, determine the symptoms and signs of tic disorder, for pathogenic wind can be characterized by vibration and involuntary movement such as convulsion and tremor. If exogenous pathogenic wind moves into half-exterior and half-interior phase from the exterior, both the exterior and interior syndromes should be treated at the same time. We should regulate the function of the liver and the lung, expel pathogenic wind by dispersing the lung, and calm endogenous wind by removing obstruction in the collaterals and soothing the liver.

  17. Sibling sRNA RyfA1 Influences Shigella dysenteriae Pathogenesis

    Directory of Open Access Journals (Sweden)

    Megan E. Fris

    2017-01-01

    Full Text Available Small regulatory RNAs (sRNAs of Shigella dysenteriae and other pathogens are vital for the regulation of virulence-associated genes and processes. Here, we characterize RyfA1, one member of a sibling pair of sRNAs produced by S. dysenteriae. Unlike its nearly identical sibling molecule, RyfA2, predicted to be encoded almost exclusively by non-pathogenic species, the presence of a gene encoding RyfA1, or a RyfA1-like molecule, is strongly correlated with virulence in a variety of enteropathogens. In S. dysenteriae, the overproduction of RyfA1 negatively impacts the virulence-associated process of cell-to-cell spread as well as the expression of ompC, a gene encoding a major outer membrane protein important for the pathogenesis of Shigella. Interestingly, the production of RyfA1 is controlled by a second sRNA, here termed RyfB1, the first incidence of one regulatory small RNA controlling another in S. dysenteriae or any Shigella species.

  18. Role of oxidative stress in the pathogenesis of oral submucous fibrosis: A preliminary prospective study

    Directory of Open Access Journals (Sweden)

    G K Shakunthala

    2015-01-01

    Full Text Available Background: In the current scenario pathogenesis of majority of the diseases is deeply linked with the oxidative stress, irrespective of its etiology. Enumerable data suggests that reactive oxygen species play a key role in multistage carcinogenesis. Oral submucous fibrosis (OSMF is considered as a potentially malignant disorder. Its increased incidence over recent years in the Indian subcontinent is a major health concern to oral physicians. However, the role of oxidative stress has not been widely investigated in OSMF. Aims: Is to evaluate both antioxidant and oxidant status in OSMF and to compare with controls. Settings and Design: Twenty patients and 20 controls of the same age group were enrolled in the study. Subjects and Methods: Five milliliters of blood were collected from each individual and serum was separated. Malondialdehyde (MDA estimation using thiobarbituric acid (TBA method, and antioxidant activity (AOA using principle of TBA reactive substances was done using this serum, with a calorimetric method. Statistical Analysis Used: Student's t-test and ANOVA test. Results: The mean serum AOA status was seen to significantly decrease in OSMF patients, as compared to controls (P = 0.013. The increase in mean serum MDA level was highly significant in OSMF patients, as compared to controls (P < 0.001. Conclusion: The disparity between AOA and MDA levels in the patients clearly demonstrates the role of oxidative stress in the disease process. The results also suggest the use of antioxidants in the management of OSMF.

  19. Pathogenesis and FDG-PET/CT findings of Epstein-Barr virus-related lymphoid neoplasms.

    Science.gov (United States)

    Toriihara, Akira; Nakajima, Reiko; Arai, Ayako; Nakadate, Masashi; Abe, Koichiro; Kubota, Kazunori; Tateishi, Ukihide

    2017-07-01

    Epstein-Barr virus (EBV) is one of the most common viruses, infecting more than 90% of the adult population worldwide. EBV genome is detected in some lymphoid neoplasms. Not only their histopathological subtypes, but also their backgrounds and their clinical courses are variable. A number of B-cell lymphoproliferative disorders associated with the immunocompromised state are related to EBV infection. The incidences of these disorders have been increasing along with generalization of organ transplantations and use of immunosuppressive treatments. Furthermore, some EBV-positive lymphoma can also occur in immunocompetent patients. While evaluating patients with generalized lymphadenopathy of unknown cause by positron emission tomography/computed tomography with 2-deoxy-2-[ 18 F]fluoro-D-glucose (FDG-PET/CT), the possibility of lymphoid neoplasms should be considered in some patients, and a careful review of the background and previous history of the patients is necessary. In this review article, we describe the pathogenesis of EBV-related lymphoid neoplasms and then present FDG-PET/CT images of representative diseases. In addition, we also present a review of other EBV-related diseases, such as infectious mononucleosis and nasopharyngeal carcinoma.

  20. Pathogenesis of and management strategies for postoperative delirium after hip fracture: a review

    DEFF Research Database (Denmark)

    Bitsch, Martin; Foss, Nicolai; Kristensen, Billy Bjarne

    2004-01-01

    BACKGROUND: Postoperative delirium is a frequent and serious complication in elderly patients following operation for hip fracture, leading to an increased risk of complications. The pathophysiological mechanisms are unresolved, but probably multifactorial. The purpose of this review is to summar......BACKGROUND: Postoperative delirium is a frequent and serious complication in elderly patients following operation for hip fracture, leading to an increased risk of complications. The pathophysiological mechanisms are unresolved, but probably multifactorial. The purpose of this review...... is to summarize current knowledge about the pathogenesis of postoperative delirium with a view to finding strategies for prevention and management. METHOD: We conducted an Internet search through the Medline database (1966-March 2003) and supplemented it with a manual search. We included 12 studies which...... specifically discussed pathogenic factors or interventions against postoperative delirium following operation for hip fracture. RESULTS: 1,823 patients were included with an average incidence of delirium of 35%. We concentrated on pre-, intra-, and postoperative risk factors. Only advanced age and dementia met...

  1. Asymptotics for incidence matrix classes

    OpenAIRE

    Cameron, Peter; Prellberg, Thomas; Stark, Dudley

    2005-01-01

    We define {\\em incidence matrices} to be zero-one matrices with no zero rows or columns. A classification of incidence matrices is considered for which conditions of symmetry by transposition, having no repeated rows/columns, or identification by permutation of rows/columns are imposed. We find asymptotics and relationships for the number of matrices with $n$ ones in these classes as $n\\to\\infty$.

  2. Incidence Handling and Response System

    OpenAIRE

    Kalbande, Prof. Dhananjay R.; Thampi, Dr. G. T.; Singh, Mr. Manish

    2009-01-01

    A computer network can be attacked in a number of ways. The security-related threats have become not only numerous but also diverse and they may also come in the form of blended attacks. It becomes difficult for any security system to block all types of attacks. This gives rise to the need of an incidence handling capability which is necessary for rapidly detecting incidents, minimizing loss and destruction, mitigating the weaknesses that were exploited and restoring the computing services. I...

  3. Cancer incidence in Spain, 2015.

    Science.gov (United States)

    Galceran, J; Ameijide, A; Carulla, M; Mateos, A; Quirós, J R; Rojas, D; Alemán, A; Torrella, A; Chico, M; Vicente, M; Díaz, J M; Larrañaga, N; Marcos-Gragera, R; Sánchez, M J; Perucha, J; Franch, P; Navarro, C; Ardanaz, E; Bigorra, J; Rodrigo, P; Bonet, R Peris

    2017-07-01

    Periodic cancer incidence estimates of Spain from all existing population-based cancer registries at any given time are required. The objective of this study was to present the current situation of cancer incidence in Spain. The Spanish Network of Cancer Registries (REDECAN) estimated the numbers of new cancer cases occurred in Spain in 2015 by applying the incidence-mortality ratios method. In the calculus, incidence data from population-based cancer registries and mortality data of all Spain were used. In 2015, nearly a quarter of a million new invasive cancer cases were diagnosed in Spain, almost 149,000 in men (60.0%) and 99,000 in women. Globally, the five most common cancers were those of colon-rectum, prostate, lung, breast and urinary bladder. By gender, the four most common cancers in men were those of prostate (22.4%), colon-rectum (16.6%), lung (15.1%) and urinary bladder (11.7%). In women, the most common ones were those of breast (28.0%), colon-rectum (16.9%), corpus uteri (6.2%) and lung (6.0%). In recent years, cancer incidence in men seems to have stabilized due to the fact that the decrease in tobacco-related cancers compensates for the increase in other types of cancer like those of colon and prostate. In women, despite the stabilization of breast cancer incidence, increased incidence is due, above all, to the rise of colorectal and tobacco-related cancers. To reduce these incident cancer cases, improvement of smoking control policies and extension of colorectal cancer screening should be the two priorities in cancer prevention for the next years.

  4. Apoptosis and pathogenesis of viral hepatitis C--an update.

    Science.gov (United States)

    Nasir, A; Arora, H S; Kaiser, H E

    2000-01-01

    Hepatitis C virus is a major causative agent of chronic liver disease. Viral genotype, mutations, virus-host interaction, expression of viral proteins and host immune-reaction are important factors in the pathogenesis of HCV infection. Precise pathogenesis and perpetuation of hepatocellular injury in hepatitis C viral infection remain unclear. Proposed mechanisms include direct viropathic effect, the host immune response mediated through cytotoxic T lymphocytes, both viropathic and cytopathic effects, and macrophages/monocytes. Apoptosis occurs both in acute or chronic hepatitis and has been suggested to be mediated through Fas antigen. In HCV infection, Fas expression is up-regulated in the liver cells in line with the severity of liver inflammation. When HCV-specific T cells migrate into hepatocytes and recognize the viral antigen via the T cell receptor, they become activated and express Fas ligand that transduces the apoptotic death signal to Fas-bearing hepatocytes resulting in their destruction. Thus, the Fas system plays an important role in liver cell injury by HCV infection. Possible inducers of apoptosis in hepatitis C include cytokines, especially tumor necrosis factor-alpha (TNF-alpha), released by inflammatory cells, and acting through TNF and other cytokine receptors.

  5. Pathogenic Leptospira: Advances in understanding the molecular pathogenesis and virulence

    Directory of Open Access Journals (Sweden)

    Ciamak Ghazaei

    2018-01-01

    Full Text Available Leptospirosis is a common zoonotic disease has emerged as a major public health problem, with developing countries bearing disproportionate burdens. Although the diverse range of clinical manifestations of the leptospirosis in humans is widely documented, the mechanisms through which the pathogen causes disease remain undetermined. In addition, leptospirosis is a much-neglected life-threatening disease although it is one of the most important zoonoses occurring in a diverse range of epidemiological distribution. Recent advances in molecular profiling of pathogenic species of the genus Leptospira have improved our understanding of the evolutionary factors that determine virulence and mechanisms that the bacteria employ to survive. However, a major impediment to the formulation of intervention strategies has been the limited understanding of the disease determinants. Consequently, the association of the biological mechanisms to the pathogenesis of Leptospira, as well as the functions of numerous essential virulence factors still remain implicit. This review examines recent advances in genetic screening technologies, the underlying microbiological processes, the virulence factors and associated molecular mechanisms driving pathogenesis of Leptospira species.

  6. Molecular pathogenesis of long QT syndrome type 1

    Directory of Open Access Journals (Sweden)

    Jie Wu, PhD

    2016-10-01

    Full Text Available Long QT syndrome type 1 (LQT1 is a subtype of a congenital cardiac syndrome caused by mutation in the KCNQ1 gene, which encodes the α-subunit of the slow component of delayed rectifier K+ current (IKs channel. Arrhythmias in LQT1 are characterized by prolongation of the QT interval on ECG, as well as the occurrence of life-threatening cardiac events, frequently triggered by adrenergic stimuli (e.g., physical or emotional stress. During the past two decades, much advancement has been made in understanding the molecular pathogenesis underlying LQT1. Uncovering the genotype-phenotype correlations in LQT1 is of clinical importance to better understand the gene-specific differences that may influence the propensity for developing life-threatening arrhythmias under specific conditions. Elucidation of these mechanisms will also help to improve the diagnosis and management of this cardiac disorder based on gene-specific considerations. This review describes the current medical consensus and recent developments regarding the molecular pathogenesis of LQT1 and provides a novel insight into the adrenergic regulation of this disease.

  7. Immunogenetics and genetic susceptibility in the pathogenesis of autoimmune hepatitis

    Directory of Open Access Journals (Sweden)

    Das Anup K

    2014-11-01

    Full Text Available vAutoimmune hepatitis is a progressive liver disease. Its pathogenesis is unclear, but needs a ‘trigger’ to initiate the disease in a genetically susceptible person. The susceptibility is partly related to MHCII class genes, and more so with human leukocyte antigen (HLA. Several mechanisms have been proposed which, however, cannot fully explain the immunologic findings in autoimmune hepatitis. The susceptibility to any autoimmune disease is determined by several factors where genetic and immunological alterations, along with, environmental factor are active. MHCII antigens as a marker for AIH, or a predictor of treatment response and prognosis has been investigated. Since MHCII antigens show significant ethnic heterogeneity, mutations in MHCII may merely act as only precursors of the surface markers of immune cells, which can be of significance, because the changes in HLA and MHC are missing in certain populations. One such marker is the CTLA-4 (CD152 gene mutation, reported in the phenotypes representing susceptibility to AIH. Other candidate genes of cytokines, TNF, TGF-beta1 etc, have also been investigated but with unvalidated results. Paediatric AIH show differences in genetic susceptibility. Genetic susceptibility or resistance to AIH may be associated with polypeptides in DRB1 with certain amino-acid sequences. Understanding which genes are implicated in genesis and/or disease progression will obviously help to identify key pathways in AIH and provide better insights into its pathogenesis. But studies to identify responsible genes are complex because of the complex trait of AIH.

  8. Glia: silent partners in energy homeostasis and obesity pathogenesis.

    Science.gov (United States)

    Douglass, John D; Dorfman, Mauricio D; Thaler, Joshua P

    2017-02-01

    Body weight stability requires homeostatic regulation to balance energy intake and energy expenditure. Research on this system and how it is affected by obesity has largely focused on the role of hypothalamic neurons as integrators of information about long-term fuel storage, short-term nutrient availability and metabolic demand. Recent studies have uncovered glial cells as additional contributors to energy balance regulation and obesity pathogenesis. Beginning with early work on leptin signalling in astrocytes, this area of research rapidly emerged after the discovery of hypothalamic inflammation and gliosis in obese rodents and humans. Current studies have revealed the involvement of a wide variety of glial cell types in the modulation of neuronal activity, regulation of hormone and nutrient availability, and participation in the physiological regulation of feeding behaviour. In addition, one glial type, microglia, has recently been implicated in susceptibility to diet-induced obesity. Together, these exciting new findings deepen our understanding of energy homeostasis regulation and raise the possibility of identifying novel mechanisms that contribute to the pathogenesis of obesity.

  9. Nucleus accumbens core and pathogenesis of compulsive checking

    Science.gov (United States)

    Ballester González, Javier; Dvorkin-Gheva, Anna; Silva, Charmaine; Foster, Jane A.

    2015-01-01

    To investigate the role of the nucleus accumbens core (NAc) in the development of quinpirole-induced compulsive checking, rats received an excitotoxic lesion of NAc or sham lesion and were injected with quinpirole (0.5 mg/kg) or saline; development of checking behavior was monitored for 10 biweekly tests. The results showed that even after the NAc lesion, quinpirole still induced compulsive checking, suggesting that the pathogenic effects produced by quinpirole lie outside the NAc. Although the NAc lesion did not prevent the induction of compulsive checking, it altered how quickly it develops, suggesting that the NAc normally contributes toward the induction of compulsive checking. Saline-treated rats with an NAc lesion were hyperactive, but did not develop compulsive checking, indicating that hyperactivity by itself is not sufficient for the pathogenesis of compulsive checking. It is proposed that compulsive checking is the exaggerated output of a security motivation system and that the NAc serves as a neural hub for coordinating the orderly activity of neural modules of this motivational system. Evidence is considered suggesting that the neurobiological condition for the pathogenesis of compulsive checking is two-fold: activation of dopamine D2/D3 receptors without concurrent stimulation of D1-like receptors and long-term plastic changes related to quinpirole-induced sensitization. PMID:25426580

  10. Endometriosis: etiology, pathogenesis, diagnostics, modern aspects of treatment

    Directory of Open Access Journals (Sweden)

    N. V. Avramenko

    2014-08-01

    Full Text Available Aim. To analyze the data of the current scientific literature on the etiology, pathogenesis, diagnosis, clinic and modern therapy of genital endometriosis, which is one of the most urgent problems of modern gynecological practice. Methods and results. The main role in the process of growth and development of endometriosis is currently attributed to changes in the function of the immune system, possibly genetically determined. Currently, it is proved that endometriosis develops immune processes against endometrial tissue. There is every reason to believe that endometrium in its unusual places can acquire antigenic properties that stimulates the body's immune system reaction. Hyperandrogenism, early menarche, heavy and prolonged menstruation, disorders of the outflow of menstrual blood, adverse environment, obesity, smoking, stress are considered as the risk factors for the development of endometriosis. Revised diagnosis is possible with laparoscopic visualization (ideally with confirming histological research. A presumptive diagnosis is based on typical clinical symptoms and signs. Laboratory methods of diagnosis: magnetic resonance imaging and ultrasound. The main methods of treatment of endometriosis are surgical, medication, combined. Conclusion. Endometriosis remains unresolved scientific and clinical problem characterized by the paradoxical aspects of the pathogenesis and clinical contrasts of course without found explanation yet.

  11. Pathogenic Leptospira: Advances in understanding the molecular pathogenesis and virulence

    Science.gov (United States)

    Ghazaei, Ciamak

    2018-01-01

    Leptospirosis is a common zoonotic disease has emerged as a major public health problem, with developing countries bearing disproportionate burdens. Although the diverse range of clinical manifestations of the leptospirosis in humans is widely documented, the mechanisms through which the pathogen causes disease remain undetermined. In addition, leptospirosis is a much-neglected life-threatening disease although it is one of the most important zoonoses occurring in a diverse range of epidemiological distribution. Recent advances in molecular profiling of pathogenic species of the genus Leptospira have improved our understanding of the evolutionary factors that determine virulence and mechanisms that the bacteria employ to survive. However, a major impediment to the formulation of intervention strategies has been the limited understanding of the disease determinants. Consequently, the association of the biological mechanisms to the pathogenesis of Leptospira, as well as the functions of numerous essential virulence factors still remain implicit. This review examines recent advances in genetic screening technologies, the underlying microbiological processes, the virulence factors and associated molecular mechanisms driving pathogenesis of Leptospira species. PMID:29445617

  12. Update on ankylosing spondylitis: current concepts in pathogenesis.

    Science.gov (United States)

    Smith, Judith A

    2015-01-01

    Ankylosing spondylitis is an insidiously progressive and debilitating form of arthritis involving the axial skeleton. The long delay in diagnosis and insufficient response to currently available therapeutics both advocate for a greater understanding of disease pathogenesis. Genome-wide association studies of this highly genetic disease have implicated specific immune pathways, including the interleukin (IL)-17/IL-23 pathway, control of nuclear factor kappa B (NF-κB) activation, amino acid trimming for major histocompatibility complex (MHC) antigen presentation, and other genes controlling CD8 and CD4 T cell subsets. The relevance of these pathways has borne out in animal and human subject studies, in particular, the response to novel therapeutic agents. Genetics and the findings of autoantibodies in ankylosing spondylitis revisit the question of autoimmune vs. autoinflammatory etiology. As environmental partners to genetics, recent attention has focused on the roles of microbiota and biomechanical stress in initiating and perpetuating inflammation. Herein, we review these current developments in the investigation of ankylosing spondylitis pathogenesis.

  13. MDS: Recent progress in molecular pathogenesis and clinical aspects.

    Science.gov (United States)

    Harada, Hironori

    2017-01-01

    Myelodysplastic syndromes (MDS) are defined as hematopoietic stem cell disorders caused by various gene abnormalities. Recent analysis using next generation sequencing has provided great progress in identifying relationships between gene mutations and clinical phenotypes of MDS. It is estimated that one or more gene mutations occur in greater than 90% of MDS patients. More than 50 gene mutations affecting RNA splicing machinery, DNA methylation, histone modifications, transcription factors, signal transduction proteins, and components of the cohesion complex participate in the pathogenesis of MDS. The sequential accumulation of additional cooperating mutations drives disease evolution from clonal hematopoiesis of indeterminate potential (CHIP) to symptomatic MDS and from MDS to acute myelogenous leukemia (AML). Mutations in RNA splicing and DNA methylation occur early and are considered founding mutations, whereas others that occur later are regarded as subclonal mutations. RUNX1 mutations are more likely to be subclonal; however, they apparently play a pivotal role in familial MDS. In addition, large alterations of chromosomes are involved in the pathogenesis of MDS. 5q- syndrome, which leads to haploinsufficiency of the located genes, has consistent clinical features. Understanding gene abnormalities of MDS patients can provide clinical information, including diagnosis, prognostic score, and prediction of response to therapy.

  14. Fetal/Neonatal Alloimmune Thrombocytopenia: Pathogenesis, Diagnostics and Prevention.

    Science.gov (United States)

    Brojer, Ewa; Husebekk, Anne; Dębska, Marzena; Uhrynowska, Małgorzata; Guz, Katarzyna; Orzińska, Agnieszka; Dębski, Romuald; Maślanka, Krystyna

    2016-08-01

    Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a relatively rare condition (1/1000-1/2000) that was granted orphan status by the European Medicines Agency in 2011. Clinical consequences of FNAIT, however, may be severe. A thrombocytopenic fetus or new-born is at risk of intracranial hemorrhage that may result in lifelong disability or death. Preventing such bleeding is thus vital and requires a solution. Anti-HPA1a antibodies are the most frequent cause of FNAIT in Caucasians. Its pathogenesis is similar to hemolytic disease of the newborn (HDN) due to anti-RhD antibodies, but is characterized by platelet destruction and is more often observed in the first pregnancy. In 75 % of these women, alloimmunization by HPA-1a antigens, however, occurs at delivery, which enables development of antibody-mediated immune suppression to prevent maternal immunization. As for HDN, the recurrence rate of FNAIT is high. For advancing diagnostic efforts and treatment, it is thereby crucial to understand the pathogenesis of FNAIT, including cellular immunity involvement. This review presents the current knowledge on FNAIT. Also described is a program for HPA-1a screening in identifying HPA-1a negative pregnant women at risk of immunization. This program is now performed at the Institute of Hematology and Transfusion Medicine in cooperation with the Department of Obstetrics and Gynecology of the Medical Centre of Postgraduate Education in Warsaw as well as the UiT The Arctic University of Norway.

  15. The Role of Extracellular Histones in Influenza Virus Pathogenesis.

    Science.gov (United States)

    Ashar, Harshini K; Mueller, Nathan C; Rudd, Jennifer M; Snider, Timothy A; Achanta, Mallika; Prasanthi, Maram; Pulavendran, Sivasami; Thomas, Paul G; Ramachandran, Akhilesh; Malayer, Jerry R; Ritchey, Jerry W; Rajasekhar, Rachakatla; Chow, Vincent T K; Esmon, Charles T; Teluguakula, Narasaraju

    2018-01-01

    Although exaggerated host immune responses have been implicated in influenza-induced lung pathogenesis, the etiologic factors that contribute to these events are not completely understood. We previously demonstrated that neutrophil extracellular traps exacerbate pulmonary injury during influenza pneumonia. Histones are the major protein components of neutrophil extracellular traps and are known to have cytotoxic effects. Here, we examined the role of extracellular histones in lung pathogenesis during influenza. Mice infected with influenza virus displayed high accumulation of extracellular histones, with widespread pulmonary microvascular thrombosis. Occluded pulmonary blood vessels with vascular thrombi often exhibited endothelial necrosis surrounded by hemorrhagic effusions and pulmonary edema. Histones released during influenza induced cytotoxicity and showed strong binding to platelets within thrombi in infected mouse lungs. Nasal wash samples from influenza-infected patients also showed increased accumulation of extracellular histones, suggesting a possible clinical relevance of elevated histones in pulmonary injury. Although histones inhibited influenza growth in vitro, in vivo treatment with histones did not yield antiviral effects and instead exacerbated lung pathology. Blocking with antihistone antibodies caused a marked decrease in lung pathology in lethal influenza-challenged mice and improved protection when administered in combination with the antiviral agent oseltamivir. These findings support the pathogenic effects of extracellular histones in that pulmonary injury during influenza was exacerbated. Targeting histones provides a novel therapeutic approach to influenza pneumonia. Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  16. Hepatic encephalopathy: An updated approach from pathogenesis to treatment

    Science.gov (United States)

    Toris, Giannakis T.; Bikis, Christos N.; Tsourouflis, Gerasimos S.; Theocharis, Stamatios E.

    2011-01-01

    Summary One of the most serious complications of chronic or fulminant liver failure is hepatic encephalopathy (HE), associated most commonly with cirrhosis. In the presence of chronic liver disease, HE is a sign of decompensation, while in fulminant liver failure its development represents a worrying sign and usually indicates that transplantation will be required. Despite the significance of HE in the course of liver disease, the progress in development of new therapeutic options has been unremarkable over the last 20 years. An up-to-date review regarding HE, including both research and review articles. HE is a serious and progressive, but potentially reversible, disorder with a wide spectrum of neuropsychiatric abnormalities and motor disturbances that ranges from mild alteration of cognitive and motor function to coma and death. Although a clear pathogenesis is yet to be determined, elevated ammonia in serum and the central nervous system is the mainstay for pathogenesis and treatment of HE. Management includes early diagnosis and prompt treatment of precipitating factors. Clinical trials and extensive clinical experience have established the efficacy of diverse substances in HE treatment. Novel therapies with clinical promise include: L-ornithine L-aspartate, sodium benzoate, phenylacetate, AST-120, and the molecular adsorbent recirculating system. Eventually, liver transplantation is often the most successful long-term therapy for HE. PMID:21278704

  17. Pathogenesis of minimal change nephrotic syndrome: an immunological concept

    Science.gov (United States)

    Kim, Seong Heon; Park, Se Jin; Han, Kyoung Hee; Kronbichler, Andreas; Saleem, Moin A.; Oh, Jun; Lim, Beom Jin

    2016-01-01

    Idiopathic nephrotic syndrome (INS) in children is characterized by massive proteinuria and hypoalbuminemia. Minimal change nephrotic syndrome (MCNS) is the most common form of INS in children. The pathogenesis of MCNS still remains unclear, however, several hypotheses have been recently proposed. For several decades, MCNS has been considered a T-cell disorder, which causes the impairment of the glomerular filtration barrier with the release of different circulating factors. Increased levels of several cytokines are also suggested. Recently, a "two-hit" theory was proposed that included the induction of CD80 (B7-1) and regulatory T-cell (Treg) dysfunction, with or without impaired autoregulatory functions of the podocyte. In contrast to the well-established involvement of T cells, the role of B cells has not been clearly identified. However, B-cell biology has recently gained more attention, because rituximab (a monoclonal antibody directed against CD20-bearing cells) demonstrated a very good therapeutic response in the treatment of childhood and adult MCNS. Here, we discuss recent insights into the pathogenesis of MCNS in children. PMID:27279884

  18. MicroRNAs in the pathogenesis of cystic kidney disease.

    Science.gov (United States)

    Phua, Yu Leng; Ho, Jacqueline

    2015-04-01

    Cystic kidney diseases are common renal disorders characterized by the formation of fluid-filled epithelial cysts in the kidneys. The progressive growth and expansion of the renal cysts replace existing renal tissue within the renal parenchyma, leading to reduced renal function. While several genes have been identified in association with inherited causes of cystic kidney disease, the molecular mechanisms that regulate these genes in the context of post-transcriptional regulation are still poorly understood. There is increasing evidence that microRNA (miRNA) dysregulation is associated with the pathogenesis of cystic kidney disease. In this review, recent studies that implicate dysregulation of miRNA expression in cystogenesis will be discussed. The relationship of specific miRNAs, such as the miR-17∼92 cluster and cystic kidney disease, miR-92a and von Hippel-Lindau syndrome, and alterations in LIN28-LET7 expression in Wilms tumor will be explored. At present, there are no specific treatments available for patients with cystic kidney disease. Understanding and identifying specific miRNAs involved in the pathogenesis of these disorders may have the potential to lead to the development of novel therapies and biomarkers.

  19. Membranous nephropathy: A review on the pathogenesis, diagnosis, and treatment

    Directory of Open Access Journals (Sweden)

    Wei Ling Lai

    2015-02-01

    Full Text Available In adults, membranous nephropathy (MN is a major cause of nephrotic syndrome. However, the etiology of approximately 75% of MN cases is idiopathic. Secondary causes of MN are autoimmune diseases, infection, drugs, and malignancy. The pathogenesis of MN involves formation of immune complex in subepithelial sites, but the definite mechanism is still unknown. There are three hypotheses about the formation of immune complex, including preformed immune complex, in situ immune-complex formation, and autoantibody against podocyte membrane antigen. The formation of immune complex initiates complement activation, which subsequently leads to glomerular damage. Recently, the antiphospholipase A2 receptor antibody was found to be associated with idiopathic MN. This finding may be useful in the diagnosis and prognosis of MN. The current treatment includes best supportive care, which consists of the use of angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers, lipid-lowering agents, and optimal control of blood pressure. Immunosuppressive agents should be used for patients who suffer from refractory proteinuria or complications associated with nephrotic syndrome. Existing evidence supports the use of a combination of steroid and alkylating agents. This article reviews the epidemiology, pathogenesis, diagnosis, and the treatment of MN.

  20. Microbiome in interstitial lung disease: from pathogenesis to treatment target.

    Science.gov (United States)

    Salisbury, Margaret L; Han, MeiLan K; Dickson, Robert P; Molyneaux, Philip L

    2017-09-01

    This review summarizes current knowledge of the role of the lung microbiome in interstitial lung disease and poses considerations of the microbiome as a therapeutic target. Although historically considered sterile, bacterial communities have now been well documented in lungs in health and disease. Studies in idiopathic pulmonary fibrosis (IPF) suggest that increased bacterial burden and/or abundance of potentially pathogenic bacteria may drive disease progression, acute exacerbations, and mortality. More recent work has highlighted the interaction between the lung microbiome and the innate immune system in IPF, strengthening the argument for the role of both host and environment interaction in disease pathogenesis. In support of this, studies of interstitial lung diseases other than IPF suggest that it may be the host immune response, which shapes the microbiome in these diseases. Some clinical and mouse model data also suggest that the lung microbiome may represent a therapeutic target, via antibiotic administration, immunization against pathogenic organisms, or treatment directed at gastroesophageal reflux. Evidence suggests that the lung microbiome may serve as a prognostic biomarker, a therapeutic target, or provide an explanation for disease pathogenesis in IPF.

  1. Neutralizing Antibodies and Pathogenesis of Hepatitis C Virus Infection

    Directory of Open Access Journals (Sweden)

    Françoise Stoll-Keller

    2012-10-01

    Full Text Available Hepatitis C virus (HCV infection is a major cause of chronic liver disease worldwide. The interplay between the virus and host innate and adaptive immune responses determines the outcome of infection. There is increasing evidence that host neutralizing responses play a relevant role in the resulting pathogenesis. Furthermore, viral evasion from host neutralizing antibodies has been revealed to be an important contributor in leading both to viral persistence in acute liver graft infection following liver transplantation, and to chronic viral infection. The development of novel model systems to study HCV entry and neutralization has allowed a detailed understanding of the molecular mechanisms of virus-host interactions during antibody-mediated neutralization. The understanding of these mechanisms will ultimately contribute to the development of novel antiviral preventive strategies for liver graft infection and an urgently needed vaccine. This review summarizes recent concepts of the role of neutralizing antibodies in viral clearance and protection, and highlights consequences of viral escape from neutralizing antibodies in the pathogenesis of HCV infection.

  2. Inflammatory Bowel Disease: Autoimmune or Immune-mediated Pathogenesis?

    Directory of Open Access Journals (Sweden)

    Zhonghui Wen

    2004-01-01

    Full Text Available The pathogenesis of Crohn's disease (CD and ulcerative colitis (UC, the two main forms of inflammatory bowel disease (IBD, is still unclear, but both autoimmune and immune-mediated phenomena are involved. Autoimmune phenomena include the presence of serum and mucosal autoantibodies against intestinal epithelial cells in either form of IBD, and against human tropomyosin fraction five selectively in UC. In addition, perinuclear antineutrophil cytoplasmic antibodies (pANCA are common in UC, whereas antibodies against Saccharomyces cerevisiae (ASCA are frequently found in CD. Immune-mediate phenomena include a variety of abnormalities of humoral and cell-mediated immunity, and a generalized enhanced reactivity against intestinal bacterial antigens in both CD and UC. It is currently believed that loss of tolerance against the indigenous enteric flora is the central event in IBD pathogenesis. Various complementary factors probably contribute to the loss of tolerance to commensal bacteria in IBD. They include defects in regulatory T-cell function, excessive stimulation of mucosal dendritic cells, infections or variants of proteins critically involved in bacterial antigen recognition, such as the products of CD-associated NOD2/CARD15 mutations.

  3. Molecular Pathogenesis of Liver Steatosis Induced by Hepatitis C Virus

    Directory of Open Access Journals (Sweden)

    Cheng Jun

    2012-09-01

    Full Text Available Liver steatosis is a pathological hallmark in patients with chronic hepatitis C (CHC. Increased lipid uptake, decreased lipid secretion, increased lipid synthesis and decreased lipid degradation are all involved in pathogenesis of steatosis induced by hepatitic C virus (HCV infection. Level of low density lipoprotein receptor (LDL-R and activity of peroxisome proliferator-activated receptor (PPAR α is related to liver uptake of lipid from circulation, and affected by HCV. Secretion via microsomal triglyceride transfer protein (MTTP, and formation of very low density lipoprotein (VLDL have been hampered by HCV infection. Up-regulation of lipid synthesis related genes, such as sterol regulatory element-binding protein (SREBP-1, SREBP-2, SREBP-1c, fatty acid synthase (FASN, HMG CoA reductase (HMGCR, liver X receptor (LXR, acetyl-CoA carboxylase 1 (ACC1, hepatic CB (1 receptors, retinoid X receptor (RXR α, were the main stay of liver steatosis pathogenesis. Degradation of lipid in liver is decreased in patients with CHC. There is strong evidence that heterogeneity of HCV core genes of different genotypes affect their effects of liver steatosis induction. A mechanism in which steatosis is involved in HCV life cycle is emerging.

  4. Cyber Incidents Involving Control Systems

    Energy Technology Data Exchange (ETDEWEB)

    Robert J. Turk

    2005-10-01

    The Analysis Function of the US-CERT Control Systems Security Center (CSSC) at the Idaho National Laboratory (INL) has prepared this report to document cyber security incidents for use by the CSSC. The description and analysis of incidents reported herein support three CSSC tasks: establishing a business case; increasing security awareness and private and corporate participation related to enhanced cyber security of control systems; and providing informational material to support model development and prioritize activities for CSSC. The stated mission of CSSC is to reduce vulnerability of critical infrastructure to cyber attack on control systems. As stated in the Incident Management Tool Requirements (August 2005) ''Vulnerability reduction is promoted by risk analysis that tracks actual risk, emphasizes high risk, determines risk reduction as a function of countermeasures, tracks increase of risk due to external influence, and measures success of the vulnerability reduction program''. Process control and Supervisory Control and Data Acquisition (SCADA) systems, with their reliance on proprietary networks and hardware, have long been considered immune to the network attacks that have wreaked so much havoc on corporate information systems. New research indicates this confidence is misplaced--the move to open standards such as Ethernet, Transmission Control Protocol/Internet Protocol, and Web technologies is allowing hackers to take advantage of the control industry's unawareness. Much of the available information about cyber incidents represents a characterization as opposed to an analysis of events. The lack of good analyses reflects an overall weakness in reporting requirements as well as the fact that to date there have been very few serious cyber attacks on control systems. Most companies prefer not to share cyber attack incident data because of potential financial repercussions. Uniform reporting requirements will do much to make this

  5. Concentrated Differential Privacy

    OpenAIRE

    Dwork, Cynthia; Rothblum, Guy N.

    2016-01-01

    We introduce Concentrated Differential Privacy, a relaxation of Differential Privacy enjoying better accuracy than both pure differential privacy and its popular "(epsilon,delta)" relaxation without compromising on cumulative privacy loss over multiple computations.

  6. Segmented polynomials for incidence rate estimation from prevalence data.

    Science.gov (United States)

    Mahiané, Severin Guy; Laeyendecker, Oliver

    2017-01-30

    The study considers the problem of estimating incidence of a non remissible infection (or disease) with possibly differential mortality using data from a(several) cross-sectional prevalence survey(s). Fitting segmented polynomial models is proposed to estimate the incidence as a function of age, using the maximum likelihood method. The approach allows automatic search for optimal position of knots, and model selection is performed using the Akaike information criterion. The method is applied to simulated data and to estimate HIV incidence among men in Zimbabwe using data from both the NIMH Project Accept (HPTN 043) and Zimbabwe Demographic Health Surveys (2005-2006). Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  7. A Possible Role for CD8+ T Lymphocytes in the Cell-Mediated Pathogenesis of Pemphigus Vulgaris

    Directory of Open Access Journals (Sweden)

    Federica Giurdanella

    2013-01-01

    Full Text Available Pemphigus vulgaris (PV is an autoimmune blistering disease whose pathogenesis involves both humoral and cell-mediated immune response. Though the pathogenetic role of autoantibodies directed against desmoglein 3 is certain, a number of other factors have been suggested to determine acantholysis in PV. In this study we examined the possible role of CD8+ T cells in the development of acantholysis by a passive transfer of PV autoantibodies using CD8 deficient mice, and we also studied the inflammatory infiltrate of PV skin lesions by immunohistochemical staining. The results of the immunohistochemical staining to study the expression of CD3, CD4, and CD8 in PV skin lesions showed that CD4+ are more expressed than CD8+ in the inflammatory infiltrate of PV lesions, confirming the data of the previous literature. The passive transfer study showed a lower incidence of pemphigus in the group of CD8 deficient mice compared to the control one of wild-type mice. These results suggest that CD8+ T cells may play a role in the pathogenesis of PV, perhaps through the Fas/FasL pathway.

  8. The Current Status of the Disease Caused by Enterovirus 71 Infections: Epidemiology, Pathogenesis, Molecular Epidemiology, and Vaccine Development.

    Science.gov (United States)

    Chang, Ping-Chin; Chen, Shou-Chien; Chen, Kow-Tong

    2016-09-09

    Enterovirus 71 (EV71) infections have a major public health impact in the Asia-Pacific region. We reviewed the epidemiology, pathogenesis, and molecular epidemiology of EV71 infection as well as EV71 vaccine development. Previous studies were found using the search terms "enterovirus 71" and "epidemiology" or "pathogenesis" or "molecular epidemiology" or "vaccine" in Medline and PubMed. Articles that were not published in the English language, manuscripts without an abstract, and opinion articles were excluded from the review. The reported epidemiology of cases caused by EV71 infection varied from country to country; seasonal variations in incidence were observed. Most cases of EV71 infection that resulted in hospitalization for complications occurred in children less than five years old. The brainstem was the most likely major target of EV71 infection. The emergence of the EV71 epidemic in the Asia-Pacific region has been associated with the circulation of different genetic lineages (genotypes B3, B4, C1, C2, and C4) that appear to be undergoing rapid evolutionary changes. The relationship between the gene structure of the EV71 virus and the factors that ensure its survival, circulation, and evasion of immunity is still unknown. EV71 infection has emerged as an important global public health problem. Vaccine development, including the development of inactivated whole-virus live attenuated, subviral particles, and DNA vaccines, has been progressing.

  9. Comparison of bone tumors induced by beta-emitting or alpha-emitting radionuclides: Schemes of pathogenesis

    International Nuclear Information System (INIS)

    Gillett, N.A.; Muggenburg, B.A.; Pool, R.R.; Hahn, F.F.

    1988-01-01

    Life-span studies in Beagle dogs have documented the occurrence of bone tumors following exposure to bone-seeking alpha- or beta-emitting radionuclides administered by different routes of exposure. Bone tumors from dogs in four different life-span studies were analyzed according to tumor phenotype, tumor location, radiographic appearance, incidence of metastasis, and association with radiation osteodystrophy. Marked differences in these parameters were observed that did not correlate with differences in radionuclide type, route of exposure, or duration of radionuclide uptake. Radiation osteodystrophy, which is postulated to be a preneoplastic lesion, was not a significant component in one of the studies. Analysis of the data from these four studies suggests that at least two different mechanisms of bone tumor pathogenesis occur for radiation-induced bone tumors. (author)

  10. Breast cancer incidence in Mongolia

    Science.gov (United States)

    Altantsetseg, Dalkhjav; Davaasambuu, Ganmaa; Rich-Edwards, Janet; Davaalkham, Dambadarjaa; Tretli, Steinar; Hoover, Robert N.; Frazier, A. Lindsay

    2013-01-01

    Purpose Data on international variation in breast cancer incidence may help to identify additional risk factors. Substantially lower breast cancer rates in Asia than in North America and Western Europe are established, but differences within Asia have been largely ignored despite heterogeneity in lifestyles and environments. Mongolia’s breast cancer experience is of interest because of its shared genetics but vastly different diet compared with other parts of Asia. Methods Age-standardized breast cancer incidence and mortality rates obtained from the International Association of Cancer Registries are presented for several Asian countries. Mongolian incidence rates obtained from its cancer registry describe incidence within the country. Results Breast cancer incidence in Mongolia (age standardized 8.0/100,000) is almost a third of rates in China (21.6/100,000), and over five times that of Japan (42.7/100,000) and Russia (43.2/100,000). Rates within Mongolia appear to have increased slightly over the last decade and are higher in urban than rural areas (annual percentage increase of age-standardized rates from 1998 to 2005 was 3.60 and 2.57%, respectively). The increase in breast cancer incidence with age plateaus at menopause, as in other Asian populations. Conclusions Mongolia’s low breast cancer incidence is of particular interest because of their unusual diet (primarily red meat and dairy) compared with other Asian countries. More intensive study of potential dietary, reproductive and lifestyle factors in Mongolia with comparison to other Asian populations may provide more clarity in what drives the international breast cancer rate differences. PMID:22543542

  11. Information sharing for traffic incident management.

    Science.gov (United States)

    2009-01-01

    Traffic incident management focuses on developing procedures, implementing policies, and deploying technologies to more quickly identify incidents, improve response times, and more effectively and efficiently manage the incident scene. Because so man...

  12. Influence of Environmental Conditions and Genetic Background of Arabica Coffee (C. arabica L on Leaf Rust (Hemileia vastatrix Pathogenesis

    Directory of Open Access Journals (Sweden)

    Lucile Toniutti

    2017-11-01

    Full Text Available Global warming is a major threat to agriculture worldwide. Between 2008 and 2013, some coffee producing countries in South and Central America suffered from severe epidemics of coffee leaf rust (CLR, resulting in high economic losses with social implications for coffee growers. The climatic events not only favored the development of the pathogen but also affected the physiological status of the coffee plant. The main objectives of the study were to evaluate how the physiological status of the coffee plant modified by different environmental conditions impact on the pathogenesis of CLR and to identify indicators of the physiological status able to predict rust incidence. Three rust susceptible genotypes (one inbred line and two hybrids were grown in controlled conditions with a combination of thermal regime (TR, nitrogen and light intensity close to the field situation before being inoculated with the rust fungus Hemileia vastatrix. It has been demonstrated that a TR of 27-22°C resulted in 2000 times higher sporulation than with a TR of 23–18°C. It has been also shown that high light intensity combined with low nitrogen fertilization modified the CLR pathogenesis resulting in huge sporulation. CLR sporulation was significantly lower in the F1 hybrids than in the inbred line. The hybrid vigor may have reduced disease incidence. Among the many parameters studied, parameters related to photosystem II and photosynthetic electron transport chain components appeared as indicators of the physiological status of the coffee plant able to predict rust sporulation intensity. Taken together, these results show that CLR sporulation not only depends on the TR but also on the physiological status of the coffee plant, which itself depends on agronomic conditions. Our work suggests that vigorous varieties combined with a shaded system and appropriate nitrogen fertilization should be part of an agro-ecological approach to disease control.

  13. Influence of Environmental Conditions and Genetic Background of Arabica Coffee (C. arabica L) on Leaf Rust (Hemileia vastatrix) Pathogenesis

    Science.gov (United States)

    Toniutti, Lucile; Breitler, Jean-Christophe; Etienne, Hervé; Campa, Claudine; Doulbeau, Sylvie; Urban, Laurent; Lambot, Charles; Pinilla, Juan-Carlos H.; Bertrand, Benoît

    2017-01-01

    Global warming is a major threat to agriculture worldwide. Between 2008 and 2013, some coffee producing countries in South and Central America suffered from severe epidemics of coffee leaf rust (CLR), resulting in high economic losses with social implications for coffee growers. The climatic events not only favored the development of the pathogen but also affected the physiological status of the coffee plant. The main objectives of the study were to evaluate how the physiological status of the coffee plant modified by different environmental conditions impact on the pathogenesis of CLR and to identify indicators of the physiological status able to predict rust incidence. Three rust susceptible genotypes (one inbred line and two hybrids) were grown in controlled conditions with a combination of thermal regime (TR), nitrogen and light intensity close to the field situation before being inoculated with the rust fungus Hemileia vastatrix. It has been demonstrated that a TR of 27-22°C resulted in 2000 times higher sporulation than with a TR of 23–18°C. It has been also shown that high light intensity combined with low nitrogen fertilization modified the CLR pathogenesis resulting in huge sporulation. CLR sporulation was significantly lower in the F1 hybrids than in the inbred line. The hybrid vigor may have reduced disease incidence. Among the many parameters studied, parameters related to photosystem II and photosynthetic electron transport chain components appeared as indicators of the physiological status of the coffee plant able to predict rust sporulation intensity. Taken together, these results show that CLR sporulation not only depends on the TR but also on the physiological status of the coffee plant, which itself depends on agronomic conditions. Our work suggests that vigorous varieties combined with a shaded system and appropriate nitrogen fertilization should be part of an agro-ecological approach to disease control. PMID:29234340

  14. Influence of Environmental Conditions and Genetic Background of Arabica Coffee (C. arabica L) on Leaf Rust (Hemileia vastatrix) Pathogenesis.

    Science.gov (United States)

    Toniutti, Lucile; Breitler, Jean-Christophe; Etienne, Hervé; Campa, Claudine; Doulbeau, Sylvie; Urban, Laurent; Lambot, Charles; Pinilla, Juan-Carlos H; Bertrand, Benoît

    2017-01-01

    Global warming is a major threat to agriculture worldwide. Between 2008 and 2013, some coffee producing countries in South and Central America suffered from severe epidemics of coffee leaf rust (CLR), resulting in high economic losses with social implications for coffee growers. The climatic events not only favored the development of the pathogen but also affected the physiological status of the coffee plant. The main objectives of the study were to evaluate how the physiological status of the coffee plant modified by different environmental conditions impact on the pathogenesis of CLR and to identify indicators of the physiological status able to predict rust incidence. Three rust susceptible genotypes (one inbred line and two hybrids) were grown in controlled conditions with a combination of thermal regime (TR), nitrogen and light intensity close to the field situation before being inoculated with the rust fungus Hemileia vastatrix . It has been demonstrated that a TR of 27-22°C resulted in 2000 times higher sporulation than with a TR of 23-18°C. It has been also shown that high light intensity combined with low nitrogen fertilization modified the CLR pathogenesis resulting in huge sporulation. CLR sporulation was significantly lower in the F1 hybrids than in the inbred line. The hybrid vigor may have reduced disease incidence. Among the many parameters studied, parameters related to photosystem II and photosynthetic electron transport chain components appeared as indicators of the physiological status of the coffee plant able to predict rust sporulation intensity. Taken together, these results show that CLR sporulation not only depends on the TR but also on the physiological status of the coffee plant, which itself depends on agronomic conditions. Our work suggests that vigorous varieties combined with a shaded system and appropriate nitrogen fertilization should be part of an agro-ecological approach to disease control.

  15. Pathogenesis of canine cortisol-secreting adrenocortical tumors

    NARCIS (Netherlands)

    Kool, Miriam

    2015-01-01

    In dogs, hypercortisolism is one of the most frequently observed endocrine disorders, with an estimated incidence of about 1-2 cases per 1000 dogs per year. Approximately 15% of these cases is due to a cortisol-secreting adrenocortical tumor (AT). Cortisol-secreting ATs are characterized by

  16. The epidemiology and pathogenesis of type 1 diabetes mellitus in ...

    African Journals Online (AJOL)

    2011-04-01

    Apr 1, 2011 ... different therapeutic options available to treat the different forms of diabetes. Worldwide, the incidence of type 1 diabetes is increasing, with more children being obese on presentation as a result of the escalating prevalence of obesity in the youth.3 In addition, there is an epidemic of type. 2 diabetes in ...

  17. The Roles of Environmental Pollutants in the Pathogenesis and ...

    African Journals Online (AJOL)

    ADOWIE PERE

    A; Overvad, K; Sørensen, M (2012). Diabetes incidence and long-term exposure to air pollution: a cohort study. Diabetes. Care. 35(1):92-8. Beyerlein, A1; Krasmann, M; Thiering, E; Kusian, D;. Markevych, I; D'Orlando, O; Warncke, K;. Jochner, S; Heinrich, J; Ziegler, AG (2015). Ambient air pollution and early manifestation of.

  18. The role of the gastrointestinal microbiome in Helicobacter pylori pathogenesis

    Science.gov (United States)

    Sheh, Alexander; Fox, James G

    2013-01-01

    The discovery of Helicobacter pylori overturned the conventional dogma that the stomach was a sterile organ and that pH values pylori are an etiological agent associated with gastritis, hypochlorhydria, duodenal ulcers, and gastric cancer. It is now appreciated that the human stomach supports a bacterial community with possibly 100s of bacterial species that influence stomach homeostasis. Other bacteria colonizing the stomach may also influence H. pylori-associated gastric pathogenesis by creating reactive oxygen and nitrogen species and modulating inflammatory responses. In this review, we summarize the available literature concerning the gastric microbiota in humans, mice, and Mongolian gerbils. We also discuss the gastric perturbations, many involving H. pylori, that facilitate the colonization by bacteria from other compartments of the gastrointestinal tract, and identify risk factors known to affect gastric homeostasis that contribute to changes in the microbiota. PMID:23962822

  19. Liver injury and disease pathogenesis in chronic hepatitis C.

    Science.gov (United States)

    Yamane, Daisuke; McGivern, David R; Masaki, Takahiro; Lemon, Stanley M

    2013-01-01

    Chronic hepatitis C virus (HCV) infection is a leading cause of liver-specific morbidity and mortality in humans, including progressive liver fibrosis, cirrhosis, and hepatocellular carcinoma. It has also been associated with altered function in other organs, including those of the endocrine, hematopoietic, and nervous systems. Disease results from both direct regulation of cellular metabolism and signaling pathways by viral proteins as well as indirect consequences of the host response to HCV infection, including inflammatory responses stemming from immune recognition of the virus. Recent in vitro studies have begun to reveal molecular mechanisms responsible for virus-induced changes in cell metabolism and cellular kinase cascades that culminate in pathologic consequences in the liver, such as steatosis, insulin resistance, and carcinogenesis. Here we discuss how these findings may be relevant to disease pathogenesis in patients, and suggest future directions in the field.

  20. Patterns of evolution of host proteins involved in retroviral pathogenesis

    Directory of Open Access Journals (Sweden)

    Kaessmann Henrik

    2006-02-01

    Full Text Available Abstract Background Evolutionary analysis may serve as a useful approach to identify and characterize host defense and viral proteins involved in genetic conflicts. We analyzed patterns of coding sequence evolution of genes with known (TRIM5α and APOBEC3G or suspected (TRIM19/PML roles in virus restriction, or in viral pathogenesis (PPIA, encoding Cyclophilin A, in the same set of human and non-human primate species. Results and conclusion This analysis revealed previously unidentified clusters of positively selected sites in APOBEC3G and TRIM5α that may delineate new virus-interaction domains. In contrast, our evolutionary analyses suggest that PPIA is not under diversifying selection in primates, consistent with the interaction of Cyclophilin A being limited to the HIV-1M/SIVcpz lineage. The strong sequence conservation of the TRIM19/PML sequences among primates suggests that this gene does not play a role in antiretroviral defense.

  1. Pathogenesis and biomarkers of carcinogenesis in ulcerative colitis

    DEFF Research Database (Denmark)

    Thorsteinsdottir, Sigrun; Gudjonsson, Thorkell; Nielsen, Ole Haagen

    2011-01-01

    One of the most serious complications of ulcerative colitis is the development of colorectal cancer. Screening patients with ulcerative colitis by standard histological examination of random intestinal biopsy samples might be inefficient as a method of cancer surveillance. This Review focuses...... on the current understanding of the pathogenesis of ulcerative colitis-associated colorectal cancer and how this knowledge can be transferred into patient management to assist clinicians and pathologists in identifying patients with ulcerative colitis who have an increased risk of colorectal cancer. Inflammation....... Although progress has been made in the understanding of inflammation-driven carcinogenesis, markers based on these findings possess insufficient sensitivity or specificity to be usable as reliable biomarkers for risk of colorectal cancer development in patients with ulcerative colitis. However, screening...

  2. Cellular microparticles in the pathogenesis of pulmonary hypertension.

    Science.gov (United States)

    Amabile, Nicolas; Guignabert, Christophe; Montani, David; Yeghiazarians, Yerem; Boulanger, Chantal M; Humbert, Marc

    2013-07-01

    Pulmonary hypertension (PH) is a fatal disease with no treatment options, characterised by elevated pulmonary vascular resistanzce and secondary right ventricular failure. The aetiology of pulmonary arterial hypertension is multiple and its pathogenesis is complex. Although the exact role of cellular microparticles remains partially understood, there is increasing evidence to suggest an active role for microparticles in PH pathophysiology. Patients with PH exhibited higher circulating levels of microparticles compared to control subjects and in vitro or in vivo generated microparticles can induce endothelial dysfunction, interfere with coagulation pathways or modulate inflammatory phenomenon. Whether or not these new conveyors of biological information contribute to the acquisition and/or maintenance of the altered endothelial phenotype is unexplored in PH and requires further study.

  3. Advances in canine distemper virus pathogenesis research: a wildlife perspective.

    Science.gov (United States)

    Loots, Angelika K; Mitchell, Emily; Dalton, Desiré L; Kotzé, Antoinette; Venter, Estelle H

    2017-03-01

    Canine distemper virus (CDV) has emerged as a significant disease of wildlife, which is highly contagious and readily transmitted between susceptible hosts. Initially described as an infectious disease of domestic dogs, it is now recognized as a global multi-host pathogen, infecting and causing mass mortalities in a wide range of carnivore species. The last decade has seen the effect of numerous CDV outbreaks in various wildlife populations. Prevention of CDV requires a clear understanding of the potential hosts in danger of infection as well as the dynamic pathways CDV uses to gain entry to its host cells and its ability to initiate viral shedding and disease transmission. We review recent research conducted on CDV infections in wildlife, including the latest findings on the causes of host specificity and cellular receptors involved in distemper pathogenesis.

  4. [Primary biliary cirrhosis (PBC): concept, pathogenesis and classification].

    Science.gov (United States)

    Aizawa, Y; Toda, G

    1994-01-01

    Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by inflammatory destruction of median size intrahepatic bile ducts. The characteristic histological process is described as chronic nonsuppurative destractive cholangitis (CNSDC). Our knowledge for the pathogenesis of PBC remains incomplete. However, immunological mechanisms seems to play one of the most important role. The immunohistochemical examination represents accumulation of stimmulated T lymphocytes in the portal area. Attachment of CD8 positive T cells to bile duct epithelial cells is observed. The animal model of PBC indicates autoreactive CD4 positive T cells seems to be important at the early stage of PBC and CD8 positive cytotoxic T cells are essential for the progression of the disease. PBC is histologically classified into four overlapping stages by Scheuer. Clinically, PBC is classified into asymptomatic PBC (aPBC), PBC with itching alone (s1PBC) and with jaundice (s2PBC).

  5. The role of the kidney in the pathogenesis of hypertension

    DEFF Research Database (Denmark)

    Evans, Roger G; Bie, Peter

    2016-01-01

    develop to hypertension characterized by increased peripheral resistance remain enigmatic. Finally, by definition, animal models of hypertension are not 'essential hypertension'; progress in our understanding of essential hypertension depends on new results on system functions in patients.......The 'Guytonian paradigm' places the direct effect of arterial pressure, on renal excretion of salt and water, at the center of long-term control of blood pressure and thus the pathogenesis of hypertension. It originated in the sixties and remains influential within the field of hypertension...... cardiac output induced by high salt intake do not necessarily lead to increased arterial pressure. Indeed, in multiple models of salt-sensitive hypertension the major abnormality appears to be failure of the vasodilator response to increased cardiac output, seen in salt-resistant animals, rather than...

  6. Pathogenesis of Hendra and Nipah virus infection in humans.

    Science.gov (United States)

    Escaffre, Olivier; Borisevich, Viktoriya; Rockx, Barry

    2013-04-17

    Hendra virus (HeV) and Nipah virus (NiV) are emerging zoonotic viruses that cause severe and often lethal respiratory illness and encephalitis in humans. Henipaviruses can infect a wide range of species and human-to-human transmission has been observed for NiV. While the exact route of transmission in humans is not known, experimental infection in different animal species suggests that infection can be efficiently initiated after respiratory challenge. The limited data on histopathological changes in fatal human cases of HeV and NiV suggest that endothelial cells are an important target during the terminal stage of infection; however, it is unknown where these viruses initially establish infection and how the virus disseminates from the respiratory tract to the central nervous system and other organs. Here we review the current concepts in henipavirus pathogenesis in humans.

  7. Co-infections and Pathogenesis of KSHV-Associated Malignancies

    Directory of Open Access Journals (Sweden)

    Suhani eThakker

    2016-02-01

    Full Text Available Kaposi’s sarcoma-associated herpesvirus (KSHV, also known as human herpes virus 8 (HHV-8 is one of the several carcinogenic viruses that infect humans. KSHV infection has been implicated in the development of Kaposi’s sarcoma (KS, primary effusion lymphoma (PEL, and multicentric Castleman’s Disease (MCD. While KSHV infection is necessary for the development of KSHV associated malignancies, it is not sufficient to induce tumoriegenesis. Evidently, other co-factors are essential for the progression of KSHV induced malignancies. One of the most important co-factors, necessary for the progression of KSHV induced tumors, is immune suppression that frequently arises during co-infection with HIV and also by other immune suppressants. In this mini-review, we discuss the roles of co-infection with HIV and other pathogens on KSHV infection and pathogenesis.

  8. Dengue Hemorrhagic Fever: Epidemiology, Pathogenesis, and Its Transmission Risk Factors

    Directory of Open Access Journals (Sweden)

    Aryu Candra

    2010-12-01

    Full Text Available Dengue hemorrhagic fever is an infectious disease resulting spectrum of clinical manifestations that vary from the lightest, dengue fever, hemorrhagic fever and dengue fever are accompanied by shock or dengue shock syndrome. Its caused by dengue virus, transmitted by Aedes mosquitoes. The case is spread in the tropics, especially in Southeast Asia, Central America, America and the Caribbean, many causes of death in children 90% of them attacking children under 15 years old. Until now pathogenesis is unclear. There are two theories or hypotheses immuno-patogenesis DHF and DSS is still controversial which secondary infections (secondary heterologus infection and antibody-dependent enhancement. Risk factors for dengue transmission are rapid urban population growth, mobilization of the population because of improved transportation facilities and disrupted or weakened so that population control. Another risk factor is poverty which result in people not has the ability to provide a decent home and healthy, drinking water supply and proper waste disposal.

  9. Recent advances in the pathogenesis and treatment of osteoporosis.

    Science.gov (United States)

    Curtis, Elizabeth M; Moon, Rebecca J; Dennison, Elaine M; Harvey, Nicholas C; Cooper, Cyrus

    2016-08-01

    Over recent decades, the perception of osteoporosis has changed from that of an inevitable consequence of ageing, to that of a well characterised and treatable chronic non-communicable disease, with major impacts on individuals, healthcare systems and societies. Characterisation of its pathophysiology from the hierarchical structure of bone and the role of its cell population, development of effective strategies for the identification of those most appropriate for treatment, and an increasing armamentarium of efficacious pharmacological therapies, have underpinned this evolution. Despite this marked progress, individuals who experience a fragility fracture remain under-treated in many areas of the world, and there is substantial need for investment both in secondary and primary prevention globally. In this brief article, we give an overview of the pathogenesis of osteoporosis, and summarise current and future approaches to its assessment and -treatment. © 2016 Royal College of Physicians.

  10. Amyloid cascade hypothesis: Pathogenesis and therapeutic strategies in Alzheimer's disease.

    Science.gov (United States)

    Barage, Sagar H; Sonawane, Kailas D

    2015-08-01

    Alzheimer's disease is an irreversible, progressive neurodegenerative disorder. Various therapeutic approaches are being used to improve the cholinergic neurotransmission, but their role in AD pathogenesis is still unknown. Although, an increase in tau protein concentration in CSF has been described in AD, but several issues remains unclear. Extensive and accurate analysis of CSF could be helpful to define presence of tau proteins in physiological conditions, or released during the progression of neurodegenerative disease. The amyloid cascade hypothesis postulates that the neurodegeneration in AD caused by abnormal accumulation of amyloid beta (Aβ) plaques in various areas of the brain. The amyloid hypothesis has continued to gain support over the last two decades, particularly from genetic studies. Therefore, current research progress in several areas of therapies shall provide an effective treatment to cure this devastating disease. This review critically evaluates general biochemical and physiological functions of Aβ directed therapeutics and their relevance. Copyright © 2015 Elsevier Ltd. All rights reserved.

  11. Atretic encephalocele/myelocele--case reports with emphasis on pathogenesis.

    Science.gov (United States)

    Hong, E. K.; Kim, N. H.; Lee, J. D.

    1996-01-01

    Atretic encephaloceles or myelomeningoceles are frequently solid due to hamartomatous proliferation of fibrous tissue and blood vessels. Because of the fibrous nature of the tumor with no cystic cavity and unusual location with no connection to CNS, they are frequently regarded as insignificant hamartomas. Apart from this terminology, they are also described as cutaneous meningiomas or hamartomas with ectopic meningothelial elements by the presence of meningothelial cells. We report a case of atretic encephalocele in the parietal scalp of an 8 year-old boy and a case of myelomeningocele in the posterior mediastinum of a 31 year-old woman. The terms atretic encephalocele and myelomeningocele are more appropriate for these cases because they include their pathogenesis and the non-neoplastic nature of the lesion. PMID:8878809

  12. Immuno-pathogenesis of Periodontal Disease: Current and Emerging Paradigms.

    Science.gov (United States)

    Huang, Nasi; Gibson, Frank C

    2014-06-01

    Periodontal disease (PD) is a highly complex disease involving many factors; however, two principal facets central to initiation and progression of the majority of PD are the composition of the microbes in the sub-gingival plaque, and the host immune response to these organisms. Numerous studies point to the complexity of PD, and to the fact that despite innate and adaptive immune activation, and resultant inflammation, our immune response fails to cure disease. Stunning new findings have begun to clarify several complexities of the host-pathogen interaction of PD pointing to key roles for microbial dysboisis and immune imbalance in the pathogenesis of disease. Furthermore, these investigations have identified novel translational opportunities to intercede in PD treatment. In this review we will highlight a select few recent findings in innate and adaptive immunity, and host pathogen interactions of PD at a micro-environmental level that may have profound impact on PD progression.

  13. Influenza pathogenesis: mechanisms of modulation by agent proteins

    Directory of Open Access Journals (Sweden)

    M. Yu. Shchelkanov

    2015-01-01

    Full Text Available Modern concepts of the influence of the proteins from viruses-etiological agents of flu – Influenzavirus A, B and C (Orthomyxoviridae – on the development of different elements of the main disease pathogenesis are analyzed in the review. In particular, the short description of life cycle of Influenza viruses is alleguered with special attention to those its stages which are capable to modulate pathogenetic mechanisms. The interrelation between the structure of hemagglutinin receptor-binding site and virus tropism as well as the influence of the receptor-destroying virus proteins on this phenomenon is described. The mechanism of suppression of interferon production in the infected cell by virus NS1 protein is presented. The induction of apoptosis by nonstructural PB1-F2 protein of Influenza A virusis described. 

  14. Therapeutic implications from the pathogenesis of Raynaud's phenomenon.

    Science.gov (United States)

    Herrick, Ariane L

    2017-07-01

    Raynaud's phenomenon (RP) can be either primary (idiopathic) or secondary to a number of different diseases/conditions, when vasopasm can be superimposed upon structural vascular abnormality or a hyperviscosity state and may then lead to severe ischaemia with tissue damage. Treatment must be tailored to the individual. Areas covered: This review discusses how increased understanding of the pathogenesis of RP has driven and is driving new approaches to therapy, and how we are now better able to predict which patients presenting with RP are likely to have an underlying disease requiring specific intervention. Medline searches (1946 to August 2016) were conducted for 'Raynaud's' in combination with relevant terms including different drugs. All papers identified were English language, with abstracts. Expert commentary: Randomised controlled trials of RP present particular challenges. The major aim must continue to be development of safe, effective treatments for patients across the spectrum of RP.

  15. Pathogenesis of the Metabolic Syndrome: Insights from Monogenic Disorders

    Directory of Open Access Journals (Sweden)

    Rinki Murphy

    2013-01-01

    Full Text Available Identifying rare human metabolic disorders that result from a single-gene defect has not only enabled improved diagnostic and clinical management of such patients, but also has resulted in key biological insights into the pathophysiology of the increasingly prevalent metabolic syndrome. Insulin resistance and type 2 diabetes are linked to obesity and driven by excess caloric intake and reduced physical activity. However, key events in the causation of the metabolic syndrome are difficult to disentangle from compensatory effects and epiphenomena. This review provides an overview of three types of human monogenic disorders that result in (1 severe, non-syndromic obesity, (2 pancreatic beta cell forms of early-onset diabetes, and (3 severe insulin resistance. In these patients with single-gene defects causing their exaggerated metabolic disorder, the primary defect is known. The lessons they provide for current understanding of the molecular pathogenesis of the common metabolic syndrome are highlighted.

  16. Pathogenesis of ankylosing spondylitis - recent advances and future directions.

    Science.gov (United States)

    Ranganathan, Vidya; Gracey, Eric; Brown, Matthew A; Inman, Robert D; Haroon, Nigil

    2017-06-01

    Over the past 5 years, advances in high-throughput techniques and studies involving large cohorts of patients have led to considerable advances in the identification of novel genetic associations and immune pathways involved in ankylosing spondylitis (AS). These discoveries include genes encoding cytokine receptors, transcription factors, signalling molecules and transport proteins. Although progress has been made in understanding the functions and potential pathogenic roles of some of these molecules, much work remains to be done to comprehend their complex interactions and therapeutic potential in AS. In this Review, we outline the current knowledge of AS pathogenesis, including genetic risk associations, HLA-B27-mediated pathology, perturbations in antigen-presentation pathways and the contribution of the type 3 immune response.

  17. Rosacea – new data on pathogenesis and treatment

    Directory of Open Access Journals (Sweden)

    Waldemar Placek

    2016-10-01

    Full Text Available Rosacea is a common dermatosis more prevalent in females, significantly impairing quality of life. Currently erythematous, papulo-pustular and phymatous subtypes are distinguished, which do not necessarily represent consecutive stages. Recent findings indicate in the pathogenesis of rosacea the role of the impaired innate immune system and vascular abnormalities. Additionally, the role of genetic and infectious factors is suggested. The therapy of rosacea is directed not only against inflammatory changes but also anti-parasitic. In topical treatment the most commonly used are metronidazole and azelaic acid. Other drugs are topical antibiotics, antiparasitic agents such as ivermectin and preparations directly influencing erythema. In more severe cases tetracyclines or macrolides are used, and in the most severe cases, isotretinoine. As ultraviolet light is a recognized trigger for rosacea, regular sunscreen use is necessary. Also, proper diet is indicated. Presently in the treatment of rosacea more and more techniques using different lights are employed.

  18. Molecular basis of pathogenesis of emerging viruses infecting aquatic animals

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    Lang Gui

    2018-01-01

    Full Text Available Aquatic vertebrates are very abundant in the world, and they are of tremendous importance in providing global food security and nutrition. However, emergent and resurgent viruses, such as ranavirus (e.g., Rana grylio virus, RGV and Andriasd avidianus ranavirus, ADRV, herpesvirus (e.g., Carassius carassius herpesvirus, CaHV, reovirus (e.g., grass carp reovirus 109, GCRV-109, Scophthal musmaximus reovirus, SMReV and Micropterus salmoides reovirus, MsReV, and rhabdovirus (e.g., Siniper cachuatsi rhabdovirus, SCRV and Scophthal musmaximus rhabdovirus, SMRV can cause severe diseases in aquaculture animals and wild lower vertebrates, such as frogs, giant salamanders, fish, and so on. Here, we will briefly describe the symptoms produced by the aforementioned viruses and the molecular basis of the virus–host interactions. This manuscript aims to provide an overview of viral diseases in lower vertebrates with an emphasis on visible symptomatic manifestations and pathogenesis.

  19. The role of platelets in the pathogenesis of systemic sclerosis

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    Giuseppe A. eRamirez

    2012-06-01

    Full Text Available Systemic sclerosis (SSc is an inflammatory disease of unknown etiology characterized by widespread organ dysfunction due to fibrosis and ischemia. Its nebulous pathogenic background and the consequent absence of an etiological therapy prevent the adoption of satisfying treatment strategies, able to improve patients' quality of life and survival and stimulate researchers to identify a unifying pathogenic target. Platelets show a unique biological behavior, lying at the crossroads between vascular function, innate and adaptive immunity and regulation of cell proliferation. Consequently they are also emerging players in the pathogenesis of many inflammatory diseases, including systemic sclerosis. In the setting of SSc platelets are detectable in a persistent activated state, which is intimately linked to the concomitant presence of an injured endothelium and to the widespread activation of the innate and adaptive immune system. As a consistent circulating source of bioactive compounds platelets contribute to the development of many characteristic phenomena of SSc, such as fibrosis and impaired vascular tone.

  20. Pathogenesis of optic disc edema in raised intracranial pressure.

    Science.gov (United States)

    Hayreh, Sohan Singh

    2016-01-01

    Optic disc edema in raised intracranial pressure was first described in 1853. Ever since, there has been a plethora of controversial hypotheses to explain its pathogenesis. I have explored the subject comprehensively by doing basic, experimental and clinical studies. My objective was to investigate the fundamentals of the subject, to test the validity of the previous theories, and finally, based on all these studies, to find a logical explanation for the pathogenesis. My studies included the following issues pertinent to the pathogenesis of optic disc edema in raised intracranial pressure: the anatomy and blood supply of the optic nerve, the roles of the sheath of the optic nerve, of the centripetal flow of fluids along the optic nerve, of compression of the central retinal vein, and of acute intracranial hypertension and its associated effects. I found that, contrary to some previous claims, an acute rise of intracranial pressure was not quickly followed by production of optic disc edema. Then, in rhesus monkeys, I produced experimentally chronic intracranial hypertension by slowly increasing in size space-occupying lesions, in different parts of the brain. Those produced raised cerebrospinal fluid pressure (CSFP) and optic disc edema, identical to those seen in patients with elevated CSFP. Having achieved that, I investigated various aspects of optic disc edema by ophthalmoscopy, stereoscopic color fundus photography and fluorescein fundus angiography, and light microscopic, electron microscopic, horseradish peroxidase and axoplasmic transport studies, and evaluated the effect of opening the sheath of the optic nerve on the optic disc edema. This latter study showed that opening the sheath resulted in resolution of optic disc edema on the side of the sheath fenestration, in spite of high intracranial CSFP, proving that a rise of CSFP in the sheath was the essential pre-requisite for the development of optic disc edema. I also investigated optic disc edema with