Sample records for acquired immune deficiency

  1. Cryptosporidiosis in the acquired immune deficiency syndrome. (United States)

    Cooper, D A; Wodak, A; Marriot, D J; Harkness, J L; Ralston, M; Hill, A; Penny, R


    Cryptosporidiosis was found in a patient with the acquired immune deficiency syndrome. The microbiological and morphological features of this newly recognized opportunistic infection are distinctive and diagnostic.

  2. An unusual ocular presentation of acquired immune deficiency syndrome

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    Arunachalam Cynthia


    Full Text Available A 50-year-old male who presented with bilateral keratomalacia and on subsequent evaluation was found to be human immunodeficiency virus (HIV positive is being reported. A MEDLINE search of the literature did not reveal any report of keratomalacia as the initial presenting feature of HIV/ acquired immune deficiency syndrome.

  3. Acquired Immune Deficiency Syndrome: A Preliminary Examination of the Effects on Gay Couples and Coupling. (United States)

    Carl, Douglas


    The Acquired Immune Deficiency Syndrome (AIDS) epidemic significantly influences attitudes about life and lifestyles. Homosexuals have to give increased consideration to coupling, the nature of coupled relationships, sex and intimacy, and death long before the normal time. Discusses impact of AIDS on the early stages of gay coupling and on the…

  4. Meningitis and stridor in advanced Human immunodeficiency virus/acquired immune deficiency syndrome

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    Naidoo P


    Full Text Available P Naidoo, D Pillay, S SamanDepartment of Internal Medicine, Port Shepstone Regional Hospital, University of KwaZulu-Natal, South AfricaAbstract: A 37-year-old female presented confused with a preceding history of severe headache. After clinical examination and investigations, she was diagnosed with disseminated tuberculosis (including central nervous system involvement, and Human immunodeficiency virus/acquired immune deficiency syndrome. Her hospital stay was complicated. She developed stridor and a cerebrovascular accident with left hemiplegia. She died approximately 2 weeks after admission. The potential causes of her stridor included a mediastinal mass or a central mechanism secondary to tuberculosis meningitis. Limited resources precluded definitive imaging of the chest to rule out a mediastinal mass. Further, an autopsy was not done. Despite these limitations, this case is unique because it reports the presence of both stridor and tuberculosis meningitis in an adult patient.Keywords: Human immunodeficiency virus, acquired immune deficiency syndrome, meningitis, stridor, tuberculosis

  5. Heterotopic ossification (myositis ossificans) in acquired immune deficiency syndrome. Detection by gallium scintigraphy. (United States)

    Drane, W E; Tipler, B M


    A case of heterotopic ossification (myositis ossificans) secondary to the central nervous system complications of acquired immune deficiency syndrome (AIDS) is reported. Because of the overwhelming suspicion of infection in this patient, this diagnosis was not considered until a gallium scan revealed the typical findings of heterotopic ossification. Because of the increasing utilization of gallium imaging in the AIDS population, every imaging specialist should be aware of this potential disorder.

  6. Heterotopic ossification (myositis ossificans) in acquired immune deficiency syndrome. Detection by gallium scintigraphy

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    Drane, W.E.; Tipler, B.M.


    A case of heterotopic ossification (myositis ossificans) secondary to the central nervous system complications of acquired immune deficiency syndrome (AIDS) is reported. Because of the overwhelming suspicion of infection in this patient, this diagnosis was not considered until a gallium scan revealed the typical findings of heterotopic ossification. Because of the increasing utilization of gallium imaging in the AIDS population, every imaging specialist should be aware of this potential disorder.

  7. Meningitis and stridor in advanced Human immunodeficiency virus/acquired immune deficiency syndrome


    Naidoo P; Pillay D; Saman S


    P Naidoo, D Pillay, S SamanDepartment of Internal Medicine, Port Shepstone Regional Hospital, University of KwaZulu-Natal, South AfricaAbstract: A 37-year-old female presented confused with a preceding history of severe headache. After clinical examination and investigations, she was diagnosed with disseminated tuberculosis (including central nervous system involvement), and Human immunodeficiency virus/acquired immune deficiency syndrome. Her hospital stay was complicated. She developed stri...

  8. Audiological and Ontological Findings in Acquired Immune-Deficiency Syndrome (AIDS

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    Farzaneh Vadoudfam


    Full Text Available The human immunodeficiency virus (HIV is the virus that causes AIDS (acquired immune-deficiency syndrome. Head and neck are the most common sites in contamination with this virus. HIV can affect outer, middle and inner parts of the ear. Changing in the color of the skin, effusion, infection and sudden hearing loss are some types of the audiological and ontological findings in such patients.

  9. Human immunodeficiency virus/acquired immune deficiency syndrome: Using drug from mathematical perceptive. (United States)

    Chatterjee, Amar Nath; Saha, Shubhankar; Roy, Priti Kumar


    Entry of acquired immune deficiency syndrome virus into the host immune cell involves the participation of various components of host and viral cell unit. These components may be categorized as attachment of the viral surface envelope protein subunit, gp120, to the CD4(+) receptor and chemokine coreceptors, CCR5 and CXCR4, present on T cell surface. The viral fusion protein, gp41, the second cleaved subunit of Env undergoes reconfiguration and the membrane fusion reaction itself. Since the CD4(+) T cell population is actively involved; the ultimate outcome of human immunodeficiency virus infection is total collapse of the host immune system. Mathematical modeling of the stages in viral membrane protein-host cell receptor-coreceptor interaction and the effect of antibody vaccine on the viral entry into the susceptible host cell has been carried out using as impulsive differential equations. We have studied the effect of antibody vaccination and determined analytically the threshold value of drug dosage and dosing interval for optimum levels of infection. We have also investigated the effect of perfect adherence of drug dose on the immune cell count in extreme cases and observed that systematic drug dosage of the immune cells leads to longer and improved lives.

  10. Social capital of Iranian patients living with acquired immune deficiency syndrome and associated factors. (United States)

    Ansari, S K; Nedjat, S; Jabbari, H; Saiepour, N; Heris, M J


    This study investigated the social capital of Iranian patients living with acquired immune deficiency syndrome (AIDS) and the associated factors. In a cross-sectional study the Integrated Social Capital Questionnaire was filled by a sequential sample of 300 patients visiting a referral counselling centre in Tehran. The patients' social capital scores were around 50% in the trust, social cohesion, collective action and cooperation and political empowerment domains. The groups and networks membership domain scored the lowest (27.1%). In regression analysis, employment status was significantly associated with groups and networks membership; age, marital status and financial status were associated with collective action and cooperation; period of disease awareness and marital status affected social cohesion and inclusion; and having risky behaviour affected empowerment and political action. Efforts are needed to enhance the social capital of those patients living with AIDS who are younger, unemployed, divorced/widowed, with risky behaviours and shorter disease awareness.

  11. Acquired color vision deficiency. (United States)

    Simunovic, Matthew P


    Acquired color vision deficiency occurs as the result of ocular, neurologic, or systemic disease. A wide array of conditions may affect color vision, ranging from diseases of the ocular media through to pathology of the visual cortex. Traditionally, acquired color vision deficiency is considered a separate entity from congenital color vision deficiency, although emerging clinical and molecular genetic data would suggest a degree of overlap. We review the pathophysiology of acquired color vision deficiency, the data on its prevalence, theories for the preponderance of acquired S-mechanism (or tritan) deficiency, and discuss tests of color vision. We also briefly review the types of color vision deficiencies encountered in ocular disease, with an emphasis placed on larger or more detailed clinical investigations.

  12. Can we find a solution to the human immunodeficiency virus/acquired immune deficiency syndrome controversy? Is acquired immune deficiency syndrome the consequence of continuous excessive stressing of the body? (United States)

    Hässig, A; Wen-Xi, L; Stampfli, K


    The time of re-evaluation of the role of human immunodeficiency viruses in the pathogenesis of acquired immune deficiency syndrome has now come, now that methods are available for the direct detection of human immunodeficiency viruses and for the detection of cellular anti-human immunodeficiency virus immune reactions. It has been shown that human immunodeficiency virus infections are common among anti-human immunodeficiency virus antibody negative high-risk individuals. The disease is brought under control by cellular immune reactions and the anti-human immunodeficiency virus antibody test remains negative. Apart from proof that infection with human immunodeficiency viruses has occurred, a positive result in an anti-human immunodeficiency virus-antibody test is also an indication of an independent immunosuppression state. According to the definition of the Centers of Disease Control classical acquired immune deficiency syndrome is the consequence of infection with human immunodeficiency virus in association with continuous excessive stress, such as observed in the known risk groups. At the center of the pathogenetic process is hypercortisolism-determined damage of T lymphocytes, in which insufficiency of thymus is prominent. For this reason, in our view, there are indications for shifting efforts from the prophylaxis of infection with human immunodeficiency viruses to the prophylaxis of acquired immune deficiency syndrome by reducing stress factors.

  13. Penicillium marneffei chylous ascites in acquired immune deficiency syndrome: A case report

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    Yin-Zhong Shen; Zhen-Yan Wang; Hong-Zhou Lu


    Penicillium marneffei (P.marneffei) infection usually occurs with skin,bone marrow,lung or hepatic involvement.However,no cases of P.marneffei infection with chylous ascites have been reported thus far.In this report,we describe the first case of acquired immune deficiency syndrome (AIDS) which has been complicated by a P.marneffei infection causing chylous ascites.We describe the details of the case,with an emphasis on treatment regimen.This patient was treated with amphotericin B for 3 mo,while receiving concomitant therapy with an efavirenz-containing antiretroviral regimen,but cultures in ascitic fluid were persistently positive for P.marneffei.The infection resolved after treatment with high-dose voriconazole (400 mg every 12 h) for 3 mo.P.marneffei should be considered in the differential diagnosis of chylous ascites in human immunodeficiency virus patients.High-dose voriconazole is an effective,well-tolerated and convenient option for the treatment of systemic infections with P.marneffei in AIDS patients on an efavirenz-containing antiretroviral regimen.

  14. Bilateral Central Retinal Vein Occlusions Combined with Artery Occlusions in A Patient with Acquired Immune Deficiency Syndrome

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    Feng Wen; Xuemei Chen; Haitai Li; Ruiduan Liao; Dezheng Wu


    Purpose: This is the first report of a bilateral nonischemic central retinal vein occlusionscombined with artery occlusions in a patient with acquired immune deficiency syndrome(AIDS). Methods: Case report. Results: A 22-year-old Chinese(male) with a positive human immunodeficiency virus(HIV) infection developed bilateral nonischemic central retinal vein occlusions combinedwith artery occlusions and severe vision loss. The manifestations of the fundus andfluorescein angiography were similar in both eyes.Conclusion: This case report provides the evidences that central retinal vein and arteryocclusions are probably part of the spectrum of AIDS vascular diseases.

  15. Roundtable for the Development of Drugs and Vaccines Against Acquired Immune Deficiency Syndrome (AIDS) (United States)


    AIDS) SUBTITLE: Workshop Summary: Government and Industry .. Collaboration in AIDS Drug Development Aoneealon Foy PTIS ’IA& ----- DTI ’ TAB PRINCIPAL ...8217 stating that the government should generally acquire the principal or exclusine rights to inventions derived from federally supported research. IPAs w, ould...obligation to adminiter its patent rights in a responsible manner that benefits societN This mean,,, for one thing. not privatizing patents covering

  16. Epstein-Barr virus myelitis and Castleman's disease in a patient with acquired immune deficiency syndrome: a case report

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    Balderacchi Jasminka


    Full Text Available Abstract Introduction Few cases of Epstein-Barr virus myelitis have been described in the literature. Multi-centric Castleman's disease is a lymphoproliferative disorder that is well known for its associations with the human immunodeficiency virus, human herpes virus 8, and Kaposi's sarcoma. The concurrent presentation of these two diseases in a patient at the same time is extremely unusual. Case Presentation We describe the case of a 43-year-old Caucasian man with acquired immune deficiency syndrome who presented with fever, weight loss and diffuse lymphadenopathy, and was diagnosed with multi-centric Castleman's disease. He presented three weeks later with lower extremity weakness and urinary retention, at which time cerebrospinal fluid contained lymphocytic pleocytosis and elevated protein. Magnetic resonance imaging demonstrated abnormal spinal cord signal intensity over several cervical and thoracic segments, suggesting the diagnosis of myelitis. Our patient was ultimately diagnosed with Epstein-Barr virus myelitis, as Epstein-Barr virus DNA was detected by polymerase chain reaction in the cerebrospinal fluid. Conclusion To the best of our knowledge, this is the first case of multi-centric Castleman's disease followed by acute Epstein-Barr virus myelitis in a human immunodeficiency virus-infected patient. Clinicians caring for human immunodeficiency virus-infected patients should be vigilant about monitoring patients with increasing lymphadenopathy, prompting thorough diagnostic investigations when necessary.

  17. Quality of life among people living with acquired immune deficiency syndrome receiving anti-retroviral therapy: a study from Nepal

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    Giri S


    Full Text Available Smith Giri, Maniraj Neupane, Sushil Pant, Utsav Timalsina, Sagar Koirala, Santosh Timalsina, Sashi Sharma Department of Medicine, Tribhuvan University Teaching Hospital, Kathmandu, Nepal Purpose: The present study was undertaken to determine the impact of acquired immune deficiency syndrome (AIDS on the quality of life of affected individuals in Nepal. Patients and methods: A cross sectional study was done among 70 individuals attending the Anti-Retroviral Therapy clinic of the University Hospital in Nepal. Quality of life (QOL was evaluated using World Health Organization Quality of life questionnaire (WHO QOL-BREF instrument. Statistical analysis was done using SPSS Version 17.0. Results: The median scores with interquartile range (IQR in four domains of QOL in descending order were physical (61; IQR 22, social (58; IQR 33, environmental (56; IQR 13, and psychological (54; IQR 8. Older age was associated with lower perceived overall QOL. Females were more likely to have lower QOL scores in the social and psychological domains. Higher CD4 counts and a married status were significant predictors of higher QOL scores in the environmental domain. Conclusion: Being older, female, single, and having advanced clinical stage is associated with lower QOL scores in people living with AIDS. Lowest QOL scores were seen in the psychological domain suggesting the need of psychological interventions. Keywords: quality of life, AIDS, Nepal, WHO QOL-BREF

  18. Effect of traditional Chinese medicine for treating human immunodeficiency virus infections and acquired immune deficiency syndrome: Boosting immune and alleviating symptoms. (United States)

    Zou, Wen; Wang, Jian; Liu, Ying


    To respond to the human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) epidemic in China, the integration of antiretroviral therapy (ART) and traditional Chinese medicine (TCM) has important implications in health outcomes, especially in China where the use of TCM is widespread. The National Free TCM Pilot Program for HIV Infected People began in 5 provinces (Henan, Hebei, Anhui, Hubei, and Guangdong) in 2004, and quickly scaled up to 19 provinces, autonomous regions, and municipalities in China including some places with high prevalence, 26,276 adults have been treated thus far. Usually, people with HIV infection seek TCM for four main reasons: to enhance immune function, to treat symptoms, to improve quality of life, and to reduce side effects related to medications. Evidences from randomized controlled clinical trials suggested some beneficial effects of use of traditional Chinese herbal medicine for HIV infections and AIDS. More proofs from large, well-designed, rigorous trials is needed to give firm support. Challenges include interaction between herbs and antiretroviral drugs, stigma and discrimination. The Free TCM Program has made considerable progress in providing the necessary alternative care and treatment for HIV-infected people in China, and has strong government support for continued improvement and expansion, establishing and improving a work mechanism integrating Chinese and Western medicines.

  19. Clinical features and treatment of hepatitis B virus and hepatitis C virus co-infection among patients with acquired immune deficiency syndrome

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    Objective To estimate the clinical features of hepatitis B virus(HBV)and hepatitis C virus(HCV)co-infection among acquired immune deficiency syndrome(AIDS)patients and the interaction of lamivudine(3 TC)contained antiretroviral therapy(ART)with hepatitis virus replication.Methods From 2004 to 2010,199human immunodeficiency virus(HIV)/HBV coinfected patients admitted to Zhongnan Hospital of Wuhan University were enrolled,including 76 cases of HIV/HBV/HCV triple infection and 123 cases of

  20. The earliest cases of human immunodeficiency virus type 1 group M in Congo-Kinshasa, Rwanda and Burundi and the origin of acquired immune deficiency syndrome. (United States)

    Vangroenweghe, D


    The early cases of acquired immune deficiency syndrome and human immunodeficiency virus type 1 (HIV-1) infection in the 1960s and 1970s in Congo-Kinshasa (Zaire), Rwanda and Burundi are reviewed. These countries appear to be the source of the HIV-1 group M epidemic, which then spread outwards to neighbouring Tanzania and Uganda in the east, and Congo-Brazzaville in the west. Further spread to Haiti and onwards to the USA can be explained by the hundreds of single men from Haiti who participated in the UNESCO educational programme in the Congo between 1960 and 1975.

  1. Unified-planning, graded-administration, and centralized-controlling: a management modality for treating acquired immune deficiency syndrome with Chinese medicine in Henan Province of China. (United States)

    Xu, Li-Ran; Guo, Hui-jun; Liu, Zhi-bin; Li, Qiang; Yang, Ji-ping; He, Ying


    Henan Province in China has a major epidemic of human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS). Chinese medicine (CM) has been used throughout the last decade, and a management modality was developed, which can be described by unified-planning, graded-administration, and centralized-controlling (UGC). The UGC modality has one primary concept (patient-centered medicine from CM theory), four basic foundations (classifying administrative region, characteristics of CM on disease treatment, health resource conditions, and distribution of patients living with HIV), six important relationships (the "three uniformities and three combinations," and the six relationships therein guide the treatment of AIDS with CM), and four key sections (management, operation, records, and evaluation). In this article, the authors introduce the UGC modality, which could be beneficial to developing countries or resource-limited areas for the management of chronic infectious disease.

  2. Epidemiology of children with acquired immune deficiency syndrome (stage 3): A referral hospital-based study in Iran. (United States)

    Movahedi, Zahra; Mahmoudi, Shima; Pourakbari, Babak; Keshavarz Valian, Nasrin; Sabouni, Farah; Ramezani, Amitis; Bahador, Abbas; Mamishi, Setareh


    Lack of recognition of human immunodeficiency virus (HIV) infection especially in children and delayed implementation of effective control programs makes HIV infection as a major cause for concern. Information on HIV epidemiology in Iran as well as other Islamic countries is limited. The aim of our study was to describe the clinical manifestation and laboratory finding of HIV infected children who were admitted to a referral Children Medical Center (CMC) in Tehran, Iran, during 11 years from January 2002 to January 2013. This was a retrospective study carried out over a period of 11 years. The records of all patients attending to the CMC with confirmed acquired immunodeficiency syndrome (AIDS) were screened. The patients were evaluated for social circumstance, family history, age, gender, clinical, and laboratory features. Clinical data including fever, respiratory distress, diarrhea, rash, etc. as well as laboratory tests including complete blood count, serum glucose level, electrolytes, liver function test, cultures, CD4 lymphocyte count were evaluated. During the study period, 32 HIV positive children were enrolled. The majority of patients were presented with weight loss, prolonged fever, respiratory infection and chronic diarrhea. In this study, salmonella infections as well as streptococcal pneumonia and candida infections followed by, tuberculosis and Pseudomonas aeruginosa infections were the predominant opportunistic infections. Since the number of HIV-positive children has been alarmingly increasing in recent years and perinatal transmission is the most common route of HIV infection in children, essential recommendations for prenatal HIV testing as well as appropriate antiretroviral therapy by HIV infected mothers are needed.

  3. The correlation between perceived social support and illness uncertainty in people with human immunodeficiency virus/acquired immune deficiency syndrome in Iran

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    Moosa Sajjadi


    Full Text Available Background: Illness uncertainty is a source of a chronic and pervasive psychological stress for people living with human immunodeficiency virus (HIV/acquired immune deficiency syndrome (AIDS (PLWH, and largely affects their quality of life and the ability to cope with the disease. Based on the uncertainty in illness theory, the social support is one of the illness uncertainty antecedents, and influences the level of uncertainty perceived by patients. Aim: To examine uncertainty in PLWH and its correlation with social support in Iran. Materials and Methods: This cross-sectional correlational study was conducted with 80 PLWH presenting to AIDS Research Center, Tehran, Iran in 2013. The data collected using illness uncertainty and social support inventories were analyzed through Pearson′s correlation coefficient, Spearman′s correlation coefficient, and regression analysis. Results: The results showed a high level of illness uncertainty in PLWH and a negative significant correlation between perceived social support and illness uncertainty ( P = 0.01, r = -0.29. Conclusion: Uncertainty is a serious aspect of illness experience in Iranian PLWH. Providing adequate, structured information to patients as well as opportunities to discuss their concerns with other PLWH and receive emotional support from their health care providers may be worthwhile.

  4. Findings from the Horizontes Acquired Immune Deficiency Syndrome Education project: the impact of indigenous outreach workers as change agents for injection drug users. (United States)

    Birkel, R C; Golaszewski, T; Koman, J J; Singh, B K; Catan, V; Souply, K


    A human immunodeficiency virus (HIV)/acquired immune deficiency syndrome (AIDS) intervention using indigenous outreach workers was implemented with Hispanic injection drug users (IDUs) and their sexual partners in three locations: Laredo, Texas; San Diego, California; and San Juan, Puerto Rico. A total of 2,169 subjects were contacted, given health education, HIV antibody testing, and follow-up counseling. This article reports on the 1,616 IDUs (75%) who completed the initial and follow-up interviews. The results indicated significant increases in health knowledge on AIDS, decreases in needle risk drug taking behaviors, some decreases in sex risk behaviors, and more realistic perceptions of personal AIDS risk. Using multivariate analyses, gender (male) and increasing age (older than age 25 years) were the strongest predictors of behavior change. Surprisingly, the identification of a positive HIV serostatus was not a significant predictor of behavior change. Although intended as a comparison study between contrasting levels of intervention, logistical and administrative problems undermined the use of a true quasi-experimental design. Nonetheless, the results from this research suggest that the use of indigenous outreach workers is an effective means of combatting the spread of HIV in this difficult to reach population. Some programmatic recommendations are provided for future efforts of this kind, particularly in relation to role conflicts experienced by outreach workers.

  5. Influence of the home environment on the prevention of mother to child transmission of human immunodeficiency virus/acquired immune-deficiency syndrome in South Africa. (United States)

    Sewnunan, A; Modiba, L M


    The human immunodeficiency virus and acquired immune-deficiency syndrome (HIV/AIDS) is still a 'family crises' which marks the beginning of the deterioration of the family unit and the trauma in the emotional, psychological and material lives of both the mother and child. In South African context where the majority of HIV-positive mothers are young single women who live in extended families, disclosure to the sexual partner alone is not an adequate condition for the success of prevention of mother to child transmission (PMTCT). In South Africa, close to one in three women who attend antenatal clinics are HIV positive. KwaZulu-Natal is one of the worst affected provinces, where as many as 40-60% of pregnant women attending antenatal services are living with HIV infection. The study sought to investigate the link between the home environment and its contribution to the success of the programme on PMTCT of HIV/AIDS. A qualitative, explorative, descriptive and contextual study was used in this study to explore whether the home environment for the support system is available for the HIV-positive women on the PMTCT programme. The population of this study included all women who have undergone counselling and tested HIV positive and who have joined the programme on PMTCT of HIV/AIDS in a specific hospital in KwaZulu-Natal Province. Although 14 women agreed to participate in the study, only 10 women were interviewed as saturation was attained. Data were collected using semi-structured interview schedule. Interviews were audio-taped and field notes were taken. Content analysis was used and it was done manually. This study revealed that one of the major issues still surrounding HIV/AIDS and PMTCT is that of non-disclosure, selective disclosure and the stigma and discrimination that surrounds this disease.

  6. Complement's participation in acquired immunity

    DEFF Research Database (Denmark)

    Nielsen, Claus Henrik; Leslie, Robert Graham Quinton


    of the B cell receptor for antigen (BCR), a complex composed of the iC3b/C3d fragment-binding complement type 2 receptor (CR2, CD21) and its signaling element CD19 and the IgG-binding receptor FcgammaRIIb (CD32). The positive or negative outcome of signaling through this triad is determined by the context...... in which antigen is seen, be it alone or in association with natural or induced antibodies and/or C3-complement fragments. The aim of this review is to describe the present status of our understanding of complement's participation in acquired immunity and the regulation of autoimmune responses....

  7. 获得性免疫缺陷综合征合并肠结核1例%A case report of acquired immune deficiency syndrome complicated with intestinal tuberculosis

    Institute of Scientific and Technical Information of China (English)

    黄绍萍; 程计林; 赵玉洁; 史佩炯; 马学东; 冯艳玲


    Acquired immune deficiency syndrome (AIDS) complicated with intestinal tuberculosis is rarely reported. Due to lack of typical clinical and endoscopic characteristics,it is easy to be misdiagnosed. In this article,we report and analyze a case of AIDS patient with intestinal tuberculosis,which might be helpful to raise awareness and reduce misdiagnosis or mistreatment.%文献报道获得性免疫缺陷综合征(acquired immune deficiency syndrome,AIDS)合并肠结核很少,临床表现和内镜特点不典型,易误诊.本文对1例手术证实为合并肠结核的AIDS病例进行分析,旨在提高对AIDS继发肠病的诊断认识,减少误诊误治.

  8. Clinical characteristics of 275 pediatric cases of acquired immune deficiency syndrome%儿童艾滋病275例临床特点分析

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    赵燕; 庞琳; 云鹰; 刘中夫; 张福杰; 豆智慧; 程跃武; 唐志荣; 刘爱文; 彭国平; 乔晓春; 赵红心


    Objective To study the clinical characteristic of acquired immune deficiency syndrome (AIDS) patients younger than 15 years old and to explore the influence of human immunodeficiency virus (HIV) infection on them. Methods The clinical information, including demographic profile, clinical stages of the disease, laboratory test results and developmental status were gathered from 275 antiretroviral therapy naive patients. Results Seventy eight point nine percent patients were infected by vertical transmission. Sixteen percent were infected by receiving blood products. The average age was (7.6±3. 7) years, with 5 cases younger than 1 year old, 104 cases ranging from 1 - 5 years and 166 cases elder than 6 years. Seventy point one percent patients were classified as stage 3 or 4 according to World Health Organization definitions. The average CD4 count was ( 137 ± 159 )/μL, ( 304 ± 317 ) /μL and ( 1 246 ± 776 )/μL respectively in children elder than 6 years, ranging from 1 to 5 years and younger than 1 year. One hundred and eighty one cases suffered from anemia on different severity grading. The most common HIV related symdromes included persistent fever, skin damage, persistent diarrhea, oral candidiasis and recurrent upper respiratory tract infection. Among these infected children, 49. 6% showed height lower than x - 2s and 19. 9% showed weight lower than x - 2s. Conclusions Most survival pediatric AIDS patients are elder than 6 years. HIV infection can significantly affect the children's immune system function,growth and development.%目的 研究15岁以下AIDS患者的临床特点,了解HIV对患儿的影响.方法 分析275例即将入选接受高效抗反转录病毒治疗患者的临床资料,对人口学、流行病学、临床分期、实验室特点及生长发育状况进行分析.结果 275例AIDS患者主要以母婴途径传播为主,占78.9%,输血及血制品传播的为16.0%.平均年龄(7.6±3.7)岁,其中1岁以内5例,1~5岁104例,6

  9. 德昌县艾滋病流行特征分析%Analysis on Epidemic Characteristics of Acquired Immune Deficiency Syndrome in Dechang County

    Institute of Scientific and Technical Information of China (English)



    Objective To understand the epidemiological trend of acquired immune deficiency syndrome (AIDS) in Dechang County so as to provide a scientific base for prevention and control of AIDS. Methods Descriptive epidemiological analysis was conducted on the AIDS epidemic data in Dechang county. Results From 1995 when the first case of HIV infection was confirmed to August 2011, a total of 262 cases of HIV/AIDS were reported with a total infection rate of 18. 95/100 000. From 2008 to 2010, the reported infections showed rapid growth. The annual infection rate of male was 26. 57/100 000 and female 11. 05/100 000 with a significant difference (Χ2 =43. 94, P = 0. 002). The ratio of male to female infections was 2. 49 : 1. Most of the AIDS cases were young adults aged between 20 and 45 years and old people aged between 55 and 75 years old who occupied 93. 49% of the total infectious cases. The number of reported AIDS cases of farmer and unknown occupations accounted for 82. 4% and there was an obvious occupations peak. Most patients in the county were infected by heterosexual sexual contact and injecting drugs, which accounted for 64. 89% and 32. 82% of the total respectively. The AIDS cases of 29 infected couples and 3 mother-to-child transmission. Conclusions AIDS epidemic growth is rapid in Dechang county with the situation being quite grim. We should enhance the AIDS prevention propaganda in the publicity, to raise national awareness of AIDS prevention. The related departments should cooperate to regulate the illegal entertainment and strengthen the management of migrant workers. The counseling and testing network should be improved so as to raise the detection rate and control the spread of AIDS.%目的 掌握德昌县艾滋病流行趋势,为制订防控措施提供准确依据.方法 利用描述流行病学方法分析德昌县1995年以来艾滋病疫情资料.结果 自1995年德昌县报告首例艾滋病感染者至2011年8月共报告艾滋病感染者/患者262

  10. Immune Gamma Globulin Therapeutic Indications in Immune Deficiency and Autoimmunity. (United States)

    Yang, Luanna; Wu, Eveline Y; Tarrant, Teresa K


    Immune gamma globulin (IgG) has a long history in the treatment of both primary immune deficiency and autoimmune disorders. Disease indications continue to expand and new-generation products increase the versatility of delivery. This review encompasses a historical perspective as well as current and future implications of human immune globulin for the treatment of immune-mediated illness.

  11. Behcet's disease in acquired immune deficiency syndrome

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    Beenish Siddiqui


    Full Text Available HIV/AIDS patients often present with orogenital ulcers. In the immunocompromised patient diagnosis of these ulcers pose a challenge, as there is a myriad of etiologies. We present a case of an HIV/AIDS patient with recurrent orogenital aphthosis that was confirmed to have concomitant diagnosis of Behcet's disease. Proper awareness of the causes of these ulcers is essential for prompt and effective treatment. While rare causes may be at the bottom of a differential list in an immunocompetent host, when HIV/AIDS is involved these rare causes often percolate to the top.

  12. [Clinical features and characteristics of community-acquired pneumonia associated with iron deficiency anemia in children of pre-school age]. (United States)

    Smiian, O I; Romanova, T O; Vasylyshyn, Kh I; Bynda, T P; Popov, S V; Vasyl'ieva, O H; Lypovs'ka, V V


    The most common clinical signs of community-acquired pneumonia associated with iron deficiency anemia in children of pre-preschool age are defined. Indicators of immunity cellular link in children with community-acquired pneumonia are studied. It is established that acute illness is characterized by disturbances in cellular immunity that are more expressed in patients with concomitant iron deficiency anemia.

  13. Antibiotic prophylaxis in primary immune deficiency disorders. (United States)

    Kuruvilla, Merin; de la Morena, Maria Teresa


    Long-term prophylactic antibiotics are being widely implemented as primary or adjunctive therapy in primary immune deficiencies. This practice has transformed clinical outcomes in the setting of chronic granulomatous disease, complement deficiencies, Mendelian susceptibility to mycobacterial disease, Wiskott-Aldrich syndrome, hyper-IgE syndrome, Toll signaling defects, and prevented Pneumocystis in patients with T-cell deficiencies. Yet, controlled trials are few in the context of primary antibody deficiency syndromes, and most of this practice has been extrapolated from data in patients who are immune competent and with recurrent acute otitis media, chronic rhinosinusitis, cystic fibrosis, and bronchiectasis. The paucity of guidelines on the subject is reflected in recent surveys among practicing immunologists that highlight differences of habit regarding this treatment. Such discrepancies reinforce the lack of standard protocols on the subject. This review will provide evidence for the use of antibiotic prophylaxis in various primary immune deficiency populations, especially highlighting the role antibiotic prophylaxis in primary antibody deficiency syndromes. We also discussed the relationship of long-term antibiotic use and the prevalence of resistant pathogens. Overall, examination of available data on the use of prophylactic antibiotics in antibody deficiency syndromes merit future investigation in well-designed multicenter prospective trials because this population has few other management options.

  14. 遵义市红花岗区艾滋病疫情分析%An Analysis on Epidemic Situation of Acquired Immune Deficiency Syndrome in Honghuagang District in Zunyi City and Adjustment of Its Prevention and Cure Strategies

    Institute of Scientific and Technical Information of China (English)

    明杰; 卢太书


    Objective: To investigate the epidemic status of acquired immune deficiency syndrome ( AIDS) in Honghuagang district, analyze the affecting factors, and so as to adjust prevention and cure strategies effectively. Methods: AIDS monitoring was carried out in high risk crowds such as drug users, sex workers, gay men, pregnant women and prisoners. Ethology data were analyzed. Prevention and cure effects were evaluated. Results: Since 2003 that the demonstration area of integrated AIDS prevention and control began to work, effectiveness of AIDS prevention and control has become remarkable in this region, showing as establishment of an effective working system, and gradual strengthening of intervention to behavior of high-risk groups. Conclusions: AIDS integrated prevention and control measures in Honghuagang district are suitable. The effects are significant. Reinforcing AIDS prevention and cure work among sex workers and gay men should be emphasized in adjusting of prevention and control strategies.%目的:了解艾滋病疫情现状,分析艾滋病流行因素,为有效调整艾滋病防治策略提供依据.方法:对吸毒人群、性服务者、男-男性行为人群、孕妇及在押人员等高危人群或重点人群作HIV监测,依据1998-2009年的调查资料和监测数据分析其行为学资料,评价防治效果.结果:1998-2003年报告5例艾滋病感染者,1998-2009年共感染123例,2009年艾滋病感染者52例;各类调查人群对艾滋病知晓率提高,性服务人群安全套使用率87.1%(2008年),2009年美沙酮治疗人数1 411人.结论:红花岗区艾滋病综合防治措施效果显著.

  15. Primary Immune Deficiency Treatment Consortium (PIDTC) report

    NARCIS (Netherlands)

    L.M. Griffith (Linda); M. Cowan (Morton); L.D. Notarangelo (Luigi Daniele); R. Kohn (Robert); J. Puck (Jennifer); S.-Y. Pai (Sung-Yun); B. Ballard (Barbara); S.C. Bauer (Sarah); J. Bleesing (Jack); M. Boyle (Marcia); R.W. Brower (Ronald); R.H. Buckley (Rebecca); M. van der Burg (Mirjam); L.M. Burroughs (Lauri); F. Candotti (Fabio); A. Cant (Andrew); T. Chatila (Talal); C. Cunningham-Rundles (Charlotte); M.C. Dinauer (Mary); J. Dvorak (Jennie); A. Filipovich (Alexandra); L.A. Fleisher (Lee); H.B. Gaspar (Bobby); T. Gungor (Tayfun); E. Haddad (Elie); E. Hovermale (Emily); F. Huang (Faith); A. Hurley (Alan); M. Hurley (Mary); S.K. Iyengar (Sudha); E.M. Kang (Elizabeth); B.R. Logan (Brent); J.R. Long-Boyle (Janel); H. Malech (Harry); S.A. McGhee (Sean); S. Modell (Sieglinde); S. Modell (Sieglinde); H.D. Ochs (Hans); R.J. O'Reilly (Richard); R. Parkman (Robertson); D. Rawlings (D.); J.M. Routes (John); P. Shearer (P.); T.N. Small (Trudy); H. Smith (H.); K.E. Sullivan (Kathleen); P. Szabolcs (Paul); A.J. Thrasher (Adrian); D. Torgerson; P. Veys (Paul); K. Weinberg (Kenneth); J.C. Zuniga-Pflucker (Juan Carlos)


    textabstractThe Primary Immune Deficiency Treatment Consortium (PIDTC) is a network of 33 centers in North America that study the treatment of rare and severe primary immunodeficiency diseases. Current protocols address the natural history of patients treated for severe combined immunodeficiency (SC

  16. Epidemiological characteristics of acquired immune deficiency syndrome in Shandong Province from 1992 to 2011%山东省1992年至2011年艾滋病流行特征分析

    Institute of Scientific and Technical Information of China (English)

    张娜; 王国永; 杨兴光; 苏生利; 康殿民; 陶小润


    目的 分析山东省AIDS的流行特征,为其预防控制提供依据.方法 对1992年至2011年山东省报告的HIV感染者和AIDS患者(HIV/AIDS)的流行病学资料进行统计分析.结果 1992年至2011年累计报告HIV/AIDS患者4313例;年均报告发病率为2.39/100万,历年报告发病率呈上升趋势;报告发病率居前5位的城市是济南市、青岛市、淄博市、潍坊市和威海市,分别为5.72/100万、4.39/100万、3.29/100万、3.10/100万和3.02/100万;报告男性年均发病率为3.74/100万,高于女性的1.39/100万,差异有统计学意义(x2=743.96,P<0.05);20岁年龄组发病率最高,为5.56/100万;57.18%为性传播感染,同性传播感染数占当年报告病例数的构成比由2004年的1.82%上升到2011年的37.49%.结论 山东省AIDS疫情形势严峻,地区分布不平衡,性传播为主要传播途径,同性传播增加明显.%Objective To investigate the epidemiological characteristics of acquired immune deficiency syndrome (AIDS) in Shandong Province,and to provide scientific evidence for formulating prevention and control strategy and carrying out effective measures.Methods Epidemiological data of reported human immunodeficiency virus (HIV) infection and AIDS cases (HIV/AIDS) in Shandong Province from 1992 to 2011 were analyzed.Results A total of 4313 cases of HIV/AIDS were confirmed and reported by the end of 2011,with an average incidence of 2.39 parts per million (ppm) annually.An upward trend was showed for annual reported incidence.The top 5 cities of incidence were Ji'nan,Qingdao,Zibo,Weifang and Weihai,which were 5.72 ppm,4.39 ppm,3.29 ppm,3.10 ppm and 3.02 ppm,respectively.The average annual reported incidence was 3.74 ppm for male,which was significantly higher than that for female (1.39 ppm; x2 =743.96,P<0.05).The reported incidence was highest among 20-29 age group (5.56 ppm),with 57.18% of homosexual transmission.The proportion of homosexual transmission in annual reported cases

  17. Ophthalmic manifestations in acquired immune deficiency syndrome patients with cryptococcal meningitis%获得性免疫缺陷综合征合并隐球菌性脑膜炎的眼部病变特征分析

    Institute of Scientific and Technical Information of China (English)

    毛菲菲; 孙挥宇; 李丹


    Objective Analysis ophthalmic manifestations in acquired immune deficiency syndrome(AIDS) patients with cryptococcal meningitis.Methods Retrospective study.Forty AIDS patients (including 32 men and 8 women) with cryptococcal meningitis were studied.The age of the patients varied from 11 to 67 years,average on (38 ± 12) years (mean ± standard deviation).All the patients underwent detailed ocular examinations including corrected visual acuity,eye movement,intraocular pressure,slit lamp microscope,indirect ophthalmoscope and color fundus photography.The CD4+ T cell count was evaluated and Lumbar puncture was done to examine the cerebral spinal fluid(CSF).Eighteen patients were followed up for a period between 2weeks to 4years.Four patients died during hospitalization.The remaining 18 patients failed to be followed up due to moving away.Results Binocular diplopia were present in 3 patients.It showed Binocular or monocular abducens nerve palsy.Papilledema were found in 37 eyes of 19 cases.One person had unilateral papilledema.Among 19 cases,24 eyes of 12 cases were accompanied with peripapillary hemorrhages and 7 cases of 13 eyes without peripapillary hemorrhages.Optic atrophy occurs in 6 cases of 12 eyes and multifocal choroiditis in 2 cases of 4 eyes.Twenty-seven eyes of 14 patients had normal fundus or cytomegalovirus retinitis(CMVR) only.Conclusions AIDS patients with cryptococcal meningitis merger may be accompanied by a variety of eye complications.Papilledema are the most common manifestations.%目的 探讨获得性免疫缺陷综合征(AIDS)合并隐球菌性脑膜炎患者眼部表现.方法 回顾性研究.观察40例AIDS合并隐球菌性脑膜炎患者眼部病变特点,其中男性32例,女性8例,男女比例4∶1,年龄11~67岁,平均年龄(38±12)岁,对所有患者均行视力、眼球运动、眼压、裂隙灯显微镜、散瞳间接检眼镜眼底检查及眼底彩色照相.所有患者进行CD4+T淋巴细胞的检测,

  18. FLASH形式在中学生预防艾滋病教育活动中的作用%Effects of FLASH on health education of acquired immune deficiency syndrome in middle school students

    Institute of Scientific and Technical Information of China (English)

    韩娟; 赵丽娜; 时俊新; 杨森焙; 宋阎超; 陈宏平


    目的:探讨FLASH形式在预防艾滋病教育活动中的作用,了解中学生对预防艾滋病的相关知识和态度.方法:在湖北省大冶市和宜昌市秭归县的4所中学采用分层整群抽样的方法抽取在校学生共1 211人,用自制的中学生预防艾滋病生活技能教育的FLASH片进行专题教育,并对其教育前后的预防艾滋病相关知识、态度进行问卷调查.结果:调查对象对艾滋病流行趋势、艾滋病与青少年的关系以及对艾滋病主要传播途径认识,教育后正确回答率提高至80%以上,而对艾滋病的概念以及蚊虫叮咬、同性恋、纹身等认识提高不足80%.结论:中学生仍需加强预防艾滋病知识的教育,教育形式应多样化.FLASH形式生动活泼,教育效果显著,但因其稍纵即逝,会影响教育效果,可作为辅助教材.%Objective: To explore the effects of FLASH on health education of acquired immune deficiency syndrome (AIDS), un-derstand the related knowledge and attitude to AIDS prevention in middle school students. Methods: 1 211 students were selected from 4 middle school by stratified cluster sampling, then health education of AIDS prevention was carried out in the form of self-designed FLASH,the related knowledge and attitude to AIDS prevention of middle school students before and after health education were observed. Results:The accuracy rates of prevailing trend of AIDS, the relationship between AIDS and adolescents, major spread approaches of AIDS after heslth education were increased to over 80%, but the others improved less than 80% such as the meaning of AIDS, mosquito and insect bite, ho-mesexuallty and tattoo and so on. Conclusion: The middle school students still need to strengthen AIDS preventive education which shouldbe multiple modes and be enjoyed by them. FLASH is a lifelike and brisk mode enjoyed by the students which education effect is marked,but it may be an assistant teaching material because it is easy to go in

  19. 艾滋病合并机会性感染的临床特征和诊疗分析%Analysis on Clinical Features of Acquired Immune Deficiency Syndrome Combined with Opportunistic Infections and Its Diagnosis and Treatment

    Institute of Scientific and Technical Information of China (English)

    赵贺红; 冯萍; 肖贵宝; 徐开菊; 杨志勇


    目的 探讨艾滋病患者合并机会性感染的临床特征并评价其治疗效果.方法 回顾分析2003年-2009年53例确诊为艾滋病患者的临床资料,对患者合并机会性感染的临床特征,包括发生机会性感染的时间、发生机会性感染时CD+T细胞计数、起病急缓、严重程度等,进行观察和分析,并给予国家推荐的标准治疗方案进行治疗,通过临床症状、病毒载量、CD+T细胞计数、影像学监测进行疗效分析,随访时间为初治至出院后6年.结果 53例艾滋病患者均为重症感染,41例为混合感染,其中2个以上部位感染者为36例(67.9%),2种以上病原体感染者为28例(52.8%),3种以上病原体感染者13例(24.5%).最常见的机会性感染为结核35.8%(19/53);其次为卡氏肺孢子菌肺炎30.2%(16/53);败血症20.8%(11/53),此外,尚有隐球菌感染15.1%(8/53)、弓形虫感染3.8%(2/53)、带状疱疹病毒感染7.5%(4/53)、念珠菌感染17.0%(9/53)、巨细胞病毒感染7.5%(4/53)、合并乙肝11.3%(6/53)、丙肝3.8%(2/53).机会性感染治疗有效率为77.4%(41/53),病死率为22.6%(12/53),其中隐球菌脑膜炎或混合感染者病死率最高.结论艾滋病患者在CD+T细胞计数<350/mm3时各种机会感染明显升高,且随着CD+4T细胞计数的下降呈增高趋势,艾滋病合并机会性感染最常见的是结核,其次卡氏肺孢子菌肺炎;合并结核的治疗效果较好,合并隐球菌脑病的病死率最高.早期启动高效抗逆转录病毒治疗效果好.%Objective To investigate the clinical characteristics of acquired immune deficiency syndrome (AIDS) combined with opportunistic infections and its treatment. Methods We retrospectively analyzed the clinical data of 53 patients diagnosed to have AIDS in our hospital between 2003 and 2009. The clinical features (such as time of the onset of opportunistic infections, CD4+ T cells value at the onset, severity of the infection, etc

  20. 艾滋病合并肠系膜淋巴结结核11例临床分析%Diagnosis and treatment of 11 patients with acquired immune deficiency syndrome complicated with tuberculosis of mesenteric lymph nodes

    Institute of Scientific and Technical Information of China (English)

    刘艳; 余卫业; 陆普选; 刘映霞; 姚思敏; 蔡雄茂; 薛海珍


    Objective To study the clinical features of acquired immune deficiency syndrome (AIDS)complicated with tuberculosis of mesenteric lymph nodes.Methods Cases(n=153)with AIDS complicated with tuberculosis hospitalized in this hospital from September 1999 to December 2008 were retrospectively analyzed.Mesenteric lymph node tuberculosis was found in 11 cases,including 7 males and 4 females.One patient was 8 years old,and the other 10 were over 22 years(ranging from 8 to 55 years).Results In patients with AIDS complicated with tuberculosis,7%(11/158)had tuberculosis of the mesenteric lymph nodes.The CD_4~+ cell count was less than 50 ×10~6 cells/L in 8 cases,and(50-100)×10~6 cells/L in 3 cases.The symptoms included fever(11/11),abdominal pain(11/11),abdominal distension(11/11),night sweat(7/11),weisgt loss(10/11),diarrhea(7/11),anemia(5/11),abdominal mass(3/11),and ascites(1/11).Abdominal ultrasound showed multiple enlarged mesenteric lymph nodes in all of the 11 cases,and abdominal CT scanning presented typical enhanced ring shadows.Biopsy of mesenteric lymph nodes was obtained from 2 cases,and both revealed tuberculoma,caseoua necrosis.Longerhan cell infiltration,and positive stain for fast anti-acid bacilli.Enlarged mesenteric lymph nodes became smaller and disappeared after treatment with antituberculous drugs for 6 months and highly active antiretroviral therapy(HAART)for 5 months in all the 11 patients.Conclusions There were no specific clinical manifestations in AIDS patients with tuberculosis of mesenteric lymph nodes.However,AIDS patients with CD_4~+ cell count less than 50×10~6 cells/L miight be more prone to developing tuberculosis of the mesenteric lymph nodes.Abdominal CT scanning with typical strengthened ring shadow is suggestive of the diagnosis.Anti-tuberculous therapy combined with HAART is recommended for the treatment of patients with suspected tuberculosis.%目的 探讨艾滋病合并肠系膜淋巴结结核的临床特点.方法 回顾性

  1. Prophylactic immunoglobulin therapy in secondary immune deficiency

    DEFF Research Database (Denmark)

    Agostini, Carlo; Blau, Igor-Wolfgang; Kimby, Eva


    INTRODUCTION: In primary immunodeficiency (PID), immunoglobulin replacement therapy (IgRT) for infection prevention is well-established and supported by a wealth of clinical data. On the contrary, very little evidence-based data is available on the challenges surrounding the use of Ig......RT in secondary immune deficiencies (SID), and most published guidelines are mere extrapolations from the experience in PID. AREAS COVERED: In this article, four European experts provide their consolidated opinion on open questions surrounding the prophylactic use of IgRT in SID, based on their clinical...

  2. Heat Shock Proteins: Stimulators of Innate and Acquired Immunity

    Directory of Open Access Journals (Sweden)

    Camilo A. Colaco


    Full Text Available Adjuvants were reintroduced into modern immunology as the dirty little secret of immunologists by Janeway and thus began the molecular definition of innate immunity. It is now clear that the binding of pathogen-associated molecular patterns (PAMPs by pattern recognition receptors (PRRs on antigen presenting cells (APCs activates the innate immune response and provides the host with a rapid mechanism for detecting infection by pathogens and initiates adaptive immunity. Ironically, in addition to advancing the basic science of immunology, Janeway’s revelation on induction of the adaptive system has also spurred an era of rational vaccine design that exploits PRRs. Thus, defined PAMPs that bind to known PRRs are being specifically coupled to antigens to improve their immunogenicity. However, while PAMPs efficiently activate the innate immune response, they do not mediate the capture of antigen that is required to elicit the specific responses of the acquired immune system. Heat shock proteins (HSPs are molecular chaperones that are found complexed to client polypeptides and have been studied as potential cancer vaccines. In addition to binding PRRs and activating the innate immune response, HSPs have been shown to both induce the maturation of APCs and provide chaperoned polypeptides for specific triggering of the acquired immune response.

  3. Acquired immune heterogeneity and its sources in human helminth infection. (United States)

    Bourke, C D; Maizels, R M; Mutapi, F


    Similarities in the immunobiology of different parasitic worm infections indicate that co-evolution of humans and helminths has shaped a common anti-helminth immune response. However, recent in vitro and immuno-epidemiological studies highlight fundamental differences and plasticity within host-helminth interactions. The 'trade-off' between immunity and immunopathology inherent in host immune responses occurs on a background of genetic polymorphism, variable exposure patterns and infection history. For the parasite, variation in life-cycle and antigen expression can influence the effector responses directed against them. This is particularly apparent when comparing gastrointestinal and tissue-dwelling helminths. Furthermore, insights into the impact of anti-helminthic treatment and co-infection on acquired immunity suggest that immune heterogeneity arises not from hosts and parasites in isolation, but also from the environment in which immune responses develop. Large-scale differences observed in the epidemiology of human helminthiases are a product of complex host-parasite-environment interactions which, given potential for exposure to parasite antigens in utero, can arise even before a parasite interacts with its human host. This review summarizes key differences identified in human acquired immune responses to nematode and trematode infections of public health importance and explores the factors contributing to these variations.

  4. 1995-2014年河南省周口市 AIDS 流行特征分析%Epidemiological Characteristics of Acquired Immune Deficiency Syndrome in Zhoukou, He′nan Province From 1995 to 2014

    Institute of Scientific and Technical Information of China (English)



    Objective To investigate the epidemiological characteristics of acquired immune deficiency syndrome (AIDS) in Zhoukou and to provide scientific evidence for the formulation of prevention and control strategies .Methods We collected the data of HIV-infected patients and AIDS patients in Zhoukou from the Information System for AIDS Prevention and Control of China′s Information System for Disease Prevention and Control , with a time range of 1995 to 2014.Results From 1995 to 2014, the total reported number of HIV -infected people and AIDS patients in Zhoukou was 9 187, among which 8 215 (89.42%) were AIDS patents and 3 254 (35.42%) died.After the exclusion of deceased patients , there were 5 933 HIV-infected patients and AIDS patients surviving , accounted for 67.37/105 in all permanent residents of Zhoukou and of which 5 164 were AIDS patients.From 1995 to 2003, with the HIV/AIDS monitoring strengthened , the detected HIV -infected and AIDS patients had been increasing year by year; 2004 witnessed more reported cases than other years , for HIV census was carried out on FPDs this year; from 2005 to 2012, the number of reported cases was in a decreasing trend; from 2013 to 2014, the disease showed a slight rebound .From 2006, death cases began to decrease year by year .HIV-infected patients and AIDS patients of Zhoukou distributed in 204 villages or towns in 10 districts or counties, and significant differences (χ2 =1 181.0, P<0.01) existed among the 10 counties or districts in the proportion of surviving cases in permanent residents .There were five first-class AIDS counties and five second -class AIDS counties.Among HIV-infected patients and AIDS patients , the number of male patients was more than female patients , with a ratio of 1.23∶1; the patients were aged from 2 to 82, with a majority ranging from 30 to 60, accounting for 83.37% (7 659/9 187).Ratio of survival cases in permanent residents varied significantly among the groups of different genders, ages


    Directory of Open Access Journals (Sweden)

    Helen eChapel


    Full Text Available Primary Immune Deficiencies (PIDs are a growing group of over 230 different disorders caused by ineffective, absent or an increasing number of gain of function mutations in immune components (mainly cells and proteins. Once recognised, these rare disorders are treatable and in some cases curable. Otherwise untreated PIDs are often chronic, serious or even fatal. The diagnosis of PIDs can be difficult due to lack of awareness and facilities for diagnosis, and management of PIDs is complex. This document was prepared by a worldwide multi-disciplinary team of specialists; it aims to set out comprehensive principles of care for PIDs. These include the role of specialised centres, the importance of registries, the need for multinational research, the role of patient organisations, management and treatment options, the requirement for sustained access to all treatments including immunoglobulin (Ig therapies and HSCT, important considerations for developing countries and suggestions for implementation. A range of healthcare policies and services have to be put into place by government agencies and healthcare providers, to ensure that PID patients world-wide have access to appropriate and sustainable medical and support services.

  6. Primary Immune Deficiencies – Principles of Care (United States)

    Chapel, Helen; Prevot, Johan; Gaspar, Hubert Bobby; Español, Teresa; Bonilla, Francisco A.; Solis, Leire; Drabwell, Josina


    Primary immune deficiencies (PIDs) are a growing group of over 230 different disorders caused by ineffective, absent or an increasing number of gain of function mutations in immune components, mainly cells and proteins. Once recognized, these rare disorders are treatable and in some cases curable. Otherwise untreated PIDs are often chronic, serious, or even fatal. The diagnosis of PIDs can be difficult due to lack of awareness or facilities for diagnosis, and management of PIDs is complex. This document was prepared by a worldwide multi-disciplinary team of specialists; it aims to set out comprehensive principles of care for PIDs. These include the role of specialized centers, the importance of registries, the need for multinational research, the role of patient organizations, management and treatment options, the requirement for sustained access to all treatments including immunoglobulin therapies and hematopoietic stem cell transplantation, important considerations for developing countries and suggestions for implementation. A range of healthcare policies and services have to be put into place by government agencies and healthcare providers, to ensure that PID patients worldwide have access to appropriate and sustainable medical and support services. PMID:25566243

  7. Non-genomic and Immune Evolution of Melanoma Acquiring MAPKi Resistance (United States)

    Hugo, Willy; Shi, Hubing; Sun, Lu; Piva, Marco; Song, ChunYing; Kong, Xiangju; Moriceau, Gatien; Hong, Aayoung; Dahlman, Kimberly B.; Johnson, Douglas B.; Sosman, Jeffrey A.; Ribas, Antoni; Lo, Roger S.


    SUMMARY Clinically acquired resistance to MAPK inhibitor (MAPKi) therapies for melanoma cannot be fully explained by genomic mechanisms and may be accompanied by co-evolution of intra-tumoral immunity. We sought to discover non-genomic mechanisms of acquired resistance and dynamic immune compositions by a comparative, transcriptomic-methylomic analysis of patient-matched melanoma tumors biopsied before therapy and during disease progression. Transcriptomic alterations across resistant tumors were highly recurrent, in contrast to mutations, and were frequently correlated with differential methylation of tumor cell-intrinsic CpG sites. We identified in the tumor cell compartment supra-physiologic c-MET up-expression, infra-physiologic LEF1 down-expression, and YAP1 signature enrichment as drivers of acquired resistance. Importantly, high intra-tumoral cytolytic T-cell inflammation prior to MAPKi therapy preceded CD8 T-cell deficiency/exhaustion and loss of antigen-presentation in half of disease-progressive melanomas, suggesting cross-resistance to salvage anti-PD-1/PD-L1 immunotherapy. Thus, melanoma acquires MAPKi-resistance with highly dynamic and recurrent non-genomic alterations and co-evolving intra-tumoral immunity. PMID:26359985

  8. The role of complement in the acquired immune response

    DEFF Research Database (Denmark)

    Nielsen, C H; Fischer, E M; Leslie, R G


    Studies over the past three decades have clearly established a central role for complement in the promotion of a humoral immune response. The primary function of complement, in this regard, is to opsonize antigen or immune complexes for uptake by complement receptor type 2 (CR2, CD21) expressed...... on B cells, follicular dendritic cells (FDC) and some T cells. A variety of mechanisms appear to be involved in complement-mediated promotion of the humoral response. These include: enhancement of antigen (Ag) uptake and processing by both Ag-specific and non-specific B cells for presentation...... participate in intercellular bridging. Finally, current studies suggest that CR2 may also play a role in the determination of B-cell tolerance towards self-antigens and thereby hold the key to the previously observed correlation between deficiencies of the early complement components and autoimmune disease....

  9. Acquired and natural immunity to gonococcal infection in chimpanzees. (United States)

    Kraus, S J; Brown, W J; Arko, R J


    Despite the fact that gonorrhea is our most common reportable infectious disease, little is known about natural and acquired resistance to Neisseria gonorrhoeae. With the chimpanzee model, which mimics human gonococcal infection in signs, symptoms, and host response, a natural resistance to gonococcal challenge was found. One aspect of this natural resistance became evident when the cervix and oral pharynx resisted more gonococci than the urethra. Natural resistance was also shown when environmental factors were found to influence resistance to gonococcal pharyngitis. In addition to natural resistance a postinfection-acquired immunity to the gonococcus was demonstrated. Following gonococcal pharyngitis, this anatomical location successfully resisted more gonococci than were initially resisted. Similarly, more gonococci were successfully resisted in rechallenging the urethra. These findings are related to the clinic situation and suggest possible new approaches to gonorrhea control. PMID:805797

  10. Primary Immune Deficiency Treatment Consortium (PIDTC) report. (United States)

    Griffith, Linda M; Cowan, Morton J; Notarangelo, Luigi D; Kohn, Donald B; Puck, Jennifer M; Pai, Sung-Yun; Ballard, Barbara; Bauer, Sarah C; Bleesing, Jack J H; Boyle, Marcia; Brower, Amy; Buckley, Rebecca H; van der Burg, Mirjam; Burroughs, Lauri M; Candotti, Fabio; Cant, Andrew J; Chatila, Talal; Cunningham-Rundles, Charlotte; Dinauer, Mary C; Dvorak, Christopher C; Filipovich, Alexandra H; Fleisher, Thomas A; Bobby Gaspar, Hubert; Gungor, Tayfun; Haddad, Elie; Hovermale, Emily; Huang, Faith; Hurley, Alan; Hurley, Mary; Iyengar, Sumathi; Kang, Elizabeth M; Logan, Brent R; Long-Boyle, Janel R; Malech, Harry L; McGhee, Sean A; Modell, Fred; Modell, Vicki; Ochs, Hans D; O'Reilly, Richard J; Parkman, Robertson; Rawlings, David J; Routes, John M; Shearer, William T; Small, Trudy N; Smith, Heather; Sullivan, Kathleen E; Szabolcs, Paul; Thrasher, Adrian; Torgerson, Troy R; Veys, Paul; Weinberg, Kenneth; Zuniga-Pflucker, Juan Carlos


    The Primary Immune Deficiency Treatment Consortium (PIDTC) is a network of 33 centers in North America that study the treatment of rare and severe primary immunodeficiency diseases. Current protocols address the natural history of patients treated for severe combined immunodeficiency (SCID), Wiskott-Aldrich syndrome, and chronic granulomatous disease through retrospective, prospective, and cross-sectional studies. The PIDTC additionally seeks to encourage training of junior investigators, establish partnerships with European and other International colleagues, work with patient advocacy groups to promote community awareness, and conduct pilot demonstration projects. Future goals include the conduct of prospective treatment studies to determine optimal therapies for primary immunodeficiency diseases. To date, the PIDTC has funded 2 pilot projects: newborn screening for SCID in Navajo Native Americans and B-cell reconstitution in patients with SCID after hematopoietic stem cell transplantation. Ten junior investigators have received grant awards. The PIDTC Annual Scientific Workshop has brought together consortium members, outside speakers, patient advocacy groups, and young investigators and trainees to report progress of the protocols and discuss common interests and goals, including new scientific developments and future directions of clinical research. Here we report the progress of the PIDTC to date, highlights of the first 2 PIDTC workshops, and consideration of future consortium objectives.

  11. Modulation of host immunity and reproduction by horizontally acquired Wolbachia. (United States)

    Pigeault, Romain; Braquart-Varnier, Christine; Marcadé, Isabelle; Mappa, Gaëtan; Mottin, Elmina; Sicard, Mathieu


    The Wolbachia are symbiotic bacteria vertically transmitted from one host generation to another. However, a growing amount of data shows that horizontal transfers of Wolbachia also frequently occur within and between host species. The consequences of the arrival of new symbionts on host physiology can be studied by their experimental introduction in asymbiotic hosts. After experimental transfers of the eight major isopod Wolbachia strains in the isopod Porcellio dilatatus only two of them (wCon and wDil) were found to (1) have no pathogenic effect on the host and (2) be able to pass vertically to the host offspring. In the present work, we studied the influence of these two strains, able to complete an horizontal transfer, on immunity and reproduction of P. dilatatus at two stages of the transfer: (1) in recipient hosts that encounter the symbionts: to test the influence of symbiont when acquired during host life and (2) in vertically infected offspring: to test the influence of a symbiotic interaction occurring all lifelong. The impact of Wolbachia varied depending on the stage: there were clearer effects in vertically infected individuals than in those that acquired the symbionts during their lives. Moreover, the two Wolbachia strains showed contrasted effects: the strain wCon tended to reduce the reproductive investment but to maintain or increase immune parameters whilst wDil had positive effects on reproductive investment but decreased the investment in some immune parameters. These results suggest that horizontally acquisition of Wolbachia can influence the balance between host immune and reproductive traits.

  12. Relationship between Acquired Deficiency of Vitamin K-dependent Clotting Factors And Hemorrhage

    Institute of Scientific and Technical Information of China (English)

    杨锐; 张小平; 魏文宁; 洪梅; 杨焰; 胡豫


    This study examined the changes of activities of vitamin K-dependent clotting factors(VKDCF) under various pathological conditions and explored the relationship between acquired deficiency of VKDCFs and hemorrhage.Clinical data of 35 patients who were diagnosed as having acquired deficiency of VKDCF were retrospectively analyzed.Coagulation factors involved in the intrinsic and extrinsic pathways were detected in these patients and 41 control subjects.The results showed that the average activities of VKDCFs...

  13. Children with congenital deficiencies or acquired amputations of the lower limbs : functional aspects

    NARCIS (Netherlands)

    Boonstra, AM; Rijnders, LJM; Groothoff, J W; Eisma, W H


    The aim of the study was to evaluate the use of prostheses, some secondary complications and functional aspects among children who had a congenital leg deficiency or an acquired leg amputation. Rehabilitation physicians were asked to refer children, aged 1-18 years, with a leg deficiency or amputati

  14. Investigation on HIV/AIDS coinfected with HBV/HCV in acquired immune deficiency syndrome area%某艾滋病治疗示范区HIV/AIDS患者合并HBV/HCV感染调查

    Institute of Scientific and Technical Information of China (English)

    梁红霞; 张倩; 余祖江; 钮正春; 李志勤; 潘延凤; 赵清霞; 李建生; 何云


    Objective To investigate the incidence of HIV/AIDS coinfected with HBV and/or HCV in some country of Henan province and the clinical features. Methods Serum samples were obtained from 187 HIV - infected patients who transmitted by paid blood donation. ELISA was used to detect HBV erologic markers( HbsAg, Anti - HBs, HbeAg, anti - Hbe and anti - HBc) and HCV antibody. Flow Cytometry were used to detect CD4 + T cell count. Nested PCR was used to amplify surface protein region of HBV DNA. Results Among 187 HIV - infected patients, 9 patients (4. 81% )were HBsAg positive, 178 patients (95. 19% ) HBsAg negative; 143 patients (76. 47% ) anti - HCV positive, 44 patients( 23. 53% ) anti - HCV negative; 6 patients HIV -1, HBV and HCV triple infection. Of the 143 anti - HCV positive patients, 42 patients (29. 37% ) were coinfected with occult HBV infection, in the 44 anti - HCV negative patients, 11 patients (25. 00% ) were coinfected with occult HBV infection, the disparity had no statistical significance (P > 0. 05 ). The positive patients of HbsAg, anti - HBs, isolated anti - HBc andthe CD4 + cell counts were undifferentiated between anti - HCV positive patients and anti - HCV negative patients ( P > 0. 05 ) . Conclusions In the HIV - infected patients who transmitted by paid blood donation, the HBsAg positive rate is lower than common population, and the HCV infection rate is higher than common population; It is found that occult HBV infection did occurs in HIV - infected patients. HBV DNA testing is necessary in the HIV - infected patients who are HBsAg negative; The occult HBV infection rate of HIV - infected patients who are coinfected with HCV isrit increase.%目的 探讨人免疫缺陷病毒-1 (HIV -1) /AIDS患者合并乙型肝炎病毒(HBV)/丙型肝炎病毒(HCV)感染情况及发病特点.方法 分析国家"十一五重大专项"课题中河南某获得性免疫缺陷综合征(Acquired immunodeficiency syndrome,AIDS)示范区中187

  15. Acquired Immune Deficiency Syndrome, Risky Sexual Behavior and Abortion

    Directory of Open Access Journals (Sweden)

    Marshall H. Medoff


    Full Text Available Problem statement: incidence of abortion in the United States has steadily declined since 1990. The question is why? Approach: This study, using multiple linear regression, examines whether women’s unprotected sexual activity is deterred by the risk of contracting AIDS as reflected in decreased abortion rates. Results: The empirical evidence consistently finds that the prevalence of AIDS reduces the risky (unprotected sexual activity of women of childbearing ages 15-44 as reflected in their abortion rates. The empirical results remain robust for the abortion rates of teens ages 15-17 and for teens ages 15-19. Conclusion: The empirical results suggest that the behavioral modification induced by the prevalence of AIDS accounted for 21% of the decrease in abortion rates over the time period 1992-2005.

  16. Analysis of 7 Misdiagnosed Cases of Acquired Immune Deficiency Syndrome with Neurological Symptoms at Onset%以神经系统症状首发的获得性免疫缺陷综合征七例误诊原因分析

    Institute of Scientific and Technical Information of China (English)

    叶茂斌; 陈研林; 叶飞; 张临洪


    目的:探讨以神经系统症状首发的获得性免疫缺陷综合征( acquired immune deficiency syndrome, AIDS)的发病机制、误诊原因及防范措施。方法回顾性分析我院2007年1月—2013年12月误诊的以神经系统症状首发的AIDS 7例的临床资料。结果本组6例以头痛、头晕就诊,伴记忆力减退2例,伴腹胀、厌食1例;1例以左上肢麻木就诊。均否认毒品接触史、冶游史及输血史。7例首诊考虑后循环缺血5例,躯体化障碍和脑梗死各1例,给予相应治疗,症状均无缓解,进一步行人类免疫缺陷病毒( human immunodeficiency virus, HIV)抗体定量检查及蛋白印迹确认试验阳性,确诊AIDS,转疾病预防控制中心治疗。结论以神经系统症状首发的AIDS易误诊。耐心细致病史询问、发散诊断思维和及时进行特异性医技检查可减少或避免其误诊误治。%Objective To investigate the first symptom of AIDS in nervous system, and analyze the misdiagnosis cause, and enhance awareness of AIDS. Methods Retrospective analysis of 7 misdiagnosed acquired immune deficiency syndrome ( AIDs) cases with neurological symptoms at onset admitted to our hospital during January 2007 and December 2013 was made. Results There were cases of headaches and dizziness in 6 patients, with memory disorder in 2 patients, with abdominal disten-sion anorexia in 1 patient;Body lack of power in 1 patient. All the patients denied drug exposure history, amusement history and blood transfusion history. In the 7 cases, 5 cases were misdiagnosed as posterior circulation ischemia, 1 case was misdiagnosed as somatization disorder, and 1 case of left upper limb weakness patient was misdiagnosed as cerebral infarction. After corre-sponding treatment there was no sings of relief in symptoms. HIV antibody test result was positive, and validation test later con-firmed AIDS, and then the patients were transferred to the center for disease control and prevention for

  17. 抗病毒联合抗结核药物在艾滋病合并肺结核患者治疗中应用分析%Analysis of the application of anti-virus combined with anti-tuberculosis drugs in the treatment of acquired immune deficiency syndrome complicated with pulmonary tuberculosis

    Institute of Scientific and Technical Information of China (English)



    Objective:To explore the application effect of anti-virus combined with anti-tuberculosis drugs in the treatment of acquired immune deficiency syndrome complicated with pulmonary tuberculosis.Methods:32 patients with AIDS combined with tuberculosis were selected.They were given AZT+NVP+DDI antiviral regimen and 2H3R3Z3E3/7H3R3 regimen for tuberculosis treatment.We compared the treatment effect.Results:In 23 cases of HIV/AIDS/TB double infections,15 cases were clinically cured;5 cases completed one course;chest X-ray of 3 cases showed focus was absorbed and they continued to take medicine.Compared with before treatment,the CD4+T lymphocyte count at 6 months and 9 months after treatment was significantly improved(P<0.05). Conclusion:The dual anti infection treatment program of anti tuberculosis and anti-virus can effectively control tuberculosis and improve the immunity of HIV patients.%目的:探讨抗病毒联合抗结核药物在艾滋病合并肺结核患者治疗中应用效果。方法:收治艾滋病合并肺结核患者32例,采用AZT+NVP+DDI抗病毒方案治疗及2H3R3Z3E3/7H3R3抗结核方案治疗,比较治疗效果。结果:23例HIV/AIDS/TB双重感染患中,15例临床治愈,5例完成1个疗程,3例胸片提示病灶吸收好转继续服药。治疗6个月、9个月的CD4+T淋巴细胞计数较治疗前均有明显提高(P<0.05)。结论:该抗结核抗病毒双重抗感染治疗方案,可达到有效控制结核病,提高HIV患者免疫力。

  18. Gene therapy for primary adaptive immune deficiencies. (United States)

    Fischer, Alain; Hacein-Bey-Abina, Salima; Cavazzana-Calvo, Marina


    Gene therapy has become an option for the treatment of 2 forms of severe combined immunodeficiency (SCID): X-linked SCID and adenosine deaminase deficiency. The results of clinical trials initiated more than 10 years ago testify to sustained and reproducible correction of the underlying T-cell immunodeficiency. Successful treatment is based on the selective advantage conferred on T-cell precursors through their expression of the therapeutic transgene. However, "first-generation" retroviral vectors also caused leukemia in some patients with X-linked SCID because of the constructs' tendency to insert into active genes (eg, proto-oncogenes) in progenitor cells and transactivate an oncogene through a viral element in the long terminal repeat. These elements have been deleted from the vectors now in use. Together with the use of lentiviral vectors (which are more potent for transducing stem cells), these advances should provide a basis for the safe and effective extension of gene therapy's indications in the field of primary immunodeficiencies. Nevertheless, this extension will have to be proved by examining the results of the ongoing clinical trials.

  19. Successful treatment of an acquired haemorrhagic diathesis due to factor X deficiency with chemotherapy

    NARCIS (Netherlands)

    de Jager, E; Bieger, R; Castel, A; Kluin, PM


    A 70-yr-old woman presented with a severe haemorrhagic diathesis due to an acquired factor X deficiency. A plasma infusion study showed that exogenous factor X was eliminated very effectively from the patient's circulation. A bone marrow biopsy was consistent with plasma cell dyscrasia. Neither an a

  20. New genetic discoveries and primary immune deficiencies. (United States)

    Hernandez-Trujillo, Vivian


    The field of immunology has undergone recent discoveries of genetic causes for many primary immunodeficiency diseases (PIDD). The ever-expanding knowledge has led to increased understanding behind the pathophysiology of these diseases. Since these diseases are rare, the patients are frequently misdiagnosed early in the presentation of their illnesses. The identification of new genes has increased our opportunities for recognizing and making the diagnosis in patients with PIDD before they succumb to infections that may result secondary to their PIDD. Some mutations lead to a variety of presentations of severe combined immunodeficiency (SCID). The myriad and ever-growing genetic mutations which lead to SCID phenotypes have been identified in recent years. Other mutations associated with some genetic syndromes have associated immunodeficiency and are important for making the diagnosis of primary immunodeficiency in patients with some syndromes, who may otherwise be missed within the larger context of their syndromes. A variety of mutations also lead to increased susceptibility to infections due to particular organisms. These patterns of infections due to specific organisms are important keys in properly identifying the part of the immune system which is affected in these patients. This review will discuss recent genetic discoveries that enhance our understanding of these complex diseases.

  1. Intravenous zinc therapy for acquired zinc deficiency secondary to gastric bypass surgery: a case report. (United States)

    Vick, Garrett; Mahmoudizad, Rod; Fiala, Katherine


    Zinc deficiency may result from either a congenitally inherited defect of zinc absorption or is acquired secondarily from a variety of factors affecting dietary zinc intake, absorption, or loss. We report a case of acquired zinc deficiency secondary to gastric bypass surgery that resulted in vulvar cutaneous manifestations of delayed onset, with failure to clear after oral supplementation with zinc. The patient experienced improvement of symptoms only after administration of intravenous zinc supplementation. Upon review of the current literature, it is thought that the patient's original suboptimal response to oral supplementation and improvement after receiving intravenous zinc were related to the intentional surgical alteration and bypass of the absorptive capacity of the duodenum and jejunum. With the current prevalence of obesity and availability of surgical weight loss therapies, it is important to be mindful of the resulting nutritional deficiencies, their clinical manifestations, and factors affecting the efficacy of therapeutic approaches as seen in this case.

  2. Psychological change of patients with human immunodeficiency virus infection or acquired immune deficiency syndrome%艾滋病患者及人类免疫缺陷病毒感染者心理健康状况及其影响因素

    Institute of Scientific and Technical Information of China (English)

    王建宁; 屈文妍


    目的 了解艾滋病患者及人类免疫缺陷病毒(HIV)感染者心理健康状况,并探讨其影响因素.方法 确诊艾滋病患者及HIV检测阳性者共94例为研究组,38名健康人作为对照组,对二者进行症状自评量表(SCL-90)、社会支持量表、应付方式问卷(CSQ)及艾森克人格问卷(EPQ)测评.结果 研究组SCL-90的强迫、抑郁、焦虑及精神病因子分显著高于对照组(P<0.05或0.01),研究组内部男性抑郁因子分和偏执因子分均高于女性,其SCL-90多个因子与CSQ和EPQ多个因子之间存在显著相关关系,相关系数在0.21~0.70之间.结论 艾滋病患者及HIV感染者心理健康状况不良,以情绪障碍为主,应进行心理社会支持和治疗.%Objective To investigate the mental health status of adults with human immunodeficiency virus (HIV)infection or acquired immune deficiency syndrome(AIDS).Methods Ninety-four patients with HIV infection or AIDS and 38 healthy subjects were enrolled and filled in the Symptom Checklist 90(SCL-90),Coping Styles Questionnaire(CSQ)and Eysenck Personality Questionnaire(EPQ).Results in SCL-90,the scores of compulsion ,depression,anxiety and psychoticism factor were significantly increased in the patient group(all P<0.05).In the study group,the scores of depression and paranoid ideation factors of male patients were higher than those of female patients.For the participants with HIV infection or AIDS,several factors of SCL-90 were correlative with CSQ and EPQ(r=0.21 to 0.70).Conclusion Emotional disorders may be the most common mental problem of patients with HIV infection or AIDS,and social and psychological supports should be needed.

  3. Defects of colour vision: A review of congenital and acquired colour vision deficiencies

    Directory of Open Access Journals (Sweden)

    Nabeela Hasrod


    Full Text Available Colour vision deficiencies (CVDs can be categorised as being congenital or acquired. Some CVDs are already present at birth, as inherited conditions that are the result of changes at the photo-pigment level and are non-pathological, incurable and do not change over time. Examples are red-green defects which are inherited as an X-linked recessive trait. Acquired CVD develops secondary to ocular and systemic conditions or as a side effect of certain medications or sometimes toxic effects of chemicals, and trauma and ageing can also be important in some CVDs.

  4. Importance of pharmacokinetic studies in the management of acquired factor X deficiency. (United States)

    Lim, Ming Y; McCarthy, Timothy; Chen, Sheh-Li; Rollins-Raval, Marian A; Ma, Alice D


    Up to 14% of individuals with systemic AL amyloidosis develop acquired factor X deficiency, which occurs due to adsorption of factor X onto amyloid fibrils. Although baseline factor X levels are not predictive of bleeding risk in these patients, serious hemorrhagic complications can occur, particularly during invasive procedures. Optimal management strategies to attenuate bleeding risk in these patients are unknown. We describe our experience in the management of acquired factor X deficiency, secondary to systemic AL amyloidosis, in a case series of three patients who received prothrombin complex concentrates (PCCs) for treatment and prevention of bleeding events. We performed a retrospective review extracting information on baseline demographics, laboratory data, pharmacokinetic (PK) studies, and clinically documented bleeding events. Our case series demonstrates that individuals with acquired factor X deficiency secondary to amyloidosis have variable laboratory and clinical responses to PCCs. This is likely due to distinct amyloid loads and fibril sequences, leading to different binding avidities for factor X. Our data emphasize the importance of performing PK testing prior to any invasive procedures to determine the dose and frequency interval to achieve adequate factor X levels for hemostasis, given the variable response between individuals.

  5. Microflora analysis of a child with severe combined immune deficiency (United States)

    Taylor, G. R.; Kropp, K. D.; Molina, T. C.


    The paper presents a microflora analysis of a 5-year-old male child with severe combined immune deficiency who was delivered by Caesarean section and continuously maintained in an isolator. Despite precautions, it was found that the child had come in contact with at least 54 different microbial contaminants. While his skin autoflora was similar to that of a reference group of healthy male adults in numbers of different species and the number of viable cells present per square centimeter of surface area, the subject's autoflora differed from the reference group in that significantly fewer anaerobic species were recovered from the patient's mouth and feces. It is suggested that the child's remaining disease free shows that the reported bacteria are noninvasive or that the unaffected components of the child's immune defense mechanisms are important.

  6. Qualitative study on the protective factors of resilience among children in rural areas in acquired immune deficiency syndrome(HIV/AIDS)-Affected families%我国部分农村地区受艾滋病影响儿童心理弹性的保护性因素研究

    Institute of Scientific and Technical Information of China (English)

    史从戎; 张曼华; 王宇; 来源; 高保兴; 乔晓春


    [目的]调查山西省某艾滋病比较集中的地区,探讨该区受艾滋病影响儿童心理弹性的保护性因素.[方法]采用儿童焦虑性情绪障碍筛查表和儿童抑郁障碍自评量表,将受艾滋病影响儿童筛分为心理弹性组与非弹性组,再采用半结构访谈的方法,对弹性组的儿童进行调查. [结果]受艾滋病影响儿童心理弹性的保护性因素可划分为四个因素.家庭因素包括父母的关心和支持、民主的教育方式、父母的榜样力量;学校包括老师的关心、同伴的支持;认知包括对父母的评价、相信自己、对未来的期望;行为包括倾诉、寻求帮助、感恩与回报. [结论]在对受艾滋病影响儿童进行心理干预时,应综合考虑家庭、学校、认知、行为等因素.促进其心理弹性的发展,增进其心理健康.%[Objective] To explore the protective factors of resilience among children in acquired immune deficiency syndrome(HIV/AIDS)-Affected families in Shanxi. [Methods] Children in HIV/AIDS families were allocated into resilience group and non-resilience group by The Screen for Child Anxiety Related Emotional Disorders and Depression Self-rating Scale for Children. Then semi-structured interviews were conducted among the resilience group. [Results] The protective factors of resilience among children include four factors. The factor of family consists of care of parents, democratic family education and a good example of parents. Care of teachers and support of peers were included in the factor of school.Estimate of parents, belief in themselves and expectation for the future were organized into the factors of cognition. Pouring out, searching for help and thanksgiving were packed in the factors of behaviors. [Conclusion] Family, school, cognition and behavior should be considered comprehensively in the psychological intervention for the children in HIV/AIDS family to make them more resilient and more healthy.

  7. BACE1-Deficient Mice Exhibit Alterations in Immune System Pathways. (United States)

    Stertz, L; Contreras-Shannon, V; Monroy-Jaramillo, N; Sun, J; Walss-Bass, C


    BACE1 encodes for the beta-site amyloid precursor protein cleaving enzyme 1 or β-secretase. Genetic deletion of Bace1 leads to behavioral alterations and affects midbrain dopaminergic signaling and memory processes. In order to further understand the role of BACE1 in brain function and behavior, we performed microarray transcriptome profiling and gene pathway analysis in the hippocampus of BACE1-deficient mice compared to wild type. We identified a total of 91 differentially expressed genes (DEGs), mostly enriched in pathways related to the immune and inflammation systems, particularly IL-9 and NF-κB activation pathways. Serum levels of IL-9 were elevated in BACE1-deficient mice. Our network analysis supports an intimate connection between immune response via NF-κB and BACE1 signaling through the NRG1/Akt1 pathway. Our findings warrant future mechanistic studies to determine if BACE1 signaling and the IL-9 pathway interact to alter behavior and brain function. This study opens new avenues in the investigation of hippocampus-related neuroimmunological and neuroinflammation-associated disorders.

  8. Toward immunogenetic studies of amphibian chytridiomycosis: Linking innate and acquired immunity (United States)

    Richmond, J.Q.; Savage, Anna E.; Zamudio, Kelly R.; Rosenblum, E.B.


    Recent declines in amphibian diversity and abundance have contributed significantly to the global loss of biodiversity. The fungal disease chytridiomycosis is widely considered to be a primary cause of these declines, yet the critical question of why amphibian species differ in susceptibility remains unanswered. Considerable evidence links environmental conditions and interspecific variability of the innate immune system to differential infection responses, but other sources of individual, population, or species-typical variation may also be important. In this article we review the preliminary evidence supporting a role for acquired immune defenses against chytridiomycosis, and advocate for targeted investigation of genes controlling acquired responses, as well as those that functionally bridge the innate and acquired immune systems. Immunogenetic data promise to answer key questions about chytridiomycosis susceptibility and host-pathogen coevolution, and will draw much needed attention to the importance of considering evolutionary processes in amphibian conservation management and practice. ?? 2009 by American Institute of Biological Sciences.

  9. Naturally acquired immunity to Plasmodium falciparum malaria in Africa

    DEFF Research Database (Denmark)

    Hviid, Lars


    vaccines against this major cause of human misery is a realistic goal, the uncertainty regarding the antigenic targets of naturally acquired protective immunity and the immunological mechanisms involved remain major vaccine development obstacles. Nevertheless, a coherent theoretical framework of how......Infection by Plasmodium falciparum parasites can lead to substantial protective immunity to malaria, and available evidence suggest that acquisition of protection against some severe malaria syndromes can be fairly rapid. Although these facts have raised hopes that the development of effective...

  10. Fundus white spots and acquired night blindness due to vitamin A deficiency. (United States)

    Genead, Mohamed A; Fishman, Gerald A; Lindeman, Martin


    To report a successfully treated case of acquired night blindness associated with fundus white spots secondary to vitamin A deficiency. An ocular examination, electrophysiologic testing, as well as visual field and OCT examinations were obtained on a 61-year-old man with vitamin A deficiency who had previously undergone gastric bypass surgery. The patient had a re-evaluation after treatment with high doses of oral vitamin A. The patient was observed to have numerous white spots in the retina of each eye. Best-corrected visual acuity was initially 20/80 in each eye, which improved to 20/40-1 OU after oral vitamin A therapy for 2 months. Full field electroretinogram (ERG) testing, showed non-detectable rod function and a 34 and 41% reduction for 32-Hz flicker and single flash cone responses, respectively, below the lower limits of normal. Both rod and cone functions markedly improved after initiation of vitamin A therapy. Vitamin A deficiency needs to be considered in a patient with white spots of the retina in the presence of poor night vision.

  11. Immune response against Sporothrix schenckii in TLR-4-deficient mice. (United States)

    Sassá, Micheli Fernanda; Ferreira, Lucas Souza; Ribeiro, Livia Carolina de Abreu; Carlos, Iracilda Zeppone


    For many fungal diseases, macrophages are the major cell population implicated in host protection, primarily by their ability to eliminate the invading fungal pathogen through phagocytosis. In sporotrichosis, this remains true, because of macrophages’ ability to recognize Sporothrix schenckii through specific receptors for some of the fungus’ cellular surface constituents. Further confirmation for macrophages’ pivotal role in fungal diseases came with the identification of toll-like receptors, and the subsequent numerous associations found between TLR-4 deficiency and host susceptibility to diverse fungal pathogens. Involvement of TLR-4 in immune response against sporotrichosis has been conducted to investigate how TLR-4 signaling could affect inflammatory response development through evaluation of H2O2 production and IL-1β, IL-6 and TGF-β release during the course of S. schenckii infection on TLR-4-deficient mice. The results showed that macrophages are largely dependent on TLR-4 for inflammatory activation and that in the absence of TLR-4 signaling, increased TGF-β release may be one of the contributing factors for the abrogated inflammatory activation of peritoneal exudate cells during mice sporotrichosis.

  12. The Study on the Ferrokinetics and Acquired Immunity in Repeated Hookworm Infections

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Mun Ho; Lee, Pyl Ung [Seoul National University College of Medicine, Seoul (Korea, Republic of)


    In order to confirm whether acquired immunity or resistance can be developed by the repeated hookworm infections, the 150 mature actively moving filariform ancylostoma duodenale larvae obtained from the severe hookworm anemia patients were orally given to 8 healthy volunteers in three divided doses, 50 in each, at 5 day interval. Also the hematological changes as well as several ferrokinetics using {sup 59}Fe were done and were compared with 10 controls. The clinical symptoms and signs were checked every day for the first 3 weeks and then twice weekly until the end of the experiment. The appearance of the ova in the stool was examined by the formalin ether method and the ova was counted by the Stoll's method. The following laboratory tests were done:1) Red blood cell count, venous blood hematocrit (micromethod), hemoglobin count (cyanomethemoglobin method) were checked every 5 to 7 day interval. 2) Plasma iron concentration (Barkan's modified method) was determined every 2 to 3 week interval. 3) Radioisotope studies:a) Ferrokinetics: Huff et al and Bothwell's method were applied. Erythropoietic Index (% of normal)= ['Subject's turnover/100 ml whole bloodX100'] over ['Average normal turnover/100 ml whole blood'] b) Quantitative measurement of the gastrointestinal absorption of iron:Radioiron ({sup 59}Fe) balance method was applied. c) Determination of the plasma erythropoietin activity: Fried's method was applied. Following were the results: 1) The serum iron level was lower. The red cell volume was decreased, but with relative increase of plasma volume. 2) The plasma iron disappearance time was accelerated and the plasma iron turnover rate was decreased. The red cell iron turnover rate was markedly increased, while all of the red cell iron concentration, circulating red cell iron, plasma iron pool were decreased. The daily iron pool turnover and red cell renewal rate were increased. 3) The erythropoietic index

  13. Relationship of levels of serum carcinoembryonic antigen and pathological imaging changes of lungs in patients with acquired immune deficiency syndrome (AIDS)%AIDS患者血清CEA水平与胸部影像学关系的临床观察

    Institute of Scientific and Technical Information of China (English)

    王家驷; 王廷杰; 王平飞; 张雪漫; 冉梅


    目的:探讨AIDS患者血清癌胚抗原(CEA)增高与胸部病变的关系。方法观察2008年1月至2011年12月间因胸部疾病入住四川省达州市中心医院呼吸内科且确诊为AIDS感染者,选取同时有胸部CT检查及血清CEA检测资料的病例68例,包括男性54例,女性14例,年龄26~78岁,平均年龄51.10岁,分析临床病史、症状、胸部CT影像学变化与血清CEA水平之间的关系。结果68例AIDS患者中,CEA增高者占44.12%,平均年龄较CEA正常组偏大3.22岁;发热、咳嗽症状患者两组间比例接近,主诉气促及合并真菌感染者是CEA正常者的1倍,而乏力盗汗、胸部不适等其他主诉则约是CEA正常者的1/2(47.83%)。CEA正常组的均值是(2.04±1.34)ng/ml,CEA增高组为(8.28±4.54)ng/ml;组间差异有显著统计学意义(P <0.001),CEA增高组发生胸部磨玻璃影(GGO)的几率是CEA正常者的4倍,而CEA正常组斑片影则约为CEA增高组的1倍;AIDS患者胸部GGO影像的密度和范围不同,其CEA的平均水平出现相应的水平差异;而未合并GGO的胸部团块影、纵膈增大及纤维索条影者CEA水平在0.00~10.93 ng/ml,与GGO者比较差异有显著统计学意义(P <0.001)。结论 AIDS患者血CEA增高可能与胸部磨玻璃影的形成相关,是CEA的一种非肿瘤性特性,可能与PCP感染相关。%Objective To approach relative of increased levels of serum carcinoembryonic antigen (CEA) to pathological changes of lunges in patients with acquired immune deficiency syndrome (AIDS). Methods The patients with diagnosed AIDS admitted on the basis of illness in department of respiratory medicine of our hospital (general hospital) from Jan 2008 to Dec 2011 were prospectively observed, in which 68 cases of patients (male 54, female 14, age range 26-78 years old, means 51.10 years old) with serum CEA data and CT detections of thorax were selected, and the relevance

  14. 用伴时Cox回归模型进行艾滋病抗病毒治疗病例的生存分析%The survival analysis on antiretroviral therapy cas es of acquired immune deficiency syndrome based on time-dependent Cox regression model

    Institute of Scientific and Technical Information of China (English)

    白芳; 樊华山; 卫军; 杜培军; 薛子东; 仇超; 徐建青


    Objective To evaluate the effectiveness of free antiretroviral therapy(ART) in adults and the factors influence ART outcome. Methods A retrospective cohort study was conducted Shanxi province. All qualified ART recipients were enrolled in the national free ART program from June 2004 to December 2012. Statistical analysis was conducted by SPSS software (version 19.0), use the t test and chi-square test, with Cox regression model for survival analysis. Results One thousand eight hundred and eighty-seven cases were included in the study. The rates for participants, who survived, who were deceased for acquired immune deficiency syndrome (AIDS) related diseases, who withdrawal from the treatment, who transferred to other hospital and who lost for follow-up were 83.1%, 13.5%, 1.4%, 1.2% and 0.8%, respectively. The cumulative survival rates were 0.91, 0.89, 0.88, 0.86, 0.85, 0.82, 0.80, 0.79 and 0.79 at 0.5, 1.0, 2.0, 3.0, 4.0, 5.0, 6.0, 7.0 and 8.0 years after treatment initiation, respectively. The medians of CD4+T cell count were 143.5 cells/μL prior to treatment and 205.3 cells/μL post treatment. 18.2% of ART recipients had their viral loads below detection limit before therapy and this percentage increased to 89.1% after therapy. In the multivariate Cox proportional hazard model, CD4+T cell count and BMI before treatment initiation, and the age start therapy were significantly associated with survival time. The Hazard ratio was 4.05, 3.44 and 3.68, respectively. Record the count of CD4+T lymphocyte after antiretroviral treatment, the difference of CD4+T lymphocyte count between before antiretroviral treatment and after, 3 covariates had been produced by the viral load program generates after antiretroviral treatment , 15 variables had been proved to be statistically and professional significance before antiretroviral treatment. Analysis above all variables based on multi factor time-dependent Cox regression model. There were statistical differences between the

  15. Predictive features of severe acquired ADAMTS13 deficiency in idiopathic thrombotic microangiopathies: the French TMA reference center experience.

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    Paul Coppo

    Full Text Available Severe ADAMTS13 deficiency occurs in 13% to 75% of thrombotic microangiopathies (TMA. In this context, the early identification of a severe, antibody-mediated, ADAMTS13 deficiency may allow to start targeted therapies such as B-lymphocytes-depleting monoclonal antibodies. To date, assays exploring ADAMTS13 activity require skill and are limited to only some specialized reference laboratories, given the very low incidence of the disease. To identify clinical features which may allow to predict rapidly an acquired ADAMTS13 deficiency, we performed a cross-sectional analysis of our national registry from 2000 to 2007. The clinical presentation of 160 patients with TMA and acquired ADAMTS13 deficiency was compared with that of 54 patients with detectable ADAMTS13 activity. ADAMTS13 deficiency was associated with more relapses during treatment and with a good renal prognosis. Patients with acquired ADAMTS13 deficiency had platelet count < 30 x 10(9/L (adjusted odds ratio [OR] 9.1, 95% confidence interval [CI] 3.4-24.2, P<.001, serum creatinine level < or =200 micromol/L (OR 23.4, 95% CI 8.8-62.5, P<.001, and detectable antinuclear antibodies (OR 2.8, 95% CI 1.0-8.0, P<.05. When at least 1 criteria was met, patients with a severe acquired ADAMTS13 deficiency were identified with positive predictive value of 85%, negative predictive value of 93.3%, sensitivity of 98.8%, and specificity of 48.1%. Our criteria should be useful to identify rapidly newly diagnosed patients with an acquired ADAMTS13 deficiency to better tailor treatment for different pathophysiological groups.

  16. How We Manage Adenosine Deaminase-Deficient Severe Combined Immune Deficiency (ADA SCID). (United States)

    Kohn, Donald B; Gaspar, H Bobby


    Adenosine deaminase-deficient severe combined immune deficiency (ADA SCID) accounts for 10-15% of cases of human SCID. From what was once a uniformly fatal disease, the prognosis for infants with ADA SCID has improved greatly based on the development of multiple therapeutic options, coupled with more frequent early diagnosis due to implementation of newborn screening for SCID. We review the various treatment approaches for ADA SCID including allogeneic hematopoietic stem cell transplantation (HSCT) from a human leukocyte antigen-matched sibling or family member or from a matched unrelated donor or a haplo-identical donor, autologous HSCT with gene correction of the hematopoietic stem cells (gene therapy-GT), and enzyme replacement therapy (ERT) with polyethylene glycol-conjugated adenosine deaminase. Based on growing evidence of safety and efficacy from GT, we propose a treatment algorithm for patients with ADA SCID that recommends HSCT from a matched family donor, when available, as a first choice, followed by GT as the next option, with allogeneic HSCT from an unrelated or haplo-identical donor or long-term ERT as other options.

  17. Immune Deficiency Influences Juvenile Social Behavior and Maternal Behavior (United States)

    Quinnies, Kayla M.; Cox, Kimberly H.; Rissman, Emilie F.


    Mice with severe combined immunodeficiency (SCID) lack functional T and B-lymphocytes, and have impaired cognitive abilities. Here, we assessed social behaviors in male SCID and C57BL/6 (B6) juvenile mice. In a social preference task, SCID mice spent more time than B6 mice investigating a novel adult male mouse. In a social recognition task, SCID mice habituated to a novel ovariectomized mouse, but failed to show dishabituation when presented with an unfamiliar individual. We hypothesized that partial immune restoration could normalize behaviors. SCID pups (postnatal day 7) received either saline or splenocytes from normal donors. Splenocyte-replaced SCID mice spent less time interacting with a novel mouse than saline-injected SCID or B6 control mice. Again, control SCID mice failed to dishabituate to a novel mouse, but splenocyte-replaced SCID mice showed dishabituation. In both of these studies B6 and SCID pairs were used to produce offspring that remained with their dams until weaning. There are no studies of maternal behavior in SCID dams; therefore to investigate the potential role for this factor we quantified maternal behavior in SCID and B6 dams; several significant differences were found. To control for differences in maternal care we mated heterozygous SCIDs to produce offspring. These homozygous SCID and WT offspring reared by dams of the same genotypes displayed similar responses to a novel mouse; however, in the social recognition task SCID males did not display dishabituation to a novel mouse. Taken together, our data indicate that gene by environment interactions influence social interactions in immune deficient mice. PMID:26030431

  18. Importance of both innate immunity and acquired immunity for rapid expulsion of S. venezuelensis.

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    Koubun eYasuda


    Full Text Available In the first part of this review, we described the relevant roles of endogenous IL-33 for accumulation of ILC2 and eosinophils even in the lungs of Rag2-/- mice. ATII cells express IL-33 in their nucleus and infection with S.venezuelensis induces IL-33 production by increasing the number of ATII cells possibly by the action of chitin. IL-33 from ATII cells induces ILC2 proliferation and at the same time activates them to produce IL-5 and IL-13, which in combination induce lung eosinophilic inflammation, aiding to expel infected worms in the lungs. In the second part, we showed that, although AID-/- mice normally develop Th2 cells and intestinal mastocytosis after infection with S.venezuelensis, they need adoptive transfers of immune sera from S.venezuelensis-infected mice to obtain the capacity to promptly expel S.venezuelensis. Thus, intestinal nematode infection induces various Th2 immune responses (eg., Th2 cell, ILC2, goblet cell hyperplasia, intestinal mastocytosis, smooth muscle cell contraction, local and systemic eosinophilia and high serum level of IgE and IgG1. However, all of them are not necessary for rapid expulsion of intestinal nematodes. Instead, some combinations of Th2 immune responses are essentially required.

  19. Potential Suppressive Effects of Two C60 Fullerene Derivatives on Acquired Immunity (United States)

    Hirai, Toshiro; Yoshioka, Yasuo; Udaka, Asako; Uemura, Eiichiro; Ohe, Tomoyuki; Aoshima, Hisae; Gao, Jian-Qing; Kokubo, Ken; Oshima, Takumi; Nagano, Kazuya; Higashisaka, Kazuma; Mashino, Tadahiko; Tsutsumi, Yasuo


    The therapeutic effects of fullerene derivatives on many models of inflammatory disease have been demonstrated. The anti-inflammatory mechanisms of these nanoparticles remain to be elucidated, though their beneficial roles in allergy and autoimmune diseases suggest their suppressive potential in acquired immunity. Here, we evaluated the effects of C60 pyrrolidine tris-acid (C60-P) and polyhydroxylated fullerene (C60(OH)36) on the acquired immune response in vitro and in vivo. In vitro, both C60 derivatives had dose-dependent suppressive effects on T cell receptor-mediated activation of T cells and antibody production by B cells under anti-CD40/IL-4 stimulation, similar to the actions of the antioxidant N-acetylcysteine. In addition, C60-P suppressed ovalbumin-specific antibody production and ovalbumin-specific T cell responses in vivo, although T cell-independent antibodies responses were not affected by C60-P. Together, our data suggest that fullerene derivatives can suppress acquired immune responses that require T cells.

  20. Haemoglobin C and S role in acquired immunity against Plasmodium falciparum malaria.

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    Federica Verra

    Full Text Available A recently proposed mechanism of protection for haemoglobin C (HbC; beta6Glu-->Lys links an abnormal display of PfEMP1, an antigen involved in malaria pathogenesis, on the surface of HbC infected erythrocytes together with the observation of reduced cytoadhesion of parasitized erythrocytes and impaired rosetting in vitro. We investigated the impact of this hypothesis on the development of acquired immunity against Plasmodium falciparum variant surface antigens (VSA encoding PfEMP1 in HbC in comparison with HbA and HbS carriers of Burkina Faso. We measured: i total IgG against a single VSA, A4U, and against a panel of VSA from severe malaria cases in human sera from urban and rural areas of Burkina Faso of different haemoglobin genotypes (CC, AC, AS, SC, SS; ii total IgG against recombinant proteins of P. falciparum asexual sporozoite, blood stage antigens, and parasite schizont extract; iii total IgG against tetanus toxoid. Results showed that the reported abnormal cell-surface display of PfEMP1 on HbC infected erythrocytes observed in vitro is not associated to lower anti- PfEMP1 response in vivo. Higher immune response against the VSA panel and malaria antigens were observed in all adaptive genotypes containing at least one allelic variant HbC or HbS in the low transmission urban area whereas no differences were detected in the high transmission rural area. In both contexts the response against tetanus toxoid was not influenced by the beta-globin genotype. These findings suggest that both HbC and HbS affect the early development of naturally acquired immunity against malaria. The enhanced immune reactivity in both HbC and HbS carriers supports the hypothesis that the protection against malaria of these adaptive genotypes might be at least partially mediated by acquired immunity against malaria.

  1. The role of acquired immunity in the spread of human papillomavirus (HPV: explorations with a microsimulation model.

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    Suzette M Matthijsse

    Full Text Available BACKGROUND: Knowledge of the natural history of human papillomavirus (HPV, in particular the role of immunity, is crucial in estimating the (cost- effectiveness of HPV vaccination and cervical cancer screening strategies, because naturally acquired immunity after clearing an infection may already protect part of the risk population against new HPV infections. METHODS: We used STDSIM, an established stochastic microsimulation model, quantified to the Netherlands. We explored different assumptions regarding the natural history of HPV-16 and HPV-18, and estimated the transmission probabilities and durations of acquired immunity necessary to reproduce age-specific prevalence. RESULTS: A model without acquired immunity cannot reproduce the age-specific patterns of HPV. Also, it is necessary to assume a high degree of individual variation in the duration of infection and acquired immunity. According to the model estimates, on average 20% of women are immune for HPV-16 and 15% for HPV-18. After an HPV-16 infection, 50% are immune for less than 1 year, whereas 20% exceed 30 years. For HPV-18, up to 12% of the individuals are immune for less than 1 year, and about 50% over 30 years. Almost half of all women will never acquire HPV-16 or HPV-18. CONCLUSIONS: Acquired immunity likely plays a major role in HPV epidemiology, but its duration shows substantial variation. Combined with the lifetime risk, this explains to a large extent why many women will never develop cervical cancer.

  2. Acquired protein C deficiency in a child with acute myelogenous leukemia, splenic, renal, and intestinal infarction. (United States)

    Farah, Roula A; Jalkh, Khalil S; Farhat, Hussein Z; Sayad, Paul E; Kadri, Adel M


    We report the case of a 6-year-old boy diagnosed with acute promyelocytic leukemia (AML-M3V) when he presented with pallor, abdominal pain, anorexia, and fatigue. Induction chemotherapy was started according to the AML-BFM 98 protocol along with Vesanoid (ATRA, All-trans retinoic acid). On the sixth day of induction, he developed splenic and gallbladder infarcts. Splenectomy and cholecystectomy were performed while chemotherapy induction continued as scheduled. Four days later, he developed ischemic areas in the kidneys and ischemic colitis in the sigmoid colon. Hypercoagulation studies showed severe deficiency of protein C. Tests showed protein C 16% (reference range 70-140%), protein S 87% (reference range 70-140%), antithrombin III 122% (reference range 80-120%), prothrombin time 13.6 s (reference = 11.3), INR (international normalized ratio) 1.21, partial thromboplastin time 33 s (reference = 33), fibrinogen 214 mg/dl, D-dimer 970 μg/ml, factor II 98%, and that antinuclear antibody, antiphospholipid antibodies, mutation for factor II gene (G20210A), and mutation for Arg506 Gln of factor V were all negative (factor V Leiden). There was no evidence of clinical disseminated intravascular coagulation (DIC). He was treated with low molecular weight heparin and did well. He continues to be in complete remission 7 years later with normal protein C levels. Acquired protein C deficiency can occur in a variety of settings and has been reported in acute myelocytic leukemia. However, clinically significant thrombosis in the absence of clinical DIC, such as our case, remains extremely rare.

  3. Antigen-specific acquired immunity in human brucellosis: implications for diagnosis, prognosis, and vaccine development

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    Anthony P Cannella


    Full Text Available Brucella spp. are facultative intracellular Gram negative bacteria with specific tropism for monocytes/macrophages. Clinical manifestations of brucellosis are primarily immune-mediated and not thought to be due to bacterial virulence factors. Acquired immunity to brucellosis has been studied through observations of naturally infected hosts (cattle, goats, laboratory mouse models, and human infection. Cell-mediated immunity drives the clinical manifestations of human disease after exposure to Brucella species but high antibody responses are not associated with protective immunity. The precise mechanisms by which cell-mediated immune responses confer protection or lead to disease manifestations remain poorly understood. Descriptive studies of immune responses in human brucellosis show that TH1 (interferon-gamma are associated with dominant immune responses, findings consistent with animal studies. Whether these T cell responses are protective, or determine the different clinical responses associated with brucellosis is unknown, especially with regard to undulant fever manifestations, relapsing disease, or are associated with responses to distinct sets of Brucella spp. antigens are unknown. Few data regarding T cell responses in terms of specific recognition of Brucella spp. protein antigens and peptidic epitopes, either by CD4+ or CD8+ T cells, have been identified in human brucellosis patients. Additionally because current attenuated Brucella vaccines used in animals cause human disease, there is a true need for a recombinant protein subunit vaccine for human brucellosis, as well as for improved diagnostics in terms of prognosis and identification of unusual forms of brucellosis. This review will focus on current understandings of antigen-specific immune responses induced by Brucella protein antigens that has promise for yielding new insights into vaccine and diagnostics development, and for understanding pathogenetic mechanisms of human

  4. Sequential Cadaveric Lung and Bone Marrow Transplant for Immune Deficiency Diseases (United States)


    Severe Combined Immunodeficiency (SCID); Immunodeficiency With Predominant T-cell Defect, Unspecified; Severe Chronic Neutropenia; Chronic Granulomatous Disease (CGD); Hyper IgE Syndromes; Hyper IgM Deficiencies; Wiskott-Aldrich Syndrome; Mendelian Susceptibility to Mycobacterial Disease; Common Variable Immune Deficiency (CVID)

  5. Does age acquired immunity confer selective protection to common serotypes of Campylobacter jejuni?

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    Ogden Iain D


    Full Text Available Abstract Background Campylobacter infection is a major cause of bacterial gastrointestinal disease. Exposure to Campylobacter is known to produce an immune response in humans that can prevent future symptomatic infections. Further, studies of the general population have shown that seroprevalence to Campylobacter increases with age. Methods A large collection of serotyped Campylobacter isolates, obtained from human clinical faecal samples, were analysed by comparing the ratio of uncommon to common serotypes by different age groups, using χ2 tests. Results We have identified that older age groups, as well as having generally lower incidence, are significantly less likely to be infected by the more common serotypes. Conclusion These results are indicative of acquired immunity, however, further studies are needed to rule out the confounding effects of the variations in exposure pathways experienced by different age groups.

  6. Regulation of naturally acquired mucosal immunity to Streptococcus pneumoniae in healthy Malawian adults and children.

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    Sarah J Glennie

    Full Text Available Worldwide, invasive pneumococcal disease caused by Streptococcus pneumoniae is most common in young children. In adults, disease rates decline following intermittent colonization and the acquisition of naturally acquired immunity. We characterized mucosal and systemic pneumococcal-specific T-cell responses in African children and adults who contend with intense rates of colonization, up to 100% and 60% respectively. We find most Malawian children have high pneumococcal-specific T-cell responses in tonsil tissue and peripheral blood. In addition, frequent commensalism generates CD25(hi (Tregs which modulate mucosal pneumococcal-specific T-cell responses in some children and ≥50% of adults. We propose that immune regulation may prolong pneumococcal colonization and predispose vulnerable individuals to disease.

  7. The Janus faces of acquired angioedema: C1-inhibitor deficiency, lymphoproliferation and autoimmunity. (United States)

    Wu, Maddalena Alessandra; Castelli, Roberto


    Several clinical and biological features of lymphoproliferative diseases have been associated with an increased risk of developing autoimmune manifestations. Acquired deficiency of C1-inhibitor (C1-INH) (AAE) is a rare syndrome clinically similar to hereditary angioedema (HAE) characterized by local increase in vascular permeability (angioedema) of the skin and the gastrointestinal and oro-pharyngo-laryngeal mucosa. Bradykinin, a potent vasoactive peptide, released from high molecular weight kininogen when it is cleaved by plasma kallikrein (a serine protease controlled by C1-INH), is the mediator of symptoms. In total 46% of AAE patients carry an underlying hematological disorder including monoclonal gammopathy of uncertain significance (MGUS) or B cell malignancies. However, 74% of AAE patients have anti-C1-INH autoantibodies without hematological, clinical or instrumental evidence of lymphoproliferative disease. Unlike HAE patients, AAE patients usually have late-onset symptoms, do not have a family history of angioedema and present variable response to treatment due to the hypercatabolism of C1-INH. Experiments show that C1-INH and/or the classical complement pathway were consumed by the neoplastic lymphatic tissues and/or anti-C1-INH neutralizing autoantibodies. Therapy of AAE follows two directions: 1) prevention/reversal of the symptoms of angioedema; and 2) treatment of the associated disease. Different forms of B cell disorders coexist and/or evolve into each other in AAE and seem to be dominated by an altered control of B cell proliferation, thus AAE represents an example of the strict link between autoimmunity and lymphoproliferation.

  8. Metreleptin for injection to treat the complications of leptin deficiency in patients with congenital or acquired generalized lipodystrophy. (United States)

    Meehan, Cristina Adelia; Cochran, Elaine; Kassai, Andrea; Brown, Rebecca J; Gorden, Phillip


    The lipodystrophies represent a class of diseases characterized by leptin deficiency. Leptin deficiency is associated with a severe form of the metabolic syndrome characterized by dyslipidemia, insulin resistance, diabetes, and ovarian dysfunction. Metreleptin is the pharmaceutical derived product that has been approved by the Food and Drug Administration (FDA) to treat the severe metabolic abnormalities of the generalized forms of lipodystrophy. Herein we describe the properties of metreleptin, its use in patients, which includes the administration of the drug and how it may be acquired by medical professionals as well as its safety, tolerability, and properties. Finally, we speculate on future uses and development of metreleptin.

  9. The role of acquired immunity in the spread of human papillomavirus (HPV): explorations with a microsimulation model

    NARCIS (Netherlands)

    Matthijsse, S.M.; Rosmalen, J. van; Hontelez, J.A.; Bakker, R; Kok, I.M. de; Ballegooijen, M. van; Vlas, S.J. de


    BACKGROUND: Knowledge of the natural history of human papillomavirus (HPV), in particular the role of immunity, is crucial in estimating the (cost-) effectiveness of HPV vaccination and cervical cancer screening strategies, because naturally acquired immunity after clearing an infection may already

  10. Salivary Defense Proteins: Their Network and Role in Innate and Acquired Oral Immunity

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    Gábor Fábián


    Full Text Available There are numerous defense proteins present in the saliva. Although some of these molecules are present in rather low concentrations, their effects are additive and/or synergistic, resulting in an efficient molecular defense network of the oral cavity. Moreover, local concentrations of these proteins near the mucosal surfaces (mucosal transudate, periodontal sulcus (gingival crevicular fluid and oral wounds and ulcers (transudate may be much greater, and in many cases reinforced by immune and/or inflammatory reactions of the oral mucosa. Some defense proteins, like salivary immunoglobulins and salivary chaperokine HSP70/HSPAs (70 kDa heat shock proteins, are involved in both innate and acquired immunity. Cationic peptides and other defense proteins like lysozyme, bactericidal/permeability increasing protein (BPI, BPI-like proteins, PLUNC (palate lung and nasal epithelial clone proteins, salivary amylase, cystatins, prolin-rich proteins, mucins, peroxidases, statherin and others are primarily responsible for innate immunity. In this paper, this complex system and function of the salivary defense proteins will be reviewed.

  11. 某艾滋病治疗示范区人免疫缺陷病毒感染者合并隐匿性乙型肝炎病毒感染的调查分析%A cross-sectional survey of occult hepatitis B virus infection in HIV-infected patients in acquired immune deficiency syndrome area

    Institute of Scientific and Technical Information of China (English)

    梁红霞; 陈媛媛; 周荣; 张倩; 潘延凤; 谷军生; 李娟; 江河清; 余祖江


    Objective To assess the prevalence of occult HBV infection in HIV-infected patients inacquired immune deficiency syndrome area. Methods Serum samples were obtained from 97 HIV-infected patients who transmitted by paid blood donation. ELISA was used to detect HBV erologic markers (HBsAg, Anti-HBs, HBeAg, anti-HBe and anti-HBc) and HCV antibody. Flow Cytometry were used to detect CD4 +T cell count. Nested PCR was used to amplify surface protein region of HBV DNA. Results Ninety two patients were HBsAg negative in the 97 HIV-infected patients(94. 85% ). Twenty seven patients were co-infected with occult hepatitis B virus infection in the 92 HBsAg negative patients (29. 35% ).Seventy three patients were co-infected with HCV in the 92 HBsAg negative patients(79.35% ). CD4 cell count of subjects with occult HBV infection were significantly lower (212. 11 ± 133. 1 cells/mm3 versus 318.9 ± 172.2 cells/mm3, respectively, P <0. 01 ). A significantly higher prevalence of isolated anti-HBc was observed in HIV-infected subjects co-infectionded with occult HBV infection [62. 96% ( 13 of 27 )versus 18.46% (15 of 65 ) , P < 0. 01]. No statistical significant association could be established between the age, sex and whether co-infected with HCV. Conclusion It is found that occult HBV infection did occurs in HIV-infected patients. Individuals co-infected with HIV and occult HBV infection are more likely to have isolated anti-HBc than subjects with HIV alone. Co-infection with HIV and occult HBV is more%目的 调查分析某艾滋病治疗示范区人免疫缺陷病毒(HIV)-1感染者中隐匿性乙型肝炎病毒(HBV)感染的情况及其影响因素.方法 采集某艾滋病治疗示范区97例经血感染HIV-1的感染者的血浆,采用酶联免疫吸附试验(ELISA)检测乙型肝炎表面抗原与抗体(HBsAg与抗HBs)、乙型肝炎e抗原与抗体(HBeAg与抗Hbe)、乙型肝炎核心抗体(抗HBc)及丙型肝炎抗体(抗HCV);采用吸附柱法抽提HBV DNA;采用巢

  12. Herd immunity acquired indirectly from interactions between the ecology of infectious diseases, demography and economics. (United States)

    Bonds, Matthew H; Rohani, Pejman


    Patterns of morbidity and mortality around the globe are determined by interactions between infectious diseases and systematic human socioeconomic processes. The most obvious of these patterns is that the greatest burdens of infectious diseases are found among the poor, who lack the basic resources for disease prevention and treatment. Yet, it is becoming increasingly clear that many infectious diseases are themselves causes of poverty owing to their effects on labour productivity. A particularly subtle phenomenon that receives little attention in the epidemiology literature and is especially important for poor communities is the role of the birth rate as an important direct cause of high disease burdens. Because of their high rates of transmission and life-long immunity, the persistence of many child diseases such as measles relies on high rates of reproduction as their source of susceptible individuals. Thus, there are significant direct health benefits of lower fertility rates, which are further enhanced by interactions with economic processes. Indeed, fertility, poverty and disease all interact with each other in important and predictable ways that can be built into traditional disease ecology models. We present such a model here that provides insights into the long-term effect of policy interventions. For example, because of indirect income effects, herd immunity may be acquired with lower vaccine coverage than previously thought. Reductions in the disease burden can also occur through lower fertility. Our model thus provides a disease ecology framework that is useful for the analysis of demographic transitions.

  13. Radiation-resistant acquired immunity of vaccinated mice to Schistosoma mansoni

    Energy Technology Data Exchange (ETDEWEB)

    Aitken, R.; Coulson, P.S.; Dixon, B.; Wilson, R.A.


    Vaccination of mice with attenuated cercariae of Schistosoma mansoni induces specific acquired resistance to challenge infection. This resistance is immunologically-mediated, possibly via a delayed-type hypersensitivity. Studies of parasite migration have shown that the protective mechanism operates most effectively in the lungs of vaccinated mice. We have probed the mechanism by exposing mice to 500 rads of gamma radiation before challenge infection. Our results show that the effector mechanism operative against challenge larvae is resistant to radiation. In contrast, classical immune responses are markedly suppressed by the same treatment. While leukocyte populations in the blood fall dramatically after irradiation, numbers of cells recoverable by bronchoalveolar lavage are unaffected. We suggest that vaccination with attenuated cercariae establishes populations of sensitized cells in the lungs which trigger the mechanism of resistance when challenge schistosomula migrate through pulmonary capillary beds. Although the cells may be partially disabled by irradiation, they remain responsive to worm antigens and thereby capable of initiating the elimination mechanism. This hypothesis would explain the radiation resistance of vaccine-induced immunity to S. mansoni.

  14. Parental vitamin deficiency affects the embryonic gene expression of immune-, lipid transport- and apolipoprotein genes (United States)

    Skjærven, Kaja H.; Jakt, Lars Martin; Dahl, John Arne; Espe, Marit; Aanes, Håvard; Hamre, Kristin; Fernandes, Jorge M. O.


    World Health Organization is concerned for parental vitamin deficiency and its effect on offspring health. This study examines the effect of a marginally dietary-induced parental one carbon (1-C) micronutrient deficiency on embryonic gene expression using zebrafish. Metabolic profiling revealed a reduced 1-C cycle efficiency in F0 generation. Parental deficiency reduced the fecundity and a total of 364 genes were differentially expressed in the F1 embryos. The upregulated genes (53%) in the deficient group were enriched in biological processes such as immune response and blood coagulation. Several genes encoding enzymes essential for the 1-C cycle and for lipid transport (especially apolipoproteins) were aberrantly expressed. We show that a parental diet deficient in micronutrients disturbs the expression in descendant embryos of genes associated with overall health, and result in inherited aberrations in the 1-C cycle and lipid metabolism. This emphasises the importance of parental micronutrient status for the health of the offspring.

  15. Acquired C1 esterase inhibitor deficiency in lymphomas: prevalence, symptoms, and response to treatment. (United States)

    Bekos, Christine; Perkmann, Thomas; Krauth, Maria; Raderer, Markus; Lechner, Klaus; Jaeger, Ulrich


    We retrospectively studied the prevalence of C1 esterase inhibitor (C1 INH) deficiency in 131 patients with various lymphomas. We determined C1 INH activity, C1 INH antigen, and C4 concentration at diagnosis and after chemotherapy. In follicular lymphoma (FL), diffuse large B-cell lymphoma (DLBCL) and chronic lymphocytic leukemia (CLL) consecutive patients were studied. In these entities, the prevalence of C1 INH deficiency was 10.2% in DLBCL, 4.1% in CLL, and 0% in FL and Hodgkin lymphoma. In indolent lymphomas, we identified only single cases of C1 INH deficiency, predominantly in splenic marginal zone lymphomas (SMZL) (four cases). Only three patients were symptomatic while the majority (11 cases) was asymptomatic. In DLBCL patients who were successfully treated with chemotherapy, complete normalization of C1 INH activity and C4 was observed. In contrast, C1 INH deficiency remained in SMZL patients after splenectomy. We conclude that C1 INH deficiency in lymphomas is frequently asymptomatic and responsive to immunochemotherapy.

  16. Impact of iron deficiency anemia on the function of the immune system in children (United States)

    Hassan, Tamer Hasan; Badr, Mohamed Ahmed; Karam, Nehad Ahmed; Zkaria, Marwa; El Saadany, Hosam Fathy; Abdel Rahman, Doaa Mohamed; Shahbah, Doaa Abdallah; Al Morshedy, Salah Mohamed; Fathy, Manar; Esh, Asmaa Mohamed Hosni; Selim, Amal Mohamed


    Abstract The importance of iron deficiency as a public health problem is based ultimately on the seriousness of its consequences on health. The most extensively investigated consequences of iron deficiency involve work performance and immune function. The significance of the effects on work performance is generally accepted. In contrast, data on the influence of iron deficiency on immune function are often perceived as being confusing and contradictory. We aimed to evaluate the effect of iron deficiency anemia on humoral, cellular, nonspecific immunity, and also the effect on the cytokines that are the key factors of many immunologic steps. Forty children with iron deficiency anemia and 20 age and sex-matched healthy children were included. All children were subjected to full medical history, thorough clinical examination, complete blood count, iron indices (serum iron, serum total iron-binding capacity, serum ferritin, and transferrin saturation), immunoglobulin assay (IgA, IgG, and IgM), interleukin (IL)-6 serum level, study of T-lymphocyte subsets, and evaluation of phagocytic function of macrophages and oxidative burst activity of neutrophils. Patients had significantly lower IgG levels, IL-6, phagocytic activity, and oxidative burst of neutrophils than controls, although there was no significant difference between patients and controls with regard to other immunoglobulins and CD4/CD8 ratio. There was significantly positive correlation between serum iron and IL-6 serum level. We concluded that humoral, nonspecific immunity (phagocytic activity and oxidative burst), and the IL-6 are influenced in patients with iron deficiency anemia. Study of these abnormalities after correction of iron deficiency is strongly needed. PMID:27893677

  17. Related progress of CT-guided percutaneous biopsy in the thoracic complications of acquired immune deficiency syndrome and occupational exposure prevention%CT引导下经皮穿刺活检术在获得性免疫缺陷综合征胸部并发症中的应用及职业暴露防护相关进展

    Institute of Scientific and Technical Information of China (English)



    CT-guided percutaneous biopsy in the thoracic complications of acquired immunodeficiency syndrome (AIDS)is the main clear diagnosis method.The application of technical solutions, complications and prevention, occupational exposure protection principles and methods of CT-guided percutaneous biopsy in thoracic complications of AIDS were reviewed in this article.%CT引导下经皮穿刺活检术是确诊获得性免疫缺陷综合征(AIDS)胸部并发症的主要方法.本文对CT引导下经皮穿刺活检术在AIDS胸部并发症中应用的技术方案、并发症及预防,职业暴露防护原则及方法进行综述.

  18. Infection-derived lipids elicit a novel immune deficiency circuitry in arthropods (United States)

    The insect Immune Deficiency (IMD) pathway resembles the tumor necrosis factor receptor network in mammals and senses diaminopimelic-type peptidoglycans present in Gram-negative bacteria. Whether unidentified chemical moieties elicit the IMD signaling cascade remains unknown. Here, we disclose thoug...

  19. 5-Lipoxygenase deficiency impairs innate and adaptive immune responses during fungal infection.

    Directory of Open Access Journals (Sweden)

    Adriana Secatto

    Full Text Available 5-Lipoxygenase-derived products have been implicated in both the inhibition and promotion of chronic infection. Here, we sought to investigate the roles of endogenous 5-lipoxygenase products and exogenous leukotrienes during Histoplasma capsulatum infection in vivo and in vitro. 5-LO deficiency led to increased lung CFU, decreased nitric oxide production and a deficient primary immune response during active fungal infection. Moreover, H. capsulatum-infected 5-LO(-/- mice showed an intense influx of neutrophils and an impaired ability to generate and recruit effector T cells to the lung. The fungal susceptibility of 5-LO(-/- mice correlated with a lower rate of macrophage ingestion of IgG-H. capsulatum relative to WT macrophages. Conversely, exogenous LTB4 and LTC4 restored macrophage phagocytosis in 5-LO deficient mice. Our results demonstrate that leukotrienes are required to control chronic fungal infection by amplifying both the innate and adaptive immune response during histoplasmosis.

  20. To Analyze the Training Effect on Clinical Nursing Practice of Acquired Immune Deifciency Syndrome for Nursing Staff%分析护理人员艾滋病临床护理实践的培训效果

    Institute of Scientific and Technical Information of China (English)



    目的:分析护理人员艾滋病临床护理实践的培训效果。方法选择我院执业护士80名,对所有护理人员均给予艾滋病临床护理实践培训,比较培训前后的艾滋病相关知识掌握情况。结果培训后护理人员的艾滋病综合知识得分优于培训前,两者比较,P<0.05,差异具有统计学意义。结论通过艾滋病临床护理实践培训,可以让护理人员更好掌握艾滋病的相关知识。%Objective Analysis analyze the training effect on clinical nursing practice of acquired immune deifciency syndrome for nursing staff. Methods Selected 80 cases nurse practitioner in our hospital, all of them were given acquired immune deficiency syndrome training for clinical nursing practice, compared the grasp knowledge situation before and after nursing practice. Results After training nursing staff's comprehensive acquired immune deficiency syndrome knowledge score was better than before the training, P<0.05, had difference statistical significance. Conclusion Nursing staff can grasp acquired immune deifciency syndrome relevant knowledge better with clinical nursing practice of acquired immune deifciency syndrome.

  1. Care for eyes of patients with acquired immune deficiency syndrome complicated with cryptococcal meningitis%获得性免疫缺陷综合征合并隐球菌性脑膜炎患者的眼部护理

    Institute of Scientific and Technical Information of China (English)

    许雪静; 柳月红; 刘彬彬; 董愉


    Objective To summarize the complications and nursing methods for eyes of the patients with acquired immunodeficiency syndrome (AIDS)and Cryptococcal meningitis. Methods Total of 42 AIDS patients complicated with Cryptococcal meningitis infection in eyes were analyzed, while the nursing plans were summarized. Results There were 19 cases (37 eyes) with papilledemas; 6 cases (12 eyes) with optic atrophy; 2 cases (4 eyes) with multifocal choroiditis; 3 cases (6 eyes) with diplopias; one eye of a patient with cytomegalovirus retinitis (CMVR). Eleven cases were with normal fundus. Among the 84 eyes, the visual acuity of 17 eyes were light perception to 0.1; 12 eyes were 0.12-0.3. The cases with the visual acuities less than 0.3 were 34.52%. The visual acuities of 55 eyes with the 0.4 to 1.0. Conclusions In clinical nursing, it is beneficial for the patients to manage the condition and improve the quality of life, by observing the change of intracranial pressure, visual acuity and fundus closely, and the exercises of life skills and vision trainings for patients with low visions were improved.%目的:总结获得性免疫缺陷综合征(AIDS)合并隐球菌性脑膜炎患者的眼部并发症及眼部护理方法。方法回顾性分析42例AIDS合并隐球菌性脑膜炎患者的眼部并发症,总结其护理方案。结果19例患者(37只眼)出现视乳头水肿,6例患者(12只眼)出现视神经萎缩,2例患者(4只眼)出现脉络膜病灶,3例患者(6只眼)出现复视,1例患者单眼合并巨细胞病毒性视网膜炎(CMVR)。11例患者眼底正常。42例患者(84只眼)中17只眼视力为光感~0.1,12只眼视力为0.12~0.3,视力≤0.3的患眼占总数的34.5%,55只眼视力为0.4~1.0。结论临床护理工作中应密切观察患者的颅内压、视力及眼底变化,对低视力患者加强生活技能及视力的训练,有利于控制病情,提高患者的生活质量。

  2. Effects of early vitamin D deficiency rickets on bone and dental health, growth and immunity. (United States)

    Zerofsky, Melissa; Ryder, Mark; Bhatia, Suruchi; Stephensen, Charles B; King, Janet; Fung, Ellen B


    Vitamin D deficiency is associated with adverse health outcomes, including impaired bone growth, gingival inflammation and increased risk for autoimmune disease, but the relationship between vitamin D deficiency rickets in childhood and long-term health has not been studied. In this study, we assessed the effect of early vitamin D deficiency on growth, bone density, dental health and immune function in later childhood to determine if children previously diagnosed with rickets were at greater risk of adverse health outcomes compared with healthy children. We measured serum 25-hydroxyvitamin D, calcium, parathyroid hormone, bone mineral density, anthropometric measures, dietary habits, dental health, general health history, and markers of inflammation in 14 previously diagnosed rickets case children at Children's Hospital Oakland Research Center. We compared the findings in the rickets cases with 11 healthy children selected from the population of CHO staff families. Fourteen mothers of the rickets cases, five siblings of the rickets cases, and seven mothers of healthy children also participated. Children diagnosed with vitamin D deficiency rickets had a greater risk of fracture, greater prevalence of asthma, and more dental enamel defects compared with healthy children. Given the widespread actions of vitamin D, it is likely that early-life vitamin D deficiency may increase the risk of disease later in childhood. Further assessment of the long-term health effects of early deficiency is necessary to make appropriate dietary recommendations for infants at risk of deficiency.

  3. Constitutive and Acquired Serotonin Deficiency Alters Memory and Hippocampal Synaptic Plasticity. (United States)

    Fernandez, Sebastian P; Muzerelle, Aude; Scotto-Lomassese, Sophie; Barik, Jacques; Gruart, Agnès; Delgado-García, José M; Gaspar, Patricia


    Serotonin (5-HT) deficiency occurs in a number of brain disorders that affect cognitive function. However, a direct causal relationship between 5-HT hypo-transmission and memory and underlying mechanisms has not been established. We used mice with a constitutive depletion of 5-HT brain levels (Pet1KO mice) to analyze the contribution of 5-HT to different forms of learning and memory. Pet1KO mice exhibited a striking deficit in novel object recognition memory, a hippocampal-dependent task. No alterations were found in tasks for social recognition, procedural learning, or fear memory. Viral delivery of designer receptors exclusively activated by designer drugs was used to selectively silence the activity of 5-HT neurons in the raphe. Inhibition of 5-HT neurons in the median raphe, but not the dorsal raphe, was sufficient to impair object recognition in adult mice. In vivo electrophysiology in behaving mice showed that long-term potentiation in the hippocampus of 5-HT-deficient mice was altered, and administration of the 5-HT1A agonist 8-OHDPAT rescued the memory deficits. Our data suggest that hyposerotonergia selectively affects declarative hippocampal-dependent memory. Serotonergic projections from the median raphe are necessary to regulate object memory and hippocampal synaptic plasticity processes, through an inhibitory control mediated by 5-HT1A receptors.

  4. Passive transfer of naturally acquired specific immunity against West Nile Virus to foals in a semi-feral pony herd. (United States)

    Wilkins, Pamela A; Glaser, Amy L; McDonnell, Sue M


    Horses naturally exposed to West Nile Virus (WNV) or vaccinated against WNV develop humoral immunity thought to be protective against development of clinical disease in exposed or infected animals. No reports evaluate the efficacy of passive transfer of naturally acquired specific WNV humoral immunity from dam to foal. The purpose of this study was to investigate passive transfer of naturally acquired immunity to WNV to foals born in a herd of semi-feral ponies, not vaccinated against WNV, in an endemic area, with many dams having seroconverted because of natural exposure. Microwell serum neutralization titers against WNV were determined in all mares and foals. Serum IgG concentration was determined in foals by serial radial immunodiffusion. Differences in IgG concentration between seropositive and seronegative foals were examined by means of the Mann-Whitney U-test. Linear regression was used to evaluate the association between mare and foal titers. Seventeen mare-foal pairs were studied; 1 foal had inadequate IgG concentration. IgG concentration was not different between seronegative and seropositive foals (P = .24). Mare and foal titers were significantly correlated in foals with adequate passive transfer of immunity (Spearman's rho = .84; P 90% of the foal's titer was explained by the mare's titer (R2 = 0.91; P immunity to WNV is present in pony foals with adequate passive transfer of immunity born to seroconverted mares.

  5. Acquired absolute vitamin K deficiency in a patient undergoing warfarin therapy. (United States)

    Takada, Hiroaki; Toru, Hifumi; Bunya, Naofumi; Kiriu, Nobuaki; Kato, Hiroshi; Koido, Yuichi; Yasuhiro, Kuroda


    We report a case of absolute vitamin K deficiency (VKD) diagnosed by measuring serum VK levels in an elderly woman undergoing warfarin therapy. A 78-year-old woman was admitted to our hospital because of dyspnea and sore throat diagnosed as pharyngitis 1 week before admission. On admission, the sore throat had exacerbated and dyspnea developed. She had history of atrial fibrillation, for which warfarin 1.5 mg/d was started approximately 10 years prior and her international normalized ratio (INR) had been maintained at an acceptable therapeutic level. Blood results revealed unmeasurable INR and abnormally prolonged activated partial thromboplastin time (APTT). She was diagnosed with adenoiditis and warfarin-related coagulopathy and administered intravenous VK (20 mg) and fresh frozen plasma (FFP; 4 U), which improved INR and APTT. Since the coagulopathy responded to intravenous VK administration, the patient was clinically diagnosed with warfarin-related relative VKD. Approximately 1 month later, she returned with complaints of sore throat. Blood results indicated abnormal INR (7.22) and APTT (N80.0 s). She was diagnosed with recurrent adenoiditis and VK deficient coagulopathy. The patient’s serum VK levels were low (VK1 level, 0.13 ng/mL; VK2 levels, 0.85 ng/mL). Initial treatment of VK (20 mg) and FFP followed by intravenous VK (20 mg/d) for 6 days, her symptoms dissipated. Warfarin was suspected to have caused absolute VKD. Severe coagulopathy in patients undergoing warfarin therapy is primarily caused by, relative VKD. However, the possibility of warfarin-related absolute VKD should be suspected when INRis not sufficiently improved by intravenous VK administration.

  6. Functions of innate and acquired immune system are reduced in domestic pigeons (Columba livia domestica) given a low protein diet. (United States)

    Mabuchi, Yuko; Frankel, Theresa L


    Racing pigeons are exposed to and act as carriers of diseases. Dietary protein requirement for their maintenance has not been determined experimentally despite their being domesticated for over 7000 years. A maintenance nitrogen (protein) requirement (MNR) for pigeons was determined in a balance study using diets containing 6, 10 and 14% crude protein (CP). Then, the effects of feeding the diets were investigated to determine whether they were adequate to sustain innate and acquired immune functions. Nitrogen intake from the 6% CP diet was sufficient to maintain nitrogen balance and body weight in pigeons. However, the immune functions of phagocytosis, oxidative burst and lymphocyte proliferation in pigeons fed this diet were reduced compared with those fed 10 and 14% CP diets. Pigeons given the 6 and 10% CP diets had lower antibody titres following inoculation against Newcastle disease (ND) than those on the 14% CP diet. A confounding factor found on autopsy was the presence of intestinal parasites in some of the pigeons given the 6 and 10% CP diets; however, none of the pigeons used to measure MNR or acquired immunity to ND were infested with parasites. In conclusion, neither the 6 nor 10% CP diets adequately sustained acquired immune function of pigeons.

  7. Acquired hookworm immunity in the golden hamster (Mesocricetus auratus) elicited by living Necator americanus third-stage infective larvae. (United States)

    Xue, Jian; Zhan, Bin; Guo, Jian; He, Na; Qiang, Hui-qing; Hotez, Peter; Xiao, Shu-hua


    The aim of the study is to demonstrate and understand the acquired immunity in golden hamsters (Mesocricetus auratus) elicited by primary Necator americanus infective third-stage larvae (L3) infection. Hamsters infected with 150 L3 for 1, 2, 3, 6 and 10 weeks, were challenged with the same number of L3 and sacrificed 25 days post challenge. The primarily infected hamsters exhibited 99-100% protection against subsequent L3 challenge compared to un-infected naive hamsters. The acquired immunity was developed as early as 1 week post L3 infection and lasted up to 10 weeks. Similar protective immunity was obtained in hamsters infected with N. americanus L3 and then treated orally with a single of 100mg/kg albendazole, followed by challenge with N. americanus L3 4 and 8 weeks post-treatment. The infected hamsters exhibited a rise in IgG antibodies against L3 and juvenile adult worm antigens. Histological examination showed that challenging L3 were trapped in the skin of primarily infected hamsters and surrounded or infiltrated by different inflammatory cells. The trapped L3 were damaged and dead followed by the formation of granulomas encasing dead worms. The results demonstrate that hamsters primarily infected with N. americanus L3 develop acquired immunity against re-infection.

  8. Suspected primary immune deficiency in a Donge de Bordeaux dog : short communication

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    R.G. Lobetti


    Full Text Available A young Donge de Bordeaux dog was presented with chronic intermittent antibiotic responsive gastrointestinal and respiratory disease. Further evaluation showed bacterial lymphadenitis, bacterial tracheitis, normal white cell and differential cell counts, hypogammaglobulinaemia, and the absence of B-lymphocytes but the presence of T-lymphocytes in the lymphoid tissue stained with lymphocyte markers. As the dog came from a narrow genetic base, with related dogs showing similar clinical signs, possible B-cell congenital immune deficiency was suspected.

  9. Nutritional zinc deficiency, immune capacity and malaria : a study on mediators of immunity to malaria caused by Plasmodium falciparum in African children

    NARCIS (Netherlands)

    Mbugi, E.V.


    This thesis aimed at investigating the role of genetic and nutritional factors that affect the immune response to malaria in Tanzanian children. The introductory chapter (Chapter 1) reviews the importance of nutritional deficiencies, particularly of zinc, and presents the hypothesis that such defici

  10. Gallium scans of the thorax in patients with acquired immune deficiency syndrome (AIDS): Description and utilization

    Energy Technology Data Exchange (ETDEWEB)

    Le, G.; Chen, D.C.P.; Siegel, M.E.


    The pattern of distribution of gallium uptake in the thorax was investigated in patients (pts) with AIDS. Eleven pts (ages 18-53), all active homosexual males suspected of having acute pulmonary infection were studied. Ga lung scans were performed at 24-48 and/or 72 hrs. post injection. The diagnosis of AIDS was based on appropriate clinical and laboratory findings. The Ga activity in the lung was graded from zero = background to 4+ which is > liver activity. Eight of eleven pts have positive Ga scan while seven of eleven pts had positive CXR. Six pts had both positive CXR and Ga scan. One pt had a positive Ga scan with negative CXR, and one with positive CXR and negative Ga scan. The positive Ga scans included 3 pts with 4+ diffuse uptake, two pts with 2+ diffuse uptake, two pts with 1+ diffuse uptake, and two with hilar node uptake. Three pts have focal increased uptake superimposed on diffuse uptake. Two pts with 4+ diffuse uptake had mild abnormality on their CXR. One pt with 4+ uptake in the initial scan shows decreased activity on follow-up with clinical improvement after therapy. Thus, all but two pts with positive Ga scans had diffuse lung uptake. These two patients alone had B cell immunoblastic sarcoma and oral candidiasis. The pattern of Ga lung uptake in pts with AIDS reveal that a majority of positive scans are diffuse (6/8) and the intensity may suggest more active disease than CXR (2 normal) and, thus, the study may be useful in detecting changes from atypical pulmonary infection in this population.

  11. A rare radiological manifestation of disseminated tuberculous spondylitisin acquired immune deficiency syndrome patient: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung Won; Koo, Joon Bum; Kim, Tae Eun [Dept. of of Radiology, Dongguk University Ilsan Hospital, Dongguk University School of Medicine, Goyang (Korea, Republic of)


    The spine is the most common site of skeletal involvement in tuberculosis. The radiologic features are reportedly characterized by destruction of the vertebral body, subligamentous extension or subchondral penetration, frequent paravertebral abscess formation and late involvement of the disk space. We experienced a case of a 25-year-old male who was a human immunodeficiency virus carrier without antiretroviral therapy. Incidental findings on abdominal computed tomography included multiple well-demarcated and ovoid osteolytic lesions with hyperdense rims disseminated in the thoracic, lumbar, and sacrum vertebrae, as well as in both ilii. On the lumbar spine magnetic resonance imaging, multiple small round lesions of isointense signal intensity with peripheral hyperintense rims were found on both T1- and T2-weighted imaging. The lesions had peripheral rim enhancement on gadolinium-enhanced T1-weighted imaging. Based on our experience, this rare image finding is one of the manifestations of disseminated tuberculosis.

  12. Pancytopenia and cutaneous cryptococcosis as an indicator disease of acquired immune deficiency syndrome

    Directory of Open Access Journals (Sweden)

    R Khuraijam


    Full Text Available We present a case of pancytopenia and cutaneous cryptococcosis in a young girl with no complaints of fever, headache and vomiting. Fine-needle aspiration cytology and further investigation for pancytopenia revealed presence of Cryptococcus in skin and bone marrow aspirates. Fungal cultures of the skin aspirates, blood and bone marrow confirmed cryptococcal infection. Counselling and human immunodeficiency virus (HIV test revealed the status of the patient to be retropositive. Although meningitis is the commonest manifestation of cryptococcosis among HIV-infected patients, rare cutaneous manifestation with pancytopenia but with no meningeal signs indicate the HIV status in an endemic area of penicilliosis, Manipur.

  13. Transgenic petunia with the iron(III-phytosiderophore transporter gene acquires tolerance to iron deficiency in alkaline environments.

    Directory of Open Access Journals (Sweden)

    Yoshiko Murata

    Full Text Available Iron is an essential nutrient for all plants. However, terrestrial plants often suffer from iron deficiency in alkaline soil due to its extremely low solubility. Alkaline soil accounts for about 30% of all cultivated ground in the world. Plants have evolved two distinct strategies, I and II, for iron uptake from the soil. Dicots and non-graminaceous monocots use Strategy I, which is primarily based on the reduction of iron(III to iron(II and the uptake of iron(II by the iron-regulated transporter, IRT1. In contrast, graminaceous plants use Strategy II to efficiently acquire insoluble iron(III. Strategy II comprises the synthesis and secretion of iron-chelating phytosiderophores, such as mugineic acids and the Yellow Stripe 1 transporter proteins of the iron(III-phytosiderophore complex. Barley, which exhibits the highest tolerance to iron deficiency in alkaline soil among graminaceous plants, utilizes mugineic acids and the specific iron(III-mugineic acids transporter, HvYS1. In this study, we established the transgenic plant Petunia hybrida, which originally had only Strategy I, by introducing the HvYS1 transporter gene derived from barley. When the transgenic plants were grown hydroponically in media containing the iron(III-2'-deoxymugineic acid complex, free 2'-deoxymugineic acid and its iron(III complex were detected in the root extract of the transgenic plant by electrospray ionization-Fourier transform-ion cyclotron resonance mass spectrometry. The growth of the transgenic petunia was significantly better than that of the control host in alkaline conditions. Consequently, the transgenic plant acquired a significantly enhanced tolerance to alkaline hydroponic media in the presence of the iron(III-2'-deoxymugineic acid complex. Furthermore, the flower color of the transgenic plant deepened. The results showed that iron-phytosiderophore complexes and their transporters can potentially be utilized to overcome the worldwide iron uptake problems

  14. Immune deficiency vs. immune excess in inflammatory bowel diseases-STAT3 as a rheo-STAT of intestinal homeostasis. (United States)

    Leppkes, Moritz; Neurath, Markus F; Herrmann, Martin; Becker, Christoph


    Genome-wide association studies have provided many genetic alterations, conferring susceptibility to multifactorial polygenic diseases, such as inflammatory bowel diseases. Yet, how specific genetic alterations functionally affect intestinal inflammation often remains elusive. It is noteworthy that a large overlap of genes involved in immune deficiencies with those conferring inflammatory bowel disease risk has been noted. This has provided new arguments for the debate on whether inflammatory bowel disease arises from either an excess or a deficiency in the immune system. In this review, we highlight the functional effect of an inflammatory bowel disease-risk allele, which cannot be deduced from genome-wide association studies data alone. As exemplified by the transcription factor signal transducer and activator of transcription 3 (STAT3), we show that a single gene can have a plethora of effects in various cell types of the gut. These effects may individually contribute to the restoration of intestinal homeostasis on the one hand or pave the way for excessive immunopathology on the other, as an inflammatory "rheo-STAT".

  15. Deficient BIM Expression as a Mechanism of Intrinsic and Acquired Resistance to Targeted Therapies in EGFR-Mutant and ALK-Positive Lung Cancers (United States)


    AWARD NUMBER: W81XWH-13-1-0227 TITLE: Deficient BIM Expression as a Mechanism of Intrinsic and Acquired Resistance to Targeted Therapies in...TYPE Annual 3. DATES COVERED 1 Aug 2014 - 31 Jul 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Deficient BIM Expression as a Mechanism of Intrinsic...time of resistance. We are now using these patient-derived cell lines to assess BIM levels and apoptotic response to next-generation inhibitors. The

  16. Acquired Form of Angioedema of the Head and Neck Related to a Deficiency in C1-Inhibitor: A Case Report with a Review of the Literature

    Directory of Open Access Journals (Sweden)

    Bassel Hallak


    Full Text Available Angioedema related to a deficiency in the C1-inhibitor protein is characterized by its lack of response to therapies including antihistamine, steroids, and epinephrine. In the case of laryngeal edema, mortality rate is approximately 30 percent. The first case of the acquired form of angioedema related to a deficiency in C1-inhibitor was published in 1972. In our paper, we present a case of an acquired form of angioedema of the oropharyngeal region secondary to the simultaneous occurrence of two causative factors: neutralization of C1-inhibitor by an autoantibody and the use of an angiotensin convertin enzyme inhibitor.

  17. Immunization with lipopolysaccharide-deficient whole cells provides protective immunity in an experimental mouse model of Acinetobacter baumannii infection. (United States)

    García-Quintanilla, Meritxell; Pulido, Marina R; Pachón, Jerónimo; McConnell, Michael J


    The increasing clinical importance of infections caused by multidrug resistant Acinetobacter baumannii warrants the development of novel approaches for prevention and treatment. In this context, vaccination of certain patient populations may contribute to reducing the morbidity and mortality caused by this pathogen. Vaccines against Gram-negative bacteria based on inactivated bacterial cells are highly immunogenic and have been shown to produce protective immunity against a number of bacterial species. However, the high endotoxin levels present in these vaccines due to the presence of lipopolysaccharide complicates their use in human vaccination. In the present study, we used a laboratory-derived strain of A. baumannii that completely lacks lipopolysaccharide due to a mutation in the lpxD gene (IB010), one of the genes involved in the first steps of lipopolysaccharide biosynthesis, for vaccination. We demonstrate that IB010 has greatly reduced endotoxin content (infection tissue bacterial loads and significantly lower serum levels of the pro-inflammatory cytokines IL-1β, TNF-α and IL-6 compared to control mice in a mouse model of disseminated A. baumannii infection. Importantly, immunized mice were protected from infection with the ATCC 19606 strain and an A. baumannii clinical isolate. These data suggest that immunization with inactivated A. baumannii whole cells deficient in lipopolysaccharide could serve as the basis for a vaccine for the prevention of infection caused by A. baumannii.

  18. Selenium Deficiency Attenuates Chicken Duodenal Mucosal Immunity via Activation of the NF-κb Signaling Pathway. (United States)

    Liu, Zhe; Qu, Yanpeng; Wang, Jianfa; Wu, Rui


    Selenium (Se) deficiency can cause intestinal mucosal inflammation, which is related to activation of nuclear transcription factor kappa-B (NF-κB) signaling pathway. However, the mechanism of inflammatory response in chicken duodenal mucosa caused by Se deficiency and its relationship with the NF-κB signaling pathway remain elusive. In this study, we firstly obtained Se-deficient chickens bred with 0.01 mg/kg Se and the normal chickens bred with 0.4 mg/kg Se for 35 days. Then, NF-κB signaling pathway, secretory immunoglobulin A (SIgA), inflammatory cytokines, oxidized glutathione, glutathione peroxidase, and glutathione activities were determined. The results showed that Se deficiency obviously enhanced p50, p65, and p65 DNA-binding activities. The phosphorylation of IκB-α and phosphorylation of kappa-B kinase subunit alpha (IKKα) and IKKα were elevated, but IκB-α was decreased (P mucosal immunity via activation of NF-κB signaling pathway regulated by redox activity, which suggested that Se is a crucial host factor involved in regulating inflammation.

  19. The immune response in SAPHO syndrome: deficiency, hyper- responsiveness, or both? (United States)

    Hayem, Gilles; Hurtado-Nedelec, Margarita; Chollet-Martin, Sylvie


    The pathophysiology of SAPHO syndrome still remains to be determined. However, like in other forms of spondylarthritides, this rare condition seems to result from the combination of genetic, environmental and immunological factors. Surely, SAPHO syndrome cannot be simply regarded as the adult form of the 'caricatural' DIRA (deficiency in interleukin-1 receptor antagonist) syndrome, although this purely genetic disease also causes multiple osteomyelitis and pustular rashes. An initial bacterial trigger, mainly represented by the cutaneous saprophyte Propionibacterium acnes, could take advantage of a selective deficiency of the innate immunity, implicating neutrophils. This could elicit thereafter a 'hyperimmune' reaction, as in other chronic inflammatory conditions like reactive arthritis, Crohn's disease or hidradenitis suppurativa. The reported efficacy of either longterm antibiotic regimens (especially with azithromycin) or immunomodulatory biologic agents targetting TNF-α or IL-1 supports the concept of a post- or para-infectious hyperresponsiveness disorder, with a convincing rationale for 'hybrid' therapies.

  20. Recent advances in transplantation for primary immune deficiency diseases: a comprehensive review. (United States)

    de la Morena, M Teresa; Nelson, Robert P


    Hematopoietic cell transplantation (HCT) is a curative therapeutic option for severe combined immunodeficiency (SCID), a group of diseases which otherwise carry life expectancies that are of limited duration and quality. Survival following HCT for SCID has improved from approximately 23 to 91 % over the last 40 years. Success with SCID prompted efforts to apply HCT to the therapeutic challenge of well over 20 molecularly defined primary immune deficiency diseases (PID). Such success is due to both early recognition of PIDs and advances in the field of transplantation. Such advances include high-resolution HLA DNA donor-recipient matching, expansion of donor sources, better tolerated conditioning, new antibiotics, and wider availability. International collaborative efforts have provided patients and caregivers information that permit better treatment decisions now, and direct clinicians and investigators to ensure progress in the future. Pioneers in screening for SCID have taken steps to correct the fundamental challenge to successful treatment, which is the rapid discovery and characterization of cases and offering the transplant option to an affected child early in life; blood spot testing for T and B cell receptor quantification is now available to a growing fraction of newborns. Organizations including the Primary Immune Deficiency Treatment Consortium in the USA, The European Society for Primary Immunodeficiency, the European Group for Blood and Marrow Transplantation, the Pediatric Blood and Marrow Transplant Consortium, the United States Immunodeficiency Network, the Immune Deficiency Foundation, and the Jeffrey Modell Foundation are contributing mightily to increase awareness and standardize optimal utilization to the benefit of patients. This review will update the allergist-immunologist concerning disease presentations, indications for transplantation, methodologies, conditioning regimens, and clinical outcomes for patients with PID for which timely HCT is

  1. Vitamin d deficiency in a multiethnic healthy control cohort and altered immune response in vitamin D deficient European-American healthy controls.

    Directory of Open Access Journals (Sweden)

    Lauren L Ritterhouse

    Full Text Available In recent years, vitamin D has been shown to possess a wide range of immunomodulatory effects. Although there is extensive amount of research on vitamin D, we lack a comprehensive understanding of the prevalence of vitamin D deficiency or the mechanism by which vitamin D regulates the human immune system. This study examined the prevalence and correlates of vitamin D deficiency and the relationship between vitamin D and the immune system in healthy individuals.Healthy individuals (n = 774 comprised of European-Americans (EA, n = 470, African-Americans (AA, n = 125, and Native Americans (NA, n = 179 were screened for 25-hydroxyvitamin D [25(OHD] levels by ELISA. To identify the most noticeable effects of vitamin D on the immune system, 20 EA individuals with severely deficient (24.8 ng/mL vitamin D levels were matched and selected for further analysis. Serum cytokine level measurement, immune cell phenotyping, and phosphoflow cytometry were performed.Vitamin D sufficiency was observed in 37.5% of the study cohort. By multivariate analysis, AA, NA, and females with a high body mass index (BMI, >30 demonstrate higher rates of vitamin D deficiency (p<0.05. Individuals with vitamin D deficiency had significantly higher levels of serum GM-CSF (p = 0.04, decreased circulating activated CD4+ (p = 0.04 and CD8+ T (p = 0.04 cell frequencies than individuals with sufficient vitamin D levels.A large portion of healthy individuals have vitamin D deficiency. These individuals have altered T and B cell responses, indicating that the absence of sufficient vitamin D levels could result in undesirable cellular and molecular alterations ultimately contributing to immune dysregulation.

  2. Depressed immune surveillance against cancer: role of deficient T cell: extracellular matrix interactions. (United States)

    Górski, A; Castronovo, V; Stepień-Sopniewska, B; Grieb, P; Ryba, M; Mrowiec, T; Korczak-Kowalska, G; Wierzbicki, P; Matysiak, W; Dybowska, B


    Although T cells infiltrate malignant tumors, the local immune response is usually inefficient and tumors escape destruction. While extracellular matrix proteins strongly costimulate T cell responses in normal individuals, our studies indicate that peripheral blood T cells from cancer patients and tumor infiltrating cells respond poorly or are resistant to stimulative signals mediated by collagen I and IV and fibronectin. Moreover, the adhesive properties of cancer T cells are markedly depressed. Those functional deficiencies are paralleled by variable deficits in integrin and non-integrin T cell receptors for extracellular matrix. Immunotherapy with BCG causes a dramatic but transient increase in T cell: ECM interactions.

  3. Hereditary and acquired angioedema: problems and progress: proceedings of the third C1 esterase inhibitor deficiency workshop and beyond. (United States)

    Agostoni, Angelo; Aygören-Pürsün, Emel; Binkley, Karen E; Blanch, Alvaro; Bork, Konrad; Bouillet, Laurence; Bucher, Christoph; Castaldo, Anthony J; Cicardi, Marco; Davis, Alvin E; De Carolis, Caterina; Drouet, Christian; Duponchel, Christiane; Farkas, Henriette; Fáy, Kálmán; Fekete, Béla; Fischer, Bettina; Fontana, Luigi; Füst, George; Giacomelli, Roberto; Gröner, Albrecht; Hack, C Erik; Harmat, George; Jakenfelds, John; Juers, Mathias; Kalmár, Lajos; Kaposi, Pál N; Karádi, István; Kitzinger, Arianna; Kollár, Tímea; Kreuz, Wolfhart; Lakatos, Peter; Longhurst, Hilary J; Lopez-Trascasa, Margarita; Martinez-Saguer, Inmaculada; Monnier, Nicole; Nagy, István; Németh, Eva; Nielsen, Erik Waage; Nuijens, Jan H; O'grady, Caroline; Pappalardo, Emanuela; Penna, Vincenzo; Perricone, Carlo; Perricone, Roberto; Rauch, Ursula; Roche, Olga; Rusicke, Eva; Späth, Peter J; Szendei, George; Takács, Edit; Tordai, Attila; Truedsson, Lennart; Varga, Lilian; Visy, Beáta; Williams, Kayla; Zanichelli, Andrea; Zingale, Lorenza


    Hereditary angioedema (HAE), a rare but life-threatening condition, manifests as acute attacks of facial, laryngeal, genital, or peripheral swelling or abdominal pain secondary to intra-abdominal edema. Resulting from mutations affecting C1 esterase inhibitor (C1-INH), inhibitor of the first complement system component, attacks are not histamine-mediated and do not respond to antihistamines or corticosteroids. Low awareness and resemblance to other disorders often delay diagnosis; despite availability of C1-INH replacement in some countries, no approved, safe acute attack therapy exists in the United States. The biennial C1 Esterase Inhibitor Deficiency Workshops resulted from a European initiative for better knowledge and treatment of HAE and related diseases. This supplement contains work presented at the third workshop and expanded content toward a definitive picture of angioedema in the absence of allergy. Most notably, it includes cumulative genetic investigations; multinational laboratory diagnosis recommendations; current pathogenesis hypotheses; suggested prophylaxis and acute attack treatment, including home treatment; future treatment options; and analysis of patient subpopulations, including pediatric patients and patients whose angioedema worsened during pregnancy or hormone administration. Causes and management of acquired angioedema and a new type of angioedema with normal C1-INH are also discussed. Collaborative patient and physician efforts, crucial in rare diseases, are emphasized. This supplement seeks to raise awareness and aid diagnosis of HAE, optimize treatment for all patients, and provide a platform for further research in this rare, partially understood disorder.

  4. Pertactin deficient Bordetella pertussis present a better fitness in mice immunized with an acellular pertussis vaccine. (United States)

    Hegerle, N; Dore, G; Guiso, N


    Bordetella pertussis is the etiologic agent of whooping cough and has been the target of vaccination for over fifty years. The latest strategies include the use of acellular pertussis vaccines that induce specific immunity against few virulence factors amongst which pertactin is included in three and five component acellular pertussis vaccines. Recently, it has been reported that B. pertussis clinical isolates loose the production of this adhesin in regions reaching high vaccine coverage with vaccines targeting this virulence factor. We here demonstrate that isolates not producing pertactin are capable of sustaining longer infection as compared to pertactin producing isolates in an in vivo model of acellular pertussis immunization. Loosing pertactin production might thus provide a selective advantage to these isolates in this background, which could account for the upraise in prevalence of these pertactin deficient isolates in the population.

  5. TREX1 deficiency triggers cell-autonomous immunity in a cGAS-dependent manner. (United States)

    Ablasser, Andrea; Hemmerling, Inga; Schmid-Burgk, Jonathan L; Behrendt, Rayk; Roers, Axel; Hornung, Veit


    Cytosolic detection of DNA is crucial for the initiation of antiviral immunity but can also cause autoimmunity in the context of endogenous nucleic acids being sensed. Mutations in the human 3' repair exonuclease 1 (TREX1) have been linked to the type I IFN-associated autoimmune disease Aicardi-Goutières syndrome. The exact mechanisms driving unabated type I IFN responses in the absence of TREX1 are only partly understood, but it appears likely that accumulation of endogenous DNA species triggers a cell-autonomous immune response by activating a cytosolic DNA receptor. In this article, we demonstrate that knocking out the DNA sensor cyclic GMP-AMP synthase completely abrogates spontaneous induction of IFN-stimulated genes in TREX1-deficient cells. These findings indicate a key role of cyclic GMP-AMP synthase for the initiation of self-DNA-induced autoimmune disorders, thus providing important implications for novel therapeutic approaches.

  6. BLyS inhibition eliminates primary B cells but leaves natural and acquired humoral immunity intact


    Scholz, Jean L.; Crowley, Jenni E.; Tomayko, Mary M.; Steinel, Natalie; O'Neill, Patrick J.; Quinn, William J; Goenka, Radhika; Miller, Juli P; Cho, Yun Hee; Long, Vatana; Ward, Chris; Migone, Thi-Sau; Shlomchik, Mark J.; Cancro, Michael P.


    We have used an inhibiting antibody to determine whether preimmune versus antigen-experienced B cells differ in their requisites for BLyS, a cytokine that controls differentiation and survival. Whereas in vivo BLyS inhibition profoundly reduced naïve B cell numbers and primary immune responses, it had a markedly smaller effect on memory B cells and long-lived plasma cells, as well as secondary immune responses. There was heterogeneity within the memory pools, because IgM-bearing memory cells ...

  7. Deficiencies (United States)

    U.S. Department of Health & Human Services — A list of all deficiencies currently listed on Nursing Home Compare, including the nursing home that received the deficiency, the associated inspection date,...

  8. Development of vaccines against Plasmodium falciparum malaria: taking lessons from naturally acquired protective immunity

    DEFF Research Database (Denmark)

    Hviid, Lars


    The acquisition of substantial anti-malarial protection in people naturally exposed to P. falciparum is often cited as evidence that malaria vaccines can be developed, but is rarely used to guide the development. We are pursuing the development of vaccines based on antigens and immune responses...

  9. Improving cellular therapy for primary immune deficiency diseases: recognition, diagnosis, and management. (United States)

    Griffith, Linda M; Cowan, Morton J; Notarangelo, Luigi D; Puck, Jennifer M; Buckley, Rebecca H; Candotti, Fabio; Conley, Mary Ellen; Fleisher, Thomas A; Gaspar, H Bobby; Kohn, Donald B; Ochs, Hans D; O'Reilly, Richard J; Rizzo, J Douglas; Roifman, Chaim M; Small, Trudy N; Shearer, William T


    More than 20 North American academic centers account for the majority of hematopoietic stem cell transplantation (HCT) procedures for primary immunodeficiency diseases (PIDs), with smaller numbers performed at additional sites. Given the importance of a timely diagnosis of these rare diseases and the diversity of practice sites, there is a need for guidance as to best practices in management of patients with PIDs before, during, and in follow-up for definitive treatment. In this conference report of immune deficiency experts and HCT physicians who care for patients with PIDs, we present expert guidance for (1) PID diagnoses that are indications for HCT, including severe combined immunodeficiency disease (SCID), combined immunodeficiency disease, and other non-SCID diseases; (2) the critical importance of a high degree of suspicion of the primary care physician and timeliness of diagnosis for PIDs; (3) the need for rapid referral to an immune deficiency expert, center with experience in HCT, or both for patients with PIDs; (4) medical management of a child with suspicion of SCID/combined immunodeficiency disease while confirming the diagnosis, including infectious disease management and workup; (5) the posttransplantation follow-up visit schedule; (6) antimicrobial prophylaxis after transplantation, including gamma globulin administration; and (7) important indications for return to the transplantation center after discharge. Finally, we discuss the role of high-quality databases in treatment of PIDs and HCT as an element of the infrastructure that will be needed for productive multicenter clinical trials in these rare diseases.

  10. Is vitamin D deficiency involved in the immune reconstitution inflammatory syndrome?

    Directory of Open Access Journals (Sweden)

    Moreno-Reyes Rodrigo


    Full Text Available Abstract Background About 20–30% of persons with HIV infection, especially those living in countries with limited resources, experience an immune reconstitution inflammatory syndrome (IRIS after starting antiretroviral treatment. The active form of vitamin D, 1,25-dihydroxyvitamin D, is a key player in the clearance of pathogens and influences the level of inflammation and macrophage activation. Presentation of the hypothesis We hypothesize that low availability of 1,25-dihydroxyvitamin D, either due to vitamin D deficiency or due to polymorphisms in the vitamin D receptor or in its activating/inactivating enzymes, contributes to the appearance of IRIS. Furthermore, drug interactions with the enzymatic pathways of vitamin D could favour the development of IRIS. Testing the hypothesis Our hypothesis could be explored by a case-control study to assess the prevalence of vitamin D deficiency in HIV-infected patients on antiretroviral treatment who develop and do not develop IRIS. Implications of the hypothesis If the role of vitamin D in IRIS is confirmed, we would be able to screen patients at risk for IRIS by screening for vitamin D deficiency. After confirmation by means of a clinical trial, vitamin D supplementation could be a cheap and safe way to reduce the incidence of IRIS.

  11. Role of B Cells and Antibodies in Acquired Immunity against Mycobacterium tuberculosis (United States)

    Achkar, Jacqueline M.; Chan, John; Casadevall, Arturo


    Accumulating evidence has documented a role for B cells and antibodies (Abs) in the immunity against Mycobacterium tuberculosis (Mtb). Passive transfer studies with monoclonal antibodies (mAbs) against mycobacterial antigens have shown protection against the tubercle bacillus. B cells and Abs are believed to contribute to an enhanced immune response against Mtb by modulating various immunological components in the infected host including the T-cell compartment. Nevertheless, the extent and contribution of B cells and Abs to protection against Mtb remains uncertain. In this article we summarize the most relevant findings supporting the role of B cells and Abs in the defense against Mtb and discuss the potential mechanisms of protection. PMID:25301934

  12. Granulomatous skin lesions complicating Varicella infection in a patient with Rothmund-Thomson syndrome and immune deficiency: case report

    Directory of Open Access Journals (Sweden)

    Van Den Oord Joost


    Full Text Available Abstract Rothmund-Thomson syndrome (RTS(OMIM 268400 is a rare autosomal recessive genodermatosis characterized by poikiloderma, small stature, skeletal and dental abnormalities, cataract and an increased risk of cancer. It is caused by mutations in RECQL4 at 8q24. Immune deficiency is not described as a classical feature of the disease. Here we report the appearance of granulomatous skin lesions complicating primary Varicella Zoster Virus infection in a toddler with Rothmund Thomson syndrome and immune deficiency. Although granulomatous disorders are sometimes seen after Herpes zoster, they are even more rare after Varicella primary infection. Granulomas have hitherto not been described in Rothmund-Thomson syndrome. With this report we aim to stress the importance of screening for immune deficiency in patients with Rothmund-Thomson syndrome.

  13. Markedly impaired humoral immune response in mice deficient in complement receptors 1 and 2. (United States)

    Molina, H; Holers, V M; Li, B; Fung, Y; Mariathasan, S; Goellner, J; Strauss-Schoenberger, J; Karr, R W; Chaplin, D D


    Complement receptor 1 (CR1, CD35) and complement receptor 2 (CR2, CD21) have been implicated as regulators of B-cell activation. We explored the role of these receptors in the development of humoral immunity by generating CR1- and CR2-deficient mice using gene-targeting techniques. These mice have normal basal levels of IgM and of IgG isotypes. B- and T-cell development are overtly normal. Nevertheless, B-cell responses to low and high doses of a T-cell-dependent antigen are impaired with decreased titers of antigen-specific IgM and IgG isotypes. This defect is not complete because there is still partial activation of B lymphocytes during the primary immune response, with generation of splenic germinal centers and a detectable, although reduced, secondary antibody response. These data suggest that certain T-dependent antigens manifest an absolute dependence on complement receptors for the initiation of a normally robust immune response.

  14. Conditional IL-4/IL-13-deficient mice reveal a critical role of innate immune cells for protective immunity against gastrointestinal helminths. (United States)

    Oeser, K; Schwartz, C; Voehringer, D


    Approximately one-third of the world population is infected with gastrointestinal helminths. Studies in mouse models have demonstrated that the cytokines interleukin (IL)-4 and IL-13 are essential for worm expulsion, but the critical cellular source of these cytokines is poorly defined. Here, we compared the immune response to Nippostrongylus brasiliensis in wild-type, T cell-specific IL-4/IL-13-deficient and general IL-4/IL-13-deficient mice. We show that T cell-derived IL-4/IL-13 promoted T helper 2 (Th2) polarization in a paracrine manner, differentiation of alternatively activated macrophages, and tissue recruitment of innate effector cells. However, innate IL-4/IL-13 played the critical role for induction of goblet cell hyperplasia and secretion of effector molecules like Mucin5ac and RELMβ in the small intestine. Surprisingly, T cell-specific IL-4/IL-13-deficient and wild-type mice cleared the parasite with comparable efficiency, whereas IL-4/IL-13-deficient mice showed impaired expulsion. These findings demonstrate that IL-4/IL-13 produced by cells of the innate immune system is required and sufficient to initiate effective type 2 immune responses resulting in protective immunity against N. brasiliensis.

  15. BLyS inhibition eliminates primary B cells but leaves natural and acquired humoral immunity intact. (United States)

    Scholz, Jean L; Crowley, Jenni E; Tomayko, Mary M; Steinel, Natalie; O'Neill, Patrick J; Quinn, William J; Goenka, Radhika; Miller, Juli P; Cho, Yun Hee; Long, Vatana; Ward, Chris; Migone, Thi-Sau; Shlomchik, Mark J; Cancro, Michael P


    We have used an inhibiting antibody to determine whether preimmune versus antigen-experienced B cells differ in their requisites for BLyS, a cytokine that controls differentiation and survival. Whereas in vivo BLyS inhibition profoundly reduced naïve B cell numbers and primary immune responses, it had a markedly smaller effect on memory B cells and long-lived plasma cells, as well as secondary immune responses. There was heterogeneity within the memory pools, because IgM-bearing memory cells were sensitive to BLyS depletion whereas IgG-bearing memory cells were not, although both were more resistant than naïve cells. There was also heterogeneity within B1 pools, as splenic but not peritoneal B1 cells were diminished by anti-BLyS treatment, yet the number of natural antibody-secreting cells remained constant. Together, these findings show that memory B cells and natural antibody-secreting cells are BLyS-independent and suggest that these pools can be separately manipulated.

  16. Innate versus acquired immune response in the pathogenesis of recurrent idiopathic pericarditis. (United States)

    Cantarini, Luca; Luca, Cantarini; Imazio, Massimo; Massimo, Imazio; Brucato, Antonio; Antonio, Brucato; Lucherini, Orso Maria; Maria, Lucherini Orso; Galeazzi, Mauro; Mauro, Galeazzi


    The pathogenesis of recurrent pericarditis is still poorly understood and may be related either to viral infections or autoimmune and autoinflammatory disorders. The immune system plays a major role in the pathogenesis of the disease, modulating individual responses to different noxa and explaining the variable reported recurrence rate (ranging from 20% to 50% of patients) following an attack of acute or recurrent pericarditis. Increasing interest is currently being devoted to autoinflammatory disorders, a group of conditions characterized by spontaneously relapsing and remitting bouts of systemic inflammation without apparent involvement of antigen-specific T cells or significant production of auto-antibodies. Ongoing basic and clinical research is needed to provide further evidence for the understanding of this common and troublesome disease, and to develop targeted and more efficacious therapies.

  17. The WOMED model of benign thyroid disease: Acquired magnesium deficiency due to physical and psychological stressors relates to dysfunction of oxidative phosphorylation

    Directory of Open Access Journals (Sweden)

    Roy Moncayo


    Conclusions: We interpret the elevated thyroid vascularization and low magnesium levels as signs of an inflammatory process related to the musculoskeletal changes. Improvement of thyroid function and morphology can be achieved after correcting the influence of stressors together with the supplementation regime. We hypothesize that the central biochemical event in thyroid disease is that of an acquired, altered mitochondrial function due to deficiency of magnesium, selenium, and coenzyme Q10.

  18. Autosomal recessive PGM3 mutations link glycosylation defects to atopy, immune deficiency, autoimmunity, and neurocognitive impairment (United States)

    Zhang, Yu; Yu, Xiaomin; Ichikawa, Mie; Lyons, Jonathan J.; Datta, Shrimati; Lamborn, Ian T.; Jing, Huie; Kim, Emily S.; Biancalana, Matthew; Wolfe, Lynne A.; DiMaggio, Thomas; Matthews, Helen F.; Kranick, Sarah M.; Stone, Kelly D.; Holland, Steven M.; Reich, Daniel S.; Hughes, Jason D.; Mehmet, Huseyin; McElwee, Joshua; Freeman, Alexandra F.; Freeze, Hudson H.; Su, Helen C.; Milner, Joshua D.


    Background Identifying genetic syndromes that lead to significant atopic disease can open new pathways for investigation and intervention in allergy. Objective To define a genetic syndrome of severe atopy, elevated serum IgE, immune deficiency, autoimmunity, and motor and neurocognitive impairment. Methods Eight patients from two families who had similar syndromic features were studied. Thorough clinical evaluations, including brain MRI and sensory evoked potentials, were performed. Peripheral lymphocyte flow cytometry, antibody responses, and T cell cytokine production were measured. Whole exome sequencing was performed to identify disease-causing mutations. Immunoblotting, qRT-PCR, enzymatic assays, nucleotide sugar and sugar phosphate analyses along with MALDI-TOF mass spectrometry of glycans were used to determine the molecular consequences of the mutations. Results Marked atopy and autoimmunity were associated with increased TH2 and TH17 cytokine production by CD4+ T cells. Bacterial and viral infection susceptibility were noted along with T cell lymphopenia, particularly of CD8+ T cells, and reduced memory B cells. Apparent brain hypomyelination resulted in markedly delayed evoked potentials and likely contributed to neurological abnormalities. Disease segregated with novel autosomal recessive mutations in a single gene, phosphoglucomutase 3 (PGM3). Although PGM3 protein expression was variably diminished, impaired function was demonstrated by decreased enzyme activity and reduced UDP-GlcNAc, along with decreased O- and N-linked protein glycosylation in patients’ cells. These results define a new Congenital Disorder of Glycosylation. Conclusions Autosomal recessive, hypomorphic PGM3 mutations underlie a disorder of severe atopy, immune deficiency, autoimmunity, intellectual disability and hypomyelination. PMID:24589341

  19. Acquired resistance to innate immune clearance promotes Klebsiella pneumoniae ST258 pulmonary infection (United States)

    Ahn, Danielle; Peñaloza, Hernán; Wang, Zheng; Wickersham, Matthew; Parker, Dane; Patel, Purvi; Koller, Antonius; Chen, Emily I.; Bueno, Susan M.; Uhlemann, Anne-Catrin; Prince, Alice


    Adaptive changes in the genome of a locally predominant clinical isolate of the multidrug-resistant Klebsiella pneumoniae ST258 (KP35) were identified and help to explain the selection of this strain as a successful pulmonary pathogen. The acquisition of 4 new ortholog groups, including an arginine transporter, enabled KP35 to outcompete related ST258 strains lacking these genes. KP35 infection elicited a monocytic response, dominated by Ly6Chi monocytic myeloid-derived suppressor cells that lacked phagocytic capabilities, expressed IL-10, arginase, and antiinflammatory surface markers. In comparison with other K. pneumoniae strains, KP35 induced global changes in the phagocytic response identified with proteomics, including evasion of Ca2+ and calpain activation necessary for phagocytic killing, confirmed in functional studies with neutrophils. This comprehensive analysis of an ST258 K. pneumoniae isolate reveals ongoing genetic adaptation to host microenvironments and innate immune clearance mechanisms that complements its repertoire of antimicrobial resistance genes and facilitates persistence in the lung. PMID:27777978

  20. TLR7 Deficiency Leads to TLR8 Compensative Regulation of Immune Response against JEV in Mice (United States)

    Awais, Muhammad; Wang, Ke; Lin, Xianwu; Qian, Wenjie; Zhang, Nan; Wang, Chong; Wang, Kunlun; Zhao, Ling; Fu, Zhen F.; Cui, Min


    Japanese encephalitis virus (JEV) is a highly fatal pathogen to human beings. Toll-like receptor 7 (TLR7) plays a role as the first host defense against most single-stranded RNA flaviviruses. This study aims to investigate the role of TLR7 in inducing adaptive immune response in mice against JEV. In vitro and in vivo studies were conducted to examine the expression of toll-like receptors (TLRs) in mice. After JEV infection, physical parameters of mice (survival rate and body weight) were evaluated, and organs or cells were collected for further analysis. The expression of TLR7 was increased significantly as compare to other TLR molecules post-JEV infection. The expression of CD80, CD86, and CD273 on bone marrow-derived dendritic cells was increased significantly in TLR7−/− mice. Furthermore, viral load was also increased significantly in TLR7−/− mice as compare to C57BL/6 mice. But there was no significant difference among survival rate and body weight in TLR7−/− mice as compare to C57BL/6. Interestingly, we also found that TLR8 was upregulated in TLR7−/− mice. The study concluded that TLR8 was upregulated in TLR7-deficient mice, and it might play a compensatory role in the immune response in TLR7−/− mice.

  1. Immune endocrinological evaluation in patients with severe vascular acquired brain injuries: therapeutical approaches. (United States)

    Amico, Angelo Paolo; Terlizzi, Annamaria; Annamaria, Terlizzi; Megna, Marisa; Marisa, Megna; Megna, Gianfranco; Gianfranco, Megna; Damiani, Sabino; Sabino, Damiani


    It is known that in severe acquired brain injuries there is process of neuroinflammation, with the activation of a local and general stress response. In our study we considered six patients with disorders of consciousness (five in vegetative state and one in minimal consciousness state) in subacute phase, which had both a clinical assessment and a functional imaging (fMRI): in all these patients we analised blood levels of osteopontin (OPN), a cytokin involved in neuroinflammation but also in neurorepair with a still discussed role. Besides we studied the lymphocyte subsets and blood levels of some hormones (ADH, ACTH, PRL, GH, TSH, fT3, fT4). We found a positive correlation between the levels of serum osteopontin (higher than normal in all subjects) and the severity of the brain injury, especially for prognosis: actually, the patient with the lowest level has emerged from minimal consciousness state, while the one with the highest level has died a few days after the evaluation. The lymphocyte subset was altered, with a general increase of CD4+/CD3+ ratio, but without a so strict correlation with clinical severity; the only hormone with a significant increase in the worse patients was prolactin. In fMRI we detected some responses to visual and acoustic stimuli also in vegetative states, which had no clinical response to this kind of stimulation but generally have had a better prognosis. So we conclude that osteopontin could be a good marker of neuroinflammation and relate to a worse prognosis of brain injuries; the lymphocyte alterations in these disorders are not clear, but we suspect an unbalance of CD4 towards Th2; PRL is the best endocrinological marker of brain injury severity; fMRI surely plays an important role in the detection of subclinical responses and in prognostic stratification, that is still to define with more studies and statistical analysis.

  2. Immunization with cationized BSA inhibits progression of disease in ApoBec-1/LDL receptor deficient mice with manifest atherosclerosis. (United States)

    Kolbus, Daniel; Wigren, Maria; Ljungcrantz, Irena; Söderberg, Ingrid; Alm, Ragnar; Björkbacka, Harry; Nilsson, Jan; Fredrikson, Gunilla N


    Immune responses against modified self-antigens generated by hypercholesterolemia play an important role in atherosclerosis identifying the immune system as a possible novel target for prevention and treatment of cardiovascular disease. It has recently been shown that these immune responses can be modulated by subcutaneous injection of adjuvant. In the present study we immunized 25-week old ApoBec-1/LDL receptor deficient mice with manifest atherosclerosis with adjuvant and two different concentrations of the carrier molecule cationized BSA (cBSA). Plasma levels of Th2-induced apolipoprotein B (apoB)/IgG1 immune complexes were increased in the cBSA immunized groups verifying induction of immunity against a self-antigen. Mice were sacrificed at 36 weeks of age and atherosclerosis was monitored by en face Oil red O staining of the aorta. Immunization with 100 μg cBSA inhibited plaque progression, whereas the lower dose (50 μg) did not. In addition, the higher dose induced a more stable plaque phenotype, indicated by a higher content of collagen and less macrophages and T cells in the plaques. Moreover, there was an increased ratio of Foxp3+/Foxp3⁻ T cells in the circulation suggesting activation of a regulatory T cell response. In conclusion, we show that immunization with cBSA induces an immune response against apoB as well as an activation of Treg cells. This was associated with development of a more stable plaque phenotype and reduced atherosclerosis progression.

  3. Selective predisposition to bacterial infections in IRAK-4-deficient children : IRAK-4-dependent TLRs are otherwise redundant in protective immunity

    NARCIS (Netherlands)

    Ku, Cheng-Lung; von Bernuth, Horst; Picard, Capucine; Zhang, Shen-Ying; Chang, Huey-Hsuan; Yang, Kun; Chrabieh, Maya; Issekutz, Andrew C.; Cunningham, Coleen K.; Gallin, John; Holland, Steven M.; Roifman, Chaim; Ehl, Stephan; Smart, Joanne; Tang, Mimi; Barrat, Franck J.; Levy, Ofer; McDonald, Douglas; Day-Good, Noorbibi K.; Miller, Richard; Takada, Hidetoshi; Hara, Toshiro; Al-Hajjar, Sami; Al-Ghonaium, Abdulaziz; Speert, David; Sanlaville, Damien; Li, Xiaoxia; Geissmann, Frederic; Vivier, Eric; Marodi, Laszlo; Garty, Ben-Zion; Chapel, Helen; Rodriguez-Gallego, Carlos; Bossuyt, Xavier; Abel, Laurent; Puel, Anne; Casanova, Jean-Laurent


    Human interleukin ( IL) 1 receptor - associated kinase 4 ( IRAK- 4) deficiency is a recently discovered primary immunodefi ciency that impairs Toll/ IL- 1R immunity, except for the Toll- like receptor ( TLR) 3 - and TLR4 - interferon ( IFN)-alpha/beta pathways. The clinical and immunological phenoty

  4. Different Candida parapsilosis clinical isolates and lipase deficient strain trigger an altered cellular immune response

    Directory of Open Access Journals (Sweden)

    Renata eToth


    Full Text Available Numerous human diseases can be associated with fungal infections either as potential causative agents or as a result of changed immune status due to a primary disease. Fungal infections caused by Candida species can vary from mild to severe dependent upon the site of infection, length of exposure and past medical history. Patients with impaired immune status are at increased risk for chronic fungal infections. Recent epidemiologic studies have revealed the increasing incidence of candidiasis caused by non-albicans species such as C. parapsilosis. Due to its increasing relevance we chose two distinct C. parapsilosis strains, to describe the cellular innate immune response towards this species. In the first section of our study we compared the interaction of CLIB 214 and GA1 cells with murine and human macrophages. Both strains are commonly used to investigate C. parapsilosis virulence properties. CLIB 214 is a rapidly pseudohyphae-forming strain and GA1 is an isolate that mainly exists in a yeast form. Our results showed, that the phagocyte response was similar in terms of overall uptake, however differences were observed in macrophage migration and engulfment of fungal cells. As C. parapsilosis releases extracellular lipases in order to promote host invasion we further investigated the role of these secreted components during the distinct stages of the phagocytic process. Using a secreted lipase deficient mutant strain and the parental strain GA1 individually and simultaneously, we confirmed that fungal secreted lipases influence the fungi’s virulence by detecting altered innate cellular responses.In this study we report that two isolates of a single species can trigger markedly distinct host responses and that lipase secretion plays a role on the cellular level of host pathogen interactions.

  5. Vitamin A supplementation in early life enhances the intestinal immune response of rats with gestational vitamin A deficiency by increasing the number of immune cells.

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    Xia Liu

    Full Text Available Vitamin A is a critical micronutrient for regulating immunity in many organisms. Our previous study demonstrated that gestational or early-life vitamin A deficiency decreases the number of immune cells in offspring. The present study aims to test whether vitamin A supplementation can restore lymphocyte pools in vitamin A-deficient rats and thereby improve the function of their intestinal mucosa; furthermore, the study aimed to identify the best time frame for vitamin A supplementation. Vitamin A-deficient pregnant rats or their offspring were administered a low-dose of vitamin A daily for 7 days starting on gestational day 14 or postnatal day 1, day 14 or day 28. Serum retinol concentrations increased significantly in all four groups that received vitamin A supplementation, as determined by high-performance liquid chromatography. The intestinal levels of secretory immunoglobulin A and polymeric immunoglobulin receptor increased significantly with lipopolysaccharide challenge in the rats that received vitamin A supplementation starting on postnatal day 1. The rats in this group had higher numbers of CD8+ intestinal intraepithelial lymphocytes, CD11C+ dendritic cells in the Peyer's patches and CD4+CD25+ T cells in the spleen compared with the vitamin A-deficient rats; flow cytometric analysis also demonstrated that vitamin A supplementation decreased the number of B cells in the mesenteric lymph nodes. Additionally, vitamin A supplementation during late gestation increased the numbers of CD8+ intestinal intraepithelial lymphocytes and decreased the numbers of B lymphocytes in the mesenteric lymph nodes. However, no significant differences in lymphocyte levels were found between the rats in the other two vitamin A supplement groups and the vitamin A-deficient group. In conclusion, the best recovery of a subset of lymphocytes in the offspring of gestational vitamin A-deficient rats and the greatest improvement in the intestinal mucosal immune

  6. Relative Contribution of Dengue IgG Antibodies Acquired during Gestation or Breastfeeding in Mediating Dengue Disease Enhancement and Protection in Type I Interferon Receptor-Deficient Mice (United States)

    Lee, Pei Xuan; Ong, Li Ching; Libau, Eshele Anak; Alonso, Sylvie


    Dengue virus (DENV) causes a spectrum of diseases ranging from self-limiting dengue fever to severe conditions such as haemorrhagic fever and dengue shock syndrome. Antibody-dependent enhancement (ADE) is thought to explain the occurrence of severe dengue whereby pre-existing binding but non-neutralising antibodies enhance DENV infection. The ADE phenomenon is supported by epidemiological findings that infants that born to dengue immune mothers are at greater risk to develop severe dengue upon primary infection. The role of maternally acquired dengue-specific antibodies in disease enhancement was recently recapitulated in a mouse model where mice born to DENV1-immune mothers experienced enhanced disease severity upon DENV2 infection. Here, this study investigates the relative contribution of maternal dengue-specific antibodies acquired during gestation and breastfeeding in dengue disease. Using a surrogate breastfeeding mother experimental approach, we showed that majority of the maternal dengue-specific antibodies were acquired during breastfeeding and conferred an extended enhancement window. On the other hand, in the context of homologous infection, breastfeeding conferred protection. Furthermore, measurement of dengue-specific antibody titres over time in mice born to dengue immune mothers revealed a biphasic pattern of antibody decay as reported in humans. Our work provides evidence of the potential contribution of breast milk-acquired dengue-specific IgG antibodies in enhancement and protection against dengue. Should such contribution be established in humans as well, it may have important implications for the development of guidelines to dengue-immune breastfeeding mothers. PMID:27341339

  7. Alkaline ceramidase 3 deficiency aggravates colitis and colitis-associated tumorigenesis in mice by hyperactivating the innate immune system. (United States)

    Wang, K; Xu, R; Snider, A J; Schrandt, J; Li, Y; Bialkowska, A B; Li, M; Zhou, J; Hannun, Y A; Obeid, L M; Yang, V W; Mao, C


    Increasing studies suggest that ceramides differing in acyl chain length and/or degree of unsaturation have distinct roles in mediating biological responses. However, still much remains unclear about regulation and role of distinct ceramide species in the immune response. Here, we demonstrate that alkaline ceramidase 3 (Acer3) mediates the immune response by regulating the levels of C18:1-ceramide in cells of the innate immune system and that Acer3 deficiency aggravates colitis in a murine model by augmenting the expression of pro-inflammatory cytokines in myeloid and colonic epithelial cells (CECs). According to the NCBI Gene Expression Omnibus (GEO) database, ACER3 is downregulated in immune cells in response to lipopolysaccharides (LPS), a potent inducer of the innate immune response. Consistent with these data, we demonstrated that LPS downregulated both Acer3 mRNA levels and its enzymatic activity while elevating C(18:1)-ceramide, a substrate of Acer3, in murine immune cells or CECs. Knocking out Acer3 enhanced the elevation of C(18:1)-ceramide and the expression of pro-inflammatory cytokines in immune cells and CECs in response to LPS challenge. Similar to Acer3 knockout, treatment with C(18:1)-ceramide, but not C18:0-ceramide, potentiated LPS-induced expression of pro-inflammatory cytokines in immune cells. In the mouse model of dextran sulfate sodium-induced colitis, Acer3 deficiency augmented colitis-associated elevation of colonic C(18:1)-ceramide and pro-inflammatory cytokines. Acer3 deficiency aggravated diarrhea, rectal bleeding, weight loss and mortality. Pathological analyses revealed that Acer3 deficiency augmented colonic shortening, immune cell infiltration, colonic epithelial damage and systemic inflammation. Acer3 deficiency also aggravated colonic dysplasia in a mouse model of colitis-associated colorectal cancer. Taken together, these results suggest that Acer3 has an important anti-inflammatory role by suppressing cellular or tissue C(18

  8. Immune Thrombocytopenia Resolved by Eltrombopag in a Carrier of Glucose-6-Phosphate Dehydrogenase Deficiency

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    Laura Scaramucci


    Full Text Available Eltrombopag, a thrombopoietin mimetic peptide, may provide excellent clinical efficacy in steroid-refractory patients with immune thrombocytopenic purpura (ITP [1,2]. Eltrombopag is generally well tolerated. However, its use in the particular setting of glucose-6-phosphate dehydrogenase (G6PD and history of acute hemolytic anemia (AHA has not been reported so far. A 51-year-old female was diagnosed as having ITP in September 2014. She was not taking any medication and her past history was negative, apart from having been diagnosed a carrier (heterozygous of G6PD deficiency (Mediterranean variant after a familial screening by molecular and biochemical methods. She presented with only slightly reduced (about 50% enzyme level, belonging to World Health Organization-defined class 3 [3,4]. In the following years, the patient experienced some episodes of AHA, which were managed at outside institutions; in particular, a severe episode of AHA, probably triggered by urinary infection and antibiotics [5], had complicated her second and last delivery. The hemolytic episodes were selflimiting and resolved without sequelae. No other causes of hemolysis were documented. When the case came to our attention, a diagnosis of ITP was made; hemolytic parameters were normal, although the G6PD enzyme concentration was not measured. Oral prednisone (1 mg/kg was given with only a transient benefit. The patient was then a candidate for elective splenectomy. However, given her extremely low platelet count, she was started in October 2014 on eltrombopag at 50 mg/day as a bridge to splenectomy. Given that, to the best of our knowledge, the use of this drug has never been reported in the particular setting of G6PD deficiency, the patient was constantly monitored. A prompt platelet increase (178x109/L was observed 1 week after the start of treatment. After she achieved the target platelet count, the dose of eltrombopag was tapered to the lowest effective dose. The patient

  9. A focused parameter update: hereditary angioedema, acquired C1 inhibitor deficiency, and angiotensin-converting enzyme inhibitor-associated angioedema. (United States)

    Zuraw, Bruce L; Bernstein, Jonathan A; Lang, David M; Craig, Timothy; Dreyfus, David; Hsieh, Fred; Khan, David; Sheikh, Javed; Weldon, David; Bernstein, David I; Blessing-Moore, Joann; Cox, Linda; Nicklas, Richard A; Oppenheimer, John; Portnoy, Jay M; Randolph, Christopher R; Schuller, Diane E; Spector, Sheldon L; Tilles, Stephen A; Wallace, Dana


    These parameters were developed by the Joint Task Force on Practice Parameters (JTFPP), representing the American Academy of Allergy, Asthma & Immunology (AAAAI); the American College of Allergy, Asthma & Immunology (ACAAI); and the Joint Council of Allergy, Asthma and Immunology. The AAAAI and the ACAAI have jointly accepted responsibility for establishing "A focused parameter update: Hereditary angioedema, acquired C1 inhibitor deficiency, and angiotensin-converting enzyme inhibitor-associated angioedema." This is a complete and comprehensive document at the current time. The medical environment is a changing environment, and not all recommendations will be appropriate for all patients. Because this document incorporated the efforts of many participants, no single individual, including those who served on the JTFPP, is authorized to provide an official AAAAI or ACAAI interpretation of these practice parameters. Any request for information about or an interpretation of these practice parameters by the AAAAI or ACAAI should be directed to the Executive Offices of the AAAAI, the ACAAI, and the Joint Council of Allergy, Asthma and Immunology. The Joint Task Force on Practice Parameters understands that the cost of diagnostic tests and therapeutic agents is an important concern that might appropriately influence the work-up and treatment chosen for a given patient. The JTFPP recognizes that the emphasis of our primary recommendations regarding a medication might vary, for example, depending on third-party payer issues and product patent expiration dates. However, because the cost of a given test or agent is so widely variable and there is a paucity of pharmacoeconomic data, the JTFPP generally does not consider cost when formulating practice parameter recommendations. In some instances the cost benefit of an intervention is considered relevant, and commentary might be provided. These parameters are not designed for use by pharmaceutical companies in drug promotion

  10. Health-Related Quality of Life in Primary Immune Deficient Patients

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    "Habibeh Mozaffari


    Full Text Available The primary immunodeficiency (PI disorders are abnormalities in development and maturation of the immune system. Individuals with PI disease may experience frequent infections, which limit their abilities to exhibit physical and psychological well-being secondary to their illness. In this survey we compared health-related quality of life of primary immune deficient patients with healthy children. The case-control study was designed for patients with PI disease who were referred to Children Medical Center in 2004-2005. Demographic information was taken and Pediatric Quality Of Life (PEDQOL questionnaire were filled for 50 PI patients and 100 healthy children. The mean age in PI patients was 12.62± 3.65 (range from 8 to 18 years and in the control group was 11.04± 3.3 years. In PI patients 68% were male and 32% female .Most patients with PI disease had a diagnosis of common variable immunodeficiency (54% or X-linked agammaglobulinemia (24%. Patients with PI disease had great limitations in physical functioning and psychological well-being (p<0.001 and p<0.001 respectively compared with children without a chronic health condition. Patients had lower PEDQOL scores in all age groups compared with normal sample (p<0.001. Long duration of disease significantly correlated with low psychological score. (r = -3.23. P= 0.03 Children with PI disease experience poorer health related quality of life than healthy children, indicating more attention should be paid to early diagnosis and treatment of PI disease, as well as more attention to their social limitation. PI patients may need psychological consultation for better coping with their illness.

  11. Adaptive immune response in JAM-C-deficient mice: normal initiation but reduced IgG memory. (United States)

    Zimmerli, Claudia; Lee, Boris P L; Palmer, Gaby; Gabay, Cem; Adams, Ralf; Aurrand-Lions, Michel; Imhof, Beat A


    We have recently shown that junctional adhesion molecule (JAM)-C-deficient mice have leukocytic pulmonary infiltrates, disturbed neutrophil homeostasis, and increased postnatal mortality. This phenotype was partially rescued when mice were housed in ventilated isolators, suggesting an inability to cope with opportunistic infections. In the present study, we further examined the adaptive immune responses in JAM-C(-/-) mice. We found that murine conventional dendritic cells express in addition to Mac-1 and CD11c also JAM-B as ligand for JAM-C. By in vitro adhesion assay, we show that murine DCs can interact with recombinant JAM-C via Mac-1. However, this interaction does not seem to be necessary for dendritic cell migration and function in vivo, even though JAM-C is highly expressed by lymphatic sinuses of lymph nodes. Nevertheless, upon immunization and boosting with a protein Ag, JAM-C-deficient mice showed decreased persistence of specific circulating Abs although the initial response was normal. Such a phenotype has also been observed in a model of Ag-induced arthritis, showing that specific IgG2a Ab titers are reduced in the serum of JAM-C(-/-) compared with wild-type mice. Taken together, these data suggest that JAM-C deficiency affects the adaptive humoral immune response against pathogens, in addition to the innate immune system.

  12. Personal and Social Predictors about Safe Sexual Behavior in Patients with Immune Deficiency Virus in Ahwaz, Iran

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    Shirin Hasanpoor


    Full Text Available Socio-demographic predictors about safe sex behaviours in individual suffering from immune deficiency virus (HIV had been tried to understand in this cross-sectional study. It was conducted on 120 individuals having immune deficiency virus (HIV. Collection of the data were based on socio-demographic and a safe sex behaviour questionnaire. To determine the socio-demographic the general linear model was used. Result revealed mean (SD of the total score of safe sexual behaviour among men and women was 66.5 (13.1, 62.2 (13.0 respectively and (Score limit: 0-100. Status of sexual partners, unprotected vaginal sex, drugs and alcohols, as well as employment status, were considered as predictors of safe sex behaviours. About 50 percent of the participants pose unsafe sexual practices, thus, it is advisable that the health promotion programs and HIV prevention should implement in various groups of the society.

  13. Site-specific influence of polyunsaturated fatty acids on atherosclerosis in immune incompetent LDL receptor deficient mice. (United States)

    Reardon, Catherine A; Blachowicz, Lydia; Gupta, Gaorav; Lukens, John; Nissenbaum, Michael; Getz, Godfrey S


    Polyunsaturated fatty acids (PUFA) are thought to influence plasma lipid levels, atherosclerosis, and the immune system. In this study, we fed male LDL receptor deficient (LDLR(-/-)) mice and immune incompetent LDLR(-/-) RAG2(-/-) mice diets containing predominantly saturated fats (milk fat) or PUFA (safflower oil) to determine if the response to diet was influenced by immune status. Relative to milk fat diet, plasma lipid and VLDL levels in both the LDLR(-/-) and LDLR(-/-) RAG2(-/-) mice fed safflower oil diet were lower, suggesting that the primary effect of PUFA on plasma lipids was not due to its inhibition of the immune system. Neither diet nor immune status influenced hepatic triglyceride production and post-heparin lipase activity, suggesting that the differences in triglyceride levels are due to differences in rates of catabolism of triglyceride-rich lipoproteins. While both diets promoted atherogenesis, both aortic root and innominate artery atherosclerosis in LDLR(-/-) mice was less in safflower oil fed animals. In contrast, a site-specific effect of PUFA was observed in the immune incompetent LDLR(-/-) RAG2(-/-). In these mice, aortic root atherosclerosis, but not innominate artery atherosclerosis, was less in PUFA fed animal. These results suggest that PUFA and the immune system may influence innominate artery atherosclerosis by some overlapping mechanisms.

  14. The case for a national service for primary immune deficiency disorders in New Zealand. (United States)

    Ameratunga, Rohan; Steele, Richard; Jordan, Anthony; Preece, Kahn; Barker, Russell; Brewerton, Maia; Lindsay, Karen; Sinclair, Jan; Storey, Peter; Woon, See-Tarn


    Primary immune deficiency disorders (PIDs) are rare conditions for which effective treatment is available. It is critical these patients are identified at an early stage to prevent unnecessary morbidity and mortality. Treatment of these disorders is expensive and expert evaluation and ongoing management by a clinical immunologist is essential. Until recently there has been a major shortage of clinical immunologists in New Zealand. While the numbers of trained immunologists have increased in recent years, most are located in Auckland. The majority of symptomatic PID patients require life-long immunoglobulin replacement. Currently there is a shortage of subcutaneous and intravenous immunoglobulin (SCIG/IVIG) in New Zealand. A recent audit by the New Zealand Blood Service (NZBS) showed that compliance with indications for SCIG/IVIG treatment was poor in District Health Boards (DHBs) without an immunology service. The NZBS audit has shown that approximately 20% of annual prescriptions for SCIG/IVIG, costing $6M, do not comply with UK or Australian guidelines. Inappropriate use may have contributed to the present shortage of SCIG/IVIG necessitating importation of the product. This is likely to have resulted in a major unnecessary financial burden to each DHB. Here we present the case for a national service responsible for the tertiary care of PID patients and oversight for immunoglobulin use for primary and non-haematological secondary immunodeficiencies. We propose that other PIDs, including hereditary angioedema, are integrated into a national PID service. Ancillary services, including the customised genetic testing service, and research are also an essential component of an integrated national PID service and are described in this review. As we show here, a hub-and-spoke model for a national service for PIDs would result in major cost savings, as well as improved patient care. It would also allow seamless transition from paediatric to adult services.

  15. Type I Interferon Receptor Deficiency in Dendritic Cells Facilitates Systemic Murine Norovirus Persistence Despite Enhanced Adaptive Immunity.

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    Timothy J Nice


    Full Text Available In order for a virus to persist, there must be a balance between viral replication and immune clearance. It is commonly believed that adaptive immunity drives clearance of viral infections and, thus, dysfunction or viral evasion of adaptive immunity is required for a virus to persist. Type I interferons (IFNs play pleiotropic roles in the antiviral response, including through innate control of viral replication. Murine norovirus (MNoV replicates in dendritic cells (DCs and type I IFN signaling in DCs is important for early control of MNoV replication. We show here that the non-persistent MNoV strain CW3 persists systemically when CD11c positive DCs are unable to respond to type I IFN. Persistence in this setting is associated with increased early viral titers, maintenance of DC numbers, increased expression of DC activation markers and an increase in CD8 T cell and antibody responses. Furthermore, CD8 T cell function is maintained during the persistent phase of infection and adaptive immune cells from persistently infected mice are functional when transferred to Rag1-/- recipients. Finally, increased early replication and persistence are also observed in mixed bone marrow chimeras where only half of the CD11c positive DCs are unable to respond to type I IFN. These findings demonstrate that increased early viral replication due to a cell-intrinsic innate immune deficiency is sufficient for persistence and a functional adaptive immune response is not sufficient for viral clearance.

  16. Zebra Fish Lacking Adaptive Immunity Acquire an Antiviral Alert State Characterized by Upregulated Gene Expression of Apoptosis, Multigene Families, and Interferon-Related Genes. (United States)

    García-Valtanen, Pablo; Martínez-López, Alicia; López-Muñoz, Azucena; Bello-Perez, Melissa; Medina-Gali, Regla M; Ortega-Villaizán, María Del Mar; Varela, Monica; Figueras, Antonio; Mulero, Víctoriano; Novoa, Beatriz; Estepa, Amparo; Coll, Julio


    To investigate fish innate immunity, we have conducted organ and cell immune-related transcriptomic as well as immunohistologic analysis in mutant zebra fish (Danio rerio) lacking adaptive immunity (rag1(-/-)) at different developmental stages (egg, larvae, and adult), before and after infection with spring viremia carp virus (SVCV). The results revealed that, compared to immunocompetent zebra fish (rag1(+/+) ), rag1(-/-) acquired increased resistance to SVCV with age, correlating with elevated transcript levels of immune genes in skin/fins and lymphoid organs (head kidney and spleen). Gene sets corresponding to apoptotic functions, immune-related multigene families, and interferon-related genes were constitutively upregulated in uninfected adult rag1(-/-) zebra fish. Overexpression of activated CASPASE-3 in different tissues before and after infection with SVCV further confirmed increased apoptotic function in rag1(-/-) zebra fish. Concurrently, staining of different tissue samples with a pan-leukocyte antibody marker showed abundant leukocyte infiltrations in SVCV-infected rag1(-/-) fish, coinciding with increased transcript expression of genes related to NK-cells and macrophages, suggesting that these genes played a key role in the enhanced immune response of rag1(-/-) zebra fish to SVCV lethal infection. Overall, we present evidence that indicates that rag1(-/-) zebra fish acquire an antiviral alert state while they reach adulthood in the absence of adaptive immunity. This antiviral state was characterized by (i) a more rapid response to viral infection, which resulted in increased survival, (ii) the involvement of NK-cell- and macrophage-mediated transcript responses rather than B- and/or T-cell dependent cells, and (iii) enhanced apoptosis, described here for the first time, as well as the similar modulation of multigene family/interferon-related genes previously associated to fish that survived lethal viral infections. From this and other studies, it might

  17. Tc17 cells mediate vaccine immunity against lethal fungal pneumonia in immune deficient hosts lacking CD4+ T cells.

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    Som Gowda Nanjappa

    Full Text Available Vaccines may help reduce the growing incidence of fungal infections in immune-suppressed patients. We have found that, even in the absence of CD4(+ T-cell help, vaccine-induced CD8(+ T cells persist and confer resistance against Blastomyces dermatitidis and Histoplasma capsulatum. Type 1 cytokines contribute to that resistance, but they also are dispensable. Although the role of T helper 17 cells in immunity to fungi is debated, IL-17 producing CD8(+ T cells (Tc17 cells have not been investigated. Here, we show that Tc17 cells are indispensable in antifungal vaccine immunity in hosts lacking CD4(+ T cells. Tc17 cells are induced upon vaccination, recruited to the lung on pulmonary infection, and act non-redundantly in mediating protection in a manner that requires neutrophils. Tc17 cells did not influence type I immunity, nor did the lack of IL-12 signaling augment Tc17 cells, indicating a distinct lineage and function. IL-6 was required for Tc17 differentiation and immunity, but IL-1R1 and Dectin-1 signaling was unexpectedly dispensable. Tc17 cells expressed surface CXCR3 and CCR6, but only the latter was essential in recruitment to the lung. Although IL-17 producing T cells are believed to be short-lived, effector Tc17 cells expressed low levels of KLRG1 and high levels of the transcription factor TCF-1, predicting their long-term survival and stem-cell like behavior. Our work has implications for designing vaccines against fungal infections in immune suppressed patients.

  18. Tc17 cells mediate vaccine immunity against lethal fungal pneumonia in immune deficient hosts lacking CD4+ T cells. (United States)

    Nanjappa, Som Gowda; Heninger, Erika; Wüthrich, Marcel; Gasper, David Joseph; Klein, Bruce S


    Vaccines may help reduce the growing incidence of fungal infections in immune-suppressed patients. We have found that, even in the absence of CD4(+) T-cell help, vaccine-induced CD8(+) T cells persist and confer resistance against Blastomyces dermatitidis and Histoplasma capsulatum. Type 1 cytokines contribute to that resistance, but they also are dispensable. Although the role of T helper 17 cells in immunity to fungi is debated, IL-17 producing CD8(+) T cells (Tc17 cells) have not been investigated. Here, we show that Tc17 cells are indispensable in antifungal vaccine immunity in hosts lacking CD4(+) T cells. Tc17 cells are induced upon vaccination, recruited to the lung on pulmonary infection, and act non-redundantly in mediating protection in a manner that requires neutrophils. Tc17 cells did not influence type I immunity, nor did the lack of IL-12 signaling augment Tc17 cells, indicating a distinct lineage and function. IL-6 was required for Tc17 differentiation and immunity, but IL-1R1 and Dectin-1 signaling was unexpectedly dispensable. Tc17 cells expressed surface CXCR3 and CCR6, but only the latter was essential in recruitment to the lung. Although IL-17 producing T cells are believed to be short-lived, effector Tc17 cells expressed low levels of KLRG1 and high levels of the transcription factor TCF-1, predicting their long-term survival and stem-cell like behavior. Our work has implications for designing vaccines against fungal infections in immune suppressed patients.

  19. [Acquired angioedema with C1-INH deficiency and accompanying chronic spontaneous urticaria in a patient with chronic lymphatic B cell leukemia]. (United States)

    Klossowski, N; Braun, S A; von Gruben, V; Losem, C; Plewe, D; Homey, B; Meller, S


    Acquired angioedema due to C1 inhibitor deficiency (C1-INH-AAE) is characterized by recurrent edema of the subcutaneous and/or submucosal tissue without wheals and negative family history of angioedema. Here, we present the case of a patient with a chronic lymphatic B cell leukemia who suffered from both C1-INH-AAE and chronic spontaneous urticaria. Oral corticosteroids, antihistamines, and the anti-IgE antibody omalizumab were applied to treat the chronic urticaria in combination with the plasma-derived C1 esterase inhibitor concentrate Berinert® and the bradykinin B2 receptor antagonist icatibant, but the symptoms did not improved significantly. Thus, polychemotherapy targeting the slow-growing lymphoproliferative disease including rituximab was initiated, which resulted in remission of both the urticaria and the angioedema.

  20. Co-existence of clonal expanded autologous and transplacental-acquired maternal T cells in recombination activating gene-deficient severe combined immunodeficiency (United States)

    Lev, A; Simon, A J; Ben-Ari, J; Takagi, D; Stauber, T; Trakhtenbrot, L; Rosenthal, E; Rechavi, G; Amariglio, N; Somech, R


    It is commonly accepted that the presence of high amounts of maternal T cells excludes Omenn syndrome (OS) in severe combined immunodeficiency (SCID). We report a SCID patient with a novel mutation in the recombination activating gene (RAG)1 gene (4-BP DEL.1406 TTGC) who presented with immunodeficiency and OS. Several assays, including representatives of specific T cell receptors (TCR), Vβ families and TCR-γ rearrangements, were performed in order to understand more clearly the nature and origin of the patient's T cells. The patient had oligoclonal T cells which, based on the patient–mother human leucocyte antigen (HLA)-B50 mismatch, were either autologous or of maternal origin. These cell populations were different in their numbers of regulatory T cells (Treg) and the diversity of TCR repertoires. This is the first description of the co-existence of large amounts of clonal expanded autologous and transplacental-acquired maternal T cells in RAG1-deficient SCID. PMID:24666246

  1. Co-existence of clonal expanded autologous and transplacental-acquired maternal T cells in recombination activating gene-deficient severe combined immunodeficiency. (United States)

    Lev, A; Simon, A J; Ben-Ari, J; Takagi, D; Stauber, T; Trakhtenbrot, L; Rosenthal, E; Rechavi, G; Amariglio, N; Somech, R


    It is commonly accepted that the presence of high amounts of maternal T cells excludes Omenn syndrome (OS) in severe combined immunodeficiency (SCID). We report a SCID patient with a novel mutation in the recombination activating gene (RAG)1 gene (4-BP DEL.1406 TTGC) who presented with immunodeficiency and OS. Several assays, including representatives of specific T cell receptors (TCR), Vβ families and TCR-γ rearrangements, were performed in order to understand more clearly the nature and origin of the patient's T cells. The patient had oligoclonal T cells which, based on the patient-mother human leucocyte antigen (HLA)-B50 mismatch, were either autologous or of maternal origin. These cell populations were different in their numbers of regulatory T cells (T(reg)) and the diversity of TCR repertoires. This is the first description of the co-existence of large amounts of clonal expanded autologous and transplacental-acquired maternal T cells in RAG1-deficient SCID.

  2. Vpu-Deficient HIV Strains Stimulate Innate Immune Signaling Responses in Target Cells


    Doehle, Brian P.; Chang, Kristina; Fleming, Lamar; McNevin, John; Hladik, Florian; McElrath, M. Juliana; Gale, Michael


    Acute virus infection induces a cell-intrinsic innate immune response comprising our first line of immunity to limit virus replication and spread, but viruses have developed strategies to overcome these defenses. HIV-1 is a major public health problem; however, the virus-host interactions that regulate innate immune defenses against HIV-1 are not fully defined. We have recently identified the viral protein Vpu to be a key determinant responsible for HIV-1 targeting and degradation of interfer...

  3. Investigation of perceived stigma among people living with human immunodeficiency virus/acquired immune deficiency syndrome in Henan Province, China

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    Zhen Li


    Conclusion: The level of perceived HIV stigma and discrimination among PLWHA in Henan Province is moderate and was affected by the level of education and route of infection. Special intervention should be established to address this problem.

  4. The socioeconomic impact of human immunodeficiency virus / acquired immune deficiency syndrome in India and its relevance to eye care

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    Murthy GVS


    Full Text Available Human immunodeficiency virus (HIV infection is aptly called the modern day ′plague′ and has the potential to decimate people in the productive age group. On the other hand, the increasing life expectancy in developing countries spirals age-related blindness. One therefore reduces economic productivity while the other increases economic dependency. Both lead to increased expenditure of households though in different proportions. Human immunodeficiency virus and blindness are both associated with discrimination, stigma and long-term consequences. They impact the socioeconomic fabric of the affected individuals, communities and countries. The loss in productivity and the cost of support to the affected individuals are seen in both. Each is a potent problem on its own but together they spell disaster in geometric proportions rather than a simple additive effect. Strategies need to be evolved to provide solace and improve the quality of life of an HIV-positive blind individual.

  5. AIDS (Acquired Immune Deficiency Syndrome): Views on the Administration’s Fiscal Year 1989 Public Health Service Budget (United States)


    police, and providers of allied health care, such as social workers, therapists , aides, and laboratory personnel. The report emphasized that a well- 1...million is also requested for bioethics and biosafety projects. Expert Views The state and local public health officials believe that patient care...million for AIDS services and drug treatment demonstration projects, $3 million for bioethics and biosafety (unchanged from the PHS budget request), and

  6. Epidemiology of Oropharyngeal Candidiasis in Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome Patients and CD4+ Counts (United States)

    Berberi, Antoine; Noujeim, Ziad; Aoun, Georges


    Background: The present study was directed to evaluate the forms of oropharyngeal candidiasis (OPC) and their correlation with CD4+ cell counts in human immunodeficiency virus (HIV) patients. Materials and Methods: This was a descriptive and analytical cross-sectional study carried out for a 2-year period, in which quantitative data collection methods were used. 50 patients with HIV infection were evaluated. Relationship between OPC and CD4+ was investigated. Results: Five different clinical forms were noticed on examination: pseudomembranous candidiasis 20/38 (P) was the most common one (52.6%) followed by erythematous 5/38 (13.15%), angular cheilitis 5/38 (13.15%) (AC), a combination of AC and E 4/38 (10.52%) or AC, E and P 4/38 (10.52%). Candida albicans was the most frequent specie isolated in 35 cases of OPC (92%). Candida tropicalis was isolated in 2 cases (5.26%) and Candida glabrata in 1 case (2.64%). The majority of patients with OPC had cell counts 28/38 (73%) <200 cells/mm3, followed by 9/38 (23%) at CD4+ cell counts of 201-499 cells/mm3. Conclusion: Oral Candida colonization and invasive infection occur more frequently in HIV-positive patient and is significantly more common in patients with CD4+ cell counts <200 cell/mm3. PMID:25878473

  7. Neurobehavioral Consequences of HTLV-III Brain Infection and Acquired Immune Deficiency Syndrome (AIDS) Encephalopathy: A Prospective Study (United States)


    0UIN) over s~x months (r=.85, p<.01). QUIN is an endogenous excitatory ncurotoxin which acts specifically at the NMDA glutamate receptors ; it wdil...response to various therapies. A small clinical trial of an NMDA receptor antagonist in seropositive patients with slowed information processing would 4...Continue on reverse itf necessary and #dentify by bNock number) FIELD GROUP SUB-GROUP RA 1, HIV, Neurology, CNS Complications, Encephalitis , 06 03

  8. Hot water extracts of Chlorella vulgaris improve immune function in protein-deficient weanling mice and immune cells. (United States)

    An, Hyo-Jin; Rim, Hong-Kun; Jeong, Hyun-Ja; Hong, Seung-Heon; Um, Jae-Young; Kim, Hyung-Min


    The objective of this study was to investigate the effects of hot water extracts of Chlorella vulgaris (CVE) on a deteriorated immune function through utilization of a protein-energy malnutrition (PEM) diet. Unicellular algae, C. vulgaris, were used as biological response modifier. PEM is associated with decreased host immune defense. Male C57BL/6J mice, initially four weeks old, were fed for 8 days with standard diet or a PEM diet. Mice in the PEM diet group were orally administered 0.1 g/kg and 0.15 g/kg of CVE for the following week. Nutritional parameters such as the total protein, albumin, glucose, and interferon γ (IFN-γ) were increased in blood serum of the CVE-treated group compared with the non-treated group. The mononuclear cell numbers from spleen, superficial, and mesenteric lymph node were reduced in mice fed with PEM diet, but numbers from the spleen and superficial lymph node were increased by the CVE (0.1 and 0.15 g/kg) treatment. We also investigated the effect of CVE on the production of cytokines in human T-cell line, MOLT-4 cells, and primary cultured splenocytes. The CVE treatment significantly increased the production of both interleukin (IL)-2 and IL-4 compared with the media control, but did not affect the production of IFN-γ. These results suggest that CVE may be useful in improving the immune function.

  9. Intracellular replication-deficient Leishmania donovani induces long lasting protective immunity against visceral leishmaniasis. (United States)

    Selvapandiyan, Angamuthu; Dey, Ranadhir; Nylen, Susanne; Duncan, Robert; Sacks, David; Nakhasi, Hira L


    No vaccine is currently available for visceral leishmaniasis (VL) caused by Leishmania donovani. This study addresses whether a live attenuated centrin gene-deleted L. donovani (LdCen1(-/-)) parasite can persist and be both safe and protective in animals. LdCen1(-/-) has a defect in amastigote replication both in vitro and ex vivo in human macrophages. Safety was shown by the lack of parasites in spleen and liver in susceptible BALB/c mice, immune compromised SCID mice, and human VL model hamsters 10 wk after infection. Mice immunized with LdCen1(-/-) showed early clearance of virulent parasite challenge not seen in mice immunized with heat killed parasites. Upon virulent challenge, the immunized mice displayed in the CD4(+) T cell population a significant increase of single and multiple cytokine (IFN-gamma, IL-2, and TNF) producing cells and IFN-gamma/IL10 ratio. Immunized mice also showed increased IgG2a immunoglobulins and NO production in macrophages. These features indicated a protective Th1-type immune response. The Th1 response correlated with a significantly reduced parasite burden in the spleen and no parasites in the liver compared with naive mice 10 wk post challenge. Protection was observed, when challenged even after 16 wk post immunization, signifying a sustained immunity. Protection by immunization with attenuated parasites was also seen in hamsters. Immunization with LdCen1(-/-) also cross-protected mice against infection with L. braziliensis that causes mucocutaneous leishmaniasis. Results indicate that LdCen1(-/-) can be a safe and effective vaccine candidate against VL as well as mucocutaneous leishmaniasis causing parasites.

  10. Zebra Fish Lacking Adaptive Immunity Acquire an Antiviral Alert State Characterized by Upregulated Gene Expression of Apoptosis, Multigene Families, and Interferon-Related Genes (United States)

    García-Valtanen, Pablo; Martínez-López, Alicia; López-Muñoz, Azucena; Bello-Perez, Melissa; Medina-Gali, Regla M.; Ortega-Villaizán, María del Mar; Varela, Monica; Figueras, Antonio; Mulero, Víctoriano; Novoa, Beatriz; Estepa, Amparo; Coll, Julio


    To investigate fish innate immunity, we have conducted organ and cell immune-related transcriptomic as well as immunohistologic analysis in mutant zebra fish (Danio rerio) lacking adaptive immunity (rag1−/−) at different developmental stages (egg, larvae, and adult), before and after infection with spring viremia carp virus (SVCV). The results revealed that, compared to immunocompetent zebra fish (rag1+/+), rag1−/− acquired increased resistance to SVCV with age, correlating with elevated transcript levels of immune genes in skin/fins and lymphoid organs (head kidney and spleen). Gene sets corresponding to apoptotic functions, immune-related multigene families, and interferon-related genes were constitutively upregulated in uninfected adult rag1−/− zebra fish. Overexpression of activated CASPASE-3 in different tissues before and after infection with SVCV further confirmed increased apoptotic function in rag1−/− zebra fish. Concurrently, staining of different tissue samples with a pan-leukocyte antibody marker showed abundant leukocyte infiltrations in SVCV-infected rag1−/− fish, coinciding with increased transcript expression of genes related to NK-cells and macrophages, suggesting that these genes played a key role in the enhanced immune response of rag1−/− zebra fish to SVCV lethal infection. Overall, we present evidence that indicates that rag1−/− zebra fish acquire an antiviral alert state while they reach adulthood in the absence of adaptive immunity. This antiviral state was characterized by (i) a more rapid response to viral infection, which resulted in increased survival, (ii) the involvement of NK-cell- and macrophage-mediated transcript responses rather than B- and/or T-cell dependent cells, and (iii) enhanced apoptosis, described here for the first time, as well as the similar modulation of multigene family/interferon-related genes previously associated to fish that survived lethal viral infections. From this and other studies

  11. Microbial Dysbiosis in Common Variable Immune Deficiencies: Evidence, Causes, and Consequences. (United States)

    Berbers, Roos-Marijn; Nierkens, Stefan; van Laar, Jacob M; Bogaert, Debby; Leavis, Helen L


    Common variable immunodeficiency (CVID) is an immune disorder that not only causes increased susceptibility to infection, but also to inflammatory complications such as autoimmunity, lymphoid proliferation, malignancy, and granulomatous disease. Recent findings implicate the microbiome as a driver of this systemic immune dysregulation. Here, we critically review the current evidence for a role of the microbiome in the pathogenesis of CVID immune dysregulation, and describe the possible immunologic mechanisms behind causes and consequences of microbial dysbiosis in CVID. We integrate this evidence into a model describing a role for the gut microbiota in the maintenance of inflammation and immune dysregulation in CVID, and suggest research strategies to contribute to the development of new diagnostic tools and therapeutic targets.

  12. Effect of bacillus Calmette-Guérin vaccination on CD4+Foxp3+ T cells during acquired immune response to Mycobacterium tuberculosis infection. (United States)

    Henao-Tamayo, Marcela I; Obregón-Henao, Andres; Arnett, Kimberly; Shanley, Crystal A; Podell, Brendan; Orme, Ian M; Ordway, Diane J


    Increasing information has shown that many newly emerging strains of Mycobacterium tuberculosis, including the highly prevalent and troublesome Beijing family of strains, can potently induce the emergence of Foxp3(+)CD4 Tregs Although the significance of this is still not fully understood, we have previously provided evidence that the emergence of this population can significantly ablate the protective effect of BCG vaccination, causing progressive fatal disease in the mouse model. However, whether the purpose of this response is to control inflammation or to directly dampen the acquired immune response is still unclear. In the present study, we have shown, using both cell depletion and adoptive transfer strategies, that Tregs can have either properties. Cell depletion resulted in a rapid, but transient, decrease in the lung bacterial load, suggesting release or temporary re-expansion of effector immunity. Transfer of Tregs into Rag2(-/-)or marked congenic mice worsened the disease course and depressed cellular influx of effector T cells into the lungs. Tregs from infected donors seemed to preferentially depress the inflammatory response and granulocytic influx. In contrast, those from BCG-vaccinated and then challenged donors seemed more focused on depression of acquired immunity. These qualitative differences might be related to increasing knowledge reflecting the plasticity of the Treg response.

  13. Common variable immune deficiency associated Hodgkin’s lymphoma complicated with EBV-linked hemophagocytic lymphohistiocytosis: a case report (United States)

    Malkan, Umit Yavuz; Gunes, Gursel; Aslan, Tuncay; Etgul, Sezgin; Aydin, Seda; Buyukasik, Yahya


    Hemophagocytic syndrome (HPS) is described by an increase in macrophages accountable for extensive phagocytosis of hematopoietic cells. Secondary HPS arises commonly in the presence of infections, neoplasia, autoimmune disorders and immune disorders. Here, we reported a patient with common variable immune deficiency (CVID) and Hodgkin’s lymphoma (HL) who later developed EBV linked hemophagocytic lymphohistiocytosis. 42 year old men underwent check-up because of back pain in July 2012. He had known CVID disease. In physical examination he had no lymphadenopathies however his spleen was palpable 3 cm under arcus costa. He had hypogammaglobulinemia with IgG levels around 500 mg/dl. In abdominal computed tomography (CT) multiple lymphadenopathies reaching maximum 26×17 cm size were seen so, PET-CT was performed. Involvement in thorax, abdomen, and bone was detected with maximum SUV max 11.5. He had undergone tru-cut biopsy from lymph node in November 2012 which revealed HL. Bone marrow investigation favored with mix cell type. His cytogenetic analysis was reported as 46 XY. He was considered as stage 4 disease and ABVD (Adriamycin, bleomycin, vincristine and dexamethasone). He was given six cycles of chemotherapy in May 2013 and complete remission was observed in control CT screening in July 2013. However pancytopenia evolved in August 2013. Bone marrow investigation revealed suspicious lymphohistiocytic infiltration. Treatment was planned to apply autologous stem cell transplantation (SCT) after salvage chemotherapy. Control bone marrow investigation again revealed the lymphohistiocytic aggregates with hemophagocytosis. Our patient showed 5 criteria of hemophagocytic syndrome. He had ferritin elevation (>5000 μg/dl), splenomegaly (13 cm) cytopenia, triglyceride elevation and hemophagocytosis. He had unrelated SCT transplantation however he died from transplant related toxicity. The primary and secondary immune deficiency caused by chemotherapy are the major causes

  14. Morph-specific genetic and environmental variation in innate and acquired immune response in a color polymorphic raptor. (United States)

    Gangoso, Laura; Roulin, Alexandre; Ducrest, Anne-Lyse; Grande, Juan Manuel; Figuerola, Jordi


    Genetic color polymorphism is widespread in nature. There is an increasing interest in understanding the adaptive value of heritable color variation and trade-off resolution by differently colored individuals. Melanin-based pigmentation is often associated with variation in many different life history traits. These associations have recently been suggested to be the outcome of pleiotropic effects of the melanocortin system. Although pharmacological research supports that MC1R, a gene with a major role in vertebrate pigmentation, has important immunomodulatory effects, evidence regarding pleiotropy at MC1R in natural populations is still under debate. We experimentally assessed whether MC1R-based pigmentation covaries with both inflammatory and humoral immune responses in the color polymorphic Eleonora's falcon. By means of a cross-fostering experiment, we disentangled potential genetic effects from environmental effects on the covariation between coloration and immunity. Variation in both immune responses was primarily due to genetic factors via the nestlings' MC1R-related color genotype/phenotype, although environmental effects via the color morph of the foster father also had an influence. Overall, dark nestlings had lower immune responses than pale ones. The effect of the color morph of the foster father was also high, but in the opposite direction, and nestlings raised by dark eumelanic foster fathers had higher immune responses than those raised by pale foster fathers. Although we cannot completely discard alternative explanations, our results suggest that MC1R might influence immunity in this species. Morph-specific variation in immunity as well as pathogen pressure may therefore contribute to the long-term maintenance of genetic color polymorphism in natural populations.

  15. Disaccharidase deficiency. (United States)

    Bayless, T M; Christopher, N L


    This review of the literature and current knowledge concerning a nutritional disorder of disaccharidase deficiency discusses the following topics: 1) a description of disorders of disaccharide digestion; 2) some historical perspective on the laboratory and bedside advances in the past 10 years that have helped define a group of these digestive disorders; 3) a classification of conditions causing disaccharide intolerance; and 4) a discussion of some of the specific clinical syndromes emphasizing nutritional consequences of these syndromes. The syndromes described include congenital lactase deficiency, acquired lactase deficiency in teenagers and adults, acquired generalized disaccharidase deficiency secondary to diffuse mucosal damage, acquired lactose intolerance secondary to alterations in the intestinal transit, sucrase-isomaltase deficiencies, and other disease associations connected with lactase deficiency such as colitis.

  16. The kinetics of early T and B cell immune recovery after bone marrow transplantation in RAG-2-deficient SCID patients.

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    Atar Lev

    Full Text Available The kinetics of T and B cell immune recovery after bone marrow transplantation (BMT is affected by many pre- and post-transplant factors. Because of the profoundly depleted baseline T and B cell immunity in recombination activating gene 2 (RAG-2-deficient severe combined immunodeficiency (SCID patients, some of these factors are eliminated, and the immune recovery after BMT can then be clearly assessed. This process was followed in ten SCID patients in parallel to their associated transplant-related complications. Early peripheral presence of T and B cells was observed in 8 and 4 patients, respectively. The latter correlated with pre-transplant conditioning therapy. Cells from these patients carried mainly signal joint DNA episomes, indicative of newly derived B and T cells. They were present before the normalization of the T cell receptor (TCR and the B cell receptor (BCR repertoire. Early presentation of the ordered TCR gene rearrangements after BMT occurred simultaneously, but this pattern was heterogeneous over time, suggesting different and individual thymic recovery processes. Our findings early after transplant could suggest the long-term patients' clinical outcome. Early peripheral presence of newly produced B and T lymphocytes from their production and maturation sites after BMT suggests donor stem cell origin rather than peripheral expansion, and is indicative of successful outcome. Peripheral detection of TCR excision circles and kappa-deleting recombination excision circles in RAG-2-deficient SCID post-BMT are early markers of T and B cell reconstitution, and can be used to monitor outcome and tailor specific therapy for patients undergoing BMT.

  17. Allogeneic Hematopoietic Stem Cell Transplant for Patients With Primary Immune Deficiencies (United States)


    SCID; Omenn's Syndrome; Reticular Dysgenesis; Wiskott-Aldrich Syndrome; Bare Lymphocyte Syndrome; Common Variable Immunodeficiency; Chronic Granulomatous Disease; CD40 Ligand Deficiency; Hyper IgM Syndrome; X-linked Lymphoproliferative Disease; Hemophagocytic Lymphohistiocytosis; Griscelli Syndrome; Chediak-Higashi Syndrome; Langerhan's Cell Histiocytosis

  18. Evaluation of a Salmonella Enteritidis vaccine and related ELISA for respective induction and assessment of acquired immunity to the vaccine and/or Echinacea purpurea in Awassi Ewes. (United States)

    Barbour, Elie K; Assi, Chibli A Abou; Shaib, Houssam; Hamadeh, Shadi; Murtada, Muhammad; Mahmoud, Ghassan; Yaghmoor, Soonham; Iyer, Archana; Harakeh, Steve; Kumosani, Taha


    The aim of this study was to evaluate an experimental Salmonella Enteritidis (SE) bacterin and an indirect ELISA system to assess quantitatively the acquired immunity in Awassi ewes to the vaccine and/or Echinacea purpurea (EP) dried roots. Four treatments of the ewes were included in the experimental design, with 6 ewes/treatment. The first treatment (T1) had the controls that were non-vaccinated and non-treated with EP. The T2 ewes were only treated with EP. The T3 and T4 ewes were vaccinated at D1 (initiation of trial) and D10, while the T4 ewes were additionally administered the EP dried roots. Blood was collected from the jugular vein of all ewes at D1, D10, D21 and D45. The construction of the vaccine and the ELISA are detailed within the manuscript. The ELISA was able to detect quantitatively the significant acquired primary and secondary immunity to the vaccine in T3 and T4 ewes, compared to their low level of background immunities at initiation of the experiment (p0.05) in T1 control ewes, and in the T2 ewes that were given only the (EP) (p>0.05). Moreover, the ELISA was able to uncover the significant seroconversion of secondary immune response in T4 ewes at D21 compared to that at D10 (p<0.05), and the absence of significant seroconversion of secondary response in T3 ewes. This is the first work in literature that reports the need to supplement the vaccination by the experimental SE bacterin with daily oral intake of 250mg of EP-dried roots, effective the first vaccination day and up to 21 days, for obtaining a statistically significant seroconversion.

  19. Molecular pathology of mismatch repair deficient tumours with emphasis on immune escape mechanisms

    NARCIS (Netherlands)

    Dierssen, Jan Willem Frederik


    This thesis describes molecular methods to distinguish separate colon tumour entities. Furthermore, it shows that distinct immune escape mechanisms, in particular distinct mechanisms of corrupting the HLA system, are operational in subsets of colon tumours. The apparent necessity of some colon tumou

  20. Immune deficiency augments the prevalence of p53 loss of heterozygosity in spontaneous tumors but not bi-directional loss of heterozygosity in bone marrow progenitors. (United States)

    Shetzer, Yoav; Napchan, Yael; Kaufman, Tom; Molchadsky, Alina; Tal, Perry; Goldfinger, Naomi; Rotter, Varda


    p53 loss of heterozygosity (LOH) is a frequent event in tumors of somatic and Li-Fraumeni syndrome patients harboring p53 mutation. Here, we focused on resolving a possible crosstalk between the immune-system and p53 LOH. Previously, we reported that p53 heterozygous bone-marrow mesenchymal progenitor cells undergo p53 LOH in-vivo. Surprisingly, the loss of either the wild-type p53 allele or mutant p53 allele was detected with a three-to-one ratio in favor of losing the mutant allele. In this study, we examined whether the immune-system can affect the LOH directionality in bone marrow progenitors. We found that mesenchymal progenitor cells derived from immune-deficient mice exhibited the same preference of losing the mutant p53 allele as immune-competent matched cells, nevertheless, these animals showed a significantly shorter tumor-free survival, indicating the possible involvement of immune surveillance in this model. Surprisingly, spontaneous tumors of p53 heterozygous immune-deficient mice exhibited a significantly higher incidence of p53 LOH compared to that observed in tumors derived of p53 heterozygous immune-competent mice. These findings indicate that the immune-system may affect the p53 LOH prevalence in spontaneous tumors. Thus suggesting that the immune-system may recognize and clear cells that underwent p53 LOH, whereas in immune-compromised mice, those cells will form tumors with shorter latency. In individuals with a competent immune-system, p53 LOH independent pathways may induce malignant transformation which requires a longer tumor latency. Moreover, this data may imply that the current immunotherapy treatment aimed at abrogating the inhibition of cellular immune checkpoints may be beneficial for LFS patients.

  1. Prenatal cadmium exposure produces persistent changes to thymus and spleen cell phenotypic repertoire as well as the acquired immune response

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    Holásková, Ida; Elliott, Meenal; Hanson, Miranda L.; Schafer, Rosana [Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, Morgantown, WV 26506 (United States); Barnett, John B., E-mail: [Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, Morgantown, WV 26506 (United States); Mary Babb Randolph Cancer Center, West Virginia University School of Medicine, Morgantown, WV 26506 (United States)


    Cadmium (Cd) is a common environmental contaminant. Adult exposure to Cd alters the immune system, however, there are limited studies on the effects of prenatal exposure to Cd. Pregnant C57Bl/6 mice were exposed to an environmentally relevant dose of CdCl{sub 2} (10 ppm) and the effects on the immune system of the offspring were assessed at 20 weeks of age. Prenatal Cd exposure caused an increase in the percent of CD4{sup −}CD8{sup −}CD44{sup +}CD25{sup −} (DN1) thymocytes in both sexes and a decrease in the percent of CD4{sup −}CD8{sup −}CD44{sup −}CD25{sup +} (DN3) thymocytes in females. Females had an increase in the percent of splenic CD4{sup +} T cells, CD8{sup +} T cells, and CD45R/B220{sup +} B cells and a decrease in the percent of NK cells and granulocytes (Gr-1{sup +}). Males had an increase in the percent of splenic CD4{sup +} T cells and CD45R/B220{sup +} B cells and a decrease in the percent of CD8{sup +} T cells, NK cells, and granulocytes. The percentage of neutrophils and myeloid-derived suppressor cells were reduced in both sexes. The percent of splenic nTreg cells was decreased in all Cd-exposed offspring. Cd-exposed offspring were immunized with a streptococcal vaccine and the antibody response was determined. PC-specific serum antibody titers were decreased in Cd exposed female offspring but increased in the males. PspA-specific serum IgG titers were increased in both females and males compared to control animals. Females had a decrease in PspA-specific serum IgM antibody titers. Females and males had a decrease in the number of splenic anti-PspA antibody-secreting cells when standardized to the number of B cells. These findings demonstrate that very low levels of Cd exposure during gestation can result in long term sex-specific alterations on the immune system of the offspring. -- Highlights: ► Prenatal exposure to cadmium alters the immune system of 20 week old offspring. ► The percentage of DN1 and DN3 thymocytes was changed

  2. Immune complex glomerulonephritis following bone marrow transplantation in C3 deficient mice.

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    Thomas R Welch

    Full Text Available BACKGROUND: The role of circulating complement in host defense and immune disease is well established. Although a number of cells and tissues are capable of synthesizing complement components locally, the importance of such local synthesis in immune disease has been difficult to establish. METHODOLOGY/PRINCIPAL FINDINGS: We used bone marrow transplantation (BMT between C3 knockout (C3KO and wild type (WT mice to construct animals that were discordant for systemic (hepatic and local (monocytic C3 synthetic capacity. An immune complex glomerulonephritis (GN was then induced using intraperitoneal injections of horse spleen apoferritin (HSA with a lipopolysaccharide (LPS adjuvant. All HSA/LPS animals developed a proliferative GN with glomerular infiltration by monocytes. By sensitive ELISA, monocyte C3 synthesis could be detected in C3KO animals transplanted with WT bone marrow cells. Despite this, there were no significant differences among groups of mice in measures of clinical (proteinuria, renal function or histologic (glomerular cellularity, crescents disease severity. CONCLUSIONS/SIGNIFICANCE: In this model of GN, local synthesis of C3 by infiltrating cells does not appear to be of pathologic importance.

  3. Knowledge, attitude, and perception of disease among persons living with human immunodeficiency virus/acquired immuno deficiency syndrome: A study from a tertiary care center in North India

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    Mrinal Gupta


    Full Text Available Background: Although modification of behavioral practices among human immunodeficiency virus (HIV-affected patients is important in decreasing HIV disease transmission, the knowledge, attitude, and perception studies about HIV infection rarely include persons living with HIV/acquired immuno deficiency syndrome (AIDS. Aims: To assess knowledge, attitude, and perceptions of persons living with HIV/AIDS for the disease and other epidemiological aspects. Materials and Methods: One-hundred and fifty consecutive persons living with HIV/AIDS were enrolled for this questionnaire-based cross-sectional, descriptive study. Results: These 150 patients comprised 93 men and 57 women, aged between 14 and 78 (mean 37.13 years. The majority, 112 (74.67% patients were between 20 and 50 years of age and 116 (77.3% patients were either illiterate or high-school dropouts. Drivers, laborers, and self-employed comprised 69 (74.2% patients among affected males. Only 129 (86% respondents had heard about HIV/AIDS and knew about its heterosexual transmission. Ninety-eight (65.3% respondents were aware of disease transmission from infected blood or needle pricks. Interestingly, 106 (70.7% respondents were aware of the importance of using condom in preventing disease transmission. Television/radio was the most common sources of information for 135 (90% patients. Nearly, 69% respondents disfavored disclosing their disease to friends/colleagues fearing stigmatization. Conclusions: Information, education, and communication activities are imperative to educate persons living with HIV/AIDS about life-long nature of the disease, modes of its transmission, and significance of preventive measures to bridge the gaps in their knowledge. While improvement in individual economic status, education, and health services remains highly desirable, mass media can play a pivotal role in creating awareness among masses.

  4. Association of human TLR1 and TLR6 deficiency with altered immune responses to BCG vaccination in South African infants.

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    April Kaur Randhawa


    Full Text Available The development of effective immunoprophylaxis against tuberculosis (TB remains a global priority, but is hampered by a partially protective Bacillus Calmette-Guérin (BCG vaccine and an incomplete understanding of the mechanisms of immunity to Mycobacterium tuberculosis. Although host genetic factors may be a primary reason for BCG's variable and inadequate efficacy, this possibility has not been intensively examined. We hypothesized that Toll-like receptor (TLR variation is associated with altered in vivo immune responses to BCG. We examined whether functionally defined TLR pathway polymorphisms were associated with T cell cytokine responses in whole blood stimulated ex vivo with BCG 10 weeks after newborn BCG vaccination of South African infants. In the primary analysis, polymorphism TLR6_C745T (P249S was associated with increased BCG-induced IFN-γ in both discovery (n = 240 and validation (n = 240 cohorts. In secondary analyses of the combined cohort, TLR1_T1805G (I602S and TLR6_G1083C (synonymous were associated with increased IFN-γ, TLR6_G1083C and TLR6_C745T were associated with increased IL-2, and TLR1_A1188T was associated with increased IFN-γ and IL-2. For each of these polymorphisms, the hypo-responsive allele, as defined by innate immunity signaling assays, was associated with increased production of TH1-type T cell cytokines (IFN-γ or IL-2. After stimulation with TLR1/6 lipopeptide ligands, PBMCs from TLR1/6-deficient individuals (stratified by TLR1_T1805G and TLR6_C745T hyporesponsive genotypes secreted lower amounts of IL-6 and IL-10 compared to those with responsive TLR1/6 genotypes. In contrast, no IL-12p70 was secreted by PBMCs or monocytes. These data support a mechanism where TLR1/6 polymorphisms modulate TH1 T-cell polarization through genetic regulation of monocyte IL-10 secretion in the absence of IL-12. These studies provide evidence that functionally defined innate immune gene variants are associated with the

  5. Seeding efficiency of primitive human hematopoietic cells in nonobese diabetic/severe combined immune deficiency mice: implications for stem cell frequency assessment

    NARCIS (Netherlands)

    P.B. van Hennik; A.E. de Koning (Alexandra); R.E. Ploemacher (Robert)


    textabstractNonobese diabetic/severe combined immune deficiency (NOD/SCID) mouse repopulating cells (SRC) have been proposed to represent a more primitive human stem cell subset than the cobblestone area-forming cell (CAFC) week (wk) 6 or the long-term culture-initiatin

  6. Human NK cells of mice with reconstituted human immune system components require preactivation to acquire functional competence. (United States)

    Strowig, Till; Chijioke, Obinna; Carrega, Paolo; Arrey, Frida; Meixlsperger, Sonja; Rämer, Patrick C; Ferlazzo, Guido; Münz, Christian


    To investigate human natural killer (NK)-cell reactivity in vivo we have reconstituted human immune system components by transplantation of human hematopoietic progenitor cells into NOD-scid IL2Rγ(null) mice. We demonstrate here that this model allows the development of all NK-cell subsets that are also found in human adult peripheral and cord blood, including NKp46(+)CD56(-) NK cells. Similar to human cord blood, NK cells from these reconstituted mice require preactivation by interleukin-15 to reach the functional competence of human adult NK cells. Mainly the terminally differentiated CD16(+) NK cells demonstrate lower reactivity without this stimulation. After preactivation, both CD16(+) and CD16(-) NK cells efficiently produce interferon-γ and degranulate in response to stimulation with NK cell-susceptible targets, including K562 erythroleukemia cells. NK-cell lines, established from reconstituted mice, demonstrate cytotoxicity against this tumor cell line. Importantly, preactivation can as well be achieved by bystander cell maturation via poly I:C stimulation in vitro and injection of this maturation stimulus in vivo. Preactivation in vivo enhances killing of human leukocyte antigen class I negative tumor cells after their adoptive transfer. These data suggest that a functional, but resting, NK-cell compartment can be established in immune-compromised mice after human hematopoietic progenitor cell transfer.

  7. B cell-specific deficiencies in mTOR limit humoral immune responses. (United States)

    Zhang, Shuling; Pruitt, Margaret; Tran, Dena; Du Bois, Wendy; Zhang, Ke; Patel, Rushi; Hoover, Shelley; Simpson, R Mark; Simmons, John; Gary, Joy; Snapper, Clifford M; Casellas, Rafael; Mock, Beverly A


    Generation of high-affinity Abs in response to Ags/infectious agents is essential for developing long-lasting immune responses. B cell maturation and Ab responses to Ag stimulation require Ig somatic hypermutation (SHM) and class-switch recombination (CSR) for high-affinity responses. Upon immunization with either the model Ag 4-hydroxy-3-nitrophenylacetyl hapten (NP) conjugated to chicken γ globulin lysine (NP-CGG) or heat-killed Streptococcus pneumoniae capsular type 14 protein (Pn14), knock-in (KI) mice hypomorphic for mTOR function had a decreased ability to form germinal centers, develop high-affinity anti-NP-specific or anti-Pn14-specific Abs, and perform SHM/CSR. Hypomorphic mTOR mice also had a high mortality (40%) compared with wild-type (WT) (0%) littermates and had lower pneumococcal surface protein A-specific Ab titers when immunized and challenged with live S. pneumoniae infection. Mice with mTOR deleted in their B cell lineage (knockout [KO]) also produced fewer splenic germinal centers and decreased high-affinity Ab responses to NP-CGG than did their WT littermates. CSR rates were lower in mTOR KI and KO mice, and pharmacologic inhibition of mTOR in WT B cells resulted in decreased rates of ex vivo CSR. RNA and protein levels of activation-induced cytidine deaminase (AID), a protein essential for SHM and CSR, were lower in B cells from both KI and B cell-specific KO mice, concomitant with increases in phosphorylated AKT and FOXO1. Rescue experiments increasing AID expression in KI B cells restored CSR levels to those in WT B cells. Thus, mTOR plays an important immunoregulatory role in the germinal center, at least partially through AID signaling, in generating high-affinity Abs.

  8. Differential Impact of LPG-and PG-Deficient Leishmania major Mutants on the Immune Response of Human Dendritic Cells.

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    Michelle A Favila


    Full Text Available Leishmania major infection induces robust interleukin-12 (IL12 production in human dendritic cells (hDC, ultimately resulting in Th1-mediated immunity and clinical resolution. The surface of Leishmania parasites is covered in a dense glycocalyx consisting of primarily lipophosphoglycan (LPG and other phosphoglycan-containing molecules (PGs, making these glycoconjugates the likely pathogen-associated molecular patterns (PAMPS responsible for IL12 induction.Here we explored the role of parasite glycoconjugates on the hDC IL12 response by generating L. major Friedlin V1 mutants defective in LPG alone, (FV1 lpg1-, or generally deficient for all PGs, (FV1 lpg2-. Infection with metacyclic, infective stage, L. major or purified LPG induced high levels of IL12B subunit gene transcripts in hDCs, which was abrogated with FV1 lpg1- infections. In contrast, hDC infections with FV1 lpg2- displayed increased IL12B expression, suggesting other PG-related/LPG2 dependent molecules may act to dampen the immune response. Global transcriptional profiling comparing WT, FV1 lpg1-, FV1 lpg2- infections revealed that FV1 lpg1- mutants entered hDCs in a silent fashion as indicated by repression of gene expression. Transcription factor binding site analysis suggests that LPG recognition by hDCs induces IL-12 in a signaling cascade resulting in Nuclear Factor κ B (NFκB and Interferon Regulatory Factor (IRF mediated transcription.These data suggest that L. major LPG is a major PAMP recognized by hDC to induce IL12-mediated protective immunity and that there is a complex interplay between PG-baring Leishmania surface glycoconjugates that result in modulation of host cellular IL12.

  9. Nogo-receptor 1 deficiency has no influence on immune cell repertoire or function during experimental autoimmune encephalomyelitis.

    Directory of Open Access Journals (Sweden)

    Sara A Litwak

    Full Text Available The potential role of Nogo-66 Receptor 1 (NgR1 on immune cell phenotypes and their activation during neuroinflammatory diseases such as multiple sclerosis (MS and its animal model, experimental autoimmune encephalomyelitis (EAE, is unclear. To further understand the function of this receptor on haematopoietically-derived cells, phenotypic and functional analyses were performed using NgR1-deficient (ngr1-/- animals. Flow cytometry-based phenotypic analyses performed on blood, spleen, thymus, lymph nodes, bone marrow and central nervous-system (CNS-infiltrating blood cells revealed no immunological defects in naïve ngr1-/- animals versus wild-type littermate (WTLM controls. EAE was induced by either recombinant myelin oligodendrocyte glycoprotein (rMOG, a model in which B cells are considered to contribute pathogenically, or by MOG35-55 peptide, a B cell-independent model. We have demonstrated that in ngr1-/- mice injected with MOG35-55, a significant reduction in the severity of EAE correlated with reduced axonal damage present in the spinal cord when compared to their WTLM controls. However, despite a reduction in axonal damage observed in the CNS of ngr1-/- mice at the chronic stage of disease, no clinical differences could be attributed to a specific genotype when rMOG was used as the encephalitogen. Following MOG35-55-induction of EAE, we could not derive any major changes to the immune cell populations analyzed between ngr1-/- and WTLM mice. Collectively, these data demonstrate that NgR1 has little if any effects on the repertoire of immune cells, their activation and trafficking to the CNS.

  10. Adaptive Immune Response to Model Antigens Is Impaired in Murine Leukocyte-Adhesion Deficiency-1 Revealing Elevated Activation Thresholds In Vivo

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    Thorsten Peters


    Full Text Available Absence of β2 integrins (CD11/CD18 leads to leukocyte-adhesion deficiency-1 (LAD1, a rare primary immunodeficiency syndrome. Although extensive in vitro work has established an essential function of β2 integrins in adhesive and signaling properties for cells of the innate and adaptive immune system, their respective participation in an altered adaptive immunity in LAD1 patients are complex and only partly understood in vivo. Therefore, we investigated adaptive immune responses towards different T-dependent antigens in a murine LAD1 model of β2 integrin-deficiency (CD18−/−. CD18−/− mice generated only weak IgG responses after immunization with tetanus toxoid (TT. In contrast, robust hapten- and protein-specific immune responses were observed after immunization with highly haptenated antigens such as (4-hydroxy-3-nitrophenyl21 acetyl chicken γ globulin (NP21-CG, even though regularly structured germinal centers with specificity for the defined antigens/haptens in CD18−/− mice remained absent. However, a decrease in the hapten/protein ratio lowered the efficacy of immune responses in CD18−/− mice, whereas a mere reduction of the antigen dose was less crucial. Importantly, haptenation of TT with NP (NP-TT efficiently restored a robust IgG response also to TT. Our findings may stimulate further studies on a modification of vaccination strategies using highly haptenated antigens in individuals suffering from LAD1.

  11. Epidermal filaggrin deficiency mediates increased systemic T-helper 17 immune response

    DEFF Research Database (Denmark)

    Bonefeld, C. M.; Petersen, T. H.; Bandier, J.


    Background: Cellular T-helper (Th)17 infiltrates dominate skin inflammation in filaggrin-deficient flaky tail (ft/ft) mice, and Th17 cells are found in both the skin and blood of patients with acute atopic dermatitis. However, the potential role of loss-of-function mutations in the filaggrin gene...... (FLG) for increased peripheral Th17 cells is unclear. Objectives: To study whether mutations in FLG influence the frequency of peripheral Th17 cells. Methods: We studied blood samples from six adults with mutations in FLG and five controls without mutations for frequencies of cytokine-producing CD4+ T...... increased frequency of peripheral Th17 cells in FLG mutation carriers when compared with WT individuals. Mouse studies showed increased frequency of peripheral Th17 cells in adult ft/ft mice but not in 2-week-old ft/ft mice. Moreover, altered TCR Vβ-chain repertoire was found in ft/ft mice when compared...

  12. Feasibility of Measuring Immune Resp, Activation in Foreskin/Mucosa in HIV-, Uncircumcised High-HIV-risk MSM, Lima Peru (United States)


    HIV Infections; Acquired Immunodeficiency Syndrome; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

  13. IL-15 deficient tax mice reveal a role for IL-1α in tumor immunity.

    Directory of Open Access Journals (Sweden)

    Daniel A Rauch

    Full Text Available IL-15 is recognized as a promising candidate for tumor immunotherapy and has been described as both a promoter of cancer and a promoter of anti-cancer immunity. IL-15 was discovered in cells transformed by HTLV-1, the etiologic agent of adult T cell leukemia/lymphoma (ATL and the human retrovirus that carries the Tax oncogene. We have developed the TAX-LUC mouse model of ATL in which Tax expression drives both malignant transformation and luciferase expression, enabling non-invasive imaging of tumorigenesis in real time. To identify the role of IL-15 in spontaneous development of lymphoma in vivo, an IL-15(-/- TAX-LUC strain was developed and examined. The absence of IL-15 resulted in aggressive tumor growth and accelerated mortality and demonstrated that IL-15 was not required for Tax-mediated lymphoma but was essential for anti-tumor immunity. Further analysis revealed a unique transcriptional profile in tumor cells that arise in the absence of IL-15 that included a significant increase in the expression of IL-1α and IL-1α-regulated cytokines. Moreover, anti-IL-1α antibodies and an IL-1 receptor antagonist (Anakinra were used to interrogate the potential of IL-1α targeted therapies in this model. Taken together, these findings identify IL-15 and IL-1α as therapeutic targets in lymphoma.

  14. IL-15 deficient tax mice reveal a role for IL-1α in tumor immunity. (United States)

    Rauch, Daniel A; Harding, John C; Ratner, Lee


    IL-15 is recognized as a promising candidate for tumor immunotherapy and has been described as both a promoter of cancer and a promoter of anti-cancer immunity. IL-15 was discovered in cells transformed by HTLV-1, the etiologic agent of adult T cell leukemia/lymphoma (ATL) and the human retrovirus that carries the Tax oncogene. We have developed the TAX-LUC mouse model of ATL in which Tax expression drives both malignant transformation and luciferase expression, enabling non-invasive imaging of tumorigenesis in real time. To identify the role of IL-15 in spontaneous development of lymphoma in vivo, an IL-15(-/-) TAX-LUC strain was developed and examined. The absence of IL-15 resulted in aggressive tumor growth and accelerated mortality and demonstrated that IL-15 was not required for Tax-mediated lymphoma but was essential for anti-tumor immunity. Further analysis revealed a unique transcriptional profile in tumor cells that arise in the absence of IL-15 that included a significant increase in the expression of IL-1α and IL-1α-regulated cytokines. Moreover, anti-IL-1α antibodies and an IL-1 receptor antagonist (Anakinra) were used to interrogate the potential of IL-1α targeted therapies in this model. Taken together, these findings identify IL-15 and IL-1α as therapeutic targets in lymphoma.

  15. Vitamin Supplementation at the Time of Immunization with a Cold-Adapted Influenza Virus Vaccine Corrects Poor Mucosal Antibody Responses in Mice Deficient for Vitamins A and D. (United States)

    Surman, S L; Penkert, R R; Jones, B G; Sealy, R E; Hurwitz, J L


    Vitamin A and D deficiencies and insufficiencies are prevalent worldwide in developed and developing countries. Vitamin metabolites are functionally intertwined in that they are high-affinity ligands for related receptors of the nuclear receptor superfamily. The effects of vitamin A deficiencies (VAD) on antibody responses to respiratory virus vaccines have already been demonstrated. Of particular concern was the reduction in IgA, a first line of defense against pathogens in the respiratory tract. Here, we describe the individual and combined effects of vitamin A and D deficiencies in mice immunized with an attenuated influenza virus vaccine. Relative to VAD, vitamin D deficiency (VDD) had a limited effect, but double deficiencies for vitamins A and D (VAD+VDD) further reduced antibody responses in the respiratory tract. The administration of supplemental vitamins A and D to VAD+VDD mice at the time of vaccination restored responses in a dose-dependent manner. Results suggest that vitamin supplementation programs may be beneficial in a clinical setting to promote healthy immune responses to respiratory virus vaccines in vitamin-deficient individuals.

  16. Efeitos da deficiência de cobre, zinco e magnésio sobre o sistema imune de crianças com desnutrição grave Effects of copper, zinc and magnesium deficiency on the immune system of severely malnourished children

    Directory of Open Access Journals (Sweden)

    Érika Michelle C. de Macêdo


    studies published during the last decade were chosen. DATA SYNTHESIS: Micronutrients are essential organic compounds. Besides their regulatory function, the minerals act on the modulation of the immune response. Their deficiency may be due to inadequate intake or associated with specific diseases. When combined with malnutrition, a multimineral deficiency can cause immune dysfunction and increased susceptibility to infections, altering the effectiveness of therapeutic interventions. Copper, zinc and magnesium act as co-factors of both enzymes responsible for several metabolic activities and associated to the innate and acquired immune response. These minerals also play an important role in the maturation of lymphoid tissues and cells. Their deficiency causes neutropenia and lymphopenia, decreasing the immunocompetence. CONCLUSIONS: Deficits of serum copper, zinc and magnesium affect the function of the immune system, leading to immunosuppression. The replacement of these elements in the management of severe malnutrition, as recommended by the World Health Organization, is essential, since such changes may be reversible.

  17. Dendritic cells treated with crude Plasmodium berghei extracts acquire immune-modulatory properties and suppress the development of autoimmune neuroinflammation. (United States)

    Thomé, Rodolfo; Issayama, Luidy K; Alves da Costa, Thiago; Gangi, Rosária D; Ferreira, Isadora T; Rapôso, Catarina; Lopes, Stefanie C P; da Cruz Höfling, Maria Alice; Costa, Fábio T M; Verinaud, Liana


    Dendritic cells (DCs) are professional antigen-presenting cells specifically targeted during Plasmodium infection. Upon infection, DCs show impaired antigen presentation and T-cell activation abilities. In this study, we aimed to evaluate whether cellular extracts obtained from Plasmodium berghei-infected erythrocytes (PbX) modulate DCs phenotypically and functionally and the potential therapeutic usage of PbX-modulated DCs in the control of experimental autoimmune encephalomyelitis (EAE, the mouse model for human multiple sclerosis). We found that PbX-treated DCs have impaired maturation and stimulated the generation of regulatory T cells when cultured with naive T lymphocytes in vitro. When adoptively transferred to C57BL/6 mice the EAE severity was reduced. Disease amelioration correlated with a diminished infiltration of cytokine-producing T cells in the central nervous system as well as the suppression of encephalitogenic T cells. Our study shows that extracts obtained from P. berghei-infected erythrocytes modulate DCs towards an immunosuppressive phenotype. In addition, the adoptive transfer of PbX-modulated DCs was able to ameliorate EAE development through the suppression of specific cellular immune responses towards neuro-antigens. To our knowledge, this is the first study to present evidence that DCs treated with P. berghei extracts are able to control autoimmune neuroinflammation.

  18. Pulmonary leukocytic responses are linked to the acquired immunity of mice vaccinated with irradiated cercariae of Schistosoma mansoni

    Energy Technology Data Exchange (ETDEWEB)

    Aitken, R.; Coulson, P.S.; Wilson, R.A.


    Pulmonary cellular responses in C57BL/6 mice exposed to Schistosoma mansoni have been investigated by sampling cells from the respiratory airways with bronchoalveolar lavage. Mice exposed to cercariae attenuated with 20 krad gamma-radiation developed stronger and more persistent pulmonary leukocytic responses than animals exposed to equal numbers of normal parasites. Although vaccination with irradiated cercariae also stimulated T cell responses of greater magnitude and duration than normal infection, the lymphocytic infiltrate elicited by each regimen did not differ substantially in its composition, 5 wk after exposure. Studies with cercariae attenuated by different treatments established that a link exists between the recruitment of leukocytes to the lungs of vaccinated mice and resistance to reinfection. There was a strong association between pulmonary leukocytic responses and the elimination of challenge infections by vaccinated mice. Animals exposed to irradiated cercariae of S. mansoni were resistant to homologous challenge infection but were not protected against Schistosoma margrebowiei. Homologous challenge of vaccinated mice stimulated anamnestic leukocytic and T lymphocytic responses in the lungs, 2 wk postinfection, but exposure of immunized animals to the heterologous species failed to trigger an expansion in these populations of cells. Our studies indicate that pulmonary leukocytes and T lymphocytes are intimately involved in the mechanism of vaccine-induced resistance to S. mansoni. It remains unclear whether these populations of cells initiate protective inflammatory reactions against challenge parasites in the lungs, or accumulate in response to the activation of the protective mechanism by other means.

  19. Expansion of inflammatory innate lymphoid cells in patients with common variable immune deficiency (United States)

    Cols, Montserrat; Rahman, Adeeb; Maglione, Paul J.; Garcia-Carmona, Yolanda; Simchoni, Noa; Ko, Huai-Bin M.; Radigan, Lin; Cerutti, Andrea; Blankenship, Derek; Pascual, Virginia; Cunningham-Rundles, Charlotte


    Background Common variable immunodeficiency (CVID) is an antibody deficiency treated with immunoglobulin; however, patients can have noninfectious inflammatory conditions that lead to heightened morbidity and mortality. Objectives Modular analyses of RNA transcripts in whole blood previously identified an upregulation of many interferon-responsive genes. In this study we sought the cell populations leading to this signature. Methods Lymphoid cells were measured in peripheral blood of 55 patients with CVID (31 with and 24 without inflammatory/autoimmune complications) by using mass cytometry and flow cytometry. Surface markers, cytokines, and transcriptional characteristics of sorted innate lymphoid cells (ILCs) were defined by using quantitative PCR. Gastrointestinal and lung biopsy specimens of subjects with inflammatory disease were stained to seek ILCs in tissues. Results The linage-negative, CD127+, CD161+ lymphoid population containing T-box transcription factor, retinoic acid–related orphan receptor (ROR) γt, IFN-γ, IL-17A, and IL-22, all hallmarks of type 3 innate lymphoid cells, were expanded in the blood of patients with CVID with inflammatory conditions (mean, 3.7% of PBMCs). ILCs contained detectable amounts of the transcription factors inhibitor of DNA binding 2, T-box transcription factor, and RORγt and increased mRNA transcripts for IL-23 receptor (IL-23R) and IL-26, demonstrating inflammatory potential. In gastrointestinal and lung biopsy tissues of patients with CVID, numerous IFN-γ+RORγt+CD3− cells were identified, suggesting a role in these mucosal inflammatory states. Conclusions An expansion of this highly inflammatory ILC population is a characteristic of patients with CVID with inflammatory disease; ILCs and the interferon signature are markers for the uncontrolled inflammatory state in these patients. PMID:26542033

  20. Exacerbated fatigue and motor deficits in interleukin-10-deficient mice after peripheral immune stimulation (United States)

    Krzyszton, C. P.; Sparkman, N. L.; Grant, R. W.; Buchanan, J. B.; Broussard, S. R.; Woods, J.; Johnson, R. W.


    The anti-inflammatory cytokine interleukin (IL)-10 is important for regulating inflammation in the periphery and brain, but whether it protects against infection- or age-related psychomotor disturbances and fatigue is unknown. Therefore, the present study evaluated motor coordination, time to fatigue, and several central and peripheral proinflammatory cytokines in male young adult (3-mo-old) and middle-aged (12-mo-old) wild-type (IL-10+/+) and IL-10-deficient (IL-10−/−) mice after intraperitoneal injection of lipopolysaccharide (LPS) or saline. No age-related differences were observed; therefore, data from the two ages were pooled and analyzed to determine effects of genotype and treatment. LPS treatment increased IL-1β, IL-6, and TNFα mRNA in all brain areas examined in IL-10+/+ and IL-10−/− mice, but to a greater extent and for a longer time in IL-10−/− mice. Plasma IL-1β and IL-6 were increased similarly in IL-10+/+ and IL-10−/− mice 4 h after LPS but remained elevated longer in IL-10−/− mice, whereas TNFα was higher in IL-10−/− mice throughout after LPS treatment. Motor performance and motor learning in IL-10+/+ mice were not affected by LPS treatment; however, both were reduced in IL-10−/− mice treated with LPS compared with those treated with saline. Furthermore, although LPS reduced the time to fatigue in IL-10+/+ and IL-10−/− mice, the effects were exacerbated in IL-10−/− mice. Thus the increased brain and peripheral inflammation induced by LPS in IL-10−/− mice was associated with increased coordination deficits and fatigue. These data suggest that IL-10 may inhibit motor deficits and fatigue associated with peripheral infections via its anti-inflammatory effects. PMID:18650318

  1. The impaired intestinal mucosal immune system by valine deficiency for young grass carp (Ctenopharyngodon idella) is associated with decreasing immune status and regulating tight junction proteins transcript abundance in the intestine. (United States)

    Luo, Jian-Bo; Feng, Lin; Jiang, Wei-Dan; Liu, Yang; Wu, Pei; Jiang, Jun; Kuang, Sheng-Yao; Tang, Ling; Zhang, Yong-An; Zhou, Xiao-Qiu


    This study investigated the effects of dietary valine on the growth, intestinal immune response, tight junction proteins transcript abundance and gene expression of immune-related signaling molecules in the intestine of young grass carp (Ctenopharyngodon idella). Six iso-nitrogenous diets containing graded levels of valine (4.3-19.1 g kg(-)(1) diet) were fed to the fish for 8 weeks. The results showed that percentage weight gain (PWG), feed intake and feed efficiency of fish were the lowest in fish fed the valine-deficient diet (P valine deficiency decreased lysozyme, acid phosphatase activities and complement 3 content in the intestine (P valine deficiency significantly decreased transcript of Occludin, Claudin b, Claudin c, Claudin 3, and ZO-1 (P valine did not have a significant effect on expression of Claudin 12 in the intestine of grass carp (P > 0.05). In conclusion, valine deficiency decreased fish growth and intestinal immune status, as well as regulated gene expression of tight junction proteins, NF-κB P65, IκBα and TOR in the fish intestine. Based on the quadratic regression analysis of lysozyme activity or PWG, the dietary valine requirement of young grass carp (268-679 g) were established to be 14.47 g kg(-1) diet (4.82 g 100 g(-1) CP) or 14.00 g kg(-1) diet (4.77 g 100 g(-1) CP), respectively.

  2. Outer membrane vesicles from flagellin-deficient Salmonella enterica serovar Typhimurium induce cross-reactive immunity and provide cross-protection against heterologous Salmonella challenge (United States)

    Liu, Qiong; Liu, Qing; Yi, Jie; Liang, Kang; Hu, Bo; Zhang, Xiangmin; Curtiss, Roy; Kong, Qingke


    Outer membrane vesicles (OMVs) isolated from Salmonella Typhimurium are potentially useful for developing subunit vaccines because of high immunogenicity and protective efficacy. However, flagella might remain in OMV pellets following OMV purification, resulting in non-essential immune responses and counteraction of bacterial protective immune responses when developing a vaccine against infection of multiple serotypes Salmonella. In this study, a flagellin-deficient S. Typhimurium mutant was constructed. Lipopolysaccharide profiles, protein profiles and cryo-electron microscopy revealed that there were no significant differences between the wild-type and mutant OMVs, with the exception of a large amount of flagellin in the wild-type OMVs. Neither the wild-type OMVs nor the non-flagellin OMVs were toxic to macrophages. Mice immunized with the non-flagellin OMVs produced high concentrations of IgG. The non-flagellin OMVs elicited strong mucosal antibody responses in mice when administered via the intranasal route in addition to provoking higher cross-reactive immune responses against OMPs isolated from S. Choleraesuis and S. Enteritidis. Both intranasal and intraperitoneal immunization with the non-flagellin OMVs provided efficient protection against heterologous S. Choleraesuis and S. Enteritidis challenge. Our results indicate that the flagellin-deficient OMVs may represent a new vaccine platform that could be exploited to facilitate the production of a broadly protective vaccine. PMID:27698383

  3. An Increased Risk of Osteoporosis during Acquired Immunodeficiency Syndrome


    Annapoorna, N.; Rao, G. Venkateswara; Reddy, N S; Rambabu, P.; Rao, K.R.S.Samabasiva


    Osteoporosis is characterized by decreased bone mineral density and mechanistic imbalances of bone tissue that may result in reduced skeletal strength and an enhanced susceptibility to fractures. Osteoporosis in its most common form affects the elderly (both sexes) and all racial groups of human beings. Multiple environmental risk factors like acquired immune deficiency syndrome (AIDS) are believed to be one of the causes of osteoporosis. Recently a high incidence of osteoporosis has been obs...

  4. The dynamics of naturally acquired immune responses to Plasmodium falciparum sexual stage antigens Pfs230 & Pfs48/45 in a low endemic area in Tanzania.

    Directory of Open Access Journals (Sweden)

    Teun Bousema

    Full Text Available BACKGROUND: Naturally acquired immune responses against sexual stages of P. falciparum can reduce the transmission of malaria from humans to mosquitoes. These antigens are candidate transmission-blocking vaccines but little is known about the acquisition of sexual stage immunity after exposure to gametocytes, or their longevity and functionality. We conducted a longitudinal study on functional sexual stage immune responses. METHODOLOGY/PRINCIPAL FINDINGS: Parasitaemic individuals (n = 116 were recruited at a health centre in Lower Moshi, Tanzania. Patients presented with gametocytes (n = 16, developed circulating gametocytes by day 7 (n = 69 or between day 7 and 14 (n = 10 after treatment or did not develop gametocytes (n = 21. Serum samples were collected on the first day of gametocytaemia and 28 and 84 days post-enrolment (or d7, 28, 84 after enrolment from gametocyte-negative individuals. Antibody responses to sexual stage antigens Pfs230 and Pfs48/45 were detected in 20.7% (72/348 and 15.2% (53/348 of the samples, respectively, and were less prevalent than antibodies against asexual stage antigens MSP-1(19 (48.1%; 137/285 and AMA-1 (52.4%; 129/246(p<0.001. The prevalence of anti-Pfs230 (p = 0.026 and anti-Pfs48/45 antibodies (p = 0.017 increased with longer duration of gametocyte exposure and had an estimated half-life of approximately 3 months. Membrane feeding experiments demonstrated a strong association between the prevalence and concentration of Pfs230 and Pfs48/45 antibodies and transmission reducing activity (TRA, p<0.01. CONCLUSIONS/SIGNIFICANCE: In a longitudinal study, anti-Pfs230 and Pfs48/45 antibodies developed rapidly after exposure to gametocytes and were strongly associated with transmission-reducing activity. Our data indicate that the extent of antigen exposure is important in eliciting functional transmission-reducing immune responses.

  5. Medawar's legacy to cellular immunology and clinical transplantation: a commentary on Billingham, Brent and Medawar (1956) 'Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance'. (United States)

    Simpson, Elizabeth


    'Quantitative studies on tissue transplantation immunity. III. Actively acquired tolerance', published in Philosophical Transactions B in 1956 by Peter Medawar and his colleagues, PhD graduate Leslie Brent and postdoctoral fellow Rupert Billingham, is a full description of the concept of acquired transplantation tolerance. Their 1953 Nature paper (Billingham RE et al. 1953 Nature 172, 603-606. (doi:10.1038/172603a0)) had provided initial evidence with experimental results from a small number of neonatal mice, with mention of similar findings in chicks. The Philosophical Transactions B 1956 paper is clothed with an astonishing amount of further experimental detail. It is written in Peter Medawar's landmark style: witty, perceptive and full of images that can be recalled even when details of the supporting information have faded. Those images are provided not just by a series of 20 colour plates showing skin graft recipient mice, rats, rabbits, chickens and duck, bearing fur or plumage of donor origin, but by his choice of metaphor, simile and analogy to express the questions being addressed and the interpretation of their results, along with those of relevant published data and his prescient ideas of what the results might portend. This work influenced both immunology researchers and clinicians and helped to lay the foundations for successful transplantation programmes. It led to the award of a Nobel prize in 1960 to Medawar, and subsequently to several scientists who advanced these areas. This commentary was written to celebrate the 350th anniversary of the journal Philosophical Transactions of the Royal Society.

  6. Regulatory T-cell depletion in the gut caused by integrin β7 deficiency exacerbates DSS colitis by evoking aberrant innate immunity. (United States)

    Zhang, H L; Zheng, Y J; Pan, Y D; Xie, C; Sun, H; Zhang, Y H; Yuan, M Y; Song, B L; Chen, J F


    Integrin α4β7 controls lymphocyte trafficking into the gut and has essential roles in inflammatory bowel disease (IBD). The α4β7-blocking antibody vedolizumab is approved for IBD treatment; however, high dose of vedolizumab aggravates colitis in a small percentage of patients. Herein, we show that integrin β7 deficiency results in colonic regulatory T (Treg) cell depletion and exacerbates dextran sulfate sodium (DSS) colitis by evoking aberrant innate immunity. In DSS-treated β7-deficient mice, the loss of colonic Treg cells induces excessive macrophage infiltration in the colon via upregulation of colonic epithelial intercellular adhesion molecule 1 and increases proinflammatory cytokine expression, thereby exacerbating DSS-induced colitis. Moreover, reconstitution of the colonic Treg cell population in β7-deficient mice suppresses aberrant innate immune response in the colon and attenuates DSS colitis. Thus, integrin α4β7 is essential for suppression of DSS colitis as it regulates the colonic Treg cell population and innate immunity.

  7. Immune and inflammatory responses in TNF alpha-deficient mice: a critical requirement for TNF alpha in the formation of primary B cell follicles, follicular dendritic cell networks and germinal centers, and in the maturation of the humoral immune response



    To investigate the role of TNF alpha in the development of in vivo immune response we have generated TNF alpha-deficient mice by gene targeting. Homozygous mutant mice are viable and fertile, develop lymph nodes and Peyer's patches and show no apparent phenotypic abnormalities, indicating that TNF alpha is not required for normal mouse development. In the absence of TNF alpha mice readily succumb to L. monocytogenes infections and show reduced contact hypersensitivity responses. Furthermore, ...

  8. Bacillus cereus AR156 activates PAMP-triggered immunity and induces a systemic acquired resistance through a NPR1-and SA-dependent signaling pathway. (United States)

    Niu, Dongdong; Wang, Xiujuan; Wang, Yanru; Song, Xiaoou; Wang, Jiansheng; Guo, Jianhua; Zhao, Hongwei


    Induced resistance responses play a potent role in plant defense system against pathogen attack. Bacillus cereus AR156 is a plant growth promoting rhizobacterium (PGPR) that installs induced systemic resistance (ISR) to Pseudomonas syringae pv. tomato (Pst) in Arabidopsis. Here, we show that AR156 leaf infiltration enhances disease resistance in Arabidopsis through the activation of a systemic acquired resistance (SAR). PR1 protein expression and reactive oxygen species (ROS) burst are strongly induced in plants treated with AR156 and inoculated with Pst than that in plants inoculated with Pst only. Moreover, AR156 can trigger SAR in jar1 or ein2 mutants, but not in the NahG transgenic and NPR1 mutant plants. Our results indicate that AR156-induced SAR depends on SA-signaling pathway and NPR1, but not JA and ET. Also, AR156-treated plants are able to rapidly activate MAPK signaling and FRK1 gene expression, which are involved in pathogen associated molecular pattern (PAMP)-triggered immunity (PTI). Altogether, our results indicate that AR156 can induce SAR by the SA-signaling pathways in an NPR1-dependent manner and involves multiple PTI components.

  9. Immune Deficiency Foundation (United States)

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  10. Primary Immune Deficiency Diseases (United States)

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  11. Self-administration of C1-inhibitor concentrate in patients with hereditary or acquired angioedema caused by C1-inhibitor deficiency

    NARCIS (Netherlands)

    Levi, M; Choi, G; Picavet, C; Hack, CE


    Background: Administration of C1-inhibitor concentrate is effective for prophylaxis and treatment of severe angioedema attacks caused by Cl-inhibitor deficiency. The concentrate should be administered intravenously and hence needs to be administered by health care professionals, which might cause co

  12. Experimental and clinical evidence of the role of cytokines and growth factors in the pathogenesis of acquired cobalamin-deficient leukoneuropathy. (United States)

    Scalabrino, Giuseppe; Veber, Daniela; Mutti, Elena


    Our experimental and clinical studies have highlighted the non-coenzyme functions of cobalamin (Cbl; vitamin B12). The neuropathy of the rat central nervous system (CNS) due to Cbl deficiency is associated with increases in CNS tissue and/or cerebrospinal fluid (CSF) levels of some neurotoxic molecules, and decreases in local and/or CSF levels of some neurotrophic molecules. The increased molecules are nerve growth factor (NGF), tumor necrosis factor (TNF)-alpha, and the soluble (s)CD40:sCD40 Ligand dyad; the decreased molecules are epidermal growth factor (EGF) and interleukin-6. The morphological lesions of the CNS white matter in Cbl-deficient (Cbl-Df) rats can be prevented to the same extent by treatments replacing Cbl or the deficient neurotrophic molecules, or treatment with agents that antagonize the excess neurotoxic molecules. Patients with neurological and/or hematological manifestations of severe Cbl deficiency also have high TNF-alpha levels and low EGF levels in CSF and serum. Cbl replacement treatment corrects cytokine and growth factor abnormalities in Cbl-Df patients and Cbl-Df rats, and so Cbl-Df CNS neuropathy is also due to an imbalance in local cytokine/growth factor networks. TNF-alpha and NGF levels are also increased in Cbl-Df rat liver, which is morphologically unaffected by Cbl deficiency. The increases in TNF-alpha and NGF levels increase nuclear factor-kappaB activity levels in both the CNS and liver, and this indirect regulation supports the idea that Cbl may modulate the expression of some cytokine/growth factor genes in rat CNS and other tissues. Finally, we have tried to harmonize our pathogenetic theory of cytokine and growth factor dysregulation with the biochemical interpretation.

  13. Urokinase-type plasminogen activator deficiency has little effect on seizure susceptibility and acquired epilepsy phenotype but reduces spontaneous exploration in mice. (United States)

    Rantala, J; Kemppainen, S; Ndode-Ekane, X E; Lahtinen, L; Bolkvadze, Tamuna; Gurevicius, K; Tanila, H; Pitkänen, A


    Urokinase-type plasminogen activator (uPA), a serine protease, converts plasminogen to plasmin. Activation of plasmin leads to degradation of the extracellular matrix, which is critical for tissue recovery, angiogenesis, cell migration, and axonal and synaptic plasticity. We hypothesized that uPA deficiency would cause an abnormal neurophenotype and would lead to exacerbated epileptogenesis after brain injury. Wild-type (Wt) and uPA-/- mice underwent a battery of neurologic behavioral tests evaluating general reactivity, spontaneous exploratory activity, motor coordination, pain threshold, fear and anxiety, and memory. We placed particular emphasis on the effect of uPA deficiency on seizure susceptibility, including the response to convulsants (pentylenetetrazol, kainate, or pilocarpine) and kainate-induced epileptogenesis and epilepsy. The uPA-/- mice showed no motor or sensory impairment compared with the Wt mice. Hippocampus-dependent spatial memory also remained intact. The uPA-/- mice, however, exhibited reduced exploratory activity and an enhanced response to a tone stimulus (p<0.05 compared with the Wt mice). The urokinase-type plasminogen activator deficient mice showed no increase in spontaneous or evoked epileptiform electrographic activity. Rather, the response to pilocarpine administration was reduced compared with the Wt mice (p<0.05). Also, the epileptogenesis and the epilepsy phenotype after intrahippocampal kainate injection were similar to those in the Wt mice. Taken together, uPA deficiency led to diminished interest in the environmental surroundings and enhanced emotional reactivity to unexpected aversive stimuli. Urokinase-type plasminogen activator deficiency was not associated with enhanced seizure susceptibility or worsened poststatus epilepticus epilepsy phenotype.

  14. Immunity

    Institute of Scientific and Technical Information of China (English)


    920630 Effects of the spleen on immunestate of patients with gastric cancer.QIUDengbo (仇登波), et al. Dept General Surg,Union Hosp, Tongji Med Univ, Wuhan, 430022.Natl Med J China 1992; 72(6): 334-337. For analysing the effects of the spleen on im-mune state of gastric cancer patients.T-lym-

  15. Complement factor I deficiency: a not so rare immune defect. Characterization of new mutations and the first large gene deletion

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    Alba-Domínguez María


    Full Text Available Abstract Background Complement Factor I (CFI is a serine protease with an important role in complement alternative pathway regulation. Complete factor I deficiency is strongly associated with severe infections. Approximately 30 families with this deficiency have been described worldwide. Patients and methods We have studied five new Spanish families suffering from CFI deficiency. From 19 screened people, 7 homozygous, 10 heterozygous and 2 healthy subjects were identified. Clinical, biochemical and genetic descriptions are included. Results Molecular studies demonstrated 4 novel mutations in the screened individuals; amongst them, we describe here the first great gene deletion reported in the CFI locus, which includes full exon 2 and part of the large intron 1. Conclusion CFI deficiency is possibly an underestimated defect and the eventual existence of this deficiency should be tested in those patients exhibiting low C3 and recurrent bacterial infections. We propose a simple diagnostic flowchart to help clinicians in the identification and correct diagnosis of such patients.

  16. Herpes Viral Origin of the Parsonage-Turner Syndrome: Highlighting of Serological Immune Anti-Herpes Deficiency Cured by Anti-Herpes Therapy

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    Jacqueline Le Goaster


    Full Text Available In 2012, a 50 year-old athletic male presented with weakness, pain and unilateral phrenic paralysis, followed by bilateral phrenic paralysis with deep dyspnea. In 2013, the Parsonage-Turner syndrome was diagnosed. When the patient was seen in September 2014 for the first time, he was facing phrenic neuromuscular failure, which led to the hypothesis of neurotropic herpes viruses. A control of the global serological anti-Herpes immunity to analyze his antibody (Ab levels confirmed herpes immune genetic deficiency. An appropriate herpes chemotherapy treatment was proposed. Immediately, a spectacular recovery of the patient was observed, and after a few weeks, the respiratory function tests showed normal values. The hypothesis of the inductive role of viruses of the herpes family in the Parsonage-Turner syndrome was thus substantiated. The patient's immune deficiency covers the HSV2, HHV3, HHV4, HHV5 and HHV6 Ab levels. This led to the control of herpes in the family lineage: indeed, his daughter presented alterations of her serological herpes Ab levels.

  17. Vitamin E deficiency depressed fish growth, disease resistance, and the immunity and structural integrity of immune organs in grass carp (Ctenopharyngodon idella): Referring to NF-κB, TOR and Nrf2 signaling. (United States)

    Pan, Jia-Hong; Feng, Lin; Jiang, Wei-Dan; Wu, Pei; Kuang, Sheng-Yao; Tang, Ling; Zhang, Yong-An; Zhou, Xiao-Qiu; Liu, Yang


    This study investigated the effects of dietary vitamin E on growth, disease resistance and the immunity and structural integrity of head kidney, spleen and skin in grass carp (Ctenopharyngodon idella). The fish were fed six diets containing graded levels of vitamin E (0, 45, 90, 135, 180 and 225 mg/kg diet) for 10 weeks. Subsequently, a challenge test was conducted by injection of Aeromonas hydrophila. The results showed that compared with optimal vitamin E supplementation, vitamin E deficiency caused depressed growth, poor survival rates and increased skin lesion morbidity in grass carp. Meanwhile, vitamin E deficiency decreased lysozyme and acid phosphatase activities, complement component 3 and complement component 4 contents in the head kidney, spleen and skin of grass carp (P E deficiency down-regulated antimicrobial peptides (Hepcidin, liver-expressed antimicrobial peptide-2A, -2B, β-defensin), IL-10, TGFβ1, IκBα, TOR and S6K1 mRNA levels (P E deficiency caused oxidative damage, decreased superoxide dismutase (SOD), glutathione peroxidase (GPx), catalase (CAT) and glutathione reductase (GR) activities, and down-regulated the mRNA levels of antioxidant enzymes and signaling molecules Nrf2 (P E deficiency also induced apoptosis by up-regulating capase-2, -3, -7, and -8 mRNA levels in the head kidney, spleen and skin of grass carp. In conclusion, this study indicated that dietary vitamin E deficiency depressed fish growth, impaired the immune function and disturbed the structural integrity of the head kidney, spleen and skin in grass carp, but optimal vitamin E supplementation can reverse those negative effects in fish. The optimal vitamin E requirements for young grass carp (266.39-1026.63 g) to achieve optimal growth performance and disease resistance based on the percent weight gain (PWG) and skin lesion morbidity were estimated to be 116.2 and 130.9 mg/kg diet, respectively. Meanwhile, based on immune indicator (LA activity in the head kidney) and

  18. Up-regulation of mitochondrial activity and acquirement of brown adipose tissue-like property in the white adipose tissue of fsp27 deficient mice.

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    Shen Yon Toh

    Full Text Available Fsp27, a member of the Cide family proteins, was shown to localize to lipid droplet and promote lipid storage in adipocytes. We aimed to understand the biological role of Fsp27 in regulating adipose tissue differentiation, insulin sensitivity and energy balance. Fsp27(-/- mice and Fsp27/lep double deficient mice were generated and we examined the adiposity, whole body metabolism, BAT and WAT morphology, insulin sensitivity, mitochondrial activity, and gene expression changes in these mouse strains. Furthermore, we isolated mouse embryonic fibroblasts (MEFs from wildtype and Fsp27(-/- mice, followed by their differentiation into adipocytes in vitro. We found that Fsp27 is expressed in both brown adipose tissue (BAT and white adipose tissue (WAT and its levels were significantly elevated in the WAT and liver of leptin-deficient ob/ob mice. Fsp27(-/- mice had increased energy expenditure, lower levels of plasma triglycerides and free fatty acids. Furthermore, Fsp27(-/-and Fsp27/lep double-deficient mice are resistant to diet-induced obesity and display increased insulin sensitivity. Moreover, white adipocytes in Fsp27(-/- mice have reduced triglycerides accumulation and smaller lipid droplets, while levels of mitochondrial proteins, mitochondrial size and activity are dramatically increased. We further demonstrated that BAT-specific genes and key metabolic controlling factors such as FoxC2, PPAR and PGC1alpha were all markedly upregulated. In contrast, factors inhibiting BAT differentiation such as Rb, p107 and RIP140 were down-regulated in the WAT of Fsp27(-/- mice. Remarkably, Fsp27(-/- MEFs differentiated in vitro show many brown adipocyte characteristics in the presence of the thyroid hormone triiodothyronine (T3. Our data thus suggest that Fsp27 acts as a novel regulator in vivo to control WAT identity, mitochondrial activity and insulin sensitivity.

  19. Campylobacter fetus Bacteremia Revealed by Cellulitis without Gastrointestinal Symptoms in the Context of Acquired Hypogammaglobulinemia: A Report of Three Cases

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    Souleymane Brah


    Full Text Available Campylobacter fetus bacteremia is rare and occurs mainly in patients with immunosuppression. This infection, which often involves secondary localizations has already been reported in some primary humoral immune deficiencies. We describe three cases of severe infection due to C. fetus with cellulitis at presentation, but without any gastrointestinal symptoms, occurring in patients with acquired hypogammaglobulinemia.

  20. Effect of dietary phosphorus deficiency on the growth, immune function and structural integrity of head kidney, spleen and skin in young grass carp (Ctenopharyngodon idella). (United States)

    Chen, Kang; Jiang, Wei-Dan; Wu, Pei; Liu, Yang; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu; Feng, Lin


    This study evaluates the effects of dietary phosphorus on the growth, immune function and structural integrity (head kidney, spleen and skin) of young grass carp (Ctenopharyngodon idella) that were fed graded levels of available phosphorus (0.95-8.75 g/kg diet). Results indicated that phosphorus deficiency decreased the growth performance of young grass carp. In addition, the results first demonstrated that compared with the optimal phosphorus level, phosphorus deficiency depressed the lysozyme (LZ) and acid phosphatase (ACP) activities and the complement 3 (C3), C4 and immunoglobulin M (IgM) contents, and down-regulated the mRNA levels of antimicrobial peptides, anti-inflammatory cytokines, inhibitor of κBα (IκBα) and target of rapamycin (TOR), whereas it up-regulated pro-inflammatory cytokines, nuclear factor kappa B (NF-κB) p65 and NF-κB p52 mRNA levels to decrease fish head kidney and spleen immune functions. Moreover, phosphorus deficiency up-regulated the mRNA levels of Kelch-like-ECH-associated protein 1a (Keap1a), Fas ligand (FasL), apoptotic protease activating factor-1 (Apaf-1), Bcl-2 associated X protein (Bax), caspase -2, -3, -7, -8 and -9, p38 mitogen-activated protein kinase (MAPK) and myosin light chain kinase (MLCK), whereas it depressed the glutathione (GSH) contents and antioxidant enzymes activities, and down-regulated the mRNA levels of antioxidant enzymes, NF-E2-related factor 2 (Nrf2), B-cell lymphoma protein-2 (Bcl-2), myeloid cell leukemia-1 (Mcl-1) and tight junction complexes to attenuate fish head kidney and spleen structural integrity. In addition, phosphorus deficiency increased skin hemorrhage and lesions morbidity. Finally, based on the percent weight gain (PWG) and the ability to combat skin hemorrhage and lesions, the dietary available phosphorus requirements for young grass carp (254.56-898.23 g) were estimated to be 4.10 and 4.13 g/kg diet, respectively. In summary, phosphorus deficiency decreases the growth

  1. Solubilization of immune complexes in complement factor deficient sera and the influence of temperature, ionic strength and divalent cations on the solubilization reaction

    DEFF Research Database (Denmark)

    Baatrup, Gunnar; Petersen, Ivan; Svehag, Svend-Erik;


    The complement-mediated solubilization (CMS) of immune complexes (IC) and the initial kinetics (IKS) of this reaction in human sera depleted of or deficient in C2, C3, C8, factors B, P and I were investigated. Sera depleted of B or P and those lacking native C3 or factor I showed virtually no CMS...... by a radioassay and kinetic data for the binding of C3b to preformed immune complexes. The CMS capacity reached maximum at 39-41 degrees C and at an ionic strength of approximately 0.20 mu. Selective chelation of Mg2+ completely abolished the CMS of IC. Maximal CMS was observed at Mg2+ concentration of about 2m...

  2. A novel role for APOBEC3: Susceptibility to sexual transmission of murine acquired immunodeficiency virus (mAIDS is aggravated in APOBEC3 deficient mice

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    Jones Philip H


    Full Text Available Abstract Background APOBEC3 proteins are host factors that restrict infection by retroviruses like HIV, MMTV, and MLV and are variably expressed in hematopoietic and non-hematopoietic cells, such as macrophages, lymphocytes, dendritic, and epithelia cells. Previously, we showed that APOBEC3 expressed in mammary epithelia cells function to limit milk-borne transmission of the beta-retrovirus, mouse mammary tumor virus. In this present study, we used APOBEC3 knockout mice and their wild type counterpart to query the role of APOBEC3 in sexual transmission of LP-BM5 MLV – the etiological agent of murine AIDs (mAIDs. Results We show that mouse APOBEC3 is expressed in murine genital tract tissues and gametes and that genital tract tissue of APOBEC3-deficient mice are more susceptible to infection by LP-BM5 virus. APOBEC3 expressed in genital tract tissues most likely plays a role in decreasing virus transmission via the sexual route, since mice deficient in APOBEC3 gene have higher genitalia and seminal plasma virus load and sexually transmit the virus more efficiently to their partners compared to APOBEC3+ mice. Moreover, we show that female mice sexually infected with LP-BM5 virus transmit the virus to their off-spring in APOBEC3-dependent manner. Conclusion Our data indicate that genital tissue intrinsic APOBEC3 restricts genital tract infection and limits sexual transmission of LP-BM5 virus.

  3. Genetically attenuated, P36p-deficient malarial sporozoites induce protective immunity and apoptosis of infected liver cells.

    NARCIS (Netherlands)

    Dijk, M.R. van; Douradinha, B.; Franke-Fayard, B.; Heussler, V.; Dooren, M.W. van; Schaijk, B.C.L. van; Gemert, G.J.A. van; Sauerwein, R.W.; Mota, M.M.; Waters, A.P.; Janse, C.J.


    Immunization with Plasmodium sporozoites that have been attenuated by gamma-irradiation or specific genetic modification can induce protective immunity against subsequent malaria infection. The mechanism of protection is only known for radiation-attenuated sporozoites, involving cell-mediated and hu

  4. LV305, a dendritic cell-targeting integration-deficient ZVex(TM)-based lentiviral vector encoding NY-ESO-1, induces potent anti-tumor immune response. (United States)

    Albershardt, Tina Chang; Campbell, David James; Parsons, Andrea Jean; Slough, Megan Merrill; Ter Meulen, Jan; Berglund, Peter


    We have engineered an integration-deficient lentiviral vector, LV305, to deliver the tumor antigen NY-ESO-1 to human dendritic cells in vivo through pseudotyping with a modified Sindbis virus envelop protein. Mice immunized once with LV305 developed strong, dose-dependent, multifunctional, and cytotoxic NY-ESO-1-specific cluster of differentiation 8 (CD8) T cells within 14 days post-immunization and could be boosted with LV305 at least twice to recall peak-level CD8 T-cell responses. Immunization with LV305 protected mice against tumor growth in an NY-ESO-1-expressing CT26 lung metastasis model, with the protective effect abrogated upon depletion of CD8 T cells. Adoptive transfer of CD8 T cells, alone or together with CD4 T cells or natural killer cells, from LV305-immunized donor mice to tumor-bearing recipient mice conferred significant protection against metastatic tumor growth. Biodistribution of injected LV305 in mice was limited to the site of injection and the draining lymph node, and injected LV305 exhibited minimal excretion. Mice injected with LV305 developed little to no adverse effects, as evaluated by toxicology studies adherent to good laboratory practices. Taken together, these data support the development of LV305 as a clinical candidate for treatment against tumors expressing NY-ESO-1.

  5. Pre-existing vector immunity does not prevent replication deficient adenovirus from inducing efficient CD8 T-cell memory and recall responses. (United States)

    Steffensen, Maria Abildgaard; Jensen, Benjamin Anderschou Holbech; Holst, Peter Johannes; Bassi, Maria Rosaria; Christensen, Jan Pravsgaard; Thomsen, Allan Randrup


    Adenoviral vectors have shown a great potential for vaccine development due to their inherent ability to induce potent and protective CD8 T-cell responses. However, a critical issue regarding the use of these vectors is the existence of inhibitory immunity against the most commonly used Ad5 vector in a large part of the human population. We have recently developed an improved adenoviral vaccine vector system in which the vector expresses the transgene tethered to the MHC class II associated invariant chain (Ii). To further evaluate the potential of this system, the concept of pre-existing inhibitory immunity to adenoviral vectors was revisited to investigate whether the inhibition previously seen with the Ad5 vector also applied to the optimized vector system. We found this to be the case, and antibodies dominated as the mechanism underlying inhibitory vector immunity. However, presence of CD8 T cells directed against epitopes in the adenoviral vector seemed to correlate with repression of the induced response in re-vaccinated B-cell deficient mice. More importantly, despite a repressed primary effector CD8 T-cell response in Ad5-immune animals subjected to vaccination, memory T cells were generated that provided the foundation for an efficient recall response and protection upon subsequent viral challenge. Furthermore, the transgene specific response could be efficiently boosted by homologous re-immunization. Taken together, these studies indicate that adenoviral vectors can be used to induce efficient CD8 T-cell memory even in individuals with pre-existing vector immunity.

  6. Pre-existing vector immunity does not prevent replication deficient adenovirus from inducing efficient CD8 T-cell memory and recall responses.

    Directory of Open Access Journals (Sweden)

    Maria Abildgaard Steffensen

    Full Text Available Adenoviral vectors have shown a great potential for vaccine development due to their inherent ability to induce potent and protective CD8 T-cell responses. However, a critical issue regarding the use of these vectors is the existence of inhibitory immunity against the most commonly used Ad5 vector in a large part of the human population. We have recently developed an improved adenoviral vaccine vector system in which the vector expresses the transgene tethered to the MHC class II associated invariant chain (Ii. To further evaluate the potential of this system, the concept of pre-existing inhibitory immunity to adenoviral vectors was revisited to investigate whether the inhibition previously seen with the Ad5 vector also applied to the optimized vector system. We found this to be the case, and antibodies dominated as the mechanism underlying inhibitory vector immunity. However, presence of CD8 T cells directed against epitopes in the adenoviral vector seemed to correlate with repression of the induced response in re-vaccinated B-cell deficient mice. More importantly, despite a repressed primary effector CD8 T-cell response in Ad5-immune animals subjected to vaccination, memory T cells were generated that provided the foundation for an efficient recall response and protection upon subsequent viral challenge. Furthermore, the transgene specific response could be efficiently boosted by homologous re-immunization. Taken together, these studies indicate that adenoviral vectors can be used to induce efficient CD8 T-cell memory even in individuals with pre-existing vector immunity.

  7. Tuberculous pericarditis in acquired immune deficiency syndrome patients Pericardite tuberculosa em portadores da síndrome de imunodeficiência adquirida

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    Ruggero Bernardo Guidugli


    Full Text Available Two quite dyspneic HIV positive patients were admitted to the Emergency Room; they presented clinical signs and images suggesting pericardial effusion. The analysis of an initial liquid puncture did not show any specificity and the patients did not exhibit any clinical improvement. Both patients were submitted to a subxiphoid pericardial window, all the effusion liquid was drained, and a biopsy of the pericardium tissue was completed, revealing a granulomatous process. Immediately after the onset of specific treatment, the patients showed a good evolution. Such findings draw attention to a high possibility of pericardial suffusion in AIDS patients being tuberculosis, particular if one considers the high prevalence of this disease in Brazil. The results also showed that the opening of a subxiphoid pericardial window and the specific triple scheme was a procedure that led to good therapeutic evolution in these patients.Dois pacientes portadores do vírus HIV deram entrada no serviço de emergência bastante dispnéicos, exibindo sinais clínicos e de imagens sugestivos de derrame pericárdico. Realizada inicialmente a punção do líquido, sua análise não mostrou especificidade e os doentes não apresentavam evidência de melhora clínica. Foram, então, submetidos a uma janela pericárdica subxifóidea, foi drenado todo o líquido de efusão e realizada a biópsia do tecido pericárdico, o que revelou processo granulomatoso. Logo após o início do tratamento específico, os pacientes apresentaram boa evolução. Tais achados chamaram a atenção para a etiologia tuberculosa como causa de sufusão pericárdica em portadores da síndrome de imunodeficiência adquirida. Essa associação pode ser mais importante no Brasil, onde existe alta prevalência de tuberculose. Os resultados mostraram também que a realização de uma janela pericárdica subxifóidea permitiu boa drenagem do fluido e, junto com a ministração do esquema tríplice, possibilitou a boa evolução dos pacientes.

  8. Terapia hipolipemiante em situações especiais: síndrome de imunodeficiência adquirida Hypolipidemic therapy under special conditions: acquired immune deficiency syndrome

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    Pai Ching Yu


    Full Text Available Dislipidemias podem ser observadas precocemente entre pacientes com AIDS. Frequentemente, estas anormalidades lipídicas incluem HDL baixo e moderado aumento dos triglicérides sanguíneos. A terapia anti-retroviral combinada (HAART pode agravar a dislipidemia nestes pacientes, com importante aumento nos triglicérides e no LDL. Vários mecanismos são propostos para explicar a dislipidemia mista observada nestes indivíduos, incluindo diferentes etapas do metabolismo lipídico. A importância do tratamento desses distúrbios lipídicos tem se tornado evidente com o aumento da expectativa de vida e os relatos de complicações cardiovasculares nestes pacientes. Existe um estado de resistência à insulina nos pacientes com AIDS em tratamento com HAART,que apresentam lipodistrofia, hipertrigliceridemia e baixos níveis de HDL. Drogas retro-antivirais são metabolizadas pelo CYP P450 3A4 e interações com algumas estatinas, especialmente com sinvastatina podem ocorrer. O tratamento com agentes hipolipemiantes deve ser baseado no perfil lipídico e no risco de coronariopatia. Para hipertrigliceridemias, fibratos (principalmente fenofibrato ou bezafibrato devem ser as drogas de escolha, bem como as estatinas (principalmente pravastatina. Terapia combinada usando estatinas mais fibratos é recomendada para dislipidemias mistas graves e sempre sob rigoroso monitoramento de efeitos adversos.Lipid alterations can be observed early among patients with AIDS disease. Commonly, these lipid abnormalities include low HDL-C and modest increase in triglyceride plasma levels. Highly Active Anti-Retroviral Therapy (HAART in these patients may aggravate the dyslipidemia, with notable increases in triglycerides as well as in LDL-C. There are several mechanisms proposed to explain the mixed hyperlipidemia observed in these subjects, including different steps in lipid metabolism. The importance of the treatment of dyslipidemia became evident with the increased life expectancy and reports of cardiovascular complications in these individuals. There is an insulin resistance state in patients with AIDS disease under treatment with HAART, who present with lypodistrophy, hypertriglyceridemia, low levels of HDL-C. Antiretroviral drugs are metabolized by CYP P450 3A4 and interactions with some statins, especially with simvastatin are expected to occur. Treatment with lipid-lowering agents should be based on lipid profile and coronary risk. For hypertriglyceridemias, fibrates (mainly fenofibrate or bezafibrate should be the drugs of choice, as well as statins (mainly pravastatin. Combined treatment using fibrates plus statins are recommended for severe mixed hyperlipidemias under very close monitoring for adverse effects.

  9. The in vitro anti-viral potential of Setarud (IMOD™, a commercial herbal medicine with protective activity against acquired immune deficiency syndrome in clinical trials

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    Rezvan Zabihollahi


    Conclusions: Data from this study indicate that IMOD has significant anti-viral activity against HIV, HSV and MLV. Setarud could be subjected to further investigation after isolation of the constituents and determination of the toxic components.

  10. Study of the morphological patterns and association of Epstein-Barr virus and human herpes virus 8 in acquired immunodeficiency deficiency syndrome-related reactive lymphadenopathy

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    Gujral S


    Full Text Available Aims: Study of the morphological patterns of acquired immunodeficiency syndrome (AIDS-related lymphadenopathy. Settings and Design: We retrospectively selected cases of AIDS-related benign lymphadenopathy. Cases with lymphomas, frank granulomas and necrosis were excluded. We analyzed different morphological patterns and correlated these with immunophenotypic markers along with viral markers human herpesvirus 8-latency-associated nuclear antigen (HHV8-LANA, and Epstein-Barr virus-encoded ribonucleic acid (EBER studies via in situ hybridization (EBER-ISH. Materials and Methods: We present the morphological patterns of 13 cases of human immunodeficiency virus (HIV-reactive lymph nodes and their clinical, hematological, biochemical and radiological parameters with special emphasis on the presence or absence of viral markers, including HHV8 and EBV. Results: Common patterns included follicular hyperplasia only (five cases, mixed pattern of follicular hyperplasia with burnt-out germinal centres (four cases, completely atretic follicle (two cases, folliculolysis (11 cases, dumbbell-shaped follicles (three each, progressive transformation of germinal centers (four cases, T-zone expansion (two cases, Reed Sternberg (RS cells like immunoblasts (two cases, Castleman′s-like features with lollipop-like follicles (three cases and a spindle cell prominence (one case. CD8+ T-cells were predominant in 12 cases. CD8+ T-cells were prominent in germinal centers (eight cases. Plasmablasts were seen in four cases within the perigerminal center area. Immunohistochemistry for HHV8, i.e. HHV8-LANA were negative in all cases while EBER was detected in 11 cases in the centrocyte-like B cells. Two cases of multicentric Castleman′s disease expressed EBER; however, they did not express HHV8. Conclusion: The wide spectrum of histological changes in HIV-associated lymphadenopathy requires recognition. The histological changes can mimic those of other infective

  11. Genetically Engineered Ascorbic acid-deficient Live Mutants of Leishmania donovani induce long lasting Protective Immunity against Visceral Leishmaniasis. (United States)

    Anand, Sneha; Madhubala, Rentala


    Visceral leishmaniasis caused by Leishmania donovani is the most severe systemic form of the disease. There are still no vaccines available for humans and there are limitations associated with the current therapeutic regimens for leishmaniasis. Recently, we reported functional importance of Arabino-1, 4-lactone oxidase (ALO) enzyme from L. donovani involved in ascorbate biosynthesis pathway. In this study, we have shown that ΔALO parasites do not affect the ability of null mutants to invade visceral organs but severely impair parasite persistence beyond 16 week in BALB/c mice and hence are safe as an immunogen. Both short term (5 week) and long term (20 week) immunization with ΔALO parasites conferred sustained protection against virulent challenge in BALB/c mice, activated splenocytes and resulted in induction of pro-inflammatory cytokine response. Protection in immunized mice after challenge correlated with the stimulation of IFN-γ producing CD4(+) and CD8(+) T cells. Antigen-mediated cell immunity correlated with robust nitrite and superoxide generation, macrophage-derived oxidants critical in controlling Leishmania infection. Our data shows that live attenuated ΔALO parasites are safe, induce protective immunity and can provide sustained protection against Leishmania donovani. We further conclude that the parasites attenuated in their anti-oxidative defence mechanism can be exploited as vaccine candidates.

  12. Synergistic effects of host B7-H4 deficiency and gemcitabine treatment on tumor regression and anti-tumor T cell immunity in a mouse model. (United States)

    Leung, Joanne; St-Onge, Philippe; Stagg, John; Suh, Woong-Kyung


    B7-H4 (B7x/B7S1), a B7 family inhibitor of T cell activity, is expressed in multiple human cancers and correlates with decreased infiltrating lymphocytes and poor prognosis. In murine models, tumor-expressed B7-H4 enhances tumor growth and reduces T cell immunity, and blockade of tumor-B7-H4 rescues T cell activity and lowers tumor burden. This implicates B7-H4 as a target for cancer immunotherapy, yet limits the efficacy of B7-H4 blockade exclusively to patients with B7-H4+ tumors. Given the expression of B7-H4 on host immune cells, we have previously shown that BALB/c mice lacking host B7-H4 have enhanced anti-tumor profiles, yet similar 4T1 tumor growth relative to control. Given that T cell-mediated immunotherapies work best for tumors presenting tumor-associated neoantigens, we further investigated the function of host B7-H4 in the growth of a more immunogenic derivative, 4T1-12B, which is known to elicit strong anti-tumor CD8 T cell responses due to expression of a surrogate tumor-specific antigen, firefly luciferase. Notably, B7-H4 knockout hosts not only mounted greater tumor-associated anti-tumor T cell responses, but also displayed reduced tumors. Additionally, B7-H4-deficiency synergized with gemcitabine to further inhibit tumor growth, often leading to tumor eradication and the generation of protective T cell immunity. These findings imply that inhibition of host B7-H4 can enhance anti-tumor T cell immunity in immunogenic cancers, and can be combined with other anti-cancer therapies to further reduce tumor burden regardless of tumor-B7-H4 positivity.

  13. An altered immune response, but not individual cationic antimicrobial peptides, is associated with the oral attenuation of Ara4N-deficient Salmonella enterica serovar Typhimurium in mice.

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    Kristi L Strandberg

    Full Text Available Salmonella enterica serovar Typhimurium (S. Typhimurium uses two-component regulatory systems (TCRS to respond to stimuli in the local microenvironment. Upon infection, the Salmonella TCRSs PhoP-PhoQ (PhoPQ and PmrA-PmrB (PmrAB are activated by environmental signals in the intestinal lumen and within host cells. TCRS-mediated gene expression results in lipopolysaccharide (LPS modification and cationic antimicrobial peptide resistance. The PmrA-regulated pmrHFIJKLM operon mediates 4-amino-4-deoxy-L-arabinose (Ara4N production and attachment to the lipid A of LPS. A ΔpmrF S. Typhimurium strain cannot produce Ara4N, exhibits increased sensitivity to cationic antimicrobial peptide (CAMP-mediated killing, and attenuated virulence in mice upon oral infection. CAMPs are predicted to play a role in elimination of Salmonella, and may activate PhoPQ and PmrAB in vivo, which could increase bacterial resistance to host defenses. Competition experiments between wild type (WT and ΔpmrF mutant strains of S. Typhimurium indicated that selection against this mutant first occurs within the intestinal lumen early during infection. However, CRAMP and active cryptdins alone are not responsible for elimination of Ara4N-deficient bacteria in vivo. Investigation into the early immune response to ΔpmrF showed that it differed slightly from the early immune response to WT S. Typhimurium. Further investigation into the early immune response to infection of Peyer's patches suggests a role for IL-13 in the attenution of the ΔpmrF mutant strain. Thus, prominent CAMPs present in the mouse intestine are not responsible for the selection against the ΔpmrF strain in this location, but limited alterations in innate immune induction were observed that affect bacterial survival and virulence.

  14. As implicações sociais da deficiência auditiva adquirida em adultos Social implications of acquired hearing impairment in adults

    Directory of Open Access Journals (Sweden)

    Madalena Aparecida Silva Francelin


    Full Text Available O objetivo deste estudo foi analisar as implicações da surdez adquirida em adultos, na vida familiar, social e no trabalho, com uma abordagem qualitativa. Foram selecionadas 27 pessoas residentes em Bauru-SP, com diagnóstico de perda auditiva de manifestação súbita na faixa etária de 18 a 60 anos, matriculados no Hospital de Reabilitação de Anomalias Craniofaciais (HRAC/USP entre janeiro de 2000 e fevereiro de 2005, sendo entrevistados 16. Utilizaram-se a entrevista e a análise de conteúdo. Constatou-se: a perda auditiva ocorreu entre os 40 e 44 anos, 37,5%; 62,5% dos que perderam a audição eram do sexo masculino, 62,5% não tinham o ensino fundamental; 62,5% eram da classe Baixa Superior; 75% apresentaram perda auditiva bilateral, 18,75% de grau moderado/profundo. Dos 13 que estavam trabalhando quando perderam a audição, 30,77% pararam de trabalhar e 15,38% mudaram de profissão. Foram relatadas situações como: afastamento do trabalho, demissão a pedido e demissão pelo empregador, dificuldade de aceitação, cobranças, falta de esclarecimentos e desconhecimento dos próprios profissionais de saúde. Os dados sugerem a necessidade dos recursos de reabilitação, de apoio terapêutico, respeito e alternativas de conhecimentos.This study aimed at analyzing, by means of a qualitative approach, the implications of acquired deafness in adults with regard to family life, social life and work. Twenty-seven individuals residing in the city of Bauru, State of São Paulo, were selected. All of them had been diagnosed with hearing impairment of sudden onset at the age range of 18 to 60 years and were registered at the Hospital for Craniofacial Anomaly Rehabilitation (HRAC/USP between January 2000 and February 2005. Sixteen of such individuals were interviewed, and content analysis was used. It was found that, for 37.5% of the subjects, hearing impairment occurred between the ages of 40 and 44 years; 62.5% were males; 62.5% had not

  15. In pulmonary paracoccidioidomycosis IL-10 deficiency leads to increased immunity and regressive infection without enhancing tissue pathology.

    Directory of Open Access Journals (Sweden)

    Tânia A Costa

    Full Text Available BACKGROUND: Cellular immunity is the main defense mechanism in paracoccidioidomycosis (PCM, the most important systemic mycosis in Latin America. Th1 immunity and IFN-γ activated macrophages are fundamental to immunoprotection that is antagonized by IL-10, an anti-inflammatory cytokine. Both in human and experimental PCM, several evidences indicate that the suppressive effect of IL-10 causes detrimental effects to infected hosts. Because direct studies have not been performed, this study was aimed to characterize the function of IL-10 in pulmonary PCM. METHODOLOGY/PRINCIPAL FINDINGS: Wild type (WT and IL-10(-/- C57BL/6 mice were used to characterize the role of IL-10 in the innate and adaptive immunity against Paracoccidioides brasiliensis (Pb infection. We verified that Pb-infected peritoneal macrophages from IL-10(-/- mice presented higher phagocytic and fungicidal activities than WT macrophages, and these activities were associated with elevated production of IFN-γ, TNF-α, nitric oxide (NO and MCP-1. For in vivo studies, IL-10(-/- and WT mice were i.t. infected with 1×10(6 Pb yeasts and studied at several post-infection periods. Compared to WT mice, IL-10(-/- mice showed increased resistance to P. brasiliensis infection as determined by the progressive control of pulmonary fungal loads and total clearance of fungal cells from dissemination organs. This behavior was accompanied by enhanced delayed-type hypersensitivity reactions, precocious humoral immunity and controlled tissue pathology resulting in increased survival times. In addition, IL-10(-/- mice developed precocious T cell immunity mediated by increased numbers of lung infiltrating effector/memory CD4(+ and CD8(+ T cells. The inflammatory reactions and the production of Th1/Th2/Th17 cytokines were reduced at late phases of infection, paralleling the regressive infection of IL-10(-/- mice. CONCLUSIONS/SIGNIFICANCE: Our work demonstrates for the first time that IL-10 plays a

  16. Immune System (United States)

    A properly functioning immune system is essential to good health. It defends the body against infectious agents and in some cases tumor cells. Individuals with immune deficiencies resulting from genetic defects, diseases (e.g., AIDS, leukemia), or drug therapies are more suscepti...

  17. RNAi knock-down of shrimp Litopenaeus vannamei Toll gene and immune deficiency gene reveals their difference in regulating antimicrobial peptides transcription. (United States)

    Hou, Fujun; He, Shulin; Liu, Yongjie; Zhu, Xiaowen; Sun, Chengbo; Liu, Xiaolin


    NF-κB dependent antimicrobial peptides (AMPs) are of critical importance in protecting insects or mammals from microorganisms infection. However, we still do not make clear signaling pathways in regulating AMPs expression in shrimps. In this study, RNAi approach was used to study differences between Toll signaling pathway and immune deficiency signaling pathway in regulating the transcription of NF-κB dependent AMPs post bacteria challenge. Results showed that the transcription level of anti-lipopolysaccharide factor was highly suppressed in Litopenaeus vannamei immune deficiency (LvIMD) silenced shrimps by gene specific dsRNA compared to Litopenaeus vannamei Toll (LvToll) silenced shrimps with or without Vibrio anguillarum and Micrococcus lysodeikticus challenge. Conversely the transcription level of penaeidin3a was significantly suppressed in LvToll silenced shrimps compared to LvIMD silenced shrimps. However, no obvious difference was found in regulating the transcription of CrustinP. Meanwhile, we found that silencing LvToll both down regulated the transcription of Dorsal and Relish while silencing LvIMD only down regulated the transcription of Relish. At last, shrimp survival experiment showed that post V. anguillarum challenge high mortality was found both in LvToll and LvIMD silenced groups while post M. lysodeikticus challenge we saw high mortality only in LvToll silenced group. Hence, we conclude that shrimp L. vannamei Toll pathway and IMD pathway might be different in regulating the transcription of NF-κB dependent AMPs and responding to bacteria challenge but not independent of each other.

  18. Leptin deficiency down-regulates IL-23 production in glomerular podocytes resulting in an attenuated immune response in nephrotoxic serum nephritis. (United States)

    Goto, Kei; Kaneko, Yoshikatsu; Sato, Yuya; Otsuka, Tadashi; Yamamoto, Suguru; Goto, Shin; Yamamoto, Keiko; Yamamoto, Tadashi; Kawachi, Hiroshi; Madaio, Michael P; Narita, Ichiei


    Leptin, one of the typical adipokines, is reported to promote Th17 cell responses and to enhance production of proinflammatory cytokines. To clarify the role of leptin in the regulation of the IL-23/IL-17 axis and the development of kidney disease, we used a murine model of nephrotoxic serum (NTS) nephritis (NTN). Sheep NTS was administered in wild-type C57BL/6J mice and food-restricted, leptin-deficient C57BL/6J-ob/ob(FR-ob/ob) mice after preimmunization with sheep IgG. The profile of mRNA expression relevant to T helper lymphocytes in the kidneys was analyzed by quantitative real-time PCR (qRT-PCR). Cultured murine glomerular podocytes and peritoneal exudate macrophages (PEMs) were used to investigate the direct effect of leptin on IL-23 or MCP-1 production by qRT-PCR. Kidney injury and macrophage infiltration were significantly attenuated in FR-ob/obmice 7 days after NTS injection. The Th17-dependent secondary immune response against deposited NTS in the glomeruli was totally impaired in FR-ob/obmice because of deteriorated IL-17 and proinflammatory cytokine production including IL-23 and MCP-1 in the kidney. IL-23 was produced in glomerular podocytes in NTN mice and cultured murine glomerular podocytes produced IL-23 under leptin stimulation. MCP-1 production in PEMs was also promoted by leptin. Induction of MCP-1 expression was observed in PEMs regardless of Ob-Rb, and the leptin signal was transduced without STAT3 phosphorylation in PEMs. Leptin deficiency impairs the secondary immune response against NTS and down-regulates IL-23 production and Th17 responses in the NTN kidney, which is accompanied by decreased MCP-1 production and macrophage infiltration in the NTN kidney.

  19. Iron deficiency. (United States)

    Scrimshaw, N S


    The world's leading nutritional problem is iron deficiency. 66% of children and women aged 15-44 years in developing countries have it. Further, 10-20% of women of childbearing age in developed countries are anemic. Iron deficiency is identified with often irreversible impairment of a child's learning ability. It is also associated with low capacity for adults to work which reduces productivity. In addition, it impairs the immune system which reduces the body's ability to fight infection. Iron deficiency also lowers the metabolic rate and the body temperature when exposed to cold. Hemoglobin contains nearly 73% of the body's iron. This iron is always being recycled as more red blood cells are made. The rest of the needed iron does important tasks for the body, such as binds to molecules that are reservoirs of oxygen for muscle cells. This iron comes from our diet, especially meat. Even though some plants, such as spinach, are high in iron, the body can only absorb 1.4-7% of the iron in plants whereas it can absorb 20% of the iron in red meat. In many developing countries, the common vegetarian diets contribute to high rates of iron deficiency. Parasitic diseases and abnormal uterine bleeding also promote iron deficiency. Iron therapy in anemic children can often, but not always, improve behavior and cognitive performance. Iron deficiency during pregnancy often contributes to maternal and perinatal mortality. Yet treatment, if given to a child in time, can lead to normal growth and hinder infections. However, excess iron can be damaging. Too much supplemental iron in a malnourished child promotes fatal infections since the excess iron is available for the pathogens use. Many countries do not have an effective system for diagnosing, treating, and preventing iron deficiency. Therefore a concerted international effort is needed to eliminate iron deficiency in the world.

  20. Immune Disorder HSCT Protocol (United States)


    Immune Deficiency Disorders; Severe Combined Immunodeficiency; Chronic Granulomatous Disease; X-linked Agammaglobulinemia; Wiskott-Aldrich Syndrome; Hyper-IgM; DiGeorge Syndrome; Chediak-Higashi Syndrome; Common Variable Immune Deficiency; Immune Dysregulatory Disorders; Hemophagocytic Lymphohistiocytosis; IPEX; Autoimmune Lymphoproliferative Syndrome; X-linked Lymphoproliferative Syndrome

  1. Fetal Hematopoietic Stem Cells Are the Canaries in the Coal Mine That Portend Later Life Immune Deficiency. (United States)

    Laiosa, Michael D; Tate, Everett R


    Disorders of the blood system are a significant and growing global health concern and include a spectrum of diseases ranging from aplastic anemia and leukemias to immune suppression. This array of hematological disorders is attributed to the fact that the blood system undergoes a perpetual cycle of turn over with aged and exhausted red and white blood cells undergoing daily replacement. The foundational cells of this replenishment process are comprised of rare hematopoietic stem cells (HSCs) located in the bone marrow that possess the dual function of long-term self-renewal and multilineage differentiation. This constant turnover makes the hematopoietic system uniquely vulnerable to changes in the environment that impact multilineage differentiation, self-renewal, or both. Notably, environmental endocrine-disrupting exposures occurring during development, when HSCs are first emerging, can lead to alterations in HSC programming that impacts the blood and immune systems throughout life. In this review, we describe the process of fetal hematopoiesis and provide an overview of the intrauterine environmental and endocrine-disrupting compounds that disrupt this process. Finally, we describe research opportunities for fetal HSCs as potential sentinels of later-life blood and immune system disorders.

  2. Deficiency in Either 4E-BP1 or 4E-BP2 Augments Innate Antiviral Immune Responses (United States)

    Nehdi, Atef; Sean, Polen; Linares, Izzar; Colina, Rodney; Jaramillo, Maritza; Alain, Tommy


    Genetic deletion of both 4E-BP1 and 4E-BP2 was found to protect cells against viral infections. Here we demonstrate that the individual loss of either 4E-BP1 or 4E-BP2 in mouse embryonic fibroblasts (MEFs) is sufficient to confer viral resistance. shRNA-mediated silencing of 4E-BP1 or 4E-BP2 renders MEFs resistant to viruses, and compared to wild type cells, MEFs knockout for either 4E-BP1 or 4E-BP2 exhibit enhanced translation of Irf-7 and consequently increased innate immune response to viruses. Accordingly, the replication of vesicular stomatitis virus, encephalomyocarditis virus, influenza virus and Sindbis virus is markedly suppressed in these cells. Importantly, expression of either 4E-BP1 or 4E-BP2 in double knockout or respective single knockout cells diminishes their resistance to viral infection. Our data show that loss of 4E-BP1 or 4E-BP2 potentiates innate antiviral immunity. These results provide further evidence for translational control of innate immunity and support targeting translational effectors as an antiviral strategy. PMID:25531441

  3. Combined effect of the environmental factors as ionizing radiation and a chronic iodine deficiency on the thyroid gland and the immune condition

    Energy Technology Data Exchange (ETDEWEB)

    Danyarova, L. [Department of Endocrynology, Research Institute of Cardiology and Internal Medicine, Almaty (Kazakhstan)


    The Semipalatinsk Test Site was the primary testing venue for the Soviet Union's nuclear weapons. It is located on the steppe in northeast Kazakhstan. The tragic situation of the Semipalatinsk region is an acute and chronic radiation, repeated in big and small doses and a total absence of territorial decontamination, created unique conditions for study of the long term influence of the radiation doses on the health of the population. The Semipalatinsk region of the Republic of Kazakhstan belongs also to an area of moderate and pronounced iodine deficiency. The purpose of the research is to study the prevalence of a thyroid gland pathology and the condition of a cytokine immune link that is likely to be influenced by a combine effect of ionizing radiation and a chronic iodine deficiency. 1100 people passed through the investigation and it appears that 56, 75% of them had a thyroid pathology. Thyroid gland functional condition analysis (TSH, FT3, FT4 a-TG, a-TPO) has shown the prevalence of a subclinical hypothyroidism (33%). 28, 8% resulted in the presence of antibodies to thyroglobulin and the thyroid peroxides, whereas in the areas located further to the nuclear range, the percentage was only 13, 0%

  4. Naturally acquired immune responses to malaria vaccine candidate antigens MSP3 and GLURP in Guahibo and Piaroa indigenous communities of the Venezuelan Amazon

    DEFF Research Database (Denmark)

    Baumann, Andreas; Magris, Magda M; Urbaez, Marie-Luz;


    in two indigenous population groups in Amazonas/Venezuela. Data from the regional malaria documentation system were extracted and participants from the ethnic groups of the Guahibo (n = 180) and Piaroa (n = 295) were investigated for the presence of Plasmodium parasites and naturally acquired antibodies...

  5. 获得性凝血因子Ⅹ缺乏症三例报告并文献复习%Acquired coagulation factor Ⅹ deficiency: three cases report and literature review

    Institute of Scientific and Technical Information of China (English)

    刘文洁; 宣旻; 薛峰; 杨仁池


    目的 加深对获得性凝血因子Ⅹ缺乏症的认识.方法 对3例获得性凝血因子Ⅹ缺乏症患者的临床资料进行分析,并复习相关文献.结果 例1,男,57岁,诊断为多发性骨髓瘤轻链型、继发性淀粉样变、获得性凝血因子Ⅹ缺乏症,表现为自发性皮肤黏膜出血,凝血因子Ⅹ活性(FⅩ∶C)1.8%,予以MP(马法兰+曲安西龙)方案联合沙利度胺及对症治疗,FⅩ∶C未见升高,因原发病进展死亡.例2,男,41岁,以颅内出血入院,FⅩ∶C 26.8%,予以补充叶酸、维生素B12、维生素K,并输注红细胞、血小板及新鲜冰冻血浆治疗,颅内出血好转.例3,女,63岁,因反复发作四肢关节出血4个月入院,FⅩ∶C 6.1%,给予凝血酶原复合物、甲泼尼龙、硫唑嘌呤、利妥昔单抗治疗,FⅩ∶C未见明显升高,关节腔出血仍反复发作.结论 获得性凝血因子Ⅹ缺乏症临床表现具有异质性,诊断依赖病史和实验室检查,治疗包括控制出血和治疗原发病,预后与患者基础疾病相关.%Objective To deepen the understanding of acquired coagulation factor Ⅹ (F Ⅹ) deficiency.Methods The clinical data of 3 patients were analyzed and related literature were reviewed.Results Case 1,a 57-year-old male,secondary to multiple myeloma and amyloidosis,was presented with spontaneous mucous hemorrhage with the level of F Ⅹ ∶ C 1.8%,which kept unchanged after chemotherapy with melphalan,glucocorticoid,and thalidomide,and died of primary disease progression.Case 2,a 41-year-old male with psoriasis,was presented with cerebral and retinal hemorrhage with the level of F Ⅹ ∶ C 26.8%.The signs of hemorrhage were alleviated after the supplement of folic acid,vitamin B12,and vitamin K,and transfusion with red blood cells,platelets,and fresh frozen plasma.Case 3,a 63-year-old female,associated with high level of lupus anticoagulant,was presented with repeated ecchymosis and haemarthrosis with the level of F Ⅹ ∶C 6.1

  6. Acquired blepharoptosis

    NARCIS (Netherlands)

    Oosterhuis, HJGH


    A review is given of the aetiology and possible treatment of acquired (non-congenital) blepharoptosis, which is a common but not specific sign of neurological disease: The diagnostic categories of upper eyelid drooping are scheduled as (a) pseudo-ptosis due to a local process or overactivity of eye

  7. Different roles of Enhanced Disease Susceptibility1 (EDS1) bound to and dissociated from Phytoalexin Deficient4 (PAD4) in Arabidopsis immunity. (United States)

    Rietz, Steffen; Stamm, Anika; Malonek, Stefan; Wagner, Stephan; Becker, Dieter; Medina-Escobar, Nieves; Vlot, A Corina; Feys, Bart J; Niefind, Karsten; Parker, Jane E


    • Enhanced Disease Susceptibility1 (EDS1) is an important regulator of plant basal and receptor-triggered immunity. Arabidopsis EDS1 interacts with two related proteins, Phytoalexin Deficient4 (PAD4) and Senescence Associated Gene101 (SAG101), whose combined activities are essential for defense signaling. The different sizes and intracellular distributions of EDS1-PAD4 and EDS1-SAG101 complexes in Arabidopsis leaf tissues suggest that they perform nonredundant functions. • The nature and biological relevance of EDS1 interactions with PAD4 and SAG101 were explored using yeast three-hybrid assays, in vitro analysis of recombinant proteins purified from Escherichia coli, and characterization of Arabidopsis transgenic plants expressing an eds1 mutant (eds1(L262P) ) protein which no longer binds PAD4 but retains interaction with SAG101. • EDS1 forms molecularly distinct complexes with PAD4 or SAG101 without additional plant factors. Loss of interaction with EDS1 reduces PAD4 post-transcriptional accumulation, consistent with the EDS1 physical association stabilizing PAD4. The dissociated forms of EDS1 and PAD4 are fully competent in signaling receptor-triggered localized cell death at infection foci. By contrast, an EDS1-PAD4 complex is necessary for basal resistance involving transcriptional up-regulation of PAD4 itself and mobilization of salicylic acid defenses. • Different EDS1 and PAD4 molecular configurations have distinct and separable functions in the plant innate immune response.

  8. The Th17/Treg Immune Balance in Ulcerative Colitis Patients with Two Different Chinese Syndromes: Dampness-Heat in Large Intestine and Spleen and Kidney Yang Deficiency Syndrome

    Directory of Open Access Journals (Sweden)

    Yang Gong


    Full Text Available Objective. To investigate the Th17/Treg immune balance in the ulcerative colitis (UC patients with two Chinese syndrome: dampness-heat in large intestine (DHLI and spleen and kidney Yang deficiency (SKYD. Methods. Ninety UC patients (45 were diagnosed with DHLI and 45 with SKYD syndrome and 23 healthy people were recruited. The serumIL-17 and TGF-β1 levels of these participants were measured with ELISA; the expression of IL-17 and TGF-β 1 in colonic mucosa tissue was determined with immunohistochemistry and the percentage of Th17 and Treg in peripheral blood with flow cytometry. Results. The levels of IL-17 and Th17 were significantly higher in both DHLI and SKYD groups than in healthy control group and higher in DHLI than in SKYD group (P<0.05. The levels of TGF-β1 and Treg were significantly lower in the two UC patients groups than in healthy control group; and lower in SKYD group than in DHLI group (P<0.05. Conclusions. UC with DHLI syndrome could be characterized by the elevation of Th17 and IL-17 levels, which indicated an accentuation of inflammatory reaction; UC with SKYD syndrome could be characterized by the reduction of serum Treg and TGF-β1 levels, which represented a depression of immune tolerance.

  9. The modulation of endoplasmic reticulum stress by chemical chaperone upregulates immune negative cytokine IL-35 in apolipoprotein E-deficient mice. (United States)

    Wang, Bo; Dai, Shen; Dong, Zhaojing; Sun, Yue; Song, Xingguo; Guo, Chun; Zhu, Faliang; Wang, Qun; Zhang, Lining


    Interleukin (IL)-35 is a newly identified immune negative molecule which is secreted by CD4(+)Foxp3(+) T regulatory cells (Tregs) and contributes to their suppressive capacity. Early data have shown that IL-35 inhibits development of several autoimmune diseases. However, the role of IL-35 in atherosclerosis, a lipid-driven chronic inflammatory disease in arterial wall, remains to be investigated. Here, we found that IL-35 was involved in atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice. ApoE(-/-) mice with established atherosclerotic lesion displayed a lower level of IL-35 compared to age-matched wild type C57BL/6 mice without plaque. However, IL-35 expression increased significantly in ApoE(-/-) mice with attenuated plaque. More importantly, we found that modulation of ER stress treated by chemical chaperone, 4-Phenyl butyric acid (PBA) in vivo, mainly upregulated immune negative regulating molecule IL-35, as well as IL-10 and Foxp3, accompanied by increased Tregs. However, no obvious impact on pro-inflammatory molecules such as TNF-α, IFN-γ, IL-17 and IL-23 was observed, which provides new insight into the benefit of ER stress recovery from attenuated plaque. Our results suggest that IL-35 might have a potential value for atherosclerotic therapy.

  10. Transcriptomic Characterization of Innate and Acquired Immune Responses in Red-Legged Partridges (Alectoris rufa: A Resource for Immunoecology and Robustness Selection.

    Directory of Open Access Journals (Sweden)

    Natalia Sevane

    Full Text Available Present and future challenges for wild partridge populations include the resistance against possible disease transmission after restocking with captive-reared individuals, and the need to cope with the stress prompted by new dynamic and challenging scenarios. Selection of individuals with the best immune ability may be a good strategy to improve general immunity, and hence adaptation to stress. In this study, non-infectious challenges with phytohemagglutinin (PHA and sheep red blood cells allowed the classification of red-legged partridges (Alectoris rufa according to their overall immune responses (IR. Skin from the area of injection of PHA and spleen, both from animals showing extreme high and low IR, were selected to investigate the transcriptional profiles underlying the different ability to cope with pathogens and external aggressions. RNA-seq yielded 97 million raw reads from eight sequencing libraries and approximately 84% of the processed reads were mapped to the reference chicken genome. Differential expression analysis identified 1488 up- and 107 down-regulated loci in individuals with high IR versus low IR. Partridges displaying higher innate IR show an enhanced activation of host defence gene pathways complemented with a tightly controlled desensitization that facilitates the return to cellular homeostasis. These findings indicate that the immune system ability to respond to aggressions (either diseases or stress produced by environmental changes involves extensive transcriptional and post-transcriptional regulations, and expand our understanding on the molecular mechanisms of the avian immune system, opening the possibility of improving disease resistance or robustness using genome assisted selection (GAS approaches for increased IR in partridges by using genes such as AVN or BF2 as markers. This study provides the first transcriptome sequencing data of the Alectoris genus, a resource for molecular ecology that enables integration

  11. Induction of Protective Immunity to Cryptococcal Infection in Mice by a Heat-Killed, Chitosan-Deficient Strain of Cryptococcus neoformans

    Directory of Open Access Journals (Sweden)

    Rajendra Upadhya


    Full Text Available Cryptococcus neoformans is a major opportunistic fungal pathogen that causes fatal meningoencephalitis in immunocompromised individuals and is responsible for a large proportion of AIDS-related deaths. The fungal cell wall is an essential organelle which undergoes constant modification during various stages of growth and is critical for fungal pathogenesis. One critical component of the fungal cell wall is chitin, which in C. neoformans is predominantly deacetylated to chitosan. We previously reported that three chitin deacetylase (CDA genes have to be deleted to generate a chitosan-deficient C. neoformans strain. This cda1Δ2Δ3Δ strain was avirulent in mice, as it was rapidly cleared from the lungs of infected mice. Here, we report that clearance of the cda1Δ2Δ3Δ strain was associated with sharply spiked concentrations of proinflammatory molecules that are known to be critical mediators of the orchestration of a protective Th1-type adaptive immune response. This was followed by the selective enrichment of the Th1-type T cell population in the cda1Δ2Δ3Δ strain-infected mouse lung. Importantly, this response resulted in the development of robust protective immunity to a subsequent lethal challenge with a virulent wild-type C. neoformans strain. Moreover, protective immunity was also induced in mice vaccinated with heat-killed cda1Δ2Δ3Δ cells and was effective in multiple mouse strains. The results presented here provide a strong framework to develop the cda1Δ2Δ3Δ strain as a potential vaccine candidate for C. neoformans infection.

  12. Effects of Trauma-Hemorrhage and IL-6 Deficiency on Splenic Immune Function in a Murine Trauma Model

    Directory of Open Access Journals (Sweden)

    P. Mommsen


    Full Text Available Splenic immune function is known to be depressed following hemorrhage. The present study investigates the effects of femoral shaft fracture, isolated or in combination with hemorrhage, on early stage cytokine production capacity of splenocytes and observes the role of IL-6 under these conditions. Male IL-6 knockout (IL-6−/− and wild-type mice (WT were randomly divided into three groups: sham (S, isolated femoral fracture (Fx, and femoral fracture + volume controlled hemorrhage (TH-Fx (=6 per group. Animals were sacrificed four hours after induction of hemorrhage and fracture. Cytokine release (TNF-α, IL-6, and IL-10 of isolated and LPS-stimulated splenocytes was determined by cytometric bead array. Femoral fracture with or without hemorrhage caused a suppression of in vitro cytokine production capacity of splenocytes at an early posttraumatic stage in WT and IL-6−/−. In the absence of IL-6, the profile of splenic cytokine secretion is significantly altered, identifying this cytokine as a potential therapeutic target to modulate the posttraumatic immune response.

  13. Acquired Methemoglobinaemia

    Directory of Open Access Journals (Sweden)

    Adil Al-Lawati


    Full Text Available Acquired methemoglobinaemia is a relatively rare condition and, therefore infrequently encountered in acute medical practice. Suspicion of the condition may be triggered when the measured PaO2 is ‘out of keeping’ with the oxygen saturations that are discovered with pulse oximetry. We describe two separate cases of acquired methemoglobinaemia secondary to the recreational use of alkyl nitrites (’poppers’. The patients presented at separate times to two different teaching hospitals in London, UK. The similarity of these cases has led the authors to conclude that a raised awareness of this potentially fatal condition, and its association with a widely-available recreational drug, is necessary to ensure a correct and timely diagnosis.

  14. Plasmodium falciparum variant surface antigen expression varies between isolates causing severe and nonsevere malaria and is modified by acquired immunity

    DEFF Research Database (Denmark)

    Nielsen, Morten A; Staalsoe, Trine; Kurtzhals, Jørgen


    of immunity, as disease-causing parasites appear to be those not controlled by preexisting VSA-specific Abs. In this work we report that VSA expressed by parasites from young Ghanaian children with P. falciparum malaria were commonly and strongly recognized by plasma Abs from healthy children in the same area...... with nonsevere disease. This was not due to a higher infection multiplicity in younger patients or in patients with severe disease. Our data suggest that acquisition of VSA-specific Ab responses gradually restricts the VSA repertoire that is compatible with parasite survival in the semi-immune host. This appears...... to limit the risk of severe disease by discriminating against the expression of VSA likely to cause life-threatening complications, such as cerebral malaria and severe anemia. Such VSA seem to be preferred by parasites infecting a nonimmune host, suggesting that VSA expression and switching are not random...

  15. Kaposi Sarcoma of Childhood: Inborn or Acquired Immunodeficiency to Oncogenic HHV-8. (United States)

    Jackson, Carolyn C; Dickson, Mark A; Sadjadi, Mahan; Gessain, Antoine; Abel, Laurent; Jouanguy, Emmanuelle; Casanova, Jean-Laurent


    Kaposi sarcoma (KS) is an endothelial malignancy caused by human herpes virus-8 (HHV-8) infection. The epidemic and iatrogenic forms of childhood KS result from a profound and acquired T cell deficiency. Recent studies have shown that classic KS of childhood can result from rare single-gene inborn errors of immunity, with mutations in WAS, IFNGR1, STIM1, and TNFRSF4. The pathogenesis of the endemic form of childhood KS has remained elusive. We review childhood KS pathogenesis and its relationship to inherited and acquired immunodeficiency to oncogenic HHV-8.

  16. Growth Hormone Deficiency

    Directory of Open Access Journals (Sweden)

    Ömer Tarım


    Full Text Available Growth hormone deficiency is the most promising entity in terms of response to therapy among the treatable causes of growth retardation. It may be due to genetic or acquired causes. It may be isolated or a part of multiple hormone deficiencies. Diagnostic criteria and therefore treatment indications are still disputed. (Journal of Current Pediatrics 2010; 8: 36-8

  17. Acquired Techniques

    DEFF Research Database (Denmark)

    Lunde Nielsen, Espen; Halse, Karianne


    Acquired Techniques - a Leap into the Archive, at Aarhus School of Architecture. In collaboration with Karianne Halse, James Martin and Mika K. Friis. Following the footsteps of past travelers this is a journey into tools and techniques of the architectural process. The workshop will focus upon...... architectural production as a conglomerate of various analogue and digital methods, and provide the basics, the tips/tricks - and how the tool themselves becomes operational for spatial/thematic investigations. Eventually, this will become a city, exhibition and phamplet inhabited by the (by...

  18. IFNγ producing CD8+ T cells modified to resist major immune checkpoints induce regression of MHC class I-deficient melanomas (United States)

    Buferne, Michel; Chasson, Lionel; Grange, Magali; Mas, Amandine; Arnoux, Fanny; Bertuzzi, Mélanie; Naquet, Philippe; Leserman, Lee; Schmitt-Verhulst, Anne-Marie; Auphan-Anezin, Nathalie


    Tumors with reduced expression of MHC class I (MHC-I) molecules may be unrecognized by tumor antigen-specific CD8+ T cells and thus constitute a challenge for cancer immunotherapy. Here we monitored development of autochthonous melanomas in TiRP mice that develop tumors expressing a known tumor antigen as well as a red fluorescent protein (RFP) reporter knock in gene. The latter permits non-invasive monitoring of tumor growth by biofluorescence. One developing melanoma was deficient in cell surface expression of MHC-I, but MHC-I expression could be rescued by exposure of these cells to IFNγ. We show that CD8+ T cells specific for tumor antigen/MHC-I were efficient at inducing regression of the MHC-I-deficient melanoma, provided that the T cells were endowed with properties permitting their migration into the tumor and their efficient production of IFNγ. This was the case for CD8+ T cells transfected to express an active form of STAT5 (STAT5CA). The amount of IFNγ produced ex vivo from T cells present in tumors after adoptive transfer of the CD8+ T cells was correlated with an increase in surface expression of MHC-I molecules by the tumor cells. We also show that these CD8+ T cells expressed PD-1 and upregulated its ligand PDL-1 on melanoma cells within the tumor. Despite upregulation of this immunosuppressive pathway, efficient IFNγ production in the melanoma microenvironment was found associated with resistance of STAT5CA-expressing CD8+ T cells to inhibition both by PD-1/PDL-1 engagement and by TGFβ1, two main immune regulatory mechanisms hampering the efficiency of immunotherapy in patients. PMID:25949872

  19. IFNγ producing CD8(+) T cells modified to resist major immune checkpoints induce regression of MHC class I-deficient melanomas. (United States)

    Buferne, Michel; Chasson, Lionel; Grange, Magali; Mas, Amandine; Arnoux, Fanny; Bertuzzi, Mélanie; Naquet, Philippe; Leserman, Lee; Schmitt-Verhulst, Anne-Marie; Auphan-Anezin, Nathalie


    Tumors with reduced expression of MHC class I (MHC-I) molecules may be unrecognized by tumor antigen-specific CD8(+) T cells and thus constitute a challenge for cancer immunotherapy. Here we monitored development of autochthonous melanomas in TiRP mice that develop tumors expressing a known tumor antigen as well as a red fluorescent protein (RFP) reporter knock in gene. The latter permits non-invasive monitoring of tumor growth by biofluorescence. One developing melanoma was deficient in cell surface expression of MHC-I, but MHC-I expression could be rescued by exposure of these cells to IFNγ. We show that CD8(+) T cells specific for tumor antigen/MHC-I were efficient at inducing regression of the MHC-I-deficient melanoma, provided that the T cells were endowed with properties permitting their migration into the tumor and their efficient production of IFNγ. This was the case for CD8(+) T cells transfected to express an active form of STAT5 (STAT5CA). The amount of IFNγ produced ex vivo from T cells present in tumors after adoptive transfer of the CD8(+) T cells was correlated with an increase in surface expression of MHC-I molecules by the tumor cells. We also show that these CD8(+) T cells expressed PD-1 and upregulated its ligand PDL-1 on melanoma cells within the tumor. Despite upregulation of this immunosuppressive pathway, efficient IFNγ production in the melanoma microenvironment was found associated with resistance of STAT5CA-expressing CD8(+) T cells to inhibition both by PD-1/PDL-1 engagement and by TGFβ1, two main immune regulatory mechanisms hampering the efficiency of immunotherapy in patients.

  20. Iron deficiency in childhood

    NARCIS (Netherlands)

    Uijterschout, L.


    Iron deficiency (ID) is the most common micronutrient deficiency in the world. Iron is involved in oxygen transport, energy metabolism, immune response, and plays an important role in brain development. In infancy, ID is associated with adverse effects on cognitive, motor, and behavioral development

  1. Antigen-Experienced CD4lo T Cells Are Linked to Deficient Contraction of the Immune Response in Autoimmune Diabetes

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    Sean Linkes


    Full Text Available Following proper activation, naïve “CD4lo” T cells differentiate into effector T cells with enhanced expression of CD4 -“CD4hi” effectors. Autoimmune diabetes-prone NOD mice display a unique set of antigen-experienced “CD4lo” T cells that persist after primary stimulation. Here, we report that a population of such cells remained after secondary and tertiary TCR stimulation and produced cytokines upon antigenic challenge. However, when NOD blasts were induced in the presence of rIL-15, the number of antigen-experienced “CD4lo” T cells was significantly reduced. Clonal contraction, mediated in part by CD95-dependent activation-induced cell death (AICD, normally regulates the accumulation of “CD4hi” effectors. Interestingly, CD95 expression was dramatically reduced on the AICD-resistant NOD “CD4lo” T cells. Thus, while autoimmune disease has often been attributed to the engagement of robust autoimmunity, we suggest that the inability to effectively contract the immune response distinguishes benign autoimmunity from progressive autoimmune diseases that are characterized by chronic T cell-mediated inflammation.

  2. Innate immune reactivity of the liver in rats fed a choline-deficient L-amino-acid-defined diet

    Institute of Scientific and Technical Information of China (English)

    Hideto Kawaratani; Tatsuhiro Tsujimoto; Toshiyuld Kitazawa; Mitsuteru Kitade; Hitoshi Yoshiji; Masahito Uemura; Hiroshi Fukui


    AIM:To investigate the innate immune reactivity of tumor necrosis factor-alpha (TNF-α),Toll-like receptor 4 (TLR4),and CD14 in the liver of non-alcoholic steatohepatitis (NASH) model rats.METHODS:Male F344 rats were fed a cholinedeficient L-amino-acid-defined (CDAA) diet.The rats were killed after 4 or 8 wk of the diet,and their livers were removed for immunohistochemical investigation and RNA extraction.The liver specimens were immunostained for TNF-α,TLR4,and CD14.The gene expressions of TNF-a,TLR4,and CD14 were determined by reverse-transcriptase polymerase chain reaction (RT-PCR).Kupffer cells were isolated from the liver by Percoll gradient centrifugation,and were then cultured to measure TNF-α production.RESULTS:The serum and liver levels of TNF-α in the CDAA-fed rats increased significantly as compared with the control group,as did the immunohistochemical values and gene expressions of TNF-α,TLR4,and CD14 with the progression of steatohepatitis.TNF-α production from the isolated Kupffer cells of the CDAAfed rats was elevated by lipopolysaccharide stimulation.CONCLUSION:The expressions of TNF-α,TLR4,and CD14 increased in the NASH model,suggesting that TLR4 and CD14-mediated endotoxin liver damage may also occur in NASH.

  3. Tracing the antibody mediated acquired immunity by Foot and Mouth disease and Rift Valley Fever combined vaccine in pregnant ewes and their lambs

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    Wael Mossad Gamal


    Full Text Available Aim: The aim of this study was to provide adequate protection to ewes and their lambs against Foot and Mouth disease (FMD and Rift Valley Fever (RVF. Materials and Methods: A combined inactivated oil vaccine was prepared successfully. Such vaccine was found to be free from foreign contaminants, safe and potent as determined by quality control tests such as challenge protection percentage for FMD and mice ED50 for RVF. Vaccination of pregnant ewes with the prepared combined vaccine and determination of the antibody level via serum neutralization test (SNT and Enzyme Linked immune sorbent assay (ELISA in the vaccinated pregnant ewes and their lambs. Results: Vaccination of pregnant ewes revealed that these ewes exhibited high levels of specific antibodies against the included vaccine antigens (Foot and Mouth disease virus type A Iran O5, O PanAsia and SAT2/EGY/2012 and RVFV-ZH501. FMD antibodies recorded their peaks by the 10th week while those of RVF recorded their peaks by the 12th week post vaccination then all antibodies began to decrease gradually to reach their lowest protective titers for FMD by the 32nd week post vaccination and those for RVF by the 34th week post vaccination. Potency test of the prepared combined vaccine expressed as protection percentage of vaccinated sheep against target virulent FMD virus serotypes reflected a protection percentage of 80% against type O and SAT2 and 100% against A while for RVF, the mice ED50 was found to be 0.009 indicating the potency of the prepared vaccine. The antibody titer in serum and colostrum of vaccinated pregnant ewes at day of parturition (10-12 week post vaccination recorded a high titer against FMD serotype (O, serotype (A, serotype (SAT2 and against RVF. It was noticed that the colostrum antibody titers were slightly higher than those in the sera of vaccinated ewes at time of parturition. The newly born lambs from vaccinated ewes, exhibited good levels of maternal immunity against the

  4. Plasmodium vivax VIR Proteins Are Targets of Naturally-Acquired Antibody and T Cell Immune Responses to Malaria in Pregnant Women (United States)

    Requena, Pilar; Rui, Edmilson; Padilla, Norma; Martínez-Espinosa, Flor E.; Castellanos, Maria Eugenia; Bôtto-Menezes, Camila; Malheiro, Adriana; Arévalo-Herrera, Myriam; Kochar, Swati; Kochar, Sanjay K.; Kochar, Dhanpat K.; Umbers, Alexandra J.; Ome-Kaius, Maria; Wangnapi, Regina; Hans, Dhiraj; Menegon, Michela; Mateo, Francesca; Sanz, Sergi; Desai, Meghna; Mayor, Alfredo; Chitnis, Chetan C.; Bardají, Azucena; Mueller, Ivo; Rogerson, Stephen; Severini, Carlo; Fernández-Becerra, Carmen; Menéndez, Clara


    P. vivax infection during pregnancy has been associated with poor outcomes such as anemia, low birth weight and congenital malaria, thus representing an important global health problem. However, no vaccine is currently available for its prevention. Vir genes were the first putative virulent factors associated with P. vivax infections, yet very few studies have examined their potential role as targets of immunity. We investigated the immunogenic properties of five VIR proteins and two long synthetic peptides containing conserved VIR sequences (PvLP1 and PvLP2) in the context of the PregVax cohort study including women from five malaria endemic countries: Brazil, Colombia, Guatemala, India and Papua New Guinea (PNG) at different timepoints during and after pregnancy. Antibody responses against all antigens were detected in all populations, with PNG women presenting the highest levels overall. P. vivax infection at sample collection time was positively associated with antibody levels against PvLP1 (fold-increase: 1.60 at recruitment -first antenatal visit-) and PvLP2 (fold-increase: 1.63 at delivery), and P. falciparum co-infection was found to increase those responses (for PvLP1 at recruitment, fold-increase: 2.25). Levels of IgG against two VIR proteins at delivery were associated with higher birth weight (27 g increase per duplicating antibody levels, p<0.05). Peripheral blood mononuclear cells from PNG uninfected pregnant women had significantly higher antigen-specific IFN-γ TH1 responses (p=0.006) and secreted less pro-inflammatory cytokines TNF and IL-6 after PvLP2 stimulation than P. vivax-infected women (p<0.05). These data demonstrate that VIR antigens induce the natural acquisition of antibody and T cell memory responses that might be important in immunity to P. vivax during pregnancy in very diverse geographical settings. PMID:27711158

  5. Molecular mechanisms of paclitaxel and NM-3 on human gastric cancer in a severe combined immune deficiency mice orthotopic implantation model

    Institute of Scientific and Technical Information of China (English)

    Jin-Shui Zhu; Ming-Quan Song; Guo-Qiang Chen; Qin Li; Qun Sun; Qiang Zhang


    AIM: To explore the molecular mechanisms of action of paclitaxel and NM-3 on human gastric cancer in severe combined immune deficiency (SCID) mice.METHODS: Human gastric cancer cells SGC-7901 were implanted into SCID mice and mice were treated with paclitaxel and NM-3. The effects of paclitaxel and NM-3 on apoptosis of human gastric cancer cells were analyzed using flow cytometry, TUNEL assays, and DNA fragment analyses.RESULTS: Apoptosis of SGC-7901 cells was successfully induced by paclitaxel, NM-3, and the combination of paclitaxel and NM-3 24 h after injection as shown by the presence of apoptotic hypodiploid peaks on the flow cytometer before G1-S and a characteristic apoptotic band pattern in the DNA electrophoresis. The apoptotic rate detected by TUNEL assay was found to be significantly higher in the paclitaxel/NM-3 compared to the control group (38.5% ± 5.14% vs 13.2% ± 1.75%,P < 0.01).CONCLUSION: Paclitaxel in combination with NM-3 is able to induce apoptosis of the human gastric cancer cells in SCID mice effectively and synergistically.

  6. The Natural History of Children with Severe Combined Immunodeficiency: Baseline Features of the First Fifty Patients of the Primary Immune Deficiency Treatment Consortium Prospective Study 6901 (United States)

    Dvorak, Christopher C.; Cowan, Morton J.; Logan, Brent R.; Notarangelo, Luigi D.; Griffith, Linda M.; Puck, Jennifer M.; Kohn, Donald B.; Shearer, William T.; O'Reilly, Richard J.; Fleisher, Thomas A.; Pai, Sung-Yun; Hanson, I. Celine; Pulsipher, Michael A.; Fuleihan, Ramsay; Filipovich, Alexandra; Goldman, Frederick; Kapoor, Neena; Small, Trudy; Smith, Angela; Chan, Ka-Wah; Cuvelier, Geoff; Heimall, Jennifer; Knutsen, Alan; Loechelt, Brett; Moore, Theodore; Buckley, Rebecca H.


    The Primary Immune Deficiency Treatment Consortium (PIDTC) consists of 33 centers in North America. We hypothesized that the analysis of uniform data on patients with severe combined immunodeficiency (SCID) enrolled in a prospective protocol will identify variables that contribute to optimal outcomes following treatment. We report baseline clinical, immunologic, and genetic features of the first 50 patients enrolled, and the initial therapies administered, reflecting current practice in the diagnosis and treatment of both typical (n = 37) and atypical forms (n = 13) of SCID. From August 2010 to May 2012, patients with suspected SCID underwent evaluation and therapy per local center practices. Diagnostic information was reviewed by the PIDTC eligibility review panel, and hematopoietic cell transplantation (HCT) details were obtained from the Center for International Blood and Marrow Transplant Research. Most patients (92%) had mutations in a known SCID gene. Half of the patients were diagnosed by newborn screening or family history, were younger than those diagnosed by clinical signs (median 15 vs. 181 days; P = <0.0001), and went to HCT at a median of 67 days vs. 214 days of life (P = <0.0001). Most patients (92%) were treated with HCT within 1–2 months of diagnosis. Three patients were treated with gene therapy and 1 with enzyme replacement. The PIDTC plans to enroll over 250 such patients and analyze short and long-term outcomes for factors beneficial or deleterious to survival, clinical outcome, and T- and B-cell reconstitution, and which biomarkers are predictive of these outcomes. PMID:23818196

  7. A new mouse model of mild ornithine transcarbamylase deficiency (spf-j displays cerebral amino acid perturbations at baseline and upon systemic immune activation.

    Directory of Open Access Journals (Sweden)

    Tatyana N Tarasenko

    Full Text Available Ornithine transcarbamylase deficiency (OTCD, OMIM# 311250 is an inherited X-linked urea cycle disorder that is characterized by hyperammonemia and orotic aciduria. In this report, we describe a new animal model of OTCD caused by a spontaneous mutation in the mouse Otc gene (c.240T>A, p.K80N. This transversion in exon 3 of ornithine transcarbamylase leads to normal levels of mRNA with low levels of mature protein and is homologous to a mutation that has also been described in a single patient affected with late-onset OTCD. With higher residual enzyme activity, spf-J were found to have normal plasma ammonia and orotate. Baseline plasma amino acid profiles were consistent with mild OTCD: elevated glutamine, and lower citrulline and arginine. In contrast to WT, spf-J displayed baseline elevations in cerebral amino acids with depletion following immune challenge with polyinosinic:polycytidylic acid. Our results indicate that the mild spf-J mutation constitutes a new mouse model that is suitable for mechanistic studies of mild OTCD and the exploration of cerebral pathophysiology during acute decompensation that characterizes proximal urea cycle dysfunction in humans.

  8. Peroxisome deficiency but not the defect in ether lipid synthesis causes activation of the innate immune system and axonal loss in the central nervous system

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    Bottelbergs Astrid


    Full Text Available Abstract Background Mice with peroxisome deficiency in neural cells (Nestin-Pex5−/− develop a neurodegenerative phenotype leading to motor and cognitive disabilities and early death. Major pathologies at the end stage of disease include severe demyelination, axonal degeneration and neuroinflammation. We now investigated the onset and progression of these pathological processes, and their potential interrelationship. In addition, the putative role of oxidative stress, the impact of plasmalogen depletion on the neurodegenerative phenotype, and the consequences of peroxisome elimination in the postnatal period were studied. Methods Immunohistochemistry in association with gene expression analysis was performed on Nestin-Pex5−/− mice to document demyelination, axonal damage and neuroinflammation. Also Gnpat−/− mice, with selective plasmalogen deficiency and CMV-Tx-Pex5−/− mice, with tamoxifen induced generalized loss of peroxisomes were analysed. Results Activation of the innate immune system is a very early event in the pathological process in Nestin-Pex5−/− mice which evolves in chronic neuroinflammation. The complement factor C1q, one of the earliest up regulated transcripts, was expressed on neurons and oligodendrocytes but not on microglia. Transcripts of other pro- and anti-inflammatory genes and markers of phagocytotic activity were already significantly induced before detecting pathologies with immunofluorescent staining. Demyelination, macrophage activity and axonal loss co-occurred throughout the brain. As in patients with mild peroxisome biogenesis disorders who develop regressive changes, demyelination in cerebellum and brain stem preceded major myelin loss in corpus callosum of both Nestin-Pex5−/− and CMV-Tx-Pex5−/− mice. These lesions were not accompanied by generalized oxidative stress throughout the brain. Although Gnpat−/− mice displayed dysmyelination and Purkinje cell axon damage in cerebellum

  9. Pregnancy Associated with Systemic Lupus Erythematosus: Immune Tolerance in Pregnancy and Its Deficiency in Systemic Lupus Erythematosus—An Immunological Dilemma

    Directory of Open Access Journals (Sweden)

    Cristina Gluhovschi


    Full Text Available Pregnancy is a physiological condition that requires immune tolerance to the product of conception. Systemic lupus erythematosus (SLE is a disease with well-represented immune mechanisms that disturb immune tolerance. The association of pregnancy with systemic lupus erythematosus creates a particular immune environment in which the immune tolerance specific of pregnancy is required to coexist with alterations of the immune system caused by SLE. The main role is played by T regulatory (Treg cells, which attempt to regulate and adapt the immune system of the mother to the new conditions of pregnancy. Other components of the immune system also participate to maintain maternal-fetal immune tolerance. If the immune system of pregnant women with SLE is not able to maintain maternal immune tolerance to the fetus, pregnancy complications (miscarriage, fetal hypotrophy, and preterm birth or maternal complications (preeclampsia or activation of SLE, especially in conditions of lupus nephritis may occur. In certain situations this can be responsible for neonatal lupus. At the same time, it must be noted that during pregnancy, the immune system is able to achieve immune tolerance while maintaining the anti-infectious immune capacity of the mother. Immunological monitoring of pregnancy during SLE, as well as of the mother’s disease, is required. It is important to understand immune tolerance to grafts in transplant pathology.

  10. Morphometrical analysis of preantral follicular survival of VEGF-treated bovine ovarian cortex tissue following xenotransplantation in an immune deficient mouse model. (United States)

    Langbeen, A; Van Ginneken, C; Fransen, E; Bosmans, E; Leroy, J L M R; Bols, P E J


    The increasing number of cancer survivors the past decades, has sparked the need for fertility preservation strategies. Due to predominantly ethical constraints, human research material is scarce. A bovine in vitro model is a valuable alternative. Therefore, the following objectives were defined: 1) to xeno-graft bovine ovarian cortex tissue in immune deficient mice as a study-model for female fertility preservation strategies; 2) to stereologically quantify vascularization in Vascular Endothelial Growth Factor (VEGF)-treated and non-treated tissue; 3) to study preantral follicular survival in situ, after xenotransplantation. Bovine ovarian tissue strips were incubated with or without VEGF prior to grafting into female, neutered BALB/c-nu mice (n=16). Non-transplanted cortical tissue was used as a control. At time zero (control), two (2 weeks) and four (4 weeks) weeks after transplantation, grafts were retrieved and assessed by von Willebrand Factor and caspase-3 immunostaining. Data were analyzed using a linear mixed model. In the VEGF+ grafts, 31% of the follicles were considered 'alive' 2 weeks after transplantation, compared to only 17% in the VEGF- grafts (P<0.05). However, no difference could be detected 4 weeks after transplantation (P=0.76) with less follicles being considered 'alive' after transplantation (22%), compared to the control (47.5%) (P<0.05). Finally, the vascular surface density was significantly less in the grafts, irrespective of the transplantation period or the use of VEGF. Although the transplantation process overall negatively influenced the number of viable follicles and vascular density, VEGF exposure prior to transplantation can favor follicle survival during a 2 weeks transplantation period.

  11. The natural history of children with severe combined immunodeficiency: baseline features of the first fifty patients of the primary immune deficiency treatment consortium prospective study 6901. (United States)

    Dvorak, Christopher C; Cowan, Morton J; Logan, Brent R; Notarangelo, Luigi D; Griffith, Linda M; Puck, Jennifer M; Kohn, Donald B; Shearer, William T; O'Reilly, Richard J; Fleisher, Thomas A; Pai, Sung-Yun; Hanson, I Celine; Pulsipher, Michael A; Fuleihan, Ramsay; Filipovich, Alexandra; Goldman, Frederick; Kapoor, Neena; Small, Trudy; Smith, Angela; Chan, Ka-Wah; Cuvelier, Geoff; Heimall, Jennifer; Knutsen, Alan; Loechelt, Brett; Moore, Theodore; Buckley, Rebecca H


    The Primary Immune Deficiency Treatment Consortium (PIDTC) consists of 33 centers in North America. We hypothesized that the analysis of uniform data on patients with severe combined immunodeficiency (SCID) enrolled in a prospective protocol will identify variables that contribute to optimal outcomes following treatment. We report baseline clinical, immunologic, and genetic features of the first 50 patients enrolled, and the initial therapies administered, reflecting current practice in the diagnosis and treatment of both typical (n = 37) and atypical forms (n = 13) of SCID. From August 2010 to May 2012, patients with suspected SCID underwent evaluation and therapy per local center practices. Diagnostic information was reviewed by the PIDTC eligibility review panel, and hematopoietic cell transplantation (HCT) details were obtained from the Center for International Blood and Marrow Transplant Research. Most patients (92 %) had mutations in a known SCID gene. Half of the patients were diagnosed by newborn screening or family history, were younger than those diagnosed by clinical signs (median 15 vs. 181 days; P = <0.0001), and went to HCT at a median of 67 days vs. 214 days of life (P = <0.0001). Most patients (92 %) were treated with HCT within 1-2 months of diagnosis. Three patients were treated with gene therapy and 1 with enzyme replacement. The PIDTC plans to enroll over 250 such patients and analyze short and long-term outcomes for factors beneficial or deleterious to survival, clinical outcome, and T- and B-cell reconstitution, and which biomarkers are predictive of these outcomes.

  12. Across sectional study: the knowledge, attitude, perception, misconception and views (KAPMV) of adult family members of people living with human immune virus-HIV acquired immune deficiency syndrome-AIDS (PLWHA). (United States)

    Bhagavathula, Akshaya Srikanth; Bandari, Deepak Kumar; Elnour, Asim Ahmad; Ahmad, Akram; Khan, Muhammad Umair; Baraka, Mohamed; Hamad, Farah; Shehab, Abdulla


    We intended to assess knowledge, attitude, perception, misconception and views (KAP-MV) of family members of PLWHA. A cross-sectional retrospective study conducted in Anti-retroviral centre of Mahatma Gandhi Memorial-MGM hospital, Warangal, Telangana, South-India from July to September 2014. A questionnaire containing 41 items was distributed among adult family members accompanying patients living with HIV/AIDS-PLWHA. Level of KAP-MV was categorized into poor (0-28), average (29-55) and good (56-82). Analysis was performed by Pearson's Chi square, analysis of variance and Spearman's correlation test on 41 variables using SPSS version 21 and p < 0.01. 538 questionnaires were distributed, response rate was (96 %). On knowledge scale, respondents had a mean score of 8.0 ± 1.7, attitude 5.8 ± 3.4, perception 23.4 ± 4.1, misconceptions 8.0 ± 2.1 and views 8.0 ± 3.9. The respondents mean score was 53.2 ± 9.1 (64.9 %). Overall, level of education, marital status, religious beliefs, and employment status has significant (p < 0.001) associations with KAP-MV. Knowledge was significantly correlated with respondents' attitude (r = -0.15, p < 0.001), perception (0.39; p < 0.001), and views (0.381; p < 0.001). Family members of PLWHA with less knowledge score had more negative attitude, perception and views. Level of education, marital status, religious beliefs and employment status were identified as key barriers. Interventions targeting family members of PLWHA are warranted. Practice implications are as follows: Encourage role of family members.Deploy interventions.Minimize barriers.Change misconceptions.

  13. Skin innate immune system

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    Berna Aksoy


    Full Text Available All multicellular organisms protect themselves from external universe and microorganisms by innate immune sytem that is constitutively present. Skin innate immune system has several different components composed of epithelial barriers, humoral factors and cellular part. In this review information about skin innate immune system and its components are presented to the reader. Innate immunity, which wasn’t adequately interested in previously, is proven to provide a powerfull early protection system, control many infections before the acquired immunity starts and directs acquired immunity to develop optimally

  14. Manganese deficiency or excess caused the depression of intestinal immunity, induction of inflammation and dysfunction of the intestinal physical barrier, as regulated by NF-κB, TOR and Nrf2 signalling, in grass carp (Ctenopharyngodon idella). (United States)

    Jiang, Wei-Dan; Tang, Ren-Jun; Liu, Yang; Kuang, Sheng-Yao; Jiang, Jun; Wu, Pei; Zhao, Juan; Zhang, Yong-An; Tang, Ling; Tang, Wu-Neng; Zhou, Xiao-Qiu; Feng, Lin


    Intestinal mucosal immune components and mRNA levels of inflammatory cytokines, tight junction proteins, antioxidant enzymes and related signalling molecules in young grass carp (Ctenopharyngodon idellus) under dietary manganese (Mn) deficiency or excess were investigated. Fish were fed the diets containing graded levels of Mn [3.65-27.86 mg Mn kg(-1) diet] for 8 weeks. The results demonstrated that Mn deficiency significantly decreased the lysozyme and acid phosphatase (ACP) activities, up-regulated tumour necrosis factor α (TNF-α), interleukin 8 and the signalling factor nuclear factor-κB p65, and down-regulated interleukin 10 (IL-10), transforming growth factor β1, inhibitor of signalling factors κB-α and target of rapamycin mRNA levels in the proximal intestine (PI), mid intestine (MI) and distal intestine (DI). However, Mn deficiency did not change the C3 content in the PI, whereas it decreased the C3 contents in the MI and DI. Additionally, Mn depletion also resulted in significantly low mRNA levels for tight junction proteins (claudin-b, claudin-c, claudin-15, occludin and zonula occludens-1), antioxidant enzymes (MnSOD, GPx and CAT) and NF-E2-related factor-2 in the intestines of fish. Excessive Mn exhibited toxic effects similar to Mn deficiency, where optimal Mn contents reversed those indicators. In conclusion, Mn deficiency or excess causes the depression of intestinal immunity, induction of inflammation and dysfunction of the intestinal physical barrier relating to NF-κB, TOR and Nrf2 signalling in grass carp. Furthermore, quadratic regression analysis at 95% maximum response of lysozyme and acid phosphatase activities in the distal intestine of young grass carp revealed the optimum dietary Mn levels to be 8.90 and 8.99 mg kg(-1) diet, respectively.

  15. Naturally-acquired humoral immune responses against the N- and C-termini of the Plasmodium vivax MSP1 protein in endemic regions of Brazil and Papua New Guinea using a multiplex assay

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    Alonso Pedro L


    Full Text Available Abstract Background Progress towards the development of a malaria vaccine against Plasmodium vivax, the most widely distributed human malaria parasite, will require a better understanding of the immune responses that confer clinical protection to patients in regions where malaria is endemic. Methods Glutathione S-transferase (GST and GST-fusion proteins representing the N- terminus of the merozoite surface protein 1 of P. vivax, PvMSP1-N, and the C-terminus, PvMSP1-C, were covalently coupled to BioPlex carboxylated beads. Recombinant proteins and coupled beads were used, respectively, in ELISA and Bioplex assays using immune sera of P. vivax patients from Brazil and PNG to determine IgG and subclass responses. Concordances between the two methods in the seropositivity responses were evaluated using the Kappa statistic and the Spearman's rank correlation. Results The results using this methodology were compared with the classical microtitre enzyme-linked immnosorbent assay (ELISA, showing that the assay was sensitive, reproducible and had good concordance with ELISA; yet, further research into different statistical analyses seems desirable before claiming conclusive results exclusively based on multiplex assays. As expected, results demonstrated that PvMSP1 was immunogenic in natural infections of patients from different endemic regions of Brazil and Papua New Guinea (PNG, and that age correlated only with antibodies against the C-terminus part of the molecule. Furthermore, the IgG subclass profiles were different in these endemic regions having IgG3 predominantly recognizing PvMSP1 in Brazil and IgG1 predominantly recognizing PvMSP1 in PNG. Conclusions This study validates the use of the multiplex assay to measure naturally-acquired IgG antibodies against the merozoite surface protein 1 of P. vivax.

  16. Interventions to screen for human immune-deficiency virus among people donating blood[Protocol]%献血员人类免疫缺陷病毒(HIV)筛检措施的系统评价的研究方案

    Institute of Scientific and Technical Information of China (English)

    王莉; 刘建平; 熊玮; 邝璞; 陶铁军


    背景艾滋病(AIDS)已经成为人类目前所面临的危害最为严重的疾病之一.艾滋病病毒(HIV)主要有三个传播途径:血液、性行为和母婴垂直传播;而通过输血传播的效率更高.由于缺乏有效的HIV筛检方法或方法应用不当以及缺乏严格的管理,通过输血传播HIV的危险极为严重,特别是在一些发展中国家.自从1985年FDA批准第一个HIV试剂用于献血员筛检以来,迄今已经生产出第4代筛检试剂.最初HIV检测试剂仅用于筛检献血员,后来成为了HIV预防工作的重要方面.目前HIV筛检已被视为国家艾滋病预防和治疗策略的重要内容. 目的评价用于献血员HIV筛检所有方法的有效性,从而找出最合适的方法,以减少HIV通过输血传播的危险. 检索策略以"HIV"、"AIDS"、"screening"、"test"、"blood donor"、"blood bank"等为主题,检索了MEDLINE、CENTRAL/CCTR、AIDSLINE、EMBASE、CBM等数据库;同时检索了WHO、UNAIDS、CDC、FDA及其相关网站,并与该领域的专家和机构联系,以获得未发表的文献. 资料纳入标准纳入了所有与献血员HIV筛检方法有关的随机对照试验(RCT)、临床对照试验(CCT);同时一些观察性研究,如队列研究、病例对照研究和历史对照研究等纳入用于敏感性分析. 评价方法参照Cochrane 系统评价的原则,选择纳入的研究,并对其进行质量评价、数据提取和分析.%Background AIDS (acquired immune deficiency syndrome) has become the most devastating disease which humankind has ever encountered.Human immune-deficiency virus(HIV) is transmitted through blood, sexual behavior and mother-to-baby, with more efficient transmission through blood transfusion. HIV risk among blood transfusion was severe due to lack of effective and correctly applied screening method and rigorous management, especially in some developing countries. Since the first HIV screening reagent was approved by FDA to screen the blood in 1985

  17. Immunity decreases, antioxidant system damages and tight junction changes in the intestine of grass carp (Ctenopharyngodon idella) during folic acid deficiency: Regulation of NF-κB, Nrf2 and MLCK mRNA levels. (United States)

    Shi, Lei; Feng, Lin; Jiang, Wei-Dan; Liu, Yang; Jiang, Jun; Wu, Pei; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu


    This investigation used the same growth trial as the previous study, which showed that folic acid deficiency retarded growth in young grass carp (the percent weight gain of Groups 1-6 were 102.32 ± 3.41%, 137.25 ± 10.48%, 179.78 ± 3.95%, 164.33 ± 3.21%, 143.35 ± 8.12% and 115.28 ± 2.66%) [1]. In the present study, we investigated the effects of dietary folic acid on the immune response, antioxidant status and tight junctions in the intestine of young grass carp (Ctenopharyngodon idella). A total of 540 young grass carp were fed diets containing graded levels of folic acid at 0.10, 0.47, 1.03, 1.48, 1.88 and 3.12 mg kg(-1) diet for 8 weeks. The results indicated that acid phosphatase and lysozyme activities, and the complement component 3 content in the proximal intestine (PI), mid intestine (MI) and distal intestine (DI) were decreased with folic acid deficiency (0.1 mg kg(-1)) (P Folic acid deficiency (0.1 mg kg(-1)) up-regulated interleukin 1β, interleukin 8, tumor necrosis factor α, nuclear factor κB p65 (NF-κB p65), IκB kinase α (IKK-α), IKK-β and IKK-γ gene expression, meanwhile down-regulated interleukin 10, transforming growth factor β, IκB and target of rapamycin gene expression in the PI, MI and DI (P folic acid deficiency decreased fish intestinal innate immune function may be partly contributed to the regulation of NF-κB p65 pathway. Moreover, the activities and corresponding gene expression of glutathione content, Cu/Zn superoxide dismutase, catalase, glutathione peroxidase, glutathione s-transferases and glutathione reductase in fish intestine were depressed by deficient folic acid diet (0.1 mg kg(-1)) (P folic acid deficiency (0.1 mg kg(-1)) down-regulated NF-E2-related factor 2 (Nrf2) gene expression, up-regulated Kelch-like-ECH-associated protein 1a (Keap1a) and Keap1b gene expression in fish intestine (P folic acid diet damaged fish intestinal antioxidant capacity partly by regulating Nrf2/Keap1 pathway

  18. 从肠黏膜免疫系统损害探讨AIDS脾虚病机%Discuss the spleen deficiency of AIDS pathogenesis from the point of view intestinal mucosal immune system damage

    Institute of Scientific and Technical Information of China (English)

    王春芳; 李真; 徐立然


    HIV/AIDS patients with intestinal mucosal immune system damage promoting the immunodeficiency of body and the incidence of opportunistic infections, which is consistent with the evolution of spleen deficiency pathogenesis point of view of TCM. This paper discusses the spleen deficiency of AIDS pathogenesis from the point of view intestinal mucosal immune system damage, and proposed strengthening the spleen to improve immune function of intestinal mucosa of AIDS.%HIV/AIDS患者肠黏膜免疫系统损害促进了机体免疫功能的缺失和机会性感染的发生,AIDS以脾虚为主的中医病机演变过程,与HIV感染所致以肠黏膜损伤为重要表现的全身免疫损伤过程相符合.文章从肠黏膜免疫系统损害角度探讨AIDS脾虚病机,提出健脾扶正以改善肠黏膜免疫功能的中医药治疗AIDS思路.

  19. Dietary vitamin C deficiency depresses the growth, head kidney and spleen immunity and structural integrity by regulating NF-κB, TOR, Nrf2, apoptosis and MLCK signaling in young grass carp (Ctenopharyngodon idella). (United States)

    Xu, Hui-Jun; Jiang, Wei-Dan; Feng, Lin; Liu, Yang; Wu, Pei; Jiang, Jun; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu


    This study investigated the effects of dietary vitamin C on the growth, and head kidney, spleen and skin immunity, structural integrity and related signaling molecules mRNA expression levels of young grass carp (Ctenopharyngodon idella). A total of 540 grass carp (264.37 ± 0.66 g) were fed six diets with graded levels of vitamin C (2.9, 44.2, 89.1, 133.8, 179.4 and 224.5 mg/kg diet) for 10 weeks. Subsequently, a challenge test was conducted by injection of Aeromonas hydrophila and the survival rate recorded for 14 days. The results indicated that compared with optimal vitamin C supplementation, vitamin C deficiency (2.9 mg/kg diet) decreased lysozyme (LA) and acid phosphatase (ACP) activities, and complement 3 and complement 4 (C4) contents (P spleen), IL-12 P40, IL-15, IL-17D, nuclear factor κB p65, IκB kinases (IKKα, IKKβ, IKKγ), target of rapamycin and ribosomal protein S6 kinase 1 mRNA levels (P spleen under injection fish of A. hydrophila, suggesting that vitamin C deficiency could decrease fish head kidney and spleen immunity and cause inflammation. Meanwhile, compared with optimal vitamin C supplementation, vitamin C deficiency decreased the activities and mRNA levels of copper/zinc superoxide dismutase, manganese superoxide dismutase (MnSOD), catalase, glutathione peroxidase, glutathione S-transferases and glutathione reductase (P spleen under injection fish of A. hydrophila, suggesting that vitamin C deficiency could decrease fish head kidney and spleen structural integrity through depression of antioxidative ability, induction of apoptosis and disruption of tight junctional complexes. In addition, except the activities of ACP and MnSOD, and mRNA expression levels of TGF-β1, Occludin and MnSOD, the effect of vitamin C on fish head kidney, spleen and skin immunity and structural integrity other indicators model are similar under infection of A. hydrophila. Finally, the vitamin C requirement for the growth performance (PWG) of young grass carp was

  20. Acquired platelet function defect (United States)

    Acquired qualitative platelet disorders; Acquired disorders of platelet function ... blood clotting. Disorders that can cause problems in platelet function include: Idiopathic thrombocytopenic purpura Chronic myelogenous leukemia Multiple ...


    Directory of Open Access Journals (Sweden)

    Lourdes eIsaac


    Full Text Available The complement system plays an important role in the innate and acquired immune response against pathogens. It consists of more than 30 proteins found in soluble form or attached to cell membranes. Most complement proteins circulate in inactive forms and can be sequentially activated by the Classical, Alternative or Lectin Pathways. Biological functions such as opsonization, removal of apoptotic cells, adjuvant function, activation of B lymphocytes, degranulation of mast cells and basophils, solubilization and clearance of immune complex and cell lysis are dependent on complement activation. Although the activation of the complement system is important to avoid infections, it also can contribute to the inflammatory response triggered by immune complex deposition in tissues in auto-immune diseases. Paradoxically, the deficiency of early complement proteins from the Classical Pathway is strongly associated with development of systemic lupus erythematous (SLE - mainly C1q deficiency (93% and C4 deficiency (75%. The aim of this review is to focus on the deficiencies of early components of the Classical Pathway (C1q, C1r, C1s, C4, C2 proteins in SLE patients.

  2. Cutting edge: FasL(+) immune cells promote resolution of fibrosis. (United States)

    Wallach-Dayan, Shulamit B; Elkayam, Liron; Golan-Gerstl, Regina; Konikov, Jenya; Zisman, Philip; Dayan, Mark Richter; Arish, Nissim; Breuer, Raphael


    Immune cells, particularly those expressing the ligand of the Fas-death receptor (FasL), e.g. cytotoxic T cells, induce apoptosis in 'undesirable' self- and non-self-cells, including lung fibroblasts, thus providing a means of immune surveillance. We aimed to validate this mechanism in resolution of lung fibrosis. In particular, we elucidated whether FasL(+) immune cells possess antifibrotic capabilities by induction of FasL-dependent myofibroblast apoptosis and whether antagonists of membrane (m) and soluble (s) FasL can inhibit these capabilities. Myofibroblast interaction with immune cells and its FasL-dependency, were investigated in vitro in coculture with T cells and in vivo, following transplantation into lungs of immune-deficient syngeneic Rag-/- as well as allogeneic SCID mice, and into lungs and air pouches of FasL-deficient (gld) mice, before and after reconstitution of the mice with wild-type (wt), FasL(+) immune cells. We found that myofibroblasts from lungs resolving fibrosis undergo FasL-dependent T cell-induced apoptosis in vitro and demonstrate susceptibility to in vivo immune surveillance in lungs of reconstituted, immune- and FasL-deficient, mice. However, immune-deficient Rag-/- and SCID mice, and gld-mice with FasL-deficiency, endure the accumulation of transplanted myofibroblasts in their lungs with subsequent development of fibrosis. Concomitantly, gld mice, in contrast to chimeric FasL-deficient mice with wt immune cells, accumulated transplanted myofibroblasts in the air pouch model. In humans we found that myofibroblasts from fibrotic lungs secrete sFasL and resist T cell-induced apoptosis, whereas normal lung myofibroblasts are susceptible to apoptosis but acquire resistance upon addition of anti-s/mFasL to the coculture. Immune surveillance, particularly functional FasL(+) immune cells, may represent an important extrinsic component in myofibroblast apoptosis and serve as a barrier to fibrosis. Factors interfering with Fas/FasL-immune

  3. Deficiency in hematopoietic phosphatase ptpn6/Shp1 hyperactivates the innate immune system and impairs control of bacterial infections in zebrafish embryos

    NARCIS (Netherlands)

    Kanwal, Z.; Zakrzewska, A.; den Hertog, J.; Spaink, H.P.; Schaaf, M.J.; Meijer, A.H.


    Deficiency in Src homology region 2 domain-containing phosphatase 1/protein tyrosine phosphatase nonreceptor type 6 (SHP1/PTPN6) is linked with chronic inflammatory diseases and hematological malignancies in humans. In this study, we exploited the embryonic and larval stages of zebrafish (Danio reri

  4. Absence of lactobacilli containing glycolipids with the α-galactose epitope and the enhanced fucosylation of a receptor glycolipid GA1 in the digestive tracts of immune-deficient scid mice. (United States)

    Iwamori, Masao; Tanaka, Kyoko; Adachi, Shigeki; Aoki, Daisuke; Nomura, Taisei


    The Lactobacillus species in the digestive tracts of immune-deficient scid mice was distinct from that in control mice, i.e. Lactobacillus murinus in scid and L. johnsonii in control mice, according to their 16S-rRNA, indicating that a symbiotic relationship between lactobacilli and a host is established under pressure from the immune system. The caecal and colonal contents rich in L. murinus of scid mice were loose with a strong sour smell, resulting in diarrhoea, and those with L. johnsonii in control mice included abundant solid materials. Lactobacillus glycolipids were revealed to be recognized by the immune system, and by TLC-immunostaining, LacTetH-DG (Galα1-6Galα1-6Galα1-2Glcα1-3'DG) of L. johnsonii was detected in the stomach, caecum and colon of control mice, but not in those of scid ones, in which fucosylation of a receptor GA1 for L. johnsonii was enhanced more than 4-fold compared with in the control mice. Thus, structural modification of receptor glycolipids was revealed to occur in the process of establishment of a symbiotic relationship between lactobacilli and a host. LacTetH-DG was also immunogenic to human, because of the presence of natural antibodies against it, and the antibody binding to it was comparable to that of blood group- and species-related glycosphingolipids.

  5. Acquired hemoglobin variants and exposure to glucose-6-phosphate dehydrogenase deficient red blood cell units during exchange transfusion for sickle cell disease in a patient requiring antigen-matched blood. (United States)

    Raciti, Patricia M; Francis, Richard O; Spitalnik, Patrice F; Schwartz, Joseph; Jhang, Jeffrey S


    Red blood cell exchange (RBCEx) is frequently used in the management of patients with sickle cell disease (SCD) and acute chest syndrome or stroke, or to maintain target hemoglobin S (HbS) levels. In these settings, RBCEx is a category I or II recommendation according to guidelines on the use of therapeutic apheresis published by the American Society for Apheresis. Matching donor red blood cells (RBCs) to recipient phenotypes (e.g., C, E, K-antigen negative) can decrease the risk of alloimmunization in patients with multi-transfused SCD. However, this may select for donors with a higher prevalence of RBC disorders for which screening is not performed. This report describes a patient with SCD treated with RBCEx using five units negative for C, E, K, Fya, Fyb (prospectively matched), four of which were from donors with hemoglobin variants and/or glucose-6-phosphate dehydrogenase (G6PD) deficiency. Pre-RBCEx HbS quantification by high performance liquid chromatography (HPLC) demonstrated 49.3% HbS and 2.8% hemoglobin C, presumably from transfusion of a hemoglobin C-containing RBC unit during a previous RBCEx. Post-RBCEx HPLC showed the appearance of hemoglobin G-Philadelphia. Two units were G6PD-deficient. The patient did well, but the consequences of transfusing RBC units that are G6PD-deficient and contain hemoglobin variants are unknown. Additional studies are needed to investigate effects on storage, in-vivo RBC recovery and survival, and physiological effects following transfusion of these units. Post-RBCEx HPLC can monitor RBCEx efficiency and detect the presence of abnormal transfused units.

  6. Pre-existing vector immunity does not prevent replication deficient adenovirus from inducing efficient CD8 T-cell memory and recall responses

    DEFF Research Database (Denmark)

    Steffensen, Maria Abildgaard; Jensen, Benjamin Anderschou Holbech; Holst, Peter Johannes


    in a large part of the human population. We have recently developed an improved adenoviral vaccine vector system in which the vector expresses the transgene tethered to the MHC class II associated invariant chain (Ii). To further evaluate the potential of this system, the concept of pre-existing inhibitory......Adenoviral vectors have shown a great potential for vaccine development due to their inherent ability to induce potent and protective CD8 T-cell responses. However, a critical issue regarding the use of these vectors is the existence of inhibitory immunity against the most commonly used Ad5 vector...... immunity to adenoviral vectors was revisited to investigate whether the inhibition previously seen with the Ad5 vector also applied to the optimized vector system. We found this to be the case, and antibodies dominated as the mechanism underlying inhibitory vector immunity. However, presence of CD8 T cells...

  7. Severe acquired anaemia in Africa: new concepts

    NARCIS (Netherlands)

    M. Boele van Hensbroek; F. Jonker; I. Bates


    Severe anaemia is common in Africa. It has a high mortality and particularly affects young children and pregnant women. Recent research provides new insights into the mechanisms and causes of severe acquired anaemia and overturns accepted dogma. Deficiencies of vitamin B12 and vitamin A, but not of

  8. Iodine Deficiency (United States)

    ... 2017 By ATA | Featured , Iodine Deficiency , News Releases , Potassium Iodide (KI) | No Comments IDD NEWSLETTER – February 2017 VOLUME ... 2016 By ATA | Featured , Iodine Deficiency , News Releases , Potassium Iodide (KI) | No Comments IDD NEWSLETTER – November 2015 (PDF ...

  9. [Psychoneuroimmunology--regulation of immunity at the systemic level]. (United States)

    Boranić, Milivoj; Sabioncello, Ante; Gabrilovac, Jelka


    Innate and acquired immune reactions are controlled by their intrinsic regulatory mechanisms, ie. by an array of cytokines that mediate communication among cells of the immune system itself and with other cells and tissues, e. g. in areas of inflammation. In addition, the immune system is also subjected to systemic regulation by the vegetative and endocrine systems since immune cells express receptors for neurotransmitters and hormones. Neuroendocrine signals may enhance or suppress the immune reaction, accelerate or slow it, but do not affect specificity. Various stressful factors, including the psychosocial ones, affect immunity. In turn, cytokines generated by the immune system influence hormonal secretion and central nervous system, producing specific behavioral changes (the "sickness behavior") accompanying infectious and inflammatory diseases. That includes somnolence, loss of apetite, depression or anxiety and decrease of cognitive abilities, attention and memory. Local immune systems in skin and mucosa are also subjected to systemic neuroendocrine regulation and possess intrinsic neuroregulatory networks as well. These mechanisms render skin and respiratory and digestive tracts responsive to various forms of stress. Examples are neurodermitis, asthma and ulcerative colitis. In children, the immune and the neuroendocrine systems are still developing, particularly in fetal, neonatal and early infant periods, and exposure to stressful experiences at that time may result in late consequences in the form of deficient immunity or greater risks for allergic or autoimmune reactions. Recognition of the participation of neuroendocrine mechanisms in regulation of immunity helps us understand alterations and disturbances of immune reactions under the influence of stressful factors but so far has not produced reliable therapeutic implications. Psychosocial interventions involving the child and its family may be useful.

  10. CD40L deficiency attenuates diet-induced adipose tissue inflammation by impairing immune cell accumulation and production of pathogenic IgG-antibodies.

    Directory of Open Access Journals (Sweden)

    Dennis Wolf

    Full Text Available BACKGROUND: Adipose tissue inflammation fuels the metabolic syndrome. We recently reported that CD40L--an established marker and mediator of cardiovascular disease--induces inflammatory cytokine production in adipose cells in vitro. Here, we tested the hypothesis that CD40L deficiency modulates adipose tissue inflammation in vivo. METHODOLOGY/PRINCIPAL FINDINGS: WT or CD40L(-/- mice consumed a high fat diet (HFD for 20 weeks. Inflammatory cell recruitment was impaired in mice lacking CD40L as shown by a decrease of adipose tissue macrophages, B-cells, and an increase in protective T-regulatory cells. Mechanistically, CD40L-deficient mice expressed significantly lower levels of the pro-inflammatory chemokine MCP-1 both, locally in adipose tissue and systemically in plasma. Moreover, levels of pro-inflammatory IgG-antibodies against oxidized lipids were reduced in CD40L(-/- mice. Also, circulating low-density lipoproteins and insulin levels were lower in CD40L(-/- mice. However, CD40L(-/- mice consuming HFD were not protected from the onset of diet-induced obesity (DIO, insulin resistance, and hepatic steatosis, suggesting that CD40L selectively limits the inflammatory features of diet-induced obesity rather than its metabolic phenotype. Interestingly, CD40L(-/- mice consuming a low fat diet (LFD showed both, a favorable inflammatory and metabolic phenotype characterized by diminished weight gain, improved insulin tolerance, and attenuated plasma adipokine levels. CONCLUSION: We present the novel finding that CD40L deficiency limits adipose tissue inflammation in vivo. These findings identify CD40L as a potential mediator at the interface of cardiovascular and metabolic disease.

  11. Frequent respiratory tract infections in the canine model of X-linked ectodermal dysplasia are not caused by an immune deficiency


    Casal, Margret L.; Mauldin, Elizabeth A.; Ryan, Sara; Scheidt, Jennifer L.; Kennedy, Jeffrey; Moore, Peter F.; Felsburg, Peter J.


    As in many human patients with X-linked hypohidrotic ectodermal dysplasia (XHED), XHED dogs are at an increased risk for pulmonary disorders. Localized immune system defects had been suspected previously in affected dogs because of frequent infections and unexpected deaths due to opportunistic respiratory tract infections. Experiments were designed to examine systemic and localized humoral and cellular responses, development and function of T cells, and thymic morphology. All dogs used in the...

  12.  Surfactant Protein D of the Innate Immune Defence is Inversely Associated with Human Obesity and SP-D Deficiency Infers Increased Body Weight in Mice

    DEFF Research Database (Denmark)

    Sørensen, Grith Lykke; Hjelmborg, Jacob v. B.; Leth-Larsen, Rikke


    of the present study was to describe the association between serum SP-D and weight, waist circumference or BMI, and furthermore to observe body weight development in SP-D-deficient (Spd-/-) mice. As a part of the Danish population-based twin study (GEMINAKAR) on the metabolic syndrome, we analysed 1476 Danish...... twins for serum SP-D and investigated associations with weight, waist circumference and BMI by multiple regression analysis. Serum SP-D was significantly and inversely associated with weight (P = 0.001) and waist circumference in men (P

  13. IFNγ producing CD8+ T cells modified to resist major immune checkpoints induce regression of MHC class I-deficient melanomas


    Buferne, Michel; Chasson, Lionel; Grange, Magali; Mas, Amandine; Arnoux, Fanny; Bertuzzi, Mélanie; Naquet, Philippe; Leserman, Lee; Schmitt-Verhulst, Anne-Marie; Auphan-Anezin, Nathalie


    Tumors with reduced expression of MHC class I (MHC-I) molecules may be unrecognized by tumor antigen-specific CD8+ T cells and thus constitute a challenge for cancer immunotherapy. Here we monitored development of autochthonous melanomas in TiRP mice that develop tumors expressing a known tumor antigen as well as a red fluorescent protein (RFP) reporter knock in gene. The latter permits non-invasive monitoring of tumor growth by biofluorescence. One developing melanoma was deficient in cell s...

  14. Lower limb deficient children in the Netherlands : epidemiological aspects

    NARCIS (Netherlands)

    Rijnders, LJM; Boonstra, AM; Groothoff, JW; Cornel, MC; Eisma, WH


    information on the characteristics of children with limb deficiencies and amputations in the Netherlands is largely lacking. The present study aimed to collect data about the prevalence of congenital deficiencies, the ratio of congenital to acquired limb deficiencies, types of lower leg deficiency o

  15. Dietary pantothenic acid deficiency and excess depress the growth, intestinal mucosal immune and physical functions by regulating NF-κB, TOR, Nrf2 and MLCK signaling pathways in grass carp (Ctenopharyngodon idella). (United States)

    Li, Li; Feng, Lin; Jiang, Wei-Dan; Jiang, Jun; Wu, Pei; Kuang, Sheng-Yao; Tang, Ling; Tang, Wu-Neng; Zhang, Yong-An; Zhou, Xiao-Qiu; Liu, Yang


    This study investigated the effects of dietary pantothenic acid (PA) on the growth, intestinal mucosal immune and physical barrier, and relative mRNA levels of signaling molecules in the intestine of grass carp (Ctenopharyngodon idella). A total of 540 grass carp (253.44 ± 0.69 g) were fed six diets with graded levels of PA (PA1, PA15, PA30, PA45, PA60 and PA75 diets) for 8 weeks. The results indicated that compared with PA deficiency (PA1 diet) and excess (PA75 diet) groups, optimal PA supplementation increased (P TOR) mRNA expression levels in some intestinal segments; (2) reactive oxygen species, malondialdehyde and protein carbonyl contents, and Kelch-like ECH-associating protein 1a, Kelch-like ECH-associating protein 1b in the intestine; (3) Claudin 12, Claudin 15a and myosin light-chain kinase (MLCK) mRNA levels in some intestinal segments of grass carp. In conclusion, optimum PA promoted growth, intestinal mucosal immune and physical function, as well as regulated mRNA levels of signaling molecules NF-κB P65, TOR, Nrf2 and MLCK in grass carp intestine. Based on the quadratic regression analysis of PWG and intestinal lysozyme activity, the optimal PA levels in grass carp (253.44-745.25 g) were estimated to be 37.73 mg/kg and 41.38 mg/kg diet, respectively.

  16. Feeding long-chain n-3 polyunsaturated fatty acids to obese leptin receptor-deficient JCR:LA- cp rats modifies immune function and lipid-raft fatty acid composition. (United States)

    Ruth, Megan R; Proctor, Spencer D; Field, Catherine J


    Dietary EPA and DHA modulate immunity and thereby may improve the aberrant immune function in obese states. To determine the effects of feeding fish oil (FO) containing EPA and DHA on splenocyte phospholipid (PL) and lipid-raft fatty acid composition, phenotypes and cytokine production, 14-week-old obese, leptin receptor-deficient JCR:LA-cp rats (cp/cp; n 10) were randomised to one of three nutritionally adequate diets for 3 weeks: control (Ctl, 0 % EPA+DHA); low FO (LFO, 0.8 % (w/w) EPA+DHA); high FO (HFO, 1.4 % (w/w) EPA+DHA). Lean JCR:LA-cp (+/ - or +/+) rats (n 5) were fed the Ctl diet. Obese Ctl rats had a higher proportion of n-3 PUFA in splenocyte PL than lean rats fed the same diet (P JCR:LA-cp rats. Feeding FO lowered the ex vivo inflammatory response, without altering IL-2 production from ConA-stimulated splenocytes which may occur independent of leptin signalling.

  17. Macrophages Subvert Adaptive Immunity to Urinary Tract Infection.

    Directory of Open Access Journals (Sweden)

    Gabriela Mora-Bau


    Full Text Available Urinary tract infection (UTI is one of the most common bacterial infections with frequent recurrence being a major medical challenge. Development of effective therapies has been impeded by the lack of knowledge of events leading to adaptive immunity. Here, we establish conclusive evidence that an adaptive immune response is generated during UTI, yet this response does not establish sterilizing immunity. To investigate the underlying deficiency, we delineated the naïve bladder immune cell compartment, identifying resident macrophages as the most populous immune cell. To evaluate their impact on the establishment of adaptive immune responses following infection, we measured bacterial clearance in mice depleted of either circulating monocytes, which give rise to macrophages, or bladder resident macrophages. Surprisingly, mice depleted of resident macrophages, prior to primary infection, exhibited a nearly 2-log reduction in bacterial burden following secondary challenge compared to untreated animals. This increased bacterial clearance, in the context of a challenge infection, was dependent on lymphocytes. Macrophages were the predominant antigen presenting cell to acquire bacteria post-infection and in their absence, bacterial uptake by dendritic cells was increased almost 2-fold. These data suggest that bacterial uptake by tissue macrophages impedes development of adaptive immune responses during UTI, revealing a novel target for enhancing host responses to bacterial infection of the bladder.

  18. Dual Effects of IL-1 Overactivity on the Immune System in a Mouse Model of Arthritis due to Deficiency of IL-1 Receptor Antagonist

    Institute of Scientific and Technical Information of China (English)

    Jian Yan; Yan Jiao; Hong Chen; Feng Jiao; Karen A.Hasty; John M.Stuart; Weikuan Gu


    Previous studies have revealed the significance of cytokine interleukin 1 (IL-1) in the onset and progression of meumatoid arthritis (RA).The precise molecular mechanisms related to IL-1 underlying RA is still elusive.We conducted a whole genome-wide transcriptomal comparison of wild-type (WT) and arthritis-prone IL-1 receptor antagonist (IL-Irn) deficient BALB/c mice to address this issue.To refine our search efforts,gene expression profiling was also performed on paired wild-type and arthritis-resis nt IL-1m deficient DBA/1 mice as internal controls when identifying causative arthritis candidate genes.Two hundred and fifteen trans dpts were found to be dysregulated greater than or equal to 2-fold in the diseased mice.The altered transcriptome in BALB/c mice revealed increased myeloid cell activities and impaired lymphocyte functionality,suggesting dual regulatory effects of IL-1 hyperactivil on immunological changes associated with arthritis development.Phase-specific gene expression changes were identified,such as early increase and late decrease of heat shock protein coding genes.Moreover,common gene expression changes were also observed,especially the upregulation of paired Ig-like receptor A (Pira) in both early and late phases of arthritis.Real-time PCR was performed to validate the expression of Pira and an intervention experiment with a major histocompatibility complex (MHC) class I inhibitor (brefeldin A) was carried out to investigate the role of suppressing Pira activity.We conclude that global pattern changes of common and distinct gene expressions may represent novel opportunities for better control of RA through early diagnosis and development of alternative therapeutic strategies.

  19. Pediatric recurrent respiratory tract infections: when and how to explore the immune system? (About 53 cases) (United States)

    El-Azami-El-Idrissi, Mohammed; Lakhdar-Idrissi, Mounia; Chaouki, Sanae; Atmani, Samir; Bouharrou, Abdelhak; Hida, Moustapha


    Recurrent respiratory tract infections are one of the most frequent reasons for pediatric visits and hospitalization. Causes of this pathology are multiple ranging from congenital to acquired and local to general. Immune deficiencies are considered as underlying conditions predisposing to this pathology. Our work is about to determine when and how to explore the immune system when facing recurrent respiratory infections. This was based on the records of 53 children hospitalized at the pediatrics unit of Hassan II University Hospital, Fez Morocco. Thirty boys and 23 girls with age ranging from 5 months to 12 years with an average age of 2 years were involved in this study. Bronchial foreign body was the main etiology in children of 3 to 6 year old. Gastro-esophageal reflux, which in some cases is a consequence of chronic cough, as well as asthma were most frequent in infants (17 and 15% respectively). Immune deficiency was described in 7.5% of patients and the only death we deplored in our series belongs to this group. Recurrent respiratory tract infections have multiple causes. In our series they are dominated by foreign body inhalation and gastroesophageal reflux, which in some cases is a consequence of a chronic cough. Immune deficiency is not frequent but could influence the prognosis. Therefore immune explorations should be well codified. PMID:27642394

  20. Prevalence of human papillomavirus infection, distribution of viral types and risk factors in cervical samples from human immunodeficiency virus-positive women attending three human immunodeficiency virus-acquired immune deficiency syndrome reference centres in northeastern Brazil

    Directory of Open Access Journals (Sweden)

    Albert Eduardo Silva Martins


    Full Text Available Human immunodeficiency virus (HIV-positive patients have a greater prevalence of coinfection with human papillomavirus (HPV is of high oncogenic risk. Indeed, the presence of the virus favours intraepithelial squamous cell lesion progression and may induce cancer. The aim of this study was to evaluate the prevalence of HPV infection, distribution of HPV types and risk factors among HIV-positive patients. Cervical samples from 450 HIV-positive patients were analysed with regard to oncotic cytology, colposcopy and HPV presence and type by means of polymerase chain reaction and sequencing. The results were analysed by comparing demographic data and data relating to HPV and HIV infection. The prevalence of HPV was 47.5%. Among the HPV-positive samples, 59% included viral types of high oncogenic risk. Multivariate analysis showed an association between HPV infection and the presence of cytological alterations (p = 0.003, age greater than or equal to 35 years (p = 0.002, number of partners greater than three (p = 0.002, CD4+ lymphocyte count < 200/mm3 (p = 0.041 and alcohol abuse (p = 0.004. Although high-risk HPV was present in the majority of the lesions studied, the low frequency of HPV 16 (3.3%, low occurrence of cervical lesions and preserved immunological state in most of the HIV-positive patients were factors that may explain the low occurrence of precancerous cervical lesions in this population.

  1. Iodine Deficiency

    NARCIS (Netherlands)

    Zimmermann, M.B.


    Iodine deficiency has multiple adverse effects in humans, termed iodine deficiency disorders, due to inadequate thyroid hormone production. Globally, it is estimated that 2 billion individuals have an insufficient iodine intake, and South Asia and sub-Saharan Africa are particularly affected. Howeve


    Institute of Scientific and Technical Information of China (English)

    章梅; 邱根全; 夏天


    Objective:To explore the effect of lipid peroxidation on red blood cell immune function in patients with spleen deficiency.Method:By the methods of TBA and red blood cell-yeast mixed flower circle,the RBC-C3b receptor rate,malonyldialdehyde(MDA) of plasma and erythrocyte membrane in patients with spleen deficiency were determined respectively.Result:The red blood cell C3b receptor rate(RBC-C3bRR)and red blood cell immune compound(RBC-IC) were lowered,but the MDA content in plasma and erythrocyte membrane were increased respectively.The relative analysis suggested that there were relationship between the RBC-C3bRR and MAD content in plasma and erythrocyte membrane.Conclusion:The lipid peroxidation lesion of red blood cell membrane had a bad effect on RBC-C3bRR.%目的:探讨脾虚患者脂质过氧化对红细胞免疫功能的影响。方法:采用红细胞酵母菌混合花环法和硫代巴比妥酸(TBA)法检测脾虚患者红细胞膜C3b受体花环率(RBC-C3bRR)、血浆及红细胞膜丙二醛(MDA)水平。结果:脾虚患者RBC-C3bRR和红细胞膜免疫复合物花环率(RBC-ICR)明显降低,血浆MDA和红细胞膜MDA明显升高;RBC-C3bRR与血浆MDA、红细胞膜MDA呈负相关,其中红细胞膜MDA和RBC-C3bRR关系更为密切。结论:红细胞膜脂质过氧化损害对RBC-C3bRR有不利影响。

  3. CD40 Ligand Deficient C57BL/6 Mouse Is a Potential Surrogate Model of Human X-Linked Hyper IgM (X-HIGM Syndrome for Characterizing Immune Responses against Pathogens

    Directory of Open Access Journals (Sweden)

    Catalina Lopez-Saucedo


    Full Text Available Individuals with X-HIGM syndrome fail to express functional CD40 ligand; consequently they cannot mount effective protective antibody responses against pathogenic bacteria. We evaluated, compared, and characterized the humoral immune response of wild type (WT and C57-CD40L deficient (C57-CD40L−/− mice infected with Citrobacter rodentium. Basal serum isotype levels were similar for IgM and IgG3 among mice, while total IgG and IgG2b concentrations were significantly lower in C57-CD40L−/− mice compared with WT. Essentially IgG1 and IgG2c levels were detectable only in WT mice. C57-CD40L−/− animals, orally inoculated with 2×109 CFU, presented several clinical manifestations since the second week of infection and eventually died. In contrast at this time point no clinical manifestations were observed among C57-CD40L−/− mice infected with 1×107 CFU. Infection was subclinical in WT mice inoculated with either bacterial dose. The serum samples from infected mice (1×107 CFU, collected at day 14 after infection, had similar C. rodentium-specific IgM titres. Although C57-CD40L−/− animals had lower IgG and IgG2b titres than WT mice, C57-CD40L−/− mice sera displayed complement-mediated bactericidal activity against C. rodentium. C. rodentium-infected C57-CD40L−/− mice are capable of producing antibodies that are protective. C57-CD40L−/− mouse is a useful surrogate model of X-HIGM syndrome for studying immune responses elicited against pathogens.

  4. Acquired inflammatory demyelinating neuropathies. (United States)

    Ensrud, E R; Krivickas, L S


    The acquired demyelinating neuropathies can be divided into those with an acute onset and course and those with a more chronic course. The acute neuropathies present as Guillain-Barré syndrome and include acute inflammatory demyelinating polyradiculoneuropathy (AIDP), Miller Fisher syndrome, acute motor axonal neuropathy (AMAN), acute motor and sensory axonal neuropathy (AMSAN), and acute pandysautonomia. The chronic neuropathies are collectively known as chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and include MADSAM (multifocal acquired demyelinating sensory and motor neuropathy, also know as Lewis-Sumner syndrome) and DADS (distal acquired demyelinating symmetric neuropathy) as variants. The clinical features, pathology, pathogenesis, diagnosis, treatment, rehabilitation, and prognosis of these neuropathies are discussed.

  5. HIV-1 and hijacking of the host immune system: the current scenario. (United States)

    Imran, Muhammad; Manzoor, Sobia; Saalim, Muhammad; Resham, Saleha; Ashraf, Javed; Javed, Aneela; Waqar, Ahmed Bilal


    Human immunodeficiency virus (HIV) infection is a major health burden across the world which leads to the development of acquired immune deficiency syndrome (AIDS). This review article discusses the prevalence of HIV, its major routes of transmission, natural immunity, and evasion from the host immune system. HIV is mostly prevalent in Sub-Saharan Africa and low income countries. It is mostly transmitted by sharing syringe needles, blood transfusion, and sexual routes. The host immune system is categorized into three main types; the innate, the adaptive, and the intrinsic immune system. Regarding the innate immune system against HIV, the key players are mucosal membrane, dendritic cells (DCs), complement system, interferon, and host Micro RNAs. The major components of the adaptive immune system exploited by HIV are T cells mainly CD4+ T cells and B cells. The intrinsic immune system confronted by HIV involves (apolipoprotein B mRNA-editing enzyme, catalytic polypeptide-like 3G) APOBEC3G, tripartite motif 5-α (TRIM5a), terherin, and (SAM-domain HD-domain containing protein) SAMHD1. HIV-1 efficiently interacts with the host immune system, exploits the host machinery, successfully replicates and transmits from one cell to another. Further research is required to explore evasion strategies of HIV to develop novel therapeutic approaches against HIV.

  6. Iron deficiency or anemia of inflammation?


    Nairz, Manfred; Theurl, Igor; Wolf, Dominik; Weiss, Günter


    Summary Iron deficiency and immune activation are the two most frequent causes of anemia, both of which are based on disturbances of iron homeostasis. Iron deficiency anemia results from a reduction of the body’s iron content due to blood loss, inadequate dietary iron intake, its malabsorption, or increased iron demand. Immune activation drives a diversion of iron fluxes from the erythropoietic bone marrow, where hemoglobinization takes place, to storage sites, particularly the mononuclear ph...

  7. Hospital-acquired pneumonia (United States)

    ... tends to be more serious than other lung infections because: People in the hospital are often very sick and cannot fight off ... prevent pneumonia. Most hospitals have programs to prevent hospital-acquired infections.

  8. Laboratory-acquired brucellosis

    DEFF Research Database (Denmark)

    Fabiansen, C.; Knudsen, J.D.; Lebech, A.M.


    Brucellosis is a rare disease in Denmark. We describe one case of laboratory-acquired brucellosis from an index patient to a laboratory technician following exposure to an infected blood culture in a clinical microbiology laboratory Udgivelsesdato: 2008/6/9......Brucellosis is a rare disease in Denmark. We describe one case of laboratory-acquired brucellosis from an index patient to a laboratory technician following exposure to an infected blood culture in a clinical microbiology laboratory Udgivelsesdato: 2008/6/9...

  9. The Leishmania promastigote surface antigen-2 (PSA-2) is specifically recognised by Th1 cells in humans with naturally acquired immunity to L. major

    DEFF Research Database (Denmark)

    Kemp, M; Handman, E; Kemp, K


    The promastigote surface antigen-2 (PSA-2) is a Leishmania parasite antigen, which can induce Th1-mediated protection against murine leishmaniasis when used as a vaccine. To evaluate PSA-2 as a human vaccine candidate the specific T-cell response to PSA-2 was characterised in individuals immune...... to cutaneous leishmaniasis. Peripheral blood mononuclear cells from Sudanese individuals with a past history of self-healing cutaneous leishmaniasis proliferated vigorously in response to PSA-2 isolated from Leishmania major, whereas the antigen did not activate cells from presumably unexposed Danes......-specific Th1-like cells, PSA-2 might be considered a vaccine candidate for human leishmaniasis....

  10. Primary parotid B-cell lymphoma successfully treated with chemotherapy plus highly active antiretroviral therapy with prolonged survival and immune reconstitution in an acquired immunodeficiency syndrome patient: Case report and review of the literature

    Directory of Open Access Journals (Sweden)

    Marcelo Corti


    Full Text Available Non-Hodgkin′s lymphoma (NHL is the second most common acquired immunodeficiency syndrome (AIDS-defining cancer. In this population, up to 70-80% of cases may present as extranodal location as the primary clinical manifestation of the neoplasm disease. Gastrointestinal tract is the most frequent location of AIDS-associated NHL. However, salivary gland involvement, including the parotid gland is a rare complication in human immunodeficiency virus (HIV-patients. Here, we describe a patient seropositive for the HIV, who developed a primary NHL of the parotid gland histologically classified as a high-grade diffuse large B-cell lymphoma. Patient was treated with a combination of chemotherapy plus highly active antiretroviral therapy with a good clinical, virological and immunological response and a prolonged survival, more than 5 years, without evidence of neoplasm relapse.

  11. Acquired cutis laxa

    Directory of Open Access Journals (Sweden)

    Musaliar S


    Full Text Available A 13-yeat-old male patient born of non consanguineous marriage with history of recurrent urticaria and angioedema for the past 2 years presented with wrinkling and laxity of the skin over the face, axilla and abdomen. Histopathology was consistent with cutis laxa. We are reporting a rare case of acquired cutis laxa due to recurrent urticaria.

  12. Acquired cutis laxa

    Directory of Open Access Journals (Sweden)

    Musaliar S


    Full Text Available A 13-yeat-old male patient born of non consanguineous marriage with history of recurrent urticaria and angioedema for the past 2 years presented with wrinkling and laxity of the skin over the face, axilla and abdomen. Histopathology was consistent with cutis laxa. We are reporting a rare case of acquired cutis laxa due to recurrent urticaria.

  13. Lower limb deficient children in the Netherlands: epidemiological aspects


    Rijnders, LJM; Boonstra, AM; Groothoff, JW; Cornel, MC; Eisma, WH


    information on the characteristics of children with limb deficiencies and amputations in the Netherlands is largely lacking. The present study aimed to collect data about the prevalence of congenital deficiencies, the ratio of congenital to acquired limb deficiencies, types of lower leg deficiency or amputation and male/female ratios. Data were obtained from a regional birth defects registry for the northern parr. of the Netherlands (EUROCAT-NNL) and from a national survey, inclusion criteria...

  14. Acquired methemoglobinemia in infants

    Directory of Open Access Journals (Sweden)

    Mehmet Mutlu


    Full Text Available Objective: This study aimed to determine the etiologic factors of acquired methemoglobinemia in infants younger than three months in our region. Material and Methods: This study was carried out retrospectively in infants with methemoglobinemia admitted to Karadeniz Technical University, Pediatric Clinic, during the period 2000-2009. Infants with methemoglobinemia were identified according to the medical records or ICD-10 code. Results: Nine infants with acquired methemoglobinemia (8 male, 1 female were included in the study. Seven cases were associated with the use of prilocaine for circumcision, one case with the use of prilocaine-lidocaine for local pain therapy, and one case with neonatal sepsis caused by Staphylococcus aureus.Conclusion: Prilocaine should not be used in infants less than three months of age because of the risk of methemoglobinemia. Ascorbic acid is an effective therapy if methylene blue is not obtained. It should not be forgotten that sepsis caused by S. aureus may cause methemoglobinemia in infants.

  15. Acquired hypertrichosis lanuginosa

    Directory of Open Access Journals (Sweden)

    Kumar Pramod


    Full Text Available Acquired hypertirichosis lanuginose developed rapidly in a patient with no detectable malignancy. Soft, fine, downy hair growth was noticed on the face, ears, limbs and trunk. Bilaterally symmetrical vitiliginous macules were present on the ear and preauricular region. This case is reported because of its rarity, absence of any detectable malignancy and development of vitiligo, which to our knowledge has not been reported earlier.

  16. Genetics Home Reference: common variable immune deficiency (United States)

    ... or Free article on PubMed Central Park JH, Resnick ES, Cunningham-Rundles C. Perspectives on common variable ... on PubMed or Free article on PubMed Central Resnick ES, Cunningham-Rundles C. The many faces of ...

  17. Primary Immune Deficiency Disease Genetics & Inheritance (United States)

    ... Respond to Pre-Award Requests Manage Your Award Negotiation & Initial Award After Award ... New Trial Launched in West Africa to Evaluate Three Vaccination Strategies , April 6, 2017 Monoclonal Antibody Cures Marburg Infection ...

  18. 健脾止泻颗粒对脾虚泄泻患儿消化吸收与 肠道局部免疫功能的影响%Effect of Jianpi Zhixie Granule on Digestion and Absorption Function and Immunity Function of Local Gut of Diarrhea Children with Spleen Deficiency

    Institute of Scientific and Technical Information of China (English)



    观察脾虚泄泻患儿消化吸收与肠道局部免疫功能以及健脾止泻颗粒的作用机制。方法:对64例脾虚泄泻患儿用健脾止泻颗粒治疗,检测其治疗前后的唾液淀粉酶活性、尿D-木糖排泄率及大便SIgA,并与30例正常儿进行对照观察。结果:脾虚泄泻患儿消化吸收与肠道局部免疫功能低下,经治疗后,上述指标明显好转。结论:健脾止泻颗粒具有促进脾虚泄泻患儿消化吸收功能和提高肠道局部免疫功能的作用。%To observe the digestion and absorption function and the immunity function of the local gut of the diarrhea children with spleen deficiency and the action mechanism of Jianpi Zhixie granule.Metheods:The salivary amylase activity,urine D-xylose excretion rate and stool SIgA of 64 diarrhea children with spleen deficiency were tested before and after treatment by Jianpi Zhixie granule.Results:The digestion and absorption function and the immunity function of the local gut of the diarrhea children with spleen deficiency were lower than the normal group(30 health children).The above indices were increased markedly after treatment.Conclusion:Jianpi Zhixie granule has the functions of promoting the digestion and absorption function of the diarrhea children with spleen deficiency and improving the immunity function of the local gut.

  19. Association between total immunoglobulin E and antibody responses to naturally acquired Ascaris lumbricoides infection and polymorphisms of immune system-related LIG4, TNFSF13B and IRS2 genes. (United States)

    Acevedo, N; Mercado, D; Vergara, C; Sánchez, J; Kennedy, M W; Jiménez, S; Fernández, A M; Gutiérrez, M; Puerta, L; Caraballo, L


    The 13q33-34 region harbours a susceptibility locus to Ascaris lumbricoides, although the underlying genes are unknown. Immunoglobulin (Ig)E and IgG confer protective immunity and here we sought to investigate in an endemic population whether LIG4, TNFSF13B and IRS2 genes influence IgE and IgG levels against Ascaris and the ABA-1 allergen as a putative resistance marker. Mite-allergic asthmatic patients were analysed for potential relationships between Ascaris predisposition and allergy. One thousand and sixty-four subjects from Cartagena, Colombia, were included. Single nucleotide polymorphisms (SNPs) were genotyped using TaqMan assays. Antibody levels were measured by enzyme-linked immunosorbent assay. Linear and logistic regressions were used to model effects of genotypes on antibody levels. The GG genotype of LIG4 (rs1805388) was associated with higher IgE levels to Ascaris compared with other genotypes. TNFSF13B (rs10508198) was associated positively with IgG levels against Ascaris extract and IgE levels against ABA-1. In asthmatics, IRS2 (rs2289046) was associated with high total IgE levels. Associations held up after correction by population stratification using a set of 52 ancestry markers, age, sex and disease status. There was no association with asthma or mite sensitization. In a tropical population, LIG4 and TNFSF13B polymorphisms are associated with specific IgE and IgG to Ascaris, supporting previous linkage studies implicating the 13q33 region. Our results suggest that genes protecting against parasite infections can be different to those predisposing to asthma and atopy.

  20. Acquired von Willebrand Syndrome

    Institute of Scientific and Technical Information of China (English)



    @@ Acquired von Willebrand syndrome (AvWS) is kind of bleeding disorder with laboratory findings similar to those in congenital yon Willebrand disease (vWD).AvWS doesn's have any personal or family history of bleeding, but is associated with certain diseases or abnormal conditions or drugs. Although AvWS is being stated as a rare disease, it has gained more and more attention during the past years. Not because of the severity of the disease, but it is more common than we thought and most patients don' t have a proper diagnosis.

  1. Acquired hyperostosis syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Dihlmann, W.; Hering, L.; Bargon, G.W.


    Sterno-costo-clavicular hyperostosis (SCCH) is the most common manifestation of a syndrome, consisting of increased bone metabolism, mostly new bone formation and heterotopic ossification of fibrous tissue, which we have characterised as the acquired hyperostosis syndrome. In part I we discuss the terminology, radiological appearances, scintigraphy, clinical and laboratory findings, bacteriology, histology, nosology, complications, treatment and differential diagnosis of SCCH. Chronic recurrent multifocal osteomyelitis (CRMO) is regarded as a phaenotype of SCCH, depending on the age. CRMO occurs in children, adolescents and young adults, SCCH predominantly in middleaged and elderly adults.

  2. "Ready to Acquire"

    DEFF Research Database (Denmark)

    Yetton, Philip; Henningsson, Stefan; Bjørn-Andersen, Niels


    This article describes the experiences of Danisco (a global food ingredients company) as it followed a growth-by-acquisition business strategy, focusing on how a new CIO built the IT resources to ensure the IT organization was "ready to acquire." We illustrate how these IT capabilities expedited...... the IT integration following two acquisitions, one of which involved Danisco expanding the scale of its business and the other extending the scope. Based on insights gained from Danisco, we provide lessons for CIOs to realize business benefits when managing post-acquisition IT integration....

  3. Maternally acquired runt disease. (United States)

    Beer, A E; Billingham, R E


    Without altering the structural integrity of the placenta by irradiation or drugs, we have shown that it is possible to immunize females both adoptively and actively against the paternally inherited transplantation antigens of their fetuses. Such immunization causes a high incidence of runt disease among the litters. Although the putative chimeric status of the affected offspring has yet to be confirmed, the results of our experiments support the thesis that runt disease is caused by the activities of "unwanted" immigrant lymphocytes from the maternal circulation. Our results suggest that immunologically activated cells are more likely to cross the placenta than normal cells and that this greater mobility may not be related to the immunologic specificity of the activated cells. Two factors may have contributed to the apparent failure of numerous previous attempts to demonstrate the capacity of transplantation immunity to affect the well-being of a fetus or, more correctly, its placenta, in the way that might be expected of a homograft. (i) Investigators were preoccupied with obtaining a classic type of rejection, in utero, analogous to the rejection of an orthotopic skin homograft. The birth of consistently healthy-looking litters, interpreted as a failure of the experiment, convinced the investigators of the efficacy of nature's solution of the homograft problem and there was no reason for them to suspect its possible limitations. Observation of the litters for several weeks might have uncovered the phenomenon of maternally induced runt disease. (ii) Most investigators resorted to hyperimmunization of the mothers. This would have facilitated the synthesis of protective isoantibodies capable of interfering with the expression of the potentially harmful cellular immune response (6). Ever since the abnormalities of runt disease were first described they have repeatedly been compared to those observed in patients with certain lymphomas (17). Various theories have been

  4. Learning-by-Being-Acquired

    DEFF Research Database (Denmark)

    Colombo, Massimo Gaetano; Moreira, Solon; Rabbiosi, Larissa


    of new teams with both inventors of the acquiring and acquired firms-and assess the impact of this integration action in the period that immediately follows the acquisition. Drawing on social identity and self-categorization theories, we argue that R&D team reorganization increases the acquired inventors......’ use of the prior stock of technological knowledge of the acquiring firm after the acquisition. Furthermore, this effect is enhanced if the focal acquired inventor has high relative innovation ability but is weakened for acquired inventors with high ingroup collaborative strength. We construct a sample...

  5. Learning-By-Being-Acquired

    DEFF Research Database (Denmark)

    Colombo, Massimo G.; Moreira, Solon; Rabbiosi, Larissa

    In this paper we study post-acquisition integration in terms of R&D team reorganization—i.e., the creation of new teams with both inventors of the acquiring and acquired firms—and assess its impact on knowledge transfer in the period that follows the acquisition. Drawing on social identity and self......-categorization theories, we argue that R&D team reorganization increases the acquired inventors’ use of the prior stock of technological knowledge of the acquiring firm after the acquisition. Furthermore, this effect is enhanced if acquired inventors have higher innovation ability relative to their acquiring peers...

  6. Iron deficiency

    DEFF Research Database (Denmark)

    Schou, Morten; Bosselmann, Helle; Gaborit, Freja


    BACKGROUND: Both iron deficiency (ID) and cardiovascular biomarkers are associated with a poor outcome in heart failure (HF). The relationship between different cardiovascular biomarkers and ID is unknown, and the true prevalence of ID in an outpatient HF clinic is probably overlooked. OBJECTIVES.......043). CONCLUSION: ID is frequent in an outpatient HF clinic. ID is not associated with cardiovascular biomarkers after adjustment for traditional confounders. Inflammation, but not neurohormonal activation is associated with ID in systolic HF. Further studies are needed to understand iron metabolism in elderly HF...

  7. Newly appreciated roles for basophils in allergy and protective immunity. (United States)

    Karasuyama, H; Obata, K; Wada, T; Tsujimura, Y; Mukai, K


    Basophils are evolutionarily conserved in many animal species, in spite of the fact that they account for basophils have an indispensable and nonredundant role in vivo, even though they show some phenotypic similarity with tissue-resident mast cells. However, their functional significance remained uncertain long after Paul Ehrlich discovered them as blood-circulating cells with basophilic granules more than 130 years ago. The study of basophils has been far behind that of mast cells, owing to the rarity of basophils and the paucity of tools for their detection and functional analysis. Recent development of novel analytical tools, including basophil-depleting antibodies and genetically engineered mice deficient only in basophils, has greatly advanced basophil research and illuminated previously unrecognized roles of basophils. We now appreciate that basophils and mast cells play distinct roles in immune responses. Basophils have crucial roles in the development of acute and chronic allergic responses, the protective immunity against ecto- and endoparasites, and the regulation of acquired immunity, including the augmentation of humoral memory responses and the initiation of Th2 responses. Thus, basophils are no longer the neglected minority and are key players in the immune system.

  8. Surgical treatment of acquired tracheocele. (United States)

    Porubsky, Edward A; Gourin, Christine G


    Acquired tracheoceles are rare clinical entities that can cause a variety of chronic and recurrent aerodigestive tract symptoms. The management of acquired tracheoceles is primarily conservative, but surgical intervention may be indicated for patients with refractory symptoms. We present a case of acquired tracheocele and describe a method of successful surgical management.

  9. Single Nutrients and Immunity (United States)


    control group, cot- vitamin C deficiencies, humoral immune re- ton- topped marmosets fed a large dietary ex- sponses do not differ appreciably from...vac- duction of interferon. They commented (61) cine (75). that "the literature in this field is bedeviled The long-term feeding of cotton- topped by...repletion: a marked numbers were also found in the lungs. sub- rebound to higher serum lgG values then maxillary glands, and lymph nodes (310). occurred over

  10. Clinical manifestation of myeloperoxidase deficiency. (United States)

    Lanza, F


    Myeloperoxidase (MPO), an iron-containing heme protein localized in the azurophilic granules of neutrophil granulocytes and in the lysosomes of monocytes, is involved in the killing of several micro-organisms and foreign cells, including bacteria, fungi, viruses, red cells, and malignant and nonmalignant nucleated cells. Despite the primary role of the oxygen-dependent MPO system in the destruction of certain phagocytosed microbes, subjects with total or partial MPO deficiency generally do not have an increased frequency of infections, probably because other MPO-independent mechanism(s) for microbicidal activity compensate for the lack of MPO. Infectious diseases, especially with species of Candida, have been observed predominantly in MPO-deficient patients who also have diabetes mellitus, but the frequency of such cases is very low, less than 5% of reported MPO-deficient subjects. Evidence from a number of investigators indicates that individuals with total MPO deficiency show a high incidence of malignant tumors. Since MPO-deficient PMNs exhibit in vitro a depressed lytic action against malignant human cells, it can be speculated that the neutrophil MPO system plays a central role in the tumor surveillance of the host. However, any definitive conclusion on the association between MPO deficiency and the occurrence of cancers needs to be confirmed in further clinical studies. Clinical manifestations of this disorder depend on the nature of the defect; an acquired abnormality associated with other hematological or nonhematological diseases has been occasionally described, but the primary deficiency is the form more commonly reported. Another area of interest pertinent to MPO expression is related to the use of anti-MPO monoclonal antibodies for the lineage assignment of acute leukemic cells, the definition of FAB MO acute myeloid leukemia, the identification of biphenotypic acute leukemias, and their distinction from acute leukemia with minimal phenotypic deviation

  11. Recombinant B domain deleted porcine factor VIII for the treatment of bleeding episodes in adults with acquired hemophilia A. (United States)

    Gomperts, Edward


    Hemophilia A is an inherited deficiency of clotting factor VIII (FVIII) often complicated by inhibitor development (CHAWI) in which neutralizing antibodies block the therapeutic benefit of replacement therapy. Inhibitors to FVIII can also be seen in an auto-immune disease known as acquired hemophilia A (AHA). 'Bypassing' therapies have been shown to provide hemostasis but dosing must be done empirically because current assays cannot measure objective markers of treatment efficacy and safety. A recombinant porcine sequence factor VIII (r-pFVIII) has been developed for the management of AHA. Preclinical, Phase I and Phase II clinical research studies in CHAWI subjects showed therapeutic potential and safety of this agent. A Phase II/III study in AHA with serious bleeding episodes shows a positive response in all subjects after administration. Based on current preclinical and clinical trial data, r-pFVIII should become the first line of treatment in the management of hemorrhage in patients with AHA.

  12. VLCAD deficiency

    DEFF Research Database (Denmark)

    Boneh, A; Andresen, B S; Gregersen, N


    -negative diagnoses of VLCADD in asymptomatic newborn babies. In view of the emerging genotype-phenotype correlation in this disorder, the information derived from mutational analysis can be helpful in designing the appropriate follow-up and therapeutic regime for these patients.......We diagnosed six newborn babies with very long-chain acyl-CoA dehydrogenase deficiency (VLCADD) through newborn screening in three years in Victoria (prevalence rate: 1:31,500). We identified seven known and two new mutations in our patients (2/6 homozygotes; 4/6 compound heterozygotes). Blood...... samples taken at age 48-72 h were diagnostic whereas repeat samples at an older age were normal in 4/6 babies. Urine analysis was normal in 5/5. We conclude that the timing of blood sampling for newborn screening is important and that it is important to perform mutation analysis to avoid false...

  13. Acquiring specific interpreting competence

    Directory of Open Access Journals (Sweden)

    Jana Zidar Forte


    Full Text Available In postgraduate interpreter training, the main objective of the course is to help trainees develop various competences, from linguistic, textual and cultural competence, to professional and specific interpreting competence. For simultaneous interpreting (SI, the main focus is on mastering the SI technique and strategies as well as on developing and strengthening communicative skills, which is discussed and illustrated with examples in the present paper. First, a brief overview is given of all the necessary competences of a professional interpreter with greater emphasis on specific interpreting competence for SI. In the second part of the paper, various approaches are described in terms of acquiring specific skills and strategies, specifically through a range of exercises. Besides interpreting entire speeches, practical courses should also consist of targeted exercises, which help trainees develop suitable coping strategies and mechanisms (later on almost automatisms, while at the same time "force" them to reflect on their individual learning process and interpreting performance. This provides a solid base on which trained interpreters can progress and develop their skills also after joining the professional sphere.

  14. Transgenesis and reverse genetics of mosquito innate immunity. (United States)

    Shin, Sang Woon; Kokoza, Vladimir A; Raikhel, Alexander S


    In recent years, mosquito molecular biology has been a scene of astounding achievements, namely the development of genetic transformation, characterization of inducible tissue-specific promoters, and acquirement of mosquito genome sequences. However, the lack of a complete genetic tool box for mosquitoes remains a serious obstacle in our ability to study essential mosquito-specific mechanisms. Unlike Drosophila, very few null mutations for mosquito genes exist. The development of reverse-genetic analyses based on RNAi and transgenic techniques will help to compensate for these deficiencies and aid in identification of critical genes in important regulatory pathways. The study of mosquito innate immunity is one example and described here. In this study, we combine mosquito transgenesis with reverse genetics. The advantage of transgenesis is the ability to establish genetically stable, dominant-negative and overexpression phenotypes. Using the blood-meal-activated vitellogenin gene (Vg) promoter, we have generated transgenic mosquitoes with blood-meal-activated, overexpressed antimicrobial peptides, Defensin A and Cecropin A. Moreover, we have recently generated a transgenic dominant-negative Relish mosquito strain, which after taking a blood meal, becomes immune-deficient to infection by Gram-negative bacteria. The latter accomplishment has opened the door to a reverse-genetic approach in mosquitoes based on transgenesis.

  15. Diabetes and risk of community-acquired Staphylococcus aureus bacteremia

    DEFF Research Database (Denmark)

    Smit, Jesper; Søgaard, Mette; Schønheyder, Henrik Carl;


    OBJECTIVE: Patients with diabetes may experience higher risk of Staphylococcus aureus bacteremia (SAB) than patients without diabetes due to decreased immunity or coexisting morbidities. We investigated the risk of community-acquired (CA) SAB in persons with and without diabetes. DESIGN: Using...

  16. Mammalian gut immunity

    Directory of Open Access Journals (Sweden)

    Benoit Chassaing


    Full Text Available The mammalian intestinal tract is the largest immune organ in the body and comprises cells from non-hemopoietic (epithelia, Paneth cells, goblet cells and hemopoietic (macrophages, dendritic cells, T-cells origin, and is also a dwelling for trillions of microbes collectively known as the microbiota. The homeostasis of this large microbial biomass is prerequisite to maintain host health by maximizing beneficial symbiotic relationships and minimizing the risks of living in such close proximity. Both microbiota and host immune system communicate with each other to mutually maintain homeostasis in what could be called a "love-hate relationship." Further, the host innate and adaptive immune arms of the immune system cooperate and compensate each other to maintain the equilibrium of a highly complex gut ecosystem in a stable and stringent fashion. Any imbalance due to innate or adaptive immune deficiency or aberrant immune response may lead to dysbiosis and low-grade to robust gut inflammation, finally resulting in metabolic diseases.

  17. Vitamin Deficiency Anemia (United States)

    Vitamin deficiency anemia Overview By Mayo Clinic Staff Vitamin deficiency anemia is a lack of healthy red ... you have lower than normal amounts of certain vitamins. Vitamins linked to vitamin deficiency anemia include folate, ...

  18. Multiple Roles of Myd88 in the Immune Response to the Plague F1-V Vaccine and in Protection against an Aerosol Challenge of Yersinia pestis CO92 in Mice

    Directory of Open Access Journals (Sweden)

    Jennifer L. Dankmeyer


    Full Text Available The current candidate vaccine against Yersinia pestis infection consists of two subunit proteins: the capsule protein or F1 protein and the low calcium response V protein or V-antigen. Little is known of the recognition of the vaccine by the host’s innate immune system and how it affects the acquired immune response to the vaccine. Thus, we vaccinated Toll-like receptor (Tlr 2, 4, and 2/4-double deficient, as well as signal adaptor protein Myd88-deficient mice. We found that Tlr4 and Myd88 appeared to be required for an optimal immune response to the F1-V vaccine but not Tlr2 when compared to wild-type mice. However, there was a difference between the requirement for Tlr4 and MyD88 in vaccinated animals. When F1-V vaccinated Tlr4 mutant (lipopolysaccharide tolerant and Myd88-deficient mice were challenged by aerosol with Y. pestis CO92, all but one Tlr4 mutant mice survived the challenge, but no vaccinated Myd88-deficient mice survived the challenge. Spleens from these latter nonsurviving mice showed that Y. pestis was not cleared from the infected mice. Our results suggest that MyD88 appears to be important for both an optimal immune response to F1-V and in protection against a lethal challenge of Y. pestis CO92 in F1-V vaccinated mice.

  19. Lower limb deficient children in The Netherlands: epidemiological aspects. (United States)

    Rijnders, L J; Boonstra, A M; Groothoff, J W; Cornel, M C; Eisma, W H


    Information on the characteristics of children with limb deficiencies and amputations in The Netherlands is largely lacking. The present study aimed to collect data about the prevalence of congenital deficiencies, the ratio of congenital to acquired limb deficiencies, types of lower leg deficiency or amputation and male/female ratios. Data were obtained from a regional birth defects registry for the northern part of The Netherlands (EUROCAT-NNL) and from a national survey. Inclusion criteria for the selection of the EUROCAT data were: children/foetuses with lower leg deficiencies born in 1981-1986. Inclusion criteria for the survey data were: children aged 1-18 years with congenital deficiencies or acquired amputations of the leg, excluding toe deficiencies/amputations. Both the regional birth defects registry and the national survey only yielded small numbers of children, which limits the validity of the authors' findings. The Eurocat data show a prevalence of lower leg deficiencies at birth of 2.07/10,000. Fifty-five (55) children/foetuses were included in the present study. The male/female ratio was 1:1. Of the live-born children, 30% also had defects of the upper limbs, while 38% had bilateral lower limb deficiencies. The national survey included 89 children, of whom 73% had congenital deficiencies, while the others had undergone amputations: of which 37% were due to malignancies, 29% to traumata, 13% to infections and 21% to other pathology. The male/female ratio was 7:3 for the children with congenital deficiencies versus 6:4 for the children with acquired amputations. In the group of congenital deficiencies, fibula deficiency was most frequently seen (36%), while in the group with acquired amputations trans-femoral amputation, knee disarticulation and trans-tibial amputation were seen with equal frequency (21%). In 40% of the children with congenital deficiency and in 8% of the children with acquired amputations the arm was also affected. Both legs were

  20. Interactions between the immune system and bone



    The relationship between the immune system, estrogen deficiency and bone loss is an intriguing and, as yet, unexplained challenge of the past two decades. Here we summarize the evidence that links immune cells, inflammation, cytokine production and osteoclast formation and activity with particular regard to humans.

  1. Self-consuming innate immunity in Arabidopsis

    DEFF Research Database (Denmark)

    Hofius, Daniel; Mundy, John; Petersen, Morten


    Programmed cell death (PCD) associated with the pathogen-induced hypersensitive response (HR) is a hallmark of plant innate immunity. HR PCD is triggered upon recognition of pathogen effector molecules by host immune receptors either directly or indirectly via effector modulation of host targets....... However, it has been unclear by which molecular mechanisms plants execute PCD during innate immune responses. We recently examined HR PCD in autophagy-deficient Arabidopsis knockout mutants (atg) and find that PCD conditioned by one class of plant innate immune receptors is suppressed in atg mutants...... with innate immune responses in eukaryotes as well as of prodeath functions for the autophagy pathway in plants....

  2. Malaria transmission model for different levels of acquired immunity and temperature-dependent parameters (vector Modelo de transmissão de malária em diferentes níveis de imunidade e de parâmetros temperatura-dependentes (vetor

    Directory of Open Access Journals (Sweden)

    Hyun M Yang


    Full Text Available OBJECTIVE: Describe the overall transmission of malaria through a compartmental model, considering the human host and mosquito vector. METHODS: A mathematical model was developed based on the following parameters: human host immunity, assuming the existence of acquired immunity and immunological memory, which boosts the protective response upon reinfection; mosquito vector, taking into account that the average period of development from egg to adult mosquito and the extrinsic incubation period of parasites (transformation of infected but non-infectious mosquitoes into infectious mosquitoes are dependent on the ambient temperature. RESULTS: The steady state equilibrium values obtained with the model allowed the calculation of the basic reproduction ratio in terms of the model's parameters. CONCLUSIONS: The model allowed the calculation of the basic reproduction ratio, one of the most important epidemiological variables.OBJETIVO: Propõe-se um modelo compartimental para descrever a transmissão de malária, levando em consideração duas populações envolvidas: o hospedeiro humano e o vetor mosquito. MÉTODOS: Desenvolveu-se um modelo matemático baseado nas seguintes características: em relação ao hospedeiro humano, assumiu-se a existência de imunidade adquirida e de memória imunológica que, em uma reinfecção, leva ao reforço da resposta imune; em relação ao vetor mosquito, levou-se em consideração que o período médio de desenvolvimento desde ovo até mosquito adulto e o período de incubação extrínseco de parasitas (transformação de mosquitos infectados mas não-infecciosos em mosquitos infecciosos são dependentes de temperatura ambiente. RESULTADOS: Foram obtidos os valores do equilíbrio no estado estacionário do modelo proposto. Da análise da estabilidade dos pontos de equilíbrio, foi determinada a razão de reprodutibilidade basal. CONCLUSÕES: Foi obtida uma variável epidemiológica importante, a razão de

  3. Role of Leptin in Immunity

    Institute of Scientific and Technical Information of China (English)

    Queenie Lai Kwan Lam; Liwei Lu


    Leptin, a protein hormone produced by the adipocytes, has long been recognized to regulate metabolism, neuroendorine and other physiological functions. Early findings of increased leptin production during infection and inflammation and dysregulated immune response in leptin signaling-deficient mice provide strong evidence for the involvement of leptin in the immune responses. Recent data have established the regulatory function for leptin in immunity similar to the function of a pro-inflammatory cytokine, while gene-targeting studies also demonstrated an essential role of leptin in regulating hematopoiesis and lymphopoiesis. Moreover, there has been increasing evidence that leptin is involved in the pathogenesis of various autoimmune diseases. This review discusses recent advances in understanding the role of leptin in immunity and leptin-signaling pathways involved in modulating immune homeostasis and autoimmune pathogenesis.

  4. Immune response (United States)

    ... and tetanus antitoxin are examples of passive immunization. BLOOD COMPONENTS The immune system includes certain types of white ... lymphocytes develop, they normally learn to tell the difference between your own body tissues and substances that ...

  5. Effects of Vitamin B6 Deficiency on the Composition and Functional Potential of T Cell Populations (United States)

    Qian, Bingjun; Shen, Shanqi; Zhang, Jianhua


    The immune system is critical in preventing infection and cancer, and malnutrition can weaken different aspects of the immune system to undermine immunity. Previous studies suggested that vitamin B6 deficiency could decrease serum antibody production with concomitant increase in IL4 expression. However, evidence on whether vitamin B6 deficiency would impair immune cell differentiation, cytokines secretion, and signal molecule expression involved in JAK/STAT signaling pathway to regulate immune response remains largely unknown. The aim of this study is to investigate the effects of vitamin B6 deficiency on the immune system through analysis of T lymphocyte differentiation, IL-2, IL-4, and INF-γ secretion, and SOCS-1 and T-bet gene transcription. We generated a vitamin B6-deficient mouse model via vitamin B6-depletion diet. The results showed that vitamin B6 deficiency retards growth, inhibits lymphocyte proliferation, and interferes with its differentiation. After ConA stimulation, vitamin B6 deficiency led to decrease in IL-2 and increase in IL-4 but had no influence on IFN-γ. Real-time PCR analysis showed that vitamin B6 deficiency downregulated T-bet and upregulated SOCS-1 transcription. This study suggested that vitamin B6 deficiency influenced the immunity in organisms. Meanwhile, the appropriate supplement of vitamin B6 could benefit immunity of the organism.

  6. Carnitine Deficiency and Pregnancy


    Anouk de Bruyn; Yves Jacquemyn; Kristof Kinget; François Eyskens


    We present two cases of carnitine deficiency in pregnancy. In our first case, systematic screening revealed L-carnitine deficiency in the first born of an asymptomatic mother. In the course of her second pregnancy, maternal carnitine levels showed a deficiency as well. In a second case, a mother known with carnitine deficiency under supplementation was followed throughout her pregnancy. Both pregnancies had an uneventful outcome. Because carnitine deficiency can have serious complications, su...

  7. In vivo mechanisms of acquired thymic tolerance

    DEFF Research Database (Denmark)

    Chen, W; Issazadeh-Navikas, Shohreh; Sayegh, M H;


    Injection of antigen into the thymus of adult animals induces specific systemic tolerance, but the mechanisms of acquired thymic tolerance are not well understood. To investigate these mechanisms we used a model of intrathymic injection of ovalbumin (OVA) in BALB/c mice. We show an antigen......-specific decrease in proliferative responses to OVA, as well as a significant decrease in antigen-specific IL-2 secretion and IFN-gamma production by splenocytes and lymph node cells of tolerant mice. Addition of recombinant IL-2 in vitro reversed the defect in IFN-gamma production by cells from OVA-tolerized...... expansion of transferred CD4+ TCR transgenic cells in tolerant mice in vivo. There was an increase in clonotype-positive T cells in the thymus after immunization, confirming that activated T cells circulate through the thymus. Furthermore, thymectomy after intrathymic injection abrogates the effect...

  8. Immunity to Diphtheria in Haemodialysis Patients


    Abdolreza S. Jahromi; Mortaza Pourahmd; Sara Azhdari; Gita Manshoori; Abdolhossain Madani; Seyed H. Moosavy


    Problem statement: The incidence of infectious diseases is increased in patients with chronic renal failure. Chronic renal failure severely influences the immune functions of the host. Diphtheria is of great epidemiological concern. Although mainly observed during childhood, unvaccinated adults and relatively immunocompromised patients are at increased risk for acquiring diphtheria. Approach: To evaluate the anti-Diphtheria immunity level in southern Iranian patients ...

  9. Acquired ichthyosis with hoffman's syndrome

    Directory of Open Access Journals (Sweden)

    Sathyanarayana B


    Full Text Available A middle aged man presented with features of acquired ichthyosis with Hoffman's syndrome. Laboratory tests support hypothyodism. Myoedema and hypertrophy of muscles were present. Patient was previously treated for Pellagra.

  10. The immune system and the impact of zinc during aging

    Directory of Open Access Journals (Sweden)

    Haase Hajo


    Full Text Available Abstract The trace element zinc is essential for the immune system, and zinc deficiency affects multiple aspects of innate and adaptive immunity. There are remarkable parallels in the immunological changes during aging and zinc deficiency, including a reduction in the activity of the thymus and thymic hormones, a shift of the T helper cell balance toward T helper type 2 cells, decreased response to vaccination, and impaired functions of innate immune cells. Many studies confirm a decline of zinc levels with age. Most of these studies do not classify the majority of elderly as zinc deficient, but even marginal zinc deprivation can affect immune function. Consequently, oral zinc supplementation demonstrates the potential to improve immunity and efficiently downregulates chronic inflammatory responses in the elderly. These data indicate that a wide prevalence of marginal zinc deficiency in elderly people may contribute to immunosenescence.

  11. The epidemiology of global micronutrient deficiencies. (United States)

    Bailey, Regan L; West, Keith P; Black, Robert E


    Micronutrients are essential to sustain life and for optimal physiological function. Widespread global micronutrient deficiencies (MNDs) exist, with pregnant women and their children under 5 years at the highest risk. Iron, iodine, folate, vitamin A, and zinc deficiencies are the most widespread MNDs, and all these MNDs are common contributors to poor growth, intellectual impairments, perinatal complications, and increased risk of morbidity and mortality. Iron deficiency is the most common MND worldwide and leads to microcytic anemia, decreased capacity for work, as well as impaired immune and endocrine function. Iodine deficiency disorder is also widespread and results in goiter, mental retardation, or reduced cognitive function. Adequate zinc is necessary for optimal immune function, and deficiency is associated with an increased incidence of diarrhea and acute respiratory infections, major causes of death in those diversification. It is widely accepted that intervention in the first 1,000 days is critical to break the cycle of malnutrition; however, a coordinated, sustainable commitment to scaling up nutrition at the global level is still needed. Understanding the epidemiology of MNDs is critical to understand what intervention strategies will work best under different conditions.

  12. In vivo anti-tumor effect of hybrid vaccine of dendritic cells and esophageal carcinoma cells on esophageal carcinoma cell line 109 in mice with severe combined immune deficiency

    Institute of Scientific and Technical Information of China (English)


    AIM: To develop a fusion vaccine of esophageal carcinoma cells and dendritic cells (DC) and observe its protective and therapeutic effect against esophageal carcinoma cell line 109 (EC109). METHODS: The fusion vaccine was produced by fusing traditional polyethyleneglycol (PEG), inducing cytokine, sorting CD34+ magnetic microbead marker and magnetic cell system (MACS). The liver, spleen and lung were pathologically tested after injection of the fusion vaccine. To study the therapeutic and protective effect of the fusion vaccine against tumor EC109, mice were divided immune group and therapeutic group. The immune group was divided into P, E, D and ED subgroups, immunized by phosphate buffered solution (PBS), inactivated EC109,DC and the fusion vaccine respectively, and attacked by EC109 cells. The tumor size, weight, latent period and mouse survival period were recorded and statistically analyzed. The therapeutic group was divided into four subgroups: P, inactivated EC109,D and ED subgroups, which were attacked by EC109 and then treated with PBS, inactivated EC109,DC,and EC109-DC respectively. Pathology and flow cytometry were also used to study the therapeutic effect of the fusion vaccine against EC109 cells. RESULTS: Flow cytometry showed that the expression of folate receptor (FR), EC109, D Cs (D) in human nasopharyngeal carcinoma cell line (HNE1) (B) was 78.21%,89.50%,and 0.18%,respectively.The fusion cells were highly expressed. No tumor was found in the spleen, lung and liver after injection of the fusion vaccine. Human IgG was tested in peripheral blood lymphocytes (PBL). In the immune group, the latent period was longer in EC109-DC subgroup than in other subgroups, while the tumor size and weight were also smaller than those in ED subgroup. In the therapeutic group, the tumor size and weight were smaller in ED subgroup than in P, inactivated EC109 and DC subgroups. CONCLUSION: Fusion cells are highly expressed not only in FR but also in CD80.The fusion

  13. Somatically acquired structural genetic differences

    DEFF Research Database (Denmark)

    Magaard Koldby, Kristina; Nygaard, Marianne; Christensen, Kaare;


    Structural genetic variants like copy number variants (CNVs) comprise a large part of human genetic variation and may be inherited as well as somatically acquired. Recent studies have reported the presence of somatically acquired structural variants in the human genome and it has been suggested t...... with age.European Journal of Human Genetics advance online publication, 20 April 2016; doi:10.1038/ejhg.2016.34.......Structural genetic variants like copy number variants (CNVs) comprise a large part of human genetic variation and may be inherited as well as somatically acquired. Recent studies have reported the presence of somatically acquired structural variants in the human genome and it has been suggested...... that they may accumulate in elderly individuals. To further explore the presence and the age-related acquisition of somatic structural variants in the human genome, we investigated CNVs acquired over a period of 10 years in 86 elderly Danish twins as well as CNV discordances between co-twins of 18 monozygotic...

  14. Folate-deficiency anemia (United States)

    ... Folate-deficiency anemia To use the sharing features on this page, please enable JavaScript. Folate-deficiency anemia is a decrease in red blood cells (anemia) ...

  15. Anemia - B12 deficiency (United States)

    ... page: // Vitamin B12 deficiency anemia To use the sharing features on ... tissues. There are many types of anemia. Vitamin B12 deficiency anemia is a low red blood cell ...

  16. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... or an inability to absorb enough iron from food. Overview Iron-deficiency anemia is a common type ... of the condition. Treatments may include dietary changes, medicines, and surgery. Severe iron-deficiency anemia may require ...

  17. Characterization of a Pipecolic Acid Biosynthesis Pathway Required for Systemic Acquired Resistance. (United States)

    Ding, Pingtao; Rekhter, Dmitrij; Ding, Yuli; Feussner, Kirstin; Busta, Lucas; Haroth, Sven; Xu, Shaohua; Li, Xin; Jetter, Reinhard; Feussner, Ivo; Zhang, Yuelin


    Systemic acquired resistance (SAR) is an immune response induced in the distal parts of plants following defense activation in local tissue. Pipecolic acid (Pip) accumulation orchestrates SAR and local resistance responses. Here, we report the identification and characterization of SAR-DEFICIENT4 (SARD4), which encodes a critical enzyme for Pip biosynthesis in Arabidopsis thaliana Loss of function of SARD4 leads to reduced Pip levels and accumulation of a Pip precursor, Δ(1)-piperideine-2-carboxylic acid (P2C). In Escherichia coli, expression of the aminotransferase ALD1 leads to production of P2C and addition of SARD4 results in Pip production, suggesting that a Pip biosynthesis pathway can be reconstituted in bacteria by coexpression of ALD1 and SARD4. In vitro experiments showed that ALD1 can use l-lysine as a substrate to produce P2C and P2C is converted to Pip by SARD4. Analysis of sard4 mutant plants showed that SARD4 is required for SAR as well as enhanced pathogen resistance conditioned by overexpression of the SAR regulator FLAVIN-DEPENDENT MONOOXYGENASE1. Compared with the wild type, pathogen-induced Pip accumulation is only modestly reduced in the local tissue of sard4 mutant plants, but it is below detection in distal leaves, suggesting that Pip is synthesized in systemic tissue by SARD4-mediated reduction of P2C and biosynthesis of Pip in systemic tissue contributes to SAR establishment.

  18. Battlefield Acquired Immunogenicity to Metals Affects Orthopaedic Implant Outcome (United States)


    Award Number: W81XWH-10-2-0138 TITLE: "Battlefield-Acquired Immunogenicity to Metals Affects Orthopaedic Implant Outcome." PRINCIPAL...Orthopaedic Implant Outcome." 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Nadim James Hallab, PhD 5d. PROJECT NUMBER 5e. TASK NUMBER 5f...battlefield injuries resulting in increased exposure to metal may sensitize individuals and lead to excessive immune responses to orthopedic implants

  19. Spatial and temporal regulation of biosynthesis of the plant immune signal salicylic acid. (United States)

    Zheng, Xiao-Yu; Zhou, Mian; Yoo, Heejin; Pruneda-Paz, Jose L; Spivey, Natalie Weaver; Kay, Steve A; Dong, Xinnian


    The plant hormone salicylic acid (SA) is essential for local defense and systemic acquired resistance (SAR). When plants, such as Arabidopsis, are challenged by different pathogens, an increase in SA biosynthesis generally occurs through transcriptional induction of the key synthetic enzyme isochorismate synthase 1 (ICS1). However, the regulatory mechanism for this induction is poorly understood. Using a yeast one-hybrid screen, we identified two transcription factors (TFs), NTM1-like 9 (NTL9) and CCA1 hiking expedition (CHE), as activators of ICS1 during specific immune responses. NTL9 is essential for inducing ICS1 and two other SA synthesis-related genes, phytoalexin-deficient 4 (PAD4) and enhanced disease susceptibility 1 (EDS1), in guard cells that form stomata. Stomata can quickly close upon challenge to block pathogen entry. This stomatal immunity requires ICS1 and the SA signaling pathway. In the ntl9 mutant, this response is defective and can be rescued by exogenous application of SA, indicating that NTL9-mediated SA synthesis is essential for stomatal immunity. CHE, the second identified TF, is a central circadian clock oscillator and is required not only for the daily oscillation in SA levels but also for the pathogen-induced SA synthesis in systemic tissues during SAR. CHE may also regulate ICS1 through the known transcription activators calmodulin binding protein 60g (CBP60g) and systemic acquired resistance deficient 1 (SARD1) because induction of these TF genes is compromised in the che-2 mutant. Our study shows that SA biosynthesis is regulated by multiple TFs in a spatial and temporal manner and therefore fills a gap in the signal transduction pathway between pathogen recognition and SA production.

  20. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... the NHLBI on Twitter. What Is Iron-Deficiency Anemia? Español Iron-deficiency anemia is a common, easily ... Featured Video Living With and Managing Iron-Deficiency Anemia 05/18/2011 This video—presented by the ...

  1. Iron-Deficiency Anemia (United States)

    ... the NHLBI on Twitter. What Is Iron-Deficiency Anemia? Español Iron-deficiency anemia is a common, easily ... Featured Video Living With and Managing Iron-Deficiency Anemia 05/18/2011 This video—presented by the ...

  2. Iron-Deficiency Anemia (United States)

    ... page from the NHLBI on Twitter. What Is Iron-Deficiency Anemia? Español Iron-deficiency anemia is a common, ... Content: NEXT >> Featured Video Living With and Managing Iron-Deficiency Anemia 05/18/2011 This video—presented by ...

  3. Folate deficiency and neurological disorders in adults. (United States)

    Botez, M I


    The restless legs syndrome could represent a folate responsive disorder in both patients with acquired-folate deficiency and those with familial symptomatology. Patients with acquired folate-deficiency could be divided into two subgroups. (i) those with minor neurological signs (restless legs syndrome, vibration sense impairment and tactile hypoesthesia in both legs with diminished ankle jerks and a prolonged or assymetrical Achilles-reflex time) and (ii) those with major neurological signs (subacute combined degeneration with or without neuropathies). In some of these patients the classical triad of the malabsorption syndrome is replaced by another triad, constipation, abnormal jejunal biopsy and abnormal d-xylose absorption. A low folic serum acid level could induce minor neuropsychiatric symptoms while an additional low CSF folate could induce major neurological symptoms in spite of the presence of a normal erythrocyte folate level and in the absence of frank anemia. Possible further studies are described.

  4. Community-acquired pneumonia in older patients: does age influence systemic cytokine levels in community-acquired pneumonia?

    LENUS (Irish Health Repository)

    Kelly, Emer


    Community-acquired pneumonia (CAP) is a major cause of death in the elderly. The age-related increase in comorbid illnesses plays a part but the effect of aging on the immune response may be equally important. We aimed to evaluate patients with CAP for evidence of a muted response to infection in elderly patients admitted to hospital compared with a younger patient group.

  5. Infections Revealing Complement Deficiency in Adults (United States)

    Audemard-Verger, A.; Descloux, E.; Ponard, D.; Deroux, A.; Fantin, B.; Fieschi, C.; John, M.; Bouldouyre, A.; Karkowsi, L.; Moulis, G.; Auvinet, H.; Valla, F.; Lechiche, C.; Davido, B.; Martinot, M.; Biron, C.; Lucht, F.; Asseray, N.; Froissart, A.; Buzelé, R.; Perlat, A.; Boutboul, D.; Fremeaux-Bacchi, V.; Isnard, S.; Bienvenu, B.


    Abstract Complement system is a part of innate immunity, its main function is to protect human from bacterial infection. As genetic disorders, complement deficiencies are often diagnosed in pediatric population. However, complement deficiencies can also be revealed in adults but have been poorly investigated. Herein, we describe a case series of infections revealing complement deficiency in adults to study clinical spectrum and management of complement deficiencies. A nationwide retrospective study was conducted in French university and general hospitals in departments of internal medicine, infectious diseases enrolling patients older than 15 years old who had presented at least one infection leading to a complement deficiency diagnosis. Forty-one patients included between 2002 and 2015 in 19 different departments were enrolled in this study. The male-to-female ratio was 1.3 and the mean age at diagnosis was 28 ± 14 (15–67) years. The main clinical feature was Neisseria meningitidis meningitis 75% (n = 31/41) often involving rare serotype: Y (n = 9) and W 135 (n = 7). The main complement deficiency observed was the common final pathway deficiency 83% (n = 34/41). Half of the cohort displayed severe sepsis or septic shock at diagnosis (n = 22/41) but no patient died. No patient had family history of complement deficiency. The mean follow-up was 1.15 ± 1.95 (0.1–10) years. Half of the patients had already suffered from at least one infection before diagnosis of complement deficiency: meningitis (n = 13), pneumonia (n = 4), fulminans purpura (n = 1), or recurrent otitis (n = 1). Near one-third (n = 10/39) had received prophylactic antibiotics (cotrimoxazole or penicillin) after diagnosis of complement deficiency. The vaccination coverage rate, at the end of the follow-up, for N meningitidis, Streptococcus pneumonia, and Haemophilius influenzae were, respectively, 90% (n = 33/37), 47% (n = 17/36), and 35

  6. Immune System

    NARCIS (Netherlands)

    Kuper, C.F.; Ruehl-Fehlert, C.; Elmore, S.A.; Parker, G.A.


    Cells of the immune system are found in every organ, from the classic lymphoid organs to tissues such as liver, mucosae, and omental adipose tissue. Toxicity to the immune system may be from a direct or indirect injury to lymphoid organs. The morphological responses range from lymphocyte depletion t

  7. Carnitine Deficiency and Pregnancy

    Directory of Open Access Journals (Sweden)

    Anouk de Bruyn


    Full Text Available We present two cases of carnitine deficiency in pregnancy. In our first case, systematic screening revealed L-carnitine deficiency in the first born of an asymptomatic mother. In the course of her second pregnancy, maternal carnitine levels showed a deficiency as well. In a second case, a mother known with carnitine deficiency under supplementation was followed throughout her pregnancy. Both pregnancies had an uneventful outcome. Because carnitine deficiency can have serious complications, supplementation with carnitine is advised. This supplementation should be continued throughout pregnancy according to plasma concentrations.

  8. Acquired aplastic anemia in children. (United States)

    Hartung, Helge D; Olson, Timothy S; Bessler, Monica


    This article provides a practice-based and concise review of the etiology, diagnosis, and management of acquired aplastic anemia in children. Bone marrow transplantation, immunosuppressive therapy, and supportive care are discussed in detail. The aim is to provide the clinician with a better understanding of the disease and to offer guidelines for the management of children with this uncommon yet serious disorder.

  9. The immune response to Trypanoplasma borreli: kinetics of immune gene expression and polyclonal lymphocyte activation

    NARCIS (Netherlands)

    Saeij, J.P.J.; Vries, de B.J.; Wiegertjes, G.F.


    Although Trypanoplasma borreli induces the production of non-specific antibodies, survival of infection is associated with the production of T. borreli specific antibodies, able to lyse this parasite in the presence of complement. During the lag phase of this acquired immune response, innate immune

  10. Multispectral Analysis of Color Vision Deficiency Tests

    Directory of Open Access Journals (Sweden)

    Sergejs FOMINS


    Full Text Available Color deficiency tests are usually produced by means of polygraphy technologies and help to diagnose the type and severity of the color deficiencies. Due to different factors, as lighting conditions or age of the test, standard characteristics of these tests fail, thus not allowing diagnosing unambiguously the degree of different color deficiency. Multispectral camera was used to acquire the spectral images of the Ishihara and Rabkin pseudoisochromatic plates in the visible spectrum. Spectral data was converted to cone signals, and successive mathematics applied to provide a simple simulation of the test performance. Colorimetric data of the each pixel of the test image can be calculated and distribution of color coordinates is presented.

  11. Sneddon syndrome associated with Protein S deficiency

    Directory of Open Access Journals (Sweden)

    Refah Sayin


    Full Text Available Sneddon syndrome (SS is rare, arterio-occlusive disorder characterized by generalized livedo racemosa of the skin and various central nervous symptoms due to occlusion of medium-sized arteries of unknown. Seizure, cognitive impairment, hypertension, and history of repetitive miscarriages are the other symptoms seen in this disease. Livedo racemosa involves persisting irreversible skin lesions red or blue in color with irregular margins. Usually, SS occurs in women of childbearing age. Protein S deficiency is an inherited or acquired disorder associated with an increased risk of thrombosis. We present a 33-year-old woman with SS with diffuse livedo racemosa, recurrent cerebrovascular diseases, migraine-type headache, sinus vein thrombosis, and protein S deficiency. Protein S deficiency and with Sneddon syndrome rarely encountered in the literature.

  12. Sneddon syndrome associated with Protein S deficiency. (United States)

    Sayin, Refah; Bilgili, Serap Gunes; Karadag, Ayse Serap; Tombul, Temel


    Sneddon syndrome (SS) is rare, arterio-occlusive disorder characterized by generalized livedo racemosa of the skin and various central nervous symptoms due to occlusion of medium-sized arteries of unknown. Seizure, cognitive impairment, hypertension, and history of repetitive miscarriages are the other symptoms seen in this disease. Livedo racemosa involves persisting irreversible skin lesions red or blue in color with irregular margins. Usually, SS occurs in women of childbearing age. Protein S deficiency is an inherited or acquired disorder associated with an increased risk of thrombosis. We present a 33-year-old woman with SS with diffuse livedo racemosa, recurrent cerebrovascular diseases, migraine-type headache, sinus vein thrombosis, and protein S deficiency. Protein S deficiency and with Sneddon syndrome rarely encountered in the literature.

  13. Extrinsic allergic alveolitis with IgA deficiency. (United States)

    Sennekamp, J; Morr, H; Behr, J


    Up to now only 3 cases of extrinsic allergic alveolitis (hypersensitivity pneumonitis) with IgA deficiency have been published worldwide. We had the opportunity to detect two additional cases which will be presented here. Summarizing all cases IgA deficiency is a risk factor for a severe course of the disease and an increased susceptibility to acquire allergic alveolitis by low dose antigen exposure.

  14. Etiology of growth hormone deficiency in children and adolescents

    Directory of Open Access Journals (Sweden)

    Mitrović Katarina


    Full Text Available Introduction. Growth hormone deficiency (GHD can be isolated or associated with deficiency of other pituitary gland hormones. According to age at diagnosis, causes of GHD are divided into congenital or acquired, and according to etiology into recognized and unknown. Objective. We analyzed etiology and prevalence of GHD, demographic data at birth, age, body height (BH and bone age at diagnosis as well as the frequency of other pituitary hormone deficiencies. Methods. The study involved 164 patients (109 male. The main criterion for the diagnosis of GHD was inadequate response of GH after two stimulation tests. The patients were classified into three groups: idiopathic, congenital and acquired GHD. Results. Idiopathic GHD was confirmed in 57.9% of patients, congenital in 11.6% and acquired in 30.5%. The mean age at diagnosis of GHD was 10.1±4.5 years. The patients with congenital GHD had most severe growth retardation (-3.4±1.4 SDS, while the patients with idiopathic GHD showed most prominent bone delay (-3.6±2.3 SDS. The prevalence of multiple pituitary hormone deficiency was 56.1%, in the group with congenital GHD 73.7%, acquired GHD 54.0% and idiopathic GHD 53.7%. The frequency of thyrotropin deficiency ranged from 88.2-100%, of adrenocorticotrophin 57.1-68.8% and of gonadotrophins deficiency 57.1- 63.0%, while deficiency of antidiuretic hormone was 2.0-25.0%. Conclusion. Although regular BH measurements enable early recognition of growth retardation, patients’ mean age and degree of growth retardation indicate that GHD is still diagnosed relatively late. A high incidence of other pituitary hormone deficiencies requires a detailed investigation of the etiology of disorders and evaluation of all pituitary functions in each child with confirmed GHD.

  15. Laryngeal Spasm Mimicking Asthma and Vitamin D Deficiency


    Masoero, Monica; Bellocchia, Michela; Ciuffreda, Antonio; Ricciardolo, Fabio LM; Rolla, Giovanni; Bucca, Caterina


    We present a woman with heterozygous carnitine palmitoyl transferase 2 (CPT-2) deficiency who in the last 6 months suffered from episodic dyspnea and choking. Symptoms could not be attributed to her muscular energy defect, since heterozygous CPT-2 deficiency is usually asymptomatic or causes only mild muscle fatigability. Myopathy is usually triggered by concurrent factors, either genetic (additional muscle enzymes defects) or acquired (metabolic stress). The patient was referred to our respi...

  16. Sculpting humoral immunity through dengue vaccination to enhance protective immunity

    Directory of Open Access Journals (Sweden)

    Wayne eCrill


    Full Text Available Dengue viruses (DENV are the most important mosquito transmitted viral pathogens infecting humans. DENV infection produces a spectrum of disease, most commonly causing a self-limiting flu-like illness known as dengue fever; yet with increased frequency, manifesting as life-threatening dengue hemorrhagic fever (DHF. Waning cross-protective immunity from any of the four dengue serotypes may enhance subsequent infection with another heterologous serotype to increase the probability of DHF. Decades of effort to develop dengue vaccines are reaching the finishing line with multiple candidates in clinical trials. Nevertheless, concerns remain that imbalanced immunity, due to the prolonged prime-boost schedules currently used in clinical trials, could leave some vaccinees temporarily unprotected or with increased susceptibility to enhanced disease. Here we develop a DENV serotype 1 (DENV-1 DNA vaccine with the immunodominant cross-reactive B cell epitopes associated with immune enhancement removed. We compare wild-type (WT with this cross-reactivity reduced (CRR vaccine and demonstrate that both vaccines are equally protective against lethal homologous DENV-1 challenge. Under conditions mimicking natural exposure prior to acquiring protective immunity, WT vaccinated mice enhanced a normally sub-lethal heterologous DENV-2 infection resulting in DHF-like disease and 95% mortality in AG129 mice. However, CRR vaccinated mice exhibited redirected serotype-specific and protective immunity, and significantly reduced morbidity and mortality not differing from naïve mice. Thus, we demonstrate in an in vivo DENV disease model, that non-protective vaccine-induced immunity can prime vaccinees for enhanced DHF-like disease and that CRR DNA immunization significantly reduces this potential vaccine safety concern. The sculpting of immune memory by the modified vaccine and resulting redirection of humoral immunity provide insight into DENV vaccine induced immune

  17. Nursing home-acquired pneumonia. (United States)

    El Solh, Ali A


    Nursing home-acquired pneumonia (NHAP) was first described in 1978. Since then there has been much written regarding NHAP and its management despite the lack of well-designed studies in this patient population. The most characteristic features of patients with NHAP are the atypical presentation, which may lead to delay in diagnosis and therapy. The microbial etiology of pneumonia encompasses a wide spectrum that spans microbes recovered from patients with community-acquired pneumonia to organisms considered specific only to nosocomial settings. Decision to transfer a nursing home patient to an acute care facility depends on a host of factors, which include the level of staffing available at the nursing home, patients' advance directives, and complexity of treatment. The presence of risk factors for multidrug-resistant pathogens dictates approach to therapy. Prevention remains the cornerstone of reducing the incidence of disease. Despite the advance in medical services, mortality from NHAP remains high.

  18. Occupationally Acquired American Cutaneous Leishmaniasis

    Directory of Open Access Journals (Sweden)

    Maria Edileuza Felinto de Brito


    Full Text Available We report two occupationally acquired cases of American cutaneous leishmaniasis (ACL: one accidental laboratory autoinoculation by contaminated needlestick while handling an ACL lesion sample, and one acquired during field studies on bird biology. Polymerase chain reaction (PCR assays of patient lesions were positive for Leishmania, subgenus Viannia. One isolate was obtained by culture (from patient 2 biopsy samples and characterized as Leishmania (Viannia naiffi through an indirect immunofluorescence assay (IFA with species-specific monoclonal antibodies (mAbs and by multilocus enzyme electrophoresis (MLEE. Patients were successfully treated with N-methyl-glucamine. These two cases highlight the potential risks of laboratory and field work and the need to comply with strict biosafety procedures in daily routines. The swab collection method, coupled with PCR detection, has greatly improved ACL laboratory diagnosis.

  19. CNOOC Acquires Oversea Assets Successfully

    Institute of Scientific and Technical Information of China (English)

    Hu Senlin


    @@ After last year CNOOC's bidding for buy the US energy company Unocal Corp lost out to the Chevron Corporation, it conducted the crossing-border asset-acquirement again in the beginning of this year. On Jan. 9, 2006,CNOOC Ltd signed a definitive agreement with Nigeria South Atlantic Petroleum Limited (SAPETRO) to acquire a 45 % working interest in an offshore oil developing license OML 130 in Nigeria for US$2.268 billion cash. The purchase will be funded by the internal capital resources of CNOOC Ltd. In which, US$1.75 billion will pay for buying SAPETRO, and the remaining cash will be used to pay for the early operation cost.

  20. Gender affects skin wound healing in plasminogen deficient mice

    DEFF Research Database (Denmark)

    Rønø, Birgitte; Engelholm, Lars Henning; Lund, Leif Røge;


    functional plasmin thus display decreased tumor growth in a variety of cancer models. Interestingly, this role of plasmin has, in regard to skin cancer, been shown to be restricted to male mice. It remains to be clarified whether gender also affects other phenotypic characteristics of plasmin deficiency...... or if this gender effect is restricted to skin cancer. To investigate this, we tested the effect of gender on plasmin dependent immune cell migration, accumulation of hepatic fibrin depositions, skin composition, and skin wound healing. Gender did not affect immune cell migration or hepatic fibrin accumulation...... in neither wildtype nor plasmin deficient mice, and the existing differences in skin composition between males and females were unaffected by plasmin deficiency. In contrast, gender had a marked effect on the ability of plasmin deficient mice to heal skin wounds, which was seen as an accelerated wound...

  1. [Acquired disorders of color vision]. (United States)

    Lascu, Lidia; Balaş, Mihaela


    This article is a general view of acquired disorders of color vision. The revision of the best known methods and of the etiopathogenic classification is not very important in ophthalmology but on the other hand, the detection of the blue defect advertise and associated ocular pathology. There is a major interest in serious diseases as multiple sclerosis, AIDS, diabetes melitus, when the first ocular sign can be a defect in the color vision.

  2. Renal AA amyloidosis in a patient with hereditary complete complement C4 deficiency

    Directory of Open Access Journals (Sweden)

    Imed Helal


    Full Text Available Hereditary complete C4 deficiency has until now been reported in 30 cases only. A disturbed clearance of immune- complexes probably predisposes these individuals to systemic lupus erythematosus, other immune- complex diseases and recurrent microbial infections. We present here a 20- year- old female with hereditary complete C4 deficiency. Renal biopsy demonstrated renal AA amyloidosis. This unique case further substantiates that deficiency of classical pathway components predisposes to the development of recurrent microbial infections and that the patients may develop AA amyloidosis. Furthermore, in clinical practice, the nephrotic syndrome occurring in a patient with hereditary complete complement C4 deficiency should lead to the suspicion of renal AA amyloidosis.

  3. Vitamin D and the Immune System


    Aranow, Cynthia


    It is now clear that vitamin D has important roles in addition to its classic effects on calcium and bone homeostasis. As the vitamin D receptor is expressed on immune cells (B cells, T cells and antigen presenting cells) and these immunologic cells are all are capable of synthesizing the active vitamin D metabolite, vitamin D has the capability of acting in an autocrine manner in a local immunologic milieu. Vitamin D can modulate the innate and adaptive immune responses. Deficiency in vitami...

  4. The essential detail: the genetics and genomics of the primate immune response. (United States)

    Shen, Shu; Pyo, Chul-Woo; Vu, Quyen; Wang, Ruihan; Geraghty, Daniel E


    Next-generation sequencing technologies have led to rapid progress in the fields of human and nonhuman primate (NHP) genomics. The less expensive and more efficient technologies have enabled the sequencing of human genomes from multiple populations and the sequencing of many NHP species. NHP genomes have been sequenced for two main reasons: (1) their importance as animal models in biomedical research and (2) their phylogenetic relationship to humans and use in derivative evolutionary studies. NHPs are valuable animal models for a variety of diseases, most notably for human immunodeficiency virus/acquired immunodeficiency syndrome research, and for vaccine development. Knowledge about the variation in primate immune response loci can provide essential insights into relevant immune function. However, perhaps ironically considering their central role in infectious disease, the accumulation of sequence detail from genomic regions harboring immune response loci, such as the major histocompatibility complex and killer immunoglobulin-like receptors, has been slow. This deficiency is, at least in part, due to the highly repetitive and polymorphic nature of these regions and is being addressed by the application of special approaches to targeted sequencing of the immune response genomic regions. We discuss one such targeting approach that has successfully yielded complete phased genomic sequences from complex genomic regions and is now being used to resequence macaque and other primate major histocompatibility complex regions. The essential detail contained within the genomics of the NHP immune response is now being assembled, and the realization of precise comparisons between NHP and human immune genomics is close at hand, further enhancing the NHP animal model in the search for effective treatments for human disease.

  5. Acquired antiprothrombin antibodies: an unusual cause of bleeding. (United States)

    Carvalho, Cristiana; Viveiro, Carolina; Maia, Paulo; Rezende, Teresa


    Acquired inhibitors of coagulation causing bleeding manifestations are rare in children. They emerge, normally in the context of autoimmune diseases or drug ingestion, but transient and self-limiting cases can occur after viral infection. We describe, an otherwise healthy, 7-year-old girl who had gingival bleeding after a tooth extraction. The prothrombin time (PT) and the activated partial thromboplastin time (APTT) were both prolonged with evidence of an immediate acting inhibitor (lupic anticoagulant). Further coagulation studies demonstrated prothrombin (FII) deficiency and prothrombin directed (FII) antibodies. The serological tests to detect an underlying autoimmune disease were all negative. The coagulation studies normalised alongside the disappearance of the antibody. This article presents lupus anticoagulant hypoprothrombinaemia syndrome (LAHS) as a rare case of acquired bleeding diathesis in childhood.

  6. Diagnosis and treatment of chronic acquired demyelinating polyneuropathies. (United States)

    Latov, Norman


    Chronic neuropathies are operationally classified as primarily demyelinating or axonal, on the basis of electrodiagnostic or pathological criteria. Demyelinating neuropathies are further classified as hereditary or acquired-this distinction is important, because the acquired neuropathies are immune-mediated and, thus, amenable to treatment. The acquired chronic demyelinating neuropathies include chronic inflammatory demyelinating polyneuropathy (CIDP), neuropathy associated with monoclonal IgM antibodies to myelin-associated glycoprotein (MAG; anti-MAG neuropathy), multifocal motor neuropathy (MMN), and POEMS syndrome. They have characteristic--though overlapping--clinical presentations, are mediated by distinct immune mechanisms, and respond to different therapies. CIDP is the default diagnosis if the neuropathy is demyelinating and no other cause is found. Anti-MAG neuropathy is diagnosed on the basis of the presence of anti-MAG antibodies, MMN is characterized by multifocal weakness and motor conduction blocks, and POEMS syndrome is associated with IgG or IgA λ-type monoclonal gammopathy and osteosclerotic myeloma. The correct diagnosis, however, can be difficult to make in patients with atypical or overlapping presentations, or nondefinitive laboratory studies. First-line treatments include intravenous immunoglobulin (IVIg), corticosteroids or plasmapheresis for CIDP; IVIg for MMN; rituximab for anti-MAG neuropathy; and irradiation or chemotherapy for POEMS syndrome. A correct diagnosis is required for choosing the appropriate treatment, with the aim of preventing progressive neuropathy.

  7. Pneumonia acquired in the Community

    Directory of Open Access Journals (Sweden)

    María Caridad Fragoso Marchante


    Full Text Available A bibliographical revision of the main aspects in the diagnosis and treatment of the patients suffering from pneumonia acquired in the community is carried out. Microorganisms responsible for this type of pneumonia are mention in this paper as well as the available diagnostic methods for germs isolation. Different guidelines for diagnosis and treatment of this disease published by several medical societies and scientific institutions are analyzed by means of a review of the stratification index of the patients used in each of them. Aspects related to the duration of the treatment and the possible causes associated with the unfavorable evolution are stated.

  8. Deficiently Extremal Gorenstein Algebras

    Indian Academy of Sciences (India)

    Pavinder Singh


    The aim of this article is to study the homological properties of deficiently extremal Gorenstein algebras. We prove that if / is an odd deficiently extremal Gorenstein algebra with pure minimal free resolution, then the codimension of / must be odd. As an application, the structure of pure minimal free resolution of a nearly extremal Gorenstein algebra is obtained.

  9. Iron deficiency anemia (United States)

    Anemia - iron deficiency ... iron from old red blood cells. Iron deficiency anemia develops when your body's iron stores run low. ... You may have no symptoms if the anemia is mild. Most of the time, ... slowly. Symptoms may include: Feeling weak or tired more often ...

  10. Muscle phosphorylase kinase deficiency

    DEFF Research Database (Denmark)

    Preisler, N; Orngreen, M C; Echaniz-Laguna, A;


    To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD).......To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD)....

  11. Iron induced nickel deficiency (United States)

    It is increasingly apparent that economic loss due to nickel (Ni) deficiency likely occurs in horticultural and agronomic crops. While most soils contain sufficient Ni to meet crop requirements, situations of Ni deficiency can arise due to antagonistic interactions with other metals. This study asse...

  12. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Blood Tests Blood Transfusion Restless Legs Syndrome Send a link to NHLBI to someone by E-MAIL | ... Iron-Deficiency Anemia? Español Iron-deficiency anemia is a common, easily treated condition that occurs if you ...

  13. Nutritional iron deficiency

    NARCIS (Netherlands)

    Zimmermann, M.B.; Hurrell, R.F.


    Iron deficiency is one of the leading risk factors for disability and death worldwide, affecting an estimated 2 billion people. Nutritional iron deficiency arises when physiological requirements cannot be met by iron absorption from diet. Dietary iron bioavailability is low in populations consuming

  14. Free-living amoebae: pathogenicity and immunity. (United States)

    Ferrante, A


    Free-living amoebae causes three well-defined disease entities: (i) primary amoebic meningoencephalitis, caused by Naegleria fowleri, (ii) granulomatous amoebic encephalitis and (iii) chronic amoebic keratitis, caused by species of Acanthamoeba. Both Naegleria infections and chronic amoebic keratitis occur in healthy individuals while granulomatous amoebic encephalitis is often associated with patients with acquired immunodeficiencies. The different pathogenic behaviour of these organisms is associated with differences in life cycle, amoeboidal locomotion, enzyme composition (such as phospholipase A), and cytotoxins, as well as natural host immunity. Immunity against these amoebae (whether acquired or natural) involves a combination of complement, antibody and cell-mediated immunity. Evidence suggests that the major mechanisms of immunity against these amoebae is activation of phagocytic cells, especially neutrophils, by lymphokines and opsonization of the amoebae by antibody which promote an antibody dependent cellular destruction of the organism.

  15. Candida Immunity

    Directory of Open Access Journals (Sweden)

    Julian R. Naglik


    Full Text Available The human pathogenic fungus Candida albicans is the predominant cause of both superficial and invasive forms of candidiasis. C. albicans primarily infects immunocompromised individuals as a result of either immunodeficiency or intervention therapy, which highlights the importance of host immune defences in preventing fungal infections. The host defence system utilises a vast communication network of cells, proteins, and chemical signals distributed in blood and tissues, which constitute innate and adaptive immunity. Over the last decade the identity of many key molecules mediating host defence against C. albicans has been identified. This review will discuss how the host recognises this fungus, the events induced by fungal cells, and the host innate and adaptive immune defences that ultimately resolve C. albicans infections during health.

  16. Foodborne listeriosis acquired in hospitals. (United States)

    Silk, Benjamin J; McCoy, Morgan H; Iwamoto, Martha; Griffin, Patricia M


    Listeriosis is characterized by bacteremia or meningitis. We searched for listeriosis case series and outbreak investigations published in English by 2013, and assessed the strength of evidence for foodborne acquisition among patients who ate hospital food. We identified 30 reports from 13 countries. Among the case series, the median proportion of cases considered to be hospital-acquired was 25% (range, 9%-67%). The median number of outbreak-related illnesses considered to be hospital-acquired was 4.0 (range, 2-16). All patients were immunosuppressed in 18 of 24 (75%) reports with available data. Eight outbreak reports with strong evidence for foodborne acquisition in a hospital implicated sandwiches (3 reports), butter, precut celery, Camembert cheese, sausage, and tuna salad (1 report each). Foodborne acquisition of listeriosis among hospitalized patients is well documented internationally. The number of listeriosis cases could be reduced substantially by establishing hospital policies for safe food preparation for immunocompromised patients and by not serving them higher-risk foods.

  17. Pruritic acquired nevus of Ota. (United States)

    Quenan, S; Strueven, V; Saxer, N; Laffitte, E; Kaya, G; Krischer, J; Hafezi, F; Le Gal, F-A


    Nevus of Ota is a unilateral, asymptomatic cutaneous and mucosal hyperpigmentation of the face that is congenital or may appear during childhood. We present a case of symptomatic acquired nevus of Ota in an adult, associated with intense pruritus, not described in the literature so far. A 32-year-old woman presented with brownish mottled macules which appeared on her face progressively over 8 days, following the distribution of the first and second divisions of the left trigeminal nerve and partially covering the iris and sclera of the left eye. She reported an intense pruritus in this area. We performed a biopsy on the left forehead, which confirmed the diagnosis of nevus of Ota. Specific stains and immunohistochemistry revealed increased numbers of mast cells. Ophthalmological tests showed acute acquired melanocytosis of the left iris and sclera. The origin of the nevus is still unclear. Several hypotheses suggest a reactivation of melanocytes during their migration from the neural crest. The pruritus reported in our patient may be explained by the increased quantity of mast cells observed in the lesion and/or neuronal stimulation of the ophthalmic and maxillary divisions of the fifth cranial nerve.

  18. Correlates of Immunity to Filovirus Infection

    Directory of Open Access Journals (Sweden)

    Sina Bavari


    Full Text Available Filoviruses can cause severe, often fatal hemorrhagic fever in humans. Recent advances in vaccine and therapeutic drug development have provided encouraging data concerning treatment of these infections. However, relatively little is known about immune responses in fatal versus non-fatal filovirus infection. This review summarizes the published literature on correlates of immunity to filovirus infection, and highlights deficiencies in our knowledge on this topic. It is likely that there are several types of successful immune responses, depending on the type of filovirus, and the presence and timing of vaccination or drug treatment.

  19. Chapter 22: Hereditary and acquired angioedema. (United States)

    Georgy, Mary S; Pongracic, Jacqueline A


    Hereditary angioedema (HAE) is an autosomal dominant disorder defined by a deficiency of functional C1 esterase inhibitor (C1-INH). Acquired angioedema (AAE) is caused by either consumption (type 1) or inactivation (type 2) of CI-INH. Both HAE and AAE can be life-threatening. The screening test for both conditions is complement component C4, which is low to absent at times of angioedema or during quiescent periods. A useful test to differentiate HAE from AAE is C1q protein, which is normal in HAE and low in AAE. There are three types of HAE: type 1 HAE is most common, occurring in ∼85% of patients and characterized by decreased production of C1-INH, resulting in reduced functional activity to 5-30% of normal. In type 2, which occurs in 15% of cases, C1-INH is detectable in normal or elevated quantities but is dysfunctional. Finally, type 3, which is rare and almost exclusively occurs in women, is estrogen dependent and associated with normal CI-INH and C4 levels. One-third of these patients have a gain-of-function mutation in clotting factor XII leading to kallikrein-driven bradykinin production. Although the anabolic steroid, danazol, is useful in increasing the concentration of C4 and reducing the episodes of angioedema in HAE and AAE, it has expected adverse effects. Fortunately, disease-specific therapies are available and include C1-INH enzyme for i.v. infusion either acutely or empirically, ecallantide, an inhibitor of kallikrein, and icatibant, a bradykinin B2-receptor antagonist, both approved for acute angioedema and administered, subcutaneously.

  20. A severe H7N9 pneumonia with syndrome of inappropriate antidiuresis and vitamin D deficiency

    Directory of Open Access Journals (Sweden)

    Leng Lin


    Conclusions: Some H7N9 pneumonia could cause SIAD. Early detection and appropriate treatment of SIAD in H7N9 pneumonia might be important. Our patient showed vitamin D deficiency and decline of cellular immune function.

  1. GLUT-1 deficiency without epilepsy - an exceptional case

    NARCIS (Netherlands)

    Overweg-Plandsoen, WCG; Groener, JEM; Onkenhout, W; Brouwer, OF; Bakker, HD; De Vivo, DC


    The GLUT-1 deficiency is a metabolic disorder caused by a defect in glucose transport across the blood-brain barrier as a result of a defect in the glucose-transport protein. Patients present with epileptic seizures, delayed development, ataxia and hypotonia, and in many cases acquired microcephaly.

  2. Lymphoma in acquired generalized lipodystrophy. (United States)

    Brown, Rebecca J; Chan, Jean L; Jaffe, Elaine S; Cochran, Elaine; DePaoli, Alex M; Gautier, Jean-Francois; Goujard, Cecile; Vigouroux, Corinne; Gorden, Phillip


    Acquired generalized lipodystrophy (AGL) is a rare disease thought to result from autoimmune destruction of adipose tissue. Peripheral T-cell lymphoma (PTCL) has been reported in two AGL patients. We report five additional cases of lymphoma in AGL, and analyze the role of underlying autoimmunity and recombinant human leptin (metreleptin) replacement in lymphoma development. Three patients developed lymphoma during metreleptin treatment (two PTCL and one ALK-positive anaplastic large cell lymphoma), and two developed lymphomas (mycosis fungoides and Burkitt lymphoma) without metreleptin. AGL is associated with high risk for lymphoma, especially PTCL. Autoimmunity likely contributes to this risk. Lymphoma developed with or without metreleptin, suggesting metreleptin does not directly cause lymphoma development; a theoretical role of metreleptin in lymphoma progression remains possible. For most patients with AGL and severe metabolic complications, the proven benefits of metreleptin on metabolic disease will likely outweigh theoretical risks of metreleptin in lymphoma development or progression.

  3. Bejel: acquirable only in childhood? (United States)

    Rothschild, Bruce M; Rothschild, Christine; Naples, Virginia; Billard, Michel; Panero, Barbara


    Bejel clearly has a long history in the Middle East and the Sudan, but was it transmitted to Europe? As the major manifestation of bejel is presence of periosteal reaction in 20-40% of afflicted populations, absence of significant population frequency of periosteal reaction in Europe would exclude that diagnosis. Examination of skeletal populations from continental Europe revealed no significant periosteal reaction at the time of and immediately subsequent to the Crusades. Thus, there is no evidence for bejel in Europe, in spite of clear contact (the mechanism of bejel transmission in children) between warring groups, at least during the Crusades. This supports the hypothesis that bejel is a childhood-acquired disease and apparently cannot be contracted in adulthood.

  4. Influência do fornecimento prolongado de colostro sobre a flutuação de proteínas séricas em bezerros com diferentes níveis de imunidade passiva sérica Influence of extended colostrum feeding on protein fluctuation of new born calves with different acquired passive immunity

    Directory of Open Access Journals (Sweden)

    R.S. Baracat


    Full Text Available O presente trabalho teve como objetivo avaliar o comportamento das proteínas séricas de 32 bezerros recém-nascidos submetidos a diferentes programas de aleitamento. Foram utilizados animais com duas diferentes condições de imunidade passiva adquirida, alta e baixa, divididos em dois grupos, com e sem fornecimento prolongado de colostra. Os tratamentos foram os seguintes: T1 - alto/leite; T2 -baixo/leite; T3 - alto/colostro; T4 - baixo/ colostro. Foram avaliados os parâmetros séricos de proteína total (PT, albumina e imunoglobulina G (IgG. O grupo alto (T1 e T3 apresentou uma concentração média superior de proteína total (p = 0,0033 e imunoglobulina (p = 0,0001 séricas comparadas com os valores encontrados para o grupo baixo (T2 e T4. Proteína total e albumina apresentaram concentrações médias superiores (p = 0,0001 e p = 0,059 no grupo colostra (T3 e T4 comparado com o grupo leite (T1 e T2. Os valores mínimos médios para PT e IgG foram superiores (p = 0,082 e p = 0,0001 no grupo alto comparado com o grupo baixo. A data de ocorrência do valor médio mínimo no grupo alto para PT foi 40 dias, valor superior (p = 0,0012 aos 20 dias encontrado para o grupo baixo. O mesmo ocorreu para IgG (p = 0,060, tendo sido obtido 50 e 40 dias, respectivamente, para os grupos alto e baixo. Os animais que receberam colostra (T3 e T4 apresentaram, apenas para PT, valor superior (p = 0,0002 para o parâmetro menor valor médio, que ocorreu aos 30 dias de idade. A data de ocorrência do valor médio mínimo para IgG não diferiu entre os animais que receberam colostro e leite (40 dias. O fornecimento prolongado de colostro na dieta pode favorecer o processo de síntese de proteínas séricas em bezerros recém-nascidos.The objective of this study was to evaluate the protein fluctuation of 32 Holstein newborn calves under different milk feeding programs. Animals with high and low condition of acquired passive immunity, were splited in two groups

  5. Polymicrobial community-acquired pneumonia: An emerging entity. (United States)

    Cillóniz, Catia; Civljak, Rok; Nicolini, Antonello; Torres, Antoni


    Polymicrobial aetiology in community-acquired pneumonia (CAP) is more common than previously recognized. This growing new entity can influence inflammation, host immunity and disease outcomes in CAP patients. However, the true incidence is complicated to determine and probably underestimated due mainly to many cases going undetected, particularly in the outpatient setting, as the diagnostic yield is restricted by the sensitivity of currently available microbiologic tests and the ability to get certain types of clinical specimens. The observed rate of polymicrobial cases may also lead to new antibiotic therapy considerations. In this review, we discuss the pathogenesis, microbial interactions in pneumonia, epidemiology, biomarkers and antibiotic therapy for polymicrobial CAP.

  6. Community-Acquired urinary tract infection by pseudomonas oryzihabitans

    Directory of Open Access Journals (Sweden)

    Sunita M Bhatawadekar


    Full Text Available Pseudomonas oryzihabitans and Chrysomonas luteola has been placed in CDC group Ve2 and Ve1 respectively. These bacteria appear to be emerging pathogens. P. oryzihabitans was isolated from cases of bacteremia, CNS infections, wound infections, peritonitis, sinusitis, catheter associated infections in AIDS patient, and pneumonia. Most of the reports of P. oryzihabitans infection were of nosocomial origin in individuals with some predisposing factors. We report here a case of community acquired UTI by P. oryzihabitans in an immune-competent patient with stricture of urethra.

  7. Iron deficiency anemia in celiac disease. (United States)

    Freeman, Hugh James


    Iron is an important micronutrient that may be depleted in celiac disease. Iron deficiency and anemia may complicate well-established celiac disease, but may also be the presenting clinical feature in the absence of diarrhea or weight loss. If iron deficiency anemia occurs, it should be thoroughly evaluated, even if celiac disease has been defined since other superimposed causes of iron deficiency anemia may be present. Most often, impaired duodenal mucosal uptake of iron is evident since surface absorptive area in the duodenum is reduced, in large part, because celiac disease is an immune-mediated disorder largely focused in the proximal small intestinal mucosa. Some studies have also suggested that blood loss may occur in celiac disease, sometimes from superimposed small intestinal disorders, including ulceration or neoplastic diseases, particularly lymphoma. In addition, other associated gastric or colonic disorders may be responsible for blood loss. Rarely, an immune-mediated hemolytic disorder with increased urine iron loss may occur that may respond to a gluten-free diet. Reduced expression of different regulatory proteins critical in iron uptake has also been defined in the presence and absence of anemia. Finally, other rare causes of microcytic anemia may occur in celiac disease, including a sideroblastic form of anemia reported to have responded to a gluten-free diet.

  8. Iron deficiency anemia in celiac disease (United States)

    Freeman, Hugh James


    Iron is an important micronutrient that may be depleted in celiac disease. Iron deficiency and anemia may complicate well-established celiac disease, but may also be the presenting clinical feature in the absence of diarrhea or weight loss. If iron deficiency anemia occurs, it should be thoroughly evaluated, even if celiac disease has been defined since other superimposed causes of iron deficiency anemia may be present. Most often, impaired duodenal mucosal uptake of iron is evident since surface absorptive area in the duodenum is reduced, in large part, because celiac disease is an immune-mediated disorder largely focused in the proximal small intestinal mucosa. Some studies have also suggested that blood loss may occur in celiac disease, sometimes from superimposed small intestinal disorders, including ulceration or neoplastic diseases, particularly lymphoma. In addition, other associated gastric or colonic disorders may be responsible for blood loss. Rarely, an immune-mediated hemolytic disorder with increased urine iron loss may occur that may respond to a gluten-free diet. Reduced expression of different regulatory proteins critical in iron uptake has also been defined in the presence and absence of anemia. Finally, other rare causes of microcytic anemia may occur in celiac disease, including a sideroblastic form of anemia reported to have responded to a gluten-free diet. PMID:26309349

  9. Immunizations: Active vs. Passive (United States)

    ... Prevention > Immunizations > Immunizations: Active vs. Passive Safety & Prevention Listen Español Text Size Email Print Share Immunizations: Active vs. Passive Page Content Article Body Pediatricians can ...

  10. Skin gene therapy for acquired and inherited disorders. (United States)

    Carretero, M; Escámez, M J; Prada, F; Mirones, I; García, M; Holguín, A; Duarte, B; Podhajcer, O; Jorcano, J L; Larcher, F; Del Río, M


    The rapid advances associated with the Human Genome Project combined with the development of proteomics technology set the bases to face the challenge of human gene therapy. Different strategies must be evaluated based on the genetic defect to be corrected. Therefore, the re-expression of the normal counterpart should be sufficient to reverse phenotype in single-gene inherited disorders. A growing number of candidate diseases are being evaluated since the ADA deficiency was selected for the first approved human gene therapy trial (Blaese et al., 1995). To cite some of them: sickle cell anemia, hemophilia, inherited immune deficiencies, hyper-cholesterolemia and cystic fibrosis. The approach does not seem to be so straightforward when a polygenic disorder is going to be treated. Many human traits like diabetes, hypertension, inflammatory diseases and cancer, appear to be due to the combined action of several genes and environment. For instance, several wizard gene therapy strategies have recently been proposed for cancer treatment, including the stimulation of the immune system of the patient (Xue et al., 2005), the targeting of particular signalling pathways to selectively kill cancer cells (Westphal and Melchner, 2002) and the modulation of the interactions with the stroma and the vasculature (Liotta, 2001; Liotta and Kohn, 2001).

  11. Vitamin D and neonatal immune function.

    LENUS (Irish Health Repository)

    Clancy, N


    Vitamin D deficiency is widespread in the neonatal and paediatric population of northern latitudes, particularly in children of African, Middle Eastern and Asian ethnicity. This is associated with diminished immune function and increases the risk of Th1 autoimmune diseases like type 1 diabetes. Epidermiological studies have also shown a link between vitamin D deficiency in children and a more severe course of illness with lower respiratory tract infection or Respiratory Syncitial Virus (RSV) bronchiolitis. The mechanism by which vitamin D enhances immunity is complex. It acts through the innate immune system by inducing antimicrobial peptides in epithelial cells, neutrophils and macrophages. The role of Vitamin D in neonatal and paediatric immunomodulation requires further study.

  12. 12 CFR 583.1 - Acquire. (United States)


    ... AND LOAN HOLDING COMPANIES § 583.1 Acquire. The term acquire means to acquire, directly or indirectly, ownership or control through an acquisition of shares, an acquisition of assets or assumption of liabilities, a merger or consolidation, or any similar transaction....

  13. Clinical Features and Outcome of Patients With IRAK-4 and MyD88 Deficiency

    NARCIS (Netherlands)

    Picard, Capucine; von Bernuth, Horst; Ghandil, Pegah; Chrabieh, Maya; Levy, Ofer; Arkwright, Peter D.; McDonald, Douglas; Geha, Raif S.; Takada, Hidetoshi; Krause, Jens C.; Creech, C. Buddy; Ku, Cheng-Lung; Ehl, Stephan; Marodi, Laszlo; Al-Muhsen, Saleh; Al-Hajjar, Sami; Al-Ghonaium, Abdulaziz; Day-Good, Noorbibi K.; Holland, Steven M.; Gallin, John I.; Chapel, Helen; Speert, David P.; Rodriguez-Gallego, Carlos; Colino, Elena; Garty, Ben-Zion; Roifman, Chaim; Hara, Toshiro; Yoshikawa, Hideto; Nonoyama, Shigeaki; Domachowske, Joseph; Issekutz, Andrew C.; Tang, Mimi; Smart, Joanne; Zitnik, Simona Eva; Hoarau, Cyrille; Kumararatne, Dinakantha S.; Thrasher, Adrian J.; Davies, E. Graham; Bethune, Claire; Sirvent, Nicolas; de Ricaud, Dominique; Camcioglu, Yildiz; Vasconcelos, Julia; Guedes, Margarida; Vitor, Artur Bonito; Rodrigo, Carlos; Almazan, Francisco; Mendez, Maria; Ignacio Arostegui, Juan; Alsina, Laia; Fortuny, Claudia; Reichenbach, Janine; Verbsky, James W.; Bossuyt, Xavier; Doffinger, Rainer; Abel, Laurent; Puel, Anne; Casanova, Jean-Laurent


    Autosomal recessive interleukin-1 receptor-associated kinase (IRAK)-4 and myeloid differentiation factor (MyD) 88 deficiencies impair Toll-like receptor (TLR)-and interleukin-1 receptor-mediated immunity. We documented the clinical features and outcome of 48 patients with IRAK-4 deficiency and 12 pa

  14. Brief Report: Immunoglobulin A Deficiency in a Subset of Autistic Subjects. (United States)

    Warren, Reed P.; And Others


    A study of 40 individuals (ages 5-31) with autism investigated immune deficiency. Results found the subjects had significantly lower serum immunoglobulin A (IgA) levels than that of age- and sex-matched controls. Seventeen subjects had one of three haplotypes associated with IgA deficiency and seven of these had decreased IgA levels. (CR)

  15. Postnatal toxic and acquired disorders. (United States)

    Saint-Amour, Dave; Dallaire, Renee; Dulac, Oliver


    To develop and function optimally, the brain requires a balanced environment of electrolytes, amino acids, neurotransmitters, and metabolic substrates. As a consequence, organ dysfunction has the potential to induce brain disorders and toxic-metabolic encephalopathies, particularly when occurring during early stages of cerebral maturation. Induced toxicity of three different organ systems that are commonly associated with brain complications are discussed. First, thyroid hormone deficiency caused by intrinsic or extrinsic factors (e.g., environmental toxins) may induce severe adverse effects on child neurological development from reversible impairments to permanent mental retardation. Second, inadequate removal of wastes due to chronic renal failure leads to the accumulation of endogenous toxins that are harmful to brain function. In uremic pediatric patients, the brain becomes more vulnerable to exogenous substances such as aluminum, which can induce aluminum encephalopathy. Following surgical procedures, neurological troubles including focal defects and severe epileptic seizures may result from hypertensive encephalopathy combined with toxicity of immunomodulating substances, or from the delayed consequences of cardiovascular defect. Taken together, this illustrates that organ disorders clearly have an impact on child brain function in various ways.

  16. Immunobiology of Primary Antibody Deficiencies: Towards a new classification

    NARCIS (Netherlands)

    G.J.A. Driessen (Gertjan)


    textabstractPrimary antibody deficiencies (PADs) are the most common primary immunodeficiencies. The hallmark of PADs is a defect in the production of normal amounts of antigen specific antibodies. These antibodies or immunoglobulins are indispensible for the adaptive immune response against a wide

  17. Neutropenia in Patients with Primary Antibody Deficiency Disorders

    Directory of Open Access Journals (Sweden)

    "Nima Rezaei


    Neutropenia may occur in any of the primary immunodeficiency disorders. Persistent or severe infections always pose a supposition, which deserves further evaluation for detecting an underlying immune deficiency syndrome and neutropenia, since a delay in diagnosis may result in a serious organ damage or even death of the patient.

  18. Reduced risk for placental malaria in iron deficient women

    NARCIS (Netherlands)

    Senga, E.L.; Harper, G.; Koshy, G.; Kazembe, P.N.; Brabin, B.J.


    Background: Nutritional iron deficiency may limit iron availability to the malaria parasite reducing infection risk, and/or impair host immunity thereby increasing this risk. In pregnant women, there is evidence of an adverse effect with iron supplementation, but the few reported studies are strongl

  19. Vitamin A, iron and zinc deficiency in Indonesia

    NARCIS (Netherlands)

    Dijkhuizen, M.A.; Wieringa, F.T.


    The research described in this thesis was concerned with vitamin A, iron and zinc deficiency in pregnant and lactating women and in infants. The effects of supplementation withβ-carotene, iron and zinc on micronutrient status, growth, pregnancy outcome and immune function, and interactions between m

  20. Development of immunization trials against Acinetobacter baumannii

    Directory of Open Access Journals (Sweden)

    Tarek A. Ahmad


    Full Text Available Acinetobacter baumannii has recently crossed all lines once considered harmless, pushing its way as a nosocomial pathogen. It had acquired resistance to almost all available chemotherapies and mainly targets intensive care residents; causing pneumonia and major outbreaks with high mortality rates. This urged the need for preventive methods, which include infection control, non-specific immune-therapy, passive, and active immunization in order to offer vulnerable immune-compromised patients a flare in the dark. Several attempts were done for constructing effective vaccines with promising results. These are precisely classified, documented, and discussed in this up-to-date review.

  1. CRISPR-Cas immunity in prokaryotes. (United States)

    Marraffini, Luciano A


    Prokaryotic organisms are threatened by a large array of viruses and have developed numerous defence strategies. Among these, only clustered, regularly interspaced short palindromic repeat (CRISPR)-Cas systems provide adaptive immunity against foreign elements. Upon viral injection, a small sequence of the viral genome, known as a spacer, is integrated into the CRISPR locus to immunize the host cell. Spacers are transcribed into small RNA guides that direct the cleavage of the viral DNA by Cas nucleases. Immunization through spacer acquisition enables a unique form of evolution whereby a population not only rapidly acquires resistance to its predators but also passes this resistance mechanism vertically to its progeny.

  2. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... chest pain, and other symptoms. Severe iron-deficiency anemia can lead to heart problems, infections, problems with growth and development in children, and other complications. Infants and young children and ...

  3. Vitamin D Deficiency (United States)

    ... fractures), muscle weakness, and the bone-thinning disease osteoporosis. Severe vitamin D deficiency can cause rickets in children and osteomalacia in adults. Both problems cause soft, weak bones, as well ...

  4. Factor II deficiency (United States)

    ... if one or more of these factors are missing or are not functioning like they should. Factor II is one such coagulation factor. Factor II deficiency runs in families (inherited) and is very rare. Both parents must ...

  5. Factor VII deficiency (United States)

    ... if one or more of these factors are missing or are not functioning like they should. Factor VII is one such coagulation factor. Factor VII deficiency runs in families (inherited) and is very rare. Both parents must ...

  6. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Events Spokespeople Email Alerts E-Newsletters About NHLBI Organization NHLBI Director Budget, Planning, & Legislative Advisory Committees Jobs ... food. Overview Iron-deficiency anemia is a common type of anemia . The term "anemia" usually refers to ...

  7. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... CAUSES WHO IS AT RISK SIGNS & SYMPTOMS DIAGNOSIS TREATMENTS PREVENTION LIVING WITH CLINICAL TRIALS LINKS Related Topics ... Doctors usually can successfully treat iron-deficiency anemia. Treatment will depend on the cause and severity of ...

  8. Manganese deficiency in plants

    DEFF Research Database (Denmark)

    Schmidt, Sidsel Birkelund; Jensen, Poul Erik; Husted, Søren


    Manganese (Mn) is an essential plant micronutrient with an indispensable function as a catalyst in the oxygen-evolving complex (OEC) of photosystem II (PSII). Even so, Mn deficiency frequently occurs without visual leaf symptoms, thereby masking the distribution and dimension of the problem...... restricting crop productivity in many places of the world. Hence, timely alleviation of latent Mn deficiency is a challenge in promoting plant growth and quality. We describe here the key mechanisms of Mn deficiency in plants by focusing on the impact of Mn on PSII stability and functionality. We also address...... the mechanisms underlying the differential tolerance towards Mn deficiency observed among plant genotypes, which enable Mn-efficient plants to grow on marginal land with poor Mn availability....

  9. Iron-Deficiency Anemia

    Medline Plus

    Full Text Available ... Digg. Share this page from the NHLBI on Facebook. Add this link to the NHLBI to my ... Deficiency Anemia article. Updated: March 26, 2014 Twitter Facebook YouTube Google+ SITE INDEX ACCESSIBILITY PRIVACY STATEMENT FOIA ...

  10. Iron, Anemia, and Iron Deficiency Anemia among Young Children in the United States


    Gupta, Priya M.; Perrine, Cria G.; Zuguo Mei; Scanlon, Kelley S.


    Iron deficiency and anemia are associated with impaired neurocognitive development and immune function in young children. Total body iron, calculated from serum ferritin and soluble transferrin receptor concentrations, and hemoglobin allow for monitoring of the iron and anemia status of children in the United States. The purpose of this analysis is to describe the prevalence of iron deficiency (ID), anemia, and iron deficiency anemia (IDA) among children 1–5 years using data from the 2007–201...

  11. Proximal Focal Femoral Deficiency


    Vishal Kalia, Vibhuti


    Proximal focal femoral deficiency (PFFD) is a developmental disorder of the proximal segment of thefemur and of acetabulum resulting in shortening of the affected limb and impairment of the function. It isa spectrum of congenital osseous anomalies characterized by a deficiency in the structure of the proximalfemur. The diagnosis is often made by radiological evaluation which includes identification and descriptionof PFFD and evaluation of associated limb anomalies by plain radiographs. Contra...

  12. Iron deficiency anemia


    Naigamwalla, Dinaz Z.; Webb, Jinelle A.; Giger, Urs


    Iron is essential to virtually all living organisms and is integral to multiple metabolic functions. The most important function is oxygen transport in hemoglobin. Iron deficiency anemia in dogs and cats is usually caused by chronic blood loss and can be discovered incidentally as animals may have adapted to the anemia. Severe iron deficiency is characterized by a microcytic, hypochromic, potentially severe anemia with a variable regenerative response. Iron metabolism and homeostasis will be ...

  13. Glucose-6-phosphatase deficiency.


    Labrune Philippe; Gajdos Vincent; Eberschweiler Pascale; Hubert-Buron Aurélie; Petit François; Vianey-Saban Christine; Boudjemline Alix; Piraud Monique; Froissart Roseline


    Abstract Glucose-6-phosphatase deficiency (G6P deficiency), or glycogen storage disease type I (GSDI), is a group of inherited metabolic diseases, including types Ia and Ib, characterized by poor tolerance to fasting, growth retardation and hepatomegaly resulting from accumulation of glycogen and fat in the liver. Prevalence is unknown and annual incidence is around 1/100,000 births. GSDIa is the more frequent type, representing about 80% of GSDI patients. The disease commonly manifests, betw...

  14. Adult Immunization

    Directory of Open Access Journals (Sweden)

    Omer Coskun


    Full Text Available Despite the many advances in modern medicine, each year thousands of people in the world die from diseases that are easily prevented by safe and effective vaccines. Few measures in preventive medicine are of such proven value and as easy to implement as routine immunization against infectious diseases. Prevention of infection by immunization is a lifelong process. There are a number of vaccines that all adults (¡I18 years require. There are also other vaccines that need to be tailored to meet individual variations in risk resulting from occupation, foreign travel, underlying illness, lifestyle and age. In this study, we tried to review this important subject. [TAF Prev Med Bull 2008; 7(2.000: 159-166

  15. Behavioral impairments in animal models for zinc deficiency

    Directory of Open Access Journals (Sweden)

    Simone eHagmeyer


    Full Text Available Apart from teratogenic and pathological effects of zinc deficiency such as the occurrence of skin lesions, anorexia, growth retardation, depressed wound healing, altered immune function, impaired night vision, and alterations in taste and smell acuity, characteristic behavioral changes in animal models and human patients suffering from zinc deficiency have been observed. Given that it is estimated that about 17% of the worldwide population are at risk for zinc deficiency and that zinc deficiency is associated with a variety of brain disorders and disease states in humans, it is of major interest to investigate, how these behavioral changes will affect the individual and a putative course of a disease. Thus, here, we provide a state of the art overview about the behavioral phenotypes observed in various models of zinc deficiency, among them environmentally produced zinc deficient animals as well as animal models based on a genetic alteration of a particular zinc homeostasis gene. Finally, we compare the behavioral phenotypes to the human condition of mild to severe zinc deficiency and provide a model, how zinc deficiency that is associated with many neurodegenerative and neuropsychological disorders might modify the disease pathologies.

  16. Music-reading deficiencies and the brain

    Directory of Open Access Journals (Sweden)

    Lola L. Cuddy


    Full Text Available This paper reviews the literature on brain damage and music-reading for the past 25 years. Acquired patterns of selective loss and sparing are described, including both the association and dissociation of music and text reading, and association and dissociation among components of music reading. As well, we suggest that developmental music - reading deficiencies may be isolated in a form analogous to developmental dyslexia for text or congenital amusia for auditory music processing. Finally, we propose that the results of brain damage studies can contribute to the development of a model of normal music reading.

  17. Inherited or acquired metabolic disorders. (United States)

    Eichler, Florian; Ratai, Eva; Carroll, Jason J; Masdeu, Joseph C


    This chapter starts with a description of imaging of inherited metabolic disorders, followed by a discussion on imaging of acquired toxic-metabolic disorders of the adult brain. Neuroimaging is crucial for the diagnosis and management of a number of inherited metabolic disorders. Among these, inherited white-matter disorders commonly affect both the nervous system and endocrine organs. Magnetic resonance imaging (MRI) has enabled new classifications of these disorders that have greatly enhanced both our diagnostic ability and our understanding of these complex disorders. Beyond the classic leukodystrophies, we are increasingly recognizing new hereditary leukoencephalopathies such as the hypomyelinating disorders. Conventional imaging can be unrevealing in some metabolic disorders, but proton magnetic resonance spectroscopy (MRS) may be able to directly visualize the metabolic abnormality in certain disorders. Hence, neuroimaging can enhance our understanding of pathogenesis, even in the absence of a pathologic specimen. This review aims to present pathognomonic brain MRI lesion patterns, the diagnostic capacity of proton MRS, and information from clinical and laboratory testing that can aid diagnosis. We demonstrate that applying an advanced neuroimaging approach enhances current diagnostics and management. Additional information on inherited and metabolic disorders of the brain can be found in Chapter 63 in the second volume of this series.

  18. [Ralph M. Steinman, 2011 Nobel for his contributions on immunity]. (United States)

    Bonifaz, Laura C


    Ralph M. Steinman was the recipient of the 2011 Nobel Prize of Physiology and Medicine due to the discovery of dendritic cells, which have a crucial role on the onset of acquired immunity, a fundamental event in the organism's defense. Today, dendritic cells are used in the development of vaccines and in cancer therapy. Steinman's contributions have been fundamental in the understanding of immunity.

  19. Female postmating immune responses, immune system evolution and immunogenic males. (United States)

    Morrow, Edward H; Innocenti, Paolo


    Females in many taxa experience postmating activation of their immune system, independently of any genital trauma or pathogenic attack arising from male-female genital contact. This response has always been interpreted as a product of natural selection as it either prepares the female immune system for antigens arising from an implanted embryo (in the case of placental mammals), or is a "pre-emptive strike" against infection or injury acquired during mating. While the first hypothesis has empirical support, the second is not entirely satisfactory. Recently, studies that have experimentally dissected the postmating responses of Drosophila melanogaster females point to a different explanation: male reproductive peptides/proteins that have evolved in response to postmating male-male competition are directly responsible for activating particular elements of the female immune system. Thus, in a broad sense, males may be said to be immunogenic to females. Here, we discuss a possible direct role of sexual selection/sexual conflict in immune system evolution, in contrast to indirect trade-offs with other life-history traits, presenting the available evidence from a range of taxa and proposing ways in which the competing hypotheses could be tested. The major implication of this review is that immune system evolution is not only a product of natural selection but also that sexual selection and potentially sexual conflict enforces a direct selective pressure. This is a significant shift, and will compel researchers studying immune system evolution and ecological immunity to look beyond the forces generated by parasites and pathogens to those generated by the male ejaculate.

  20. Defence mechanisms and immune evasion in the interplay between the humane immune system and Plasmodium falciparum

    DEFF Research Database (Denmark)

    Theander, T G


    Immunity to P. falciparum malaria is developed as a result of long term exposure to the parasite and depends on immunological memory. The key directors in immune recognition and regulation of the immunological responses are the T-cells. It seems reasonable to propose that immunity is acquired when...... a critical mass of T-cells, recognizing relevant malaria antigens, has been developed. These T-cells mediate immunity by regulating macrophage and B-cell activity, but they may also act directly as cytotoxic cells on infected hepatocytes and through production of parasite-toxic cytokines. The potential...... with development of immunity. Several mechanisms seem to be operating. 1) Induction of the immune response to some macromolecules is avoided because the parasites are living inside host cells during part of their life cycle, and the reaction to other molecules is apparently avoided by mimicry of host molecules. 2...

  1. Chronic mucocutaneous candidiasis disease associated with inborn errors of IL-17 immunity (United States)

    Okada, Satoshi; Puel, Anne; Casanova, Jean-Laurent; Kobayashi, Masao


    Chronic mucocutaneous candidiasis (CMC) is characterized by recurrent or persistent infections affecting the nails, skin and oral and genital mucosae caused by Candida spp., mainly Candida albicans. CMC is an infectious phenotype in patients with inherited or acquired T-cell deficiency. Patients with autosomal-dominant (AD) hyper IgE syndrome (HIES), AD signal transducer and activator of transcription 1 (STAT1) gain-of-function, autosomal-recessive (AR) deficiencies in interleukin (IL)-12 receptor β1 (IL-12Rβ1), IL-12p40, caspase recruitment domain-containing protein 9 (CARD9) or retinoic acid-related orphan receptor γT (RORγT) or AR autoimmune polyendocrinopathy–candidiasis–ectodermal dystrophy (APECED) develop CMC as a major infectious phenotype that is categorized as Syndromic CMC. In contrast, CMC disease (CMCD) is typically defined as CMC in patients in the absence of any other prominent clinical signs. This definition is not strict; thus, CMCD is currently used to refer to patients presenting with CMC as the main clinical phenotype. The etiology of CMCD is not related to genes that cause severe combined immunodeficiency or combined immunodeficiency, nor to genes responsible for Syndromic CMC. Four genetic etiologies, AR IL-17 receptor A, IL-17 receptor C and ACT1 deficiencies, and AD IL-17F deficiency, are reported to underlie CMCD. Each of these gene defects directly has an impact on IL-17 signaling, suggesting their nonredundant role in host mucosal immunity to Candida. Here, we review current knowledge focusing on IL-17 signaling and the genetic etiologies responsible for, and associated with, CMC. PMID:28090315

  2. 17 CFR 210.8-04 - Financial statements of businesses acquired or to be acquired. (United States)


    ... businesses acquired or to be acquired. (a) If a business combination has occurred or is probable, financial... section. The required financial statements of related businesses may be presented on a combined basis for... financial statements of the business acquired or to be acquired and the smaller reporting company's...

  3. Primary murine CD4+ T cells fail to acquire the ability to produce effector cytokines when active Ras is present during Th1/Th2 differentiation.

    Directory of Open Access Journals (Sweden)

    Sujit V Janardhan

    Full Text Available Constitutive Ras signaling has been shown to augment IL-2 production, reverse anergy, and functionally replace many aspects of CD28 co-stimulation in CD4+ T cells. These data raise the possibility that introduction of active Ras into primary T cells might result in improved functionality in pathologic situations of T cell dysfunction, such as cancer or chronic viral infection. To test the biologic effects of active Ras in primary T cells, CD4+ T cells from Coxsackie-Adenovirus Receptor Transgenic mice were transduced with an adenovirus encoding active Ras. As expected, active Ras augmented IL-2 production in naive CD4+ T cells. However, when cells were cultured for 4 days under conditions to promote effector cell differentiation, active Ras inhibited the ability of CD4+ T cells to acquire a Th1 or Th2 effector cytokine profile. This differentiation defect was not due to deficient STAT4 or STAT6 activation by IL-12 or IL-4, respectively, nor was it associated with deficient induction of T-bet and GATA-3 expression. Impaired effector cytokine production in active Ras-transduced cells was associated with deficient demethylation of the IL-4 gene locus. Our results indicate that, despite augmenting acute activation of naïve T cells, constitutive Ras signaling inhibits the ability of CD4+ T cells to properly differentiate into Th1/Th2 effector cytokine-producing cells, in part by interfering with epigenetic modification of effector gene loci. Alternative strategies to potentiate Ras pathway signaling in T cells in a more regulated fashion should be considered as a therapeutic approach to improve immune responses in vivo.

  4. Characteristics of opportunistic infections and the isolated pathogens in human immunodeficiency virus/acquired immune deficiency syndrome patients%人类免疫缺陷病毒感染者或艾滋病患者机会性感染和菌群分布特点

    Institute of Scientific and Technical Information of China (English)

    陈友鹏; 赵介; 梁旭竞; Christian Traeder; 唐永煌; Keikawus Arastéh


    目的 了解柏林HIV-1感染者或AIDS患者机会性感染的菌群分布特点,及其与CD4+细胞数、病毒载量的关系.方法 将2000年5月至2001年4月在德国柏林Vivantes Auguste-Viktoria医院收治的269例患者,于入院当天采用FACScan流式细胞仪检测外周血CD4-细胞数和RT-PCR检测血浆HIV-1病毒载量.机会性感染以出院诊断为准,根据临床表现和实验室检查确诊.结果 84例出现过机会性感染,48例次为二重或多重感染.机会性感染者外周血CD4+细胞数明显低于无机会性感染者,差异有统计学意义(P<0.01);而平均病毒载量则明显高于后者(P<0.01).在病原学方面,以念珠菌、CMV、单纯疱疹病毒或带状疱疹病毒、卡氏肺孢子菌、非结核性分枝杆菌和弓形虫为主.主要感染部位是呼吸系统、血液和消化系统.分离出致病菌30余种,共193株,主要为葡萄球菌属、链球菌属、念珠菌、流感嗜血杆菌和大肠埃希菌.获得甲氧西林耐药金黄色葡萄球菌(MRSA)2株和多重耐药流感嗜血杆菌1株.结论 本组患者机会性感染发生率较高.致病菌株分布广泛,二重和多重菌株感染较为普遍,但未出现严重的多重耐药株.

  5. 281例艾滋病患者采用高效抗反转录病毒疗法后血脂变化与中医证型临床分析%Clinical analysis on lipid metabolism and syndrome of TCM in 281 cases of acquired immune deficiency syndrome treating by HAART

    Institute of Scientific and Technical Information of China (English)

    李强; 郭会军; 蒋自强; 张晓伟; 谢正


    Objective: Highly active antiretroviral therapy (HAART) has a significant impact on the natural history of human immunodeficiency virus (HIV) infection, leading to a remarkable decrease in its morbidity and mortality, but is frequently associated with metabolic complications, such as dyslipidemia and cardiovascular complications. The purpose of this study is to explore the possible complications of HAART in treated patients on lipid metabolism and syndrome of TCM (TCM). Methods: A retrospective study was conducted in the outpatients. We selected 281 infected men who were receiving HAART. Fasting total cholesterol, triglyceride, high-density lipopmtein cholesterol (HDL), low-density lipopmtein (LDL), cholesterol values were compared in various treatment prescription. Statistic analysis of the data was carried out on lipid metabolism and syndrome of TCM. Results: Protease inhibitors (Pis) the incidence of dyslipidemia was significantly higher than other drug combinations in their programs the incidence of dyslipidemia. AIDS patients receiving HAART lipid levels in triglycerides (TGs) increased more in various treatment perscription (82%). Syndrome differentiation type was mainly phlegm or phlegm stasis (78%). Conclusion: These data suggested that HAART was associated with dyslipidemia in patients. In addition to AIDS patients on HAART conventional treatment, and related lipid changes also should pay attention to, TCM treatment should mainly invigorate the spleen and eliminate phlegm.%目的:探讨艾滋病患者HAART后血脂变化与中医证型的关系.方法:对281例艾滋病接受HAART患者,采用BECKMAN全自动生化分析仪测定血清总胆固醇(TC)、甘油三酯(TGs)、低密度脂蛋白胆固醇( LDL-C)和高密度脂蛋白胆固醇(HDL-C)指标.同时对检测指标达到血脂异常标准者进行中医辨证分型.结果:使用蛋白酶抑制剂血脂异常发病率明显高于其他药物在各自组合方案中血脂异常发病率.在接受HAART艾滋病患者中血脂变化以TGs升高多见(82%),中医辨证分型以脾虚痰阻或痰浊瘀阻为主(78%).结论:对艾滋病患者除进行HAART常规治疗外,相关血脂变化也应重视,中医辨证治疗应以健脾祛痰为主,兼以化瘀降浊.

  6. Feeding Our Immune System: Impact on Metabolism

    Directory of Open Access Journals (Sweden)

    Isabelle Wolowczuk


    Full Text Available Endogenous intestinal microflora and environmental factors, such as diet, play a central role in immune homeostasis and reactivity. In addition, microflora and diet both influence body weight and insulin-resistance, notably through an action on adipose cells. Moreover, it is known since a long time that any disturbance in metabolism, like obesity, is associated with immune alteration, for example, inflammation. The purpose of this review is to provide an update on how nutrients-derived factors (mostly focusing on fatty acids and glucose impact the innate and acquired immune systems, including the gut immune system and its associated bacterial flora. We will try to show the reader how the highly energy-demanding immune cells use glucose as a main source of fuel in a way similar to that of insulin-responsive adipose tissue and how Toll-like receptors (TLRs of the innate immune system, which are found on immune cells, intestinal cells, and adipocytes, are presently viewed as essential actors in the complex balance ensuring bodily immune and metabolic health. Understanding more about these links will surely help to study and understand in a more fundamental way the common observation that eating healthy will keep you and your immune system healthy.

  7. Hereditary and Acquired Thrombophilia in Splanchnic Vein Thrombosis: A Single-Center Experience. (United States)

    Mutreja, Deepti; Kotru, Mrinalini; Sazawal, Sudha; Ranjan, Ravi; Sharma, Amit; Acharya, Subrat Kumar; Saxena, Renu


    The purpose of this study was to characterize differences in the prevalence of hereditary and acquired thrombophilia in patients with splanchnic vein thrombosis (SVT). A total of 88 consecutive patients with SVT, including Budd Chiari Syndrome (n = 47) and portal extrahepatic portal vein obstruction (n = 41), underwent comprehensive thrombophilia testing, including testing for heritable and acquired causes. In 33 (37.5%) patients, etiology could be explained by at least 1 of the heritable etiologic factors, and 31 (35.2%) patients could be explained by at least 1 of the acquired causes studied. The combination of multiple concurrent factors was present in 9 (11.4%) patients. Among the heritable causes, the risk of SVT was found increased in the presence of thrombophilia resulting from the deficiencies of the naturally occurring anticoagulant proteins, and the acquired thrombogenic factors were significantly associated with causation of thrombosis in adult patients with SVT.

  8. Staphylococcal biofilm exopolysaccharide protects against Caenorhabditis elegans immune defenses.

    Directory of Open Access Journals (Sweden)

    Jakob Begun


    Full Text Available Staphylococcus epidermidis and Staphylococcus aureus are leading causes of hospital-acquired infections that have become increasingly difficult to treat due to the prevalence of antibiotic resistance in these organisms. The ability of staphylococci to produce biofilm is an important virulence mechanism that allows bacteria both to adhere to living and artificial surfaces and to resist host immune factors and antibiotics. Here, we show that the icaADBC locus, which synthesizes the biofilm-associated polysaccharide intercellular adhesin (PIA in staphylococci, is required for the formation of a lethal S. epidermidis infection in the intestine of the model nematode Caenorhabditis elegans. Susceptibility to S. epidermidis infection is influenced by mutation of the C. elegans PMK-1 p38 mitogen-activated protein (MAP kinase or DAF-2 insulin-signaling pathways. Loss of PIA production abrogates nematocidal activity and leads to reduced bacterial accumulation in the C. elegans intestine, while overexpression of the icaADBC locus in S. aureus augments virulence towards nematodes. PIA-producing S. epidermidis has a significant survival advantage over ica-deficient S. epidermidis within the intestinal tract of wild-type C. elegans, but not in immunocompromised nematodes harboring a loss-of-function mutation in the p38 MAP kinase pathway gene sek-1. Moreover, sek-1 and pmk-1 mutants are equally sensitive to wild-type and icaADBC-deficient S. epidermidis. These results suggest that biofilm exopolysaccharide enhances virulence by playing an immunoprotective role during colonization of the C. elegans intestine. These studies demonstrate that C. elegans can serve as a simple animal model for studying host-pathogen interactions involving staphylococcal biofilm exopolysaccharide and suggest that the protective activity of biofilm matrix represents an ancient conserved function for resisting predation.

  9. Iron deficiency anaemia. (United States)

    Lopez, Anthony; Cacoub, Patrice; Macdougall, Iain C; Peyrin-Biroulet, Laurent


    Anaemia affects roughly a third of the world's population; half the cases are due to iron deficiency. It is a major and global public health problem that affects maternal and child mortality, physical performance, and referral to health-care professionals. Children aged 0-5 years, women of childbearing age, and pregnant women are particularly at risk. Several chronic diseases are frequently associated with iron deficiency anaemia--notably chronic kidney disease, chronic heart failure, cancer, and inflammatory bowel disease. Measurement of serum ferritin, transferrin saturation, serum soluble transferrin receptors, and the serum soluble transferrin receptors-ferritin index are more accurate than classic red cell indices in the diagnosis of iron deficiency anaemia. In addition to the search for and treatment of the cause of iron deficiency, treatment strategies encompass prevention, including food fortification and iron supplementation. Oral iron is usually recommended as first-line therapy, but the most recent intravenous iron formulations, which have been available for nearly a decade, seem to replenish iron stores safely and effectively. Hepcidin has a key role in iron homoeostasis and could be a future diagnostic and therapeutic target. In this Seminar, we discuss the clinical presentation, epidemiology, pathophysiology, diagnosis, and acute management of iron deficiency anaemia, and outstanding research questions for treatment.

  10. Generalized verrucosis in a patient with GATA2 deficiency. (United States)

    West, E S; Kingsbery, M Y; Mintz, E M; Hsu, A P; Holland, S M; Rady, P L; Tyring, S K; Grossman, M E


    Generalized verrucosis is a characteristic of several genetic and immunodeficiency disorders including epidermodysplasia verruciformis; warts, hypogammaglobulinaemia, infections and myelokathexis (WHIM) syndrome; warts, immunodeficiency, lymphoedema and anogenital dysplasia (WILD) syndrome; severe combined immune deficiency and HIV, among others. In recent years, it has been consistently recognized in patients with GATA2 deficiency, a novel immunodeficiency syndrome characterized by monocytopenia, B-cell and natural killer-cell lymphopenia, and a tendency to develop myeloid leukaemias and disseminated mycobacterial, human papillomavirus (HPV) and opportunistic fungal infections. Mutations in GATA2 cause haploinsufficiency and track in families as an autosomal dominant immunodeficiency. GATA2 is a transcription factor involved in early haematopoietic differentiation and lymphatic and vascular development. We describe a case of generalized verrucosis with HPV type 57 presenting in a young man with GATA2 deficiency. GATA2 deficiency is a novel dominant immunodeficiency that is often recognized later in life and should be considered in the differential diagnosis of patients with generalized verrucosis.

  11. Nutritional iron deficiency: the role of oral iron supplementation. (United States)

    Lachowicz, J I; Nurchi, V M; Fanni, D; Gerosa, C; Peana, M; Zoroddu, M A


    Nutritional iron deficiency represents a relevant health problem mainly in developing countries. Children and pregnant women represent the main target of this disease, and the low amount of bio-available iron mostly depends on plant-based diets. Iron deficiency may have serious consequences, with severe impairment of the immune function leading to infectious diseases. The brain development in embryos and fetuses during gestation can be greatly affected by iron deficiency of the mother with heavy outcomes on the cognition status of children. A better understanding of molecular pathways involved in iron absorption and metabolism are the basis for new strategies for developing a therapy for iron deficiency. Different therapeutic strategies are summarized, and iron fortification appears the best tool.

  12. [Vitamin deficiencies and hypervitaminosis]. (United States)

    Mino, M


    There have recently been very few deficiencies with respect to fat soluble and water soluble vitamins in Japan All-trans-retinoic acid as induction or maintenance treatment improves disease free and overall survival against acute promyelocytic leukemia. In the isolated vitamin E deficiencies gene mutation has been cleared for alpha-tocopherol transferprotein. Recently, a relation of nutritional vitamin K intake and senile osteoporosis in women was epidemiologically demonstrated on a prospective study. Thiamin was yet noticed as development of deficiency in alcoholism, while the importance of supplemental folic acid during pregnancy has become especially clear in light of studies showing that folic acid supplements reduce the risk of neural tube defects in the fetus. With respect to hypervitaminosis, the Council for Responsible Nutrition (CRN), USA, has established safe intakes by identifying the NOAEL (No Observed Adverse Effect Level) and LOAEL (Lowest Observed Adverse Effect Level). Summaries of NOAEL and LOAEL for individual vitamins were shown.

  13. Antepartum Ornithine Transcarbamylase Deficiency

    Directory of Open Access Journals (Sweden)

    Hitoshi Nakajima


    Full Text Available Ornithine transcarbamylase deficiency (OTCD is the most common type urea cycle enzyme deficiencies. This syndrome results from a deficiency of the mitochondrial enzyme ornithine transcarbamylase, which catalyzes the conversion of ornithine and carbamoyl phosphate to citrullin. Our case was a 28-year-old female diagnosed with OTCD following neurocognitive deficit during her first pregnancy. Although hyperammonemia was suspected as the cause of the patient's mental changes, there was no evidence of chronic liver disease. Plasma amino acid and urine organic acid analysis revealed OTCD. After combined modality treatment with arginine, sodium benzoate and hemodialysis, the patient's plasma ammonia level stabilized and her mental status returned to normal. At last she recovered without any damage left.

  14. Immune response to fungal infections. (United States)

    Blanco, Jose L; Garcia, Marta E


    The immune mechanisms of defence against fungal infections are numerous, and range from protective mechanisms that were present early in evolution (innate immunity) to sophisticated adaptive mechanisms that are induced specifically during infection and disease (adaptive immunity). The first-line innate mechanism is the presence of physical barriers in the form of skin and mucous membranes, which is complemented by cell membranes, cellular receptors and humoral factors. There has been a debate about the relative contribution of humoral and cellular immunity to host defence against fungal infections. For a long time it was considered that cell-mediated immunity (CMI) was important, but humoral immunity had little or no role. However, it is accepted now that CMI is the main mechanism of defence, but that certain types of antibody response are protective. In general, Th1-type CMI is required for clearance of a fungal infection, while Th2 immunity usually results in susceptibility to infection. Aspergillosis, which is a disease caused by the fungus Aspergillus, has been the subject of many studies, including details of the immune response. Attempts to relate aspergillosis to some form of immunosuppression in animals, as is the case with humans, have not been successful to date. The defence against Aspergillus is based on recognition of the pathogen, a rapidly deployed and highly effective innate effector phase, and a delayed but robust adaptive effector phase. Candida albicans, part of the normal microbial flora associated with mucous surfaces, can be present as congenital candidiasis or as acquired defects of cell-mediated immunity. Resistance to this yeast is associated with Th1 CMI, whereas Th2 immunity is associated with susceptibility to systemic infection. Dermatophytes produce skin alterations in humans and other animals, and the essential role of the CMI response is to destroy the fungi and produce an immunoprotective status against re-infection. The resolution

  15. Rituximab therapy in a patient with low grade B-cell lymphoproliferative disease and concomitant acquired angioedema

    Directory of Open Access Journals (Sweden)

    Kaur R


    Full Text Available Ravdeep Kaur, Aerik Anthony Williams, Catherine Baker Swift, Jason W Caldwell Wake Forest University School of Medicine, Wake Forest University, Winston-Salem, NC, USA Abstract: Acquired angioedema is often associated with significant morbidity. An underlying lymphatic malignancy, autoimmune disorder, adenocarcinoma, or other malignancy may be present. Screening for these disorders should occur in all patients with acquired angioedema as treatment may result in resolution of angioedema. Keywords: complement, C1-INH deficiency, ecallantide, hemopathy

  16. Gender affects skin wound healing in plasminogen deficient mice.

    Directory of Open Access Journals (Sweden)

    Birgitte Rønø

    Full Text Available The fibrinolytic activity of plasmin plays a fundamental role in resolution of blood clots and clearance of extravascular deposited fibrin in damaged tissues. These vital functions of plasmin are exploited by malignant cells to accelerate tumor growth and facilitate metastases. Mice lacking functional plasmin thus display decreased tumor growth in a variety of cancer models. Interestingly, this role of plasmin has, in regard to skin cancer, been shown to be restricted to male mice. It remains to be clarified whether gender also affects other phenotypic characteristics of plasmin deficiency or if this gender effect is restricted to skin cancer. To investigate this, we tested the effect of gender on plasmin dependent immune cell migration, accumulation of hepatic fibrin depositions, skin composition, and skin wound healing. Gender did not affect immune cell migration or hepatic fibrin accumulation in neither wildtype nor plasmin deficient mice, and the existing differences in skin composition between males and females were unaffected by plasmin deficiency. In contrast, gender had a marked effect on the ability of plasmin deficient mice to heal skin wounds, which was seen as an accelerated wound closure in female versus male plasmin deficient mice. Further studies showed that this gender effect could not be reversed by ovariectomy, suggesting that female sex-hormones did not mediate the accelerated skin wound healing in plasmin deficient female mice. Histological examination of healed wounds revealed larger amounts of fibrotic scars in the provisional matrix of plasmin deficient male mice compared to female mice. These fibrotic scars correlated to an obstruction of cell infiltration of the granulation tissue, which is a prerequisite for wound healing. In conclusion, the presented data show that the gender dependent effect of plasmin deficiency is tissue specific and may be secondary to already established differences between genders, such as skin

  17. Mortality and GH deficiency

    DEFF Research Database (Denmark)

    Stochholm, Kirstine; Gravholt, Claus Højbjerg; Laursen, Torben;


    OBJECTIVE: To estimate the mortality in Denmark in patients suffering from GH deficiency (GHD). DESIGN: Mortality was analyzed in 1794 GHD patients and 8014 controls matched on age and gender. All records in GHD patients were studied and additional morbidity noted. Patients were divided into chil......OBJECTIVE: To estimate the mortality in Denmark in patients suffering from GH deficiency (GHD). DESIGN: Mortality was analyzed in 1794 GHD patients and 8014 controls matched on age and gender. All records in GHD patients were studied and additional morbidity noted. Patients were divided...

  18. Flu Vaccine Guidance for Patients with Immune Deficiency (United States)

    ... Education Center Fellows-in-Training Grants & Awards Program Directors Practice Resources ASTHMA IQ Consultation and Referral Guidelines Practice Financial Survey Practice Tools Running a Practice Statements and Practice Parameters About AAAAI Advocacy Allergist / Immunologists: ...

  19. PLCG2-associatiated antibody deficiency immune dysregulation (PLAID) (United States)

    ... Respond to Pre-Award Requests Manage Your Award Negotiation & Initial Award After Award ... New Trial Launched in West Africa to Evaluate Three Vaccination Strategies , April 6, 2017 Monoclonal Antibody Cures Marburg Infection ...

  20. Talking to Your Doctor about Primary Immune Deficiency Diseases (United States)

    ... Respond to Pre-Award Requests Manage Your Award Negotiation & Initial Award After Award ... New Trial Launched in West Africa to Evaluate Three Vaccination Strategies , April 6, 2017 Monoclonal Antibody Cures Marburg Infection ...

  1. Role of innate immunity in neonatal infection. (United States)

    Cuenca, Alex G; Wynn, James L; Moldawer, Lyle L; Levy, Ofer


    Newborns are at increased risk of infection due to genetic, epigenetic, and environmental factors. Herein we examine the roles of the neonatal innate immune system in host defense against bacterial and viral infections. Full-term newborns express a distinct innate immune system biased toward T(H)2-/T(H)17-polarizing and anti-inflammatory cytokine production with relative impairment in T(H)1-polarizing cytokine production that leaves them particularly vulnerable to infection with intracellular pathogens. In addition to these distinct features, preterm newborns also have fragile skin, impaired T(H)17-polarizing cytokine production, and deficient expression of complement and of antimicrobial proteins and peptides (APPs) that likely contribute to susceptibility to pyogenic bacteria. Ongoing research is identifying APPs, including bacterial/permeability-increasing protein and lactoferrin, as well as pattern recognition receptor agonists that may serve to enhance protective newborn and infant immune responses as stand-alone immune response modifiers or vaccine adjuvants.

  2. Influence of antimalarial treatment on acquisition of immunity in Plasmodium berghei NK65 malaria. (United States)

    Long, Ton That Ai; Nakazawa, Shusuke; Huaman, Maria Cecilia; Kanbara, Hiroji


    Antimalarial treatments during primary Plasmodium berghei NK65 infection in BALB/c mice influenced the acquisition of protective immunity against reinfection. Among subcurative treatments, lower doses better enable mice to acquire protective immunity than do higher doses. Eradication of parasites from the start of infection did not promote protective immunity.

  3. Severe Dermatophytosis and Acquired or Innate Immunodeficiency: A Review

    Directory of Open Access Journals (Sweden)

    Claire Rouzaud


    Full Text Available Dermatophytes are keratinophilic fungi responsible for benign and common forms of infection worldwide. However, they can lead to rare and severe diseases in immunocompromised patients. Severe forms include extensive and/or invasive dermatophytosis, i.e., deep dermatophytosis and Majocchi’s granuloma. They are reported in immunocompromised hosts with primary (autosomal recessive CARD9 deficiency or acquired (solid organ transplantation, autoimmune diseases requiring immunosuppressive treatments, HIV infection immunodeficiencies. The clinical manifestations of the infection are not specific. Lymph node and organ involvement may also occur. Diagnosis requires both mycological and histological findings. There is no consensus on treatment. Systemic antifungal agents such as terbinafine and azoles (itraconazole or posaconazole are effective. However, long-term outcome and treatment management depend on the site and extent of the infection and the nature of the underlying immunodeficiency.

  4. Methylenetetrahydrofolate reductase (MTHFR) deficiency presenting as a rash.

    LENUS (Irish Health Repository)

    Crushell, Ellen


    We report on the case of a 2-year-old girl recently diagnosed with Methylenetetrahydrofolate reductase (MTHFR) deficiency who originally presented in the neonatal period with a distinctive rash. At 11 weeks of age she developed seizures, she had acquired microcephaly and developmental delay. The rash deteriorated dramatically following commencement of phenobarbitone; both rash and seizures abated following empiric introduction of pyridoxine and folinic acid as treatment of possible vitamin responsive seizures. We postulate that phenobarbitone in combination with MTHFR deficiency may have caused her rash to deteriorate and subsequent folinic acid was helpful in treating the rash and preventing further acute neurological decline as commonly associated with this condition.

  5. Diagnosing oceanic nutrient deficiency (United States)

    Moore, C. Mark


    The supply of a range of nutrient elements to surface waters is an important driver of oceanic production and the subsequent linked cycling of the nutrients and carbon. Relative deficiencies of different nutrients with respect to biological requirements, within both surface and internal water masses, can be both a key indicator and driver of the potential for these nutrients to become limiting for the production of new organic material in the upper ocean. The availability of high-quality, full-depth and global-scale datasets on the concentrations of a wide range of both macro- and micro-nutrients produced through the international GEOTRACES programme provides the potential for estimation of multi-element deficiencies at unprecedented scales. Resultant coherent large-scale patterns in diagnosed deficiency can be linked to the interacting physical-chemical-biological processes which drive upper ocean nutrient biogeochemistry. Calculations of ranked deficiencies across multiple elements further highlight important remaining uncertainties in the stoichiometric plasticity of nutrient ratios within oceanic microbial systems and caveats with regards to linkages to upper ocean nutrient limitation. This article is part of the themed issue 'Biological and climatic impacts of ocean trace element chemistry'.

  6. Factor V deficiency (United States)

    ... When certain blood clotting factors are low or missing, your blood does not clot properly. Factor V deficiency is rare. It may be caused by: A defective Factor V gene passed down through families (inherited) An antibody that interferes with normal Factor ...

  7. Iodine-deficiency disorders

    NARCIS (Netherlands)

    Zimmermann, M.B.; Jooste, P.L.; Pandav, C.S.


    billion individuals worldwide have insufficient iodine intake, with those in south Asia and sub-Saharan Africa particularly affected. Iodine deficiency has many adverse effects on growth and development. These effects are due to inadequate production of thyroid hormone and are termed iodine-deficien

  8. Alpha1-antitrypsin deficiency

    DEFF Research Database (Denmark)

    Stolk, Jan; Seersholm, Niels; Kalsheker, Noor


    biennially to exchange views and research findings. The fourth biennial meeting was held in Copenhagen, Denmark, on 2-3 June 2005. This review covers the wide range of AAT deficiency-related topics that were addressed encompassing advances in genetic characterization, risk factor identification, clinical...... epidemiology, inflammatory and signalling processes, therapeutic advances, and lung imaging techniques....

  9. Sleep Deprivation and Deficiency (United States)

    ... page from the NHLBI on Twitter. What Are Sleep Deprivation and Deficiency? Sleep deprivation (DEP-rih-VA-shun) is a condition that ... the following: You don't get enough sleep (sleep deprivation) You sleep at the wrong time of day ( ...

  10. Morbidity and GH deficiency

    DEFF Research Database (Denmark)

    Stochholm, Kirstine; Laursen, Torben; Green, Anders;


    OBJECTIVE: To estimate morbidity in Denmark in all patients with GH deficiency (GHD). DESIGN: Morbidity was analyzed in 1794 GHD patients and 8014 controls matched on age and gender. All records in the GHD patients were studied and additional morbidity noted. Diagnoses and dates of admissions were...

  11. [Olive oil, immune system and infection]. (United States)

    Puertollano, M A; Puertollano, E; Alvarez de Cienfuegos, G; de Pablo Martínez, Manuel Antonio


    Polyunsaturated fatty acids contribute to the suppression of immune system functions. For this reason, n-3 polyunsaturated fatty acids have been applied in the resolution of inflammatory disorders. Although the inhibition of several immune functions promotes beneficial effects on the human health, this state may lead to a significant reduction of immune protection against infectious microorganisms (viruses, bacteria, fungi and parasites). Nevertheless, less attention has been paid to the action of olive oil in immunonutrition. Olive oil, a main constituent of the Mediterranean diet, is capable of modulating several immune functions, but it does not reduce host immune resistance to infectious microorganisms. Based on these criteria, we corroborate that olive oil administration may exert beneficial effects on the human health and especially on immune system, because it contributes to the reduction of typical inflammatory activity observed in patients suffering from autoimmune disorders, but without exacerbating the susceptibility to pathogen agents. The administration of olive oil in lipid emulsions may exert beneficial effects on the health and particularly on the immune system of immunocompromised patients. Therefore, this fact acquires a crucial importance in clinical nutrition. This review contributes to clarify the interaction between the administration of diets containing olive oil and immune system, as well as to determine the effect promoted by this essential component of Mediterranean diet in the immunomodulation against an infectious agent.

  12. And the Winner is – Acquired

    DEFF Research Database (Denmark)

    Henkel, Joachim; Rønde, Thomas; Wagner, Marcus

    value in case of success—that is, a more radical innovation. In the second stage, successful entrants bid to be acquired by the incumbent. We assume that entrants cannot survive on their own, so being acquired amounts to a ‘prize’ in a contest. We identify an equilibrium in which the incumbent chooses...

  13. Iron-refractory iron deficiency anemia. (United States)

    Yılmaz Keskin, Ebru; Yenicesu, İdil


    Iron is essential for life because it is indispensable for several biological reactions, such as oxygen transport, DNA synthesis, and cell proliferation. Over the past few years, our understanding of iron metabolism and its regulation has changed dramatically. New disorders of iron metabolism have emerged, and the role of iron as a cofactor in other disorders has begun to be recognized. The study of genetic conditions such as hemochromatosis and iron-refractory iron deficiency anemia (IRIDA) has provided crucial insights into the molecular mechanisms controlling iron homeostasis. In the future, these advances may be exploited to improve treatment of both genetic and acquired iron disorders. IRIDA is caused by mutations in TMPRSS6, the gene encoding matriptase-2, which downregulates hepcidin expression under conditions of iron deficiency. The typical features of this disorder are hypochromic, microcytic anemia with a very low mean corpuscular volume of erythrocytes, low transferrin saturation, no (or inadequate) response to oral iron, and only a partial response to parenteral iron. In contrast to classic iron deficiency anemia, serum ferritin levels are usually low-normal, and serum or urinary hepcidin levels are inappropriately high for the degree of anemia. Although the number of cases reported thus far in the literature does not exceed 100, this disorder is considered the most common of the "atypical" microcytic anemias. The aim of this review is to share the current knowledge on IRIDA and increase awareness in this field.

  14. Iron-Refractory Iron Deficiency Anemia (United States)

    Yılmaz Keskin, Ebru; Yenicesu, İdil


    Iron is essential for life because it is indispensable for several biological reactions, such as oxygen transport, DNA synthesis, and cell proliferation. Over the past few years, our understanding of iron metabolism and its regulation has changed dramatically. New disorders of iron metabolism have emerged, and the role of iron as a cofactor in other disorders has begun to be recognized. The study of genetic conditions such as hemochromatosis and iron-refractory iron deficiency anemia (IRIDA) has provided crucial insights into the molecular mechanisms controlling iron homeostasis. In the future, these advances may be exploited to improve treatment of both genetic and acquired iron disorders. IRIDA is caused by mutations in TMPRSS6, the gene encoding matriptase-2, which downregulates hepcidin expression under conditions of iron deficiency. The typical features of this disorder are hypochromic, microcytic anemia with a very low mean corpuscular volume of erythrocytes, low transferrin saturation, no (or inadequate) response to oral iron, and only a partial response to parenteral iron. In contrast to classic iron deficiency anemia, serum ferritin levels are usually low-normal, and serum or urinary hepcidin levels are inappropriately high for the degree of anemia. Although the number of cases reported thus far in the literature does not exceed 100, this disorder is considered the most common of the “atypical” microcytic anemias. The aim of this review is to share the current knowledge on IRIDA and increase awareness in this field. PMID:25805669

  15. Protective immune barrier against hepatitis B is needed in individuals born before infant HBV vaccination program in China. (United States)

    Yang, Shigui; Yu, Chengbo; Chen, Ping; Deng, Min; Cao, Qing; Li, Yiping; Ren, Jingjing; Xu, Kaijin; Yao, Jun; Xie, Tiansheng; Wang, Chencheng; Cui, Yuanxia; Ding, Cheng; Tian, Guo; Wang, Bing; Zhang, Xiaoyan; Ruan, Bing; Li, Lanjuan


    The hepatitis B prevalence rate in adults is still at a high to intermediate level in China. Our purpose was to explore the incidence rate and protective immune barrier against hepatitis B in adults in China. A sample of 317961 participants was multi-screened for hepatitis B surface antigens (HBsAg) in a large-scale cohort of the National Hepatitis B Demonstration Project. A total of 5401 persons were newly-infected, representing an incidence rate of 0.81 (95% CI: 0.77-0.85) per 100 person-years after adjusted by gender and age. History of acquired immune deficiency syndrome, birth prior to 1992, coastal residence, family history of HBV, and migrant worker status were significantly associated with higher incidence, while HBV vaccination and greater exercise with lower incidence. The hepatitis B surface antibody (HBsAb) positive rate was negatively correlated with the incidence rate of hepatitis B (r = -0.826). Linear fitting yielded an incidence rate of 1.23 plus 0.02 multiplied by HBsAb positive rate. The study firstly identified the HBsAg incidence rate, which was reduced to 0.1 per 100 person-years after vaccination coverage of about 64%. The protective immune barrier against hepatitis B needs to be established in individuals born prior to the advent of infant HBV vaccination.

  16. Glucose-6-phosphate dehydrogenase deficiency (United States)

    ... Glucose-6-phosphate dehydrogenase deficiency To use the sharing features on this page, please enable JavaScript. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a condition in which ...

  17. Growth Hormone Deficiency in Children (United States)

    ... c m y one in Children What is growth hormone deficiency? Growth hormone deficiency (GHD) is a rare condition in which the body does not make enough growth hormone (GH). GH is made by the pituitary gland, ...

  18. Immunity and immunization in elderly. (United States)

    Bourée, Patrice


    As the average life expectancy increases, retired people want to travel. Five to 8% of travellers in tropical areas are old persons. Immune system suffers of old age as the other organs. The number and the functions of the T-lymphocytes decrease, but the B-lymphocytes are not altered. So, the response to the vaccinations is slower and lower in the elderly. Influenza is a great cause of death rate in old people. The seroconversion, after vaccine, is 50% from 60 to 70 years old, 31% from 70 to 80 years old, and only 11% after 80 years old. But in public health, the vaccination reduced the morbidity by 25%, admission to hospital by 20%, pneumonia by 50%, and mortality by 70%. Antipoliomyelitis vaccine is useful for travellers, as the vaccines against hepatitis and typhoid fever. Pneumococcal vaccine is effective in 60%. Tetanus is fatal in at last 32% of the people above 80 years, therefore this vaccine is very important.

  19. New insights on the development of fungal vaccines: from immunity to recent challenges. (United States)

    Medici, Natasha P; Del Poeta, Maurizio


    Fungal infections are emerging as a major problem in part due to high mortality associated with systemic infections, especially in the case of immunocompromised patients. With the development of new treatments for diseases such as cancer and the acquired immune deficiency syndrome pandemic, the number of immunosuppressed patients has increased and, as a consequence, also the number of invasive fungal infections has increased. Several studies have proposed new strategies for the development of effective fungal vaccines. In addition, better understanding of how the immune system works against fungal pathogens has improved the further development of these new vaccination strategies. As a result, some fungal vaccines have advanced through clinical trials. However, there are still many challenges that prevent the clinical development of fungal vaccines that can efficiently immunise subjects at risk of developing invasive fungal infections. In this review, we will discuss these new vaccination strategies and the challenges that they present. In the future with proper investments, fungal vaccines may soon become a reality.

  20. New insights on the development of fungal vaccines: from immunity to recent challenges

    Directory of Open Access Journals (Sweden)

    Natasha P Medici


    Full Text Available Fungal infections are emerging as a major problem in part due to high mortality associated with systemic infections, especially in the case of immunocompromised patients. With the development of new treatments for diseases such as cancer and the acquired immune deficiency syndrome pandemic, the number of immunosuppressed patients has increased and, as a consequence, also the number of invasive fungal infections has increased. Several studies have proposed new strategies for the development of effective fungal vaccines. In addition, better understanding of how the immune system works against fungal pathogens has improved the further development of these new vaccination strategies. As a result, some fungal vaccines have advanced through clinical trials. However, there are still many challenges that prevent the clinical development of fungal vaccines that can efficiently immunise subjects at risk of developing invasive fungal infections. In this review, we will discuss these new vaccination strategies and the challenges that they present. In the future with proper investments, fungal vaccines may soon become a reality.

  1. The diagnostic value of protein induced by vitamin K absence or antagonist-ii in non-infant patients with acquired deficiency of vitamin K-dependent coagulation factors%维生素K缺乏或拮抗剂诱导的蛋白-Ⅱ在非婴儿获得性维生素K依赖性凝血因子缺乏症中的诊断意义

    Institute of Scientific and Technical Information of China (English)

    王静; 吴天勤; 任传路; 沈红石; 陈海飞; 余自强; 王兆钺


    目的 探讨维生素K缺乏或拮抗剂诱导的蛋白-Ⅱ(PIVKA-Ⅱ)在非婴儿获得性维生素K依赖性凝血因子缺乏症(ADVKCF)中的诊断价值.方法 对临床确诊的50例ADVKCF患者采用ELISA法检测治疗0、3、7d的血浆中PIVKA-Ⅱ水平,同时分析不同时间点凝血常规和凝血因子促凝活性,并以20例健康体检者作为对照.结果 患者PIVKA-Ⅱ水平为(3.83±1.40) μg/L,健康对照组为(1.30±0.54) μg/L,差异有统计学意义(P<0.05),患者接受维生素K治疗3d后其值与治疗前相比差异无统计学意义[(3.83±1.40) μg/L比(3.79 ±0.66)μg/L,P>0.05],7d后其值降低但仍高于对照组水平.近期输注血浆组PIVKA-Ⅱ水平为(3.78±1.30)μg/L,同未输注组[(3.91±1.49)μg/L]相比,差异无统计学意义(P>0.05).治疗前患者凝血因子Ⅱ、Ⅶ、Ⅸ及Ⅹ活性明显降低(3.68%~12.28%),而凝血酶原时间(PT)、APTT明显延长(>100 s),治疗1周后基本恢复正常.结论 ADVKCF患者血浆PIVKA-Ⅱ的水平升高,维生素K治疗1周后其值仍高于正常人的水平,且不受血浆输注的影响,PIVKA-Ⅱ较凝血常规、凝血因子活性检测更为灵敏,具有早期辅助诊断本病的价值.%Objective To explore the diagnostic value of protein induced by vitamin K absence or antagonist-Ⅱ (PIVKA-Ⅱ) in non-infant with acquired deficiency of vitamin K-dependent coagulation factors (ADVKCF).Methods PIVKA-Ⅱ levels were measured by ELISA in 50 patients with ADVKCF on day 0,3,7 after vitamin K treatment.Prothrombin time(PT),APTT,FⅡ ∶ C,FⅦ∶ C,FⅨ∶ C,and FⅩ∶ C were analyzed simultaneously.Twenty healthy subjects were enrolled as controls.Results The average level of PIVKA-Ⅱ in ADVKCF group was (3.83 ± 1.40) μg/L,while (1.30 ± 0.54) μg/L in the control group (P < 0.05).The PIVKA-Ⅱ levels on day 0 and 3 did not show significant difference [(3.83 ± 1.40) μg/Lvs (3.79 ± 0.66) μg/L,P > 0.05],but decreasing significantly on day 7

  2. Amphibians acquire resistance to live and dead fungus overcoming fungal immunosuppression. (United States)

    McMahon, Taegan A; Sears, Brittany F; Venesky, Matthew D; Bessler, Scott M; Brown, Jenise M; Deutsch, Kaitlin; Halstead, Neal T; Lentz, Garrett; Tenouri, Nadia; Young, Suzanne; Civitello, David J; Ortega, Nicole; Fites, J Scott; Reinert, Laura K; Rollins-Smith, Louise A; Raffel, Thomas R; Rohr, Jason R


    Emerging fungal pathogens pose a greater threat to biodiversity than any other parasitic group, causing declines of many taxa, including bats, corals, bees, snakes and amphibians. Currently, there is little evidence that wild animals can acquire resistance to these pathogens. Batrachochytrium dendrobatidis is a pathogenic fungus implicated in the recent global decline of amphibians. Here we demonstrate that three species of amphibians can acquire behavioural or immunological resistance to B. dendrobatidis. Frogs learned to avoid the fungus after just one B. dendrobatidis exposure and temperature-induced clearance. In subsequent experiments in which B. dendrobatidis avoidance was prevented, the number of previous exposures was a negative predictor of B. dendrobatidis burden on frogs and B. dendrobatidis-induced mortality, and was a positive predictor of lymphocyte abundance and proliferation. These results suggest that amphibians can acquire immunity to B. dendrobatidis that overcomes pathogen-induced immunosuppression and increases their survival. Importantly, exposure to dead fungus induced a similar magnitude of acquired resistance as exposure to live fungus. Exposure of frogs to B. dendrobatidis antigens might offer a practical way to protect pathogen-naive amphibians and facilitate the reintroduction of amphibians to locations in the wild where B. dendrobatidis persists. Moreover, given the conserved nature of vertebrate immune responses to fungi and the fact that many animals are capable of learning to avoid natural enemies, these results offer hope that other wild animal taxa threatened by invasive fungi might be rescued by management approaches based on herd immunity.

  3. Iron deficiency and cognitive functions

    Directory of Open Access Journals (Sweden)

    Jáuregui-Lobera I


    Full Text Available Ignacio Jáuregui-Lobera Department of Nutrition and Bromatology, Pablo de Olavide University, Seville, Spain Abstract: Micronutrient deficiencies, especially those related to iodine and iron, are linked to different cognitive impairments, as well as to potential long-term behavioral changes. Among the cognitive impairments caused by iron deficiency, those referring to attention span, intelligence, and sensory perception functions are mainly cited, as well as those associated with emotions and behavior, often directly related to the presence of iron deficiency anemia. In addition, iron deficiency without anemia may cause cognitive disturbances. At present, the prevalence of iron deficiency and iron deficiency anemia is 2%–6% among European children. Given the importance of iron deficiency relative to proper cognitive development and the alterations that can persist through adulthood as a result of this deficiency, the objective of this study was to review the current state of knowledge about this health problem. The relevance of iron deficiency and iron deficiency anemia, the distinction between the cognitive consequences of iron deficiency and those affecting specifically cognitive development, and the debate about the utility of iron supplements are the most relevant and controversial topics. Despite there being methodological differences among studies, there is some evidence that iron supplementation improves cognitive functions. Nevertheless, this must be confirmed by means of adequate follow-up studies among different groups. Keywords: iron deficiency, anemia, cognitive functions, supplementation

  4. Stroke in an Infant; Its Association with Antiphospholipid Antibody and Acquired Protein C and S Deficiencies

    Directory of Open Access Journals (Sweden)

    Soroor Inaloo Mohammad Ghofrani


    Full Text Available We present the first reported case of antiphospholipid syndrome with stroke in an Iranian boy (7-month-old who had two ischemic strokes within a period of 2 months. Serum anticardiolipid antibody was positive and the patient had low levels of protein S and C. This case emphasizes the importance of antiphospholipid antibody in children with unexplained ischemic stroke.

  5. Roundtable for the Development of Drugs and Vaccines Against Acquired Immuno Deficiency Syndrome (AIDS). (United States)


    begin the first of tbree phases of clinical trials -that is, the sponsor files an IND. Phase I studies usually take a year and may involve up to 50...three phases of clinical trials arc favorable and the sponsor decides to market the drug, it submits a new drug application to the FDA. The NDA must

  6. Acquired von Willebrand disease as a cause of recurrent mucocutaneous bleeding in primary thrombocythemia: Relationship with platelet count

    NARCIS (Netherlands)

    P.J.J. van Genderen (Perry); J.J. Michiels (Jan); S.C. van der Poel-van de Luytgaarde (Sonja); H.H.D.M. van Vliet (Huib)


    textabstractWe present a 4-year follow-up of a 42-year-old patient with primary thrombocythemia whose clinical course was complicated by two major mucocutaneous bleeding episodes. On both occasions an acquired functional von Willebrand factor deficiency was demonstrated. In contrast to what is repor

  7. A New Cultivation-Evolution Technology of Accident Immune Function for a Petrochemical Enterprise

    Institute of Scientific and Technical Information of China (English)

    Yang Zhenhong; Zhang Xuhua; Wang Xiangyao; Wang Zhihu; Liu Yan; Zhang Xuan


    For the purpose of developing an immune function on production accidents in a petrochemical enterprise, a new cultivation-evolution approach of preventive mechanism is suggested by analyzing various factors relating to immune deficiency syndrome and by referring to immunity genetic algorithm and relevant concepts applied in medicine science. Accident-immunity system for highly hazardous petrochemical enterprise, which is made up of its productive system's Safety Organ and Safety Organization, is typically an evolution-cultivation progress for immune function, The new B immune cell is generated after several layers' screening, clone expanding, receptor editing, organizing in immune system of work accident in petrochemical enterprise. There is a B immune cell with high appetency and a manipulative function chain for accident-immunity. Taking the antigen of accidents in industry as the target function and the immune antibody as the solution, the authors carried out a computation diagram for prediction of appetency between the antigen and antibody.

  8. Proximal Focal Femoral Deficiency

    Directory of Open Access Journals (Sweden)

    Vishal Kalia, Vibhuti


    Full Text Available Proximal focal femoral deficiency (PFFD is a developmental disorder of the proximal segment of thefemur and of acetabulum resulting in shortening of the affected limb and impairment of the function. It isa spectrum of congenital osseous anomalies characterized by a deficiency in the structure of the proximalfemur. The diagnosis is often made by radiological evaluation which includes identification and descriptionof PFFD and evaluation of associated limb anomalies by plain radiographs. Contrast arthrography orMagnetic Resonance Imaging is indicated when radiological features are questionable and to disclose thepresence and location of the femoral head and any cartilagenous anlage. The disorder is more commonlyunilateral and is apparent at birth. However, bilateral involvement is rarely seen. Therapy of the disorder isdirected towards satisfactory ambulation and specific treatment depending on the severity of dysplasia.

  9. Micronutrient deficiency in children. (United States)

    Bhan, M K; Sommerfelt, H; Strand, T


    Malnutrition increases morbidity and mortality and affects physical growth and development, some of these effects resulting from specific micronutrient deficiencies. While public health efforts must be targeted to improve dietary intakes in children through breast feeding and appropriate complementary feeding, there is a need for additional measures to increase the intake of certain micronutrients. Food-based approaches are regarded as the long-term strategy for improving nutrition, but for certain micronutrients, supplementation, be it to the general population or to high risk groups or as an adjunct to treatment must also be considered. Our understanding of the prevalence and consequences of iron, vitamin A and iodine deficiency in children and pregnant women has advanced considerably while there is still a need to generate more knowledge pertaining to many other micronutrients, including zinc, selenium and many of the B-vitamins. For iron and vitamin A, the challenge is to improve the delivery to target populations. For disease prevention and growth promotion, the need to deliver safe but effective amounts of micronutrients such as zinc to children and women of fertile age can be determined only after data on deficiency prevalence becomes available and the studies on mortality reduction following supplementation are completed. Individual or multiple micronutrients must be used as an adjunct to treatment of common infectious diseases and malnutrition only if the gains are substantial and the safety window sufficiently wide. The available data for zinc are promising with regard to the prevention of diarrhea and pneumonia. It should be emphasized that there must be no displacement of important treatment such as ORS in acute diarrhea by adjunct therapy such as zinc. Credible policy making requires description of not only the clinical effects but also the underlying biological mechanisms. As findings of experimental studies are not always feasible to extrapolate to

  10. Orexin deficiency and narcolepsy


    Sakurai, Takeshi


    Orexin deficiency results in the sleep disorder narcolepsy in many mammalian species, including mice, dogs, and humans, suggesting that the orexin system is particularly important for normal regulation of sleep/wakefulness states, and especially for maintenance of wakefulness. This review discusses animal models of narcolepsy; the contribution of each orexin receptor subtype to the narcoleptic phenotypes; and the etiology of orexin neuronal death. It also raises the possibility of novel thera...

  11. Systemic Acquired Resistance and Signal Transduction in Plant

    Institute of Scientific and Technical Information of China (English)

    ZHAO Shu-qing; GUO Jian-bo


    Systemic acquired resistance (SAR), known as the broad-spectrum, inducible plant immunity,is a defense response triggered by pathogen infection. The response starts from the recognition of plant resist-ance (R) with the corresponding avirulence (avr) gene from the pathogen. There are some genes for conver-gence of signals downstream of different R/avr interacting partners into a single signaling pathway. Salicylicacid (SA) is required for the induction of SAR and involved in transducing the signal in target tissues. The SAsignal is transduced through NPR1, a nuclear-localized protein that interacts with transcription factors thatare involved in regulating SA-mediated gene expression. Some chemicals that mimic natural signaling com-pounds can also activate SAR. The application of biochemical activators to agriculture for plant protection is anovel idea for developing green chemical pesticide.

  12. A Case of angioedema : C1 inhibitor deficiency

    Directory of Open Access Journals (Sweden)

    Arijit Sinha


    Full Text Available Angioedema is rapid swelling (oedema of subcutaneous tissue involving dermis, mucosa and sub mucosal tissues. It may be IgE dependant, bradykinin mediated, complement mediated, non immunologic or idiopathic. It may be heriditory or acquired. In our case the child was suffering from recurrent episodes of angioedema and found to be due to C1 inhibitor deficiency. [Natl J Med Res 2015; 5(1.000: 89-90

  13. The scrutiny of identifying community-acquired pneumonia episodes quantified bias in absolute effect estimation in a population-based pneumococcal vaccination trial

    NARCIS (Netherlands)

    Van Werkhoven, Cornelis H.; Huijts, Susanne M.; Paling, Fleur P.; Bonten, Marc J M


    Objectives To determine the accurateness of detecting community-acquired pneumonia (CAP) in the Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA), a community-based, double-blind, randomized placebo-controlled trial in which the needed to treat (NNT) for prevention of vaccine-type p

  14. Iron-Deficiency Anemia (For Parents) (United States)

    ... Your 1- to 2-Year-Old Iron-Deficiency Anemia KidsHealth > For Parents > Iron-Deficiency Anemia Print A ... common nutritional deficiency in children. About Iron-Deficiency Anemia Every red blood cell in the body contains ...

  15. Iron-Deficiency Anemia (For Parents) (United States)

    ... Your 1- to 2-Year-Old Iron-Deficiency Anemia KidsHealth > For Parents > Iron-Deficiency Anemia A A ... common nutritional deficiency in children. About Iron-Deficiency Anemia Every red blood cell in the body contains ...

  16. Antigen-specific IgA titres after 23-valent pneumococcal vaccine indicate transient antibody deficiency disease in children

    NARCIS (Netherlands)

    Janssen, Willemijn J M; Nierkens, Stefan; Sanders, Elisabeth A; Boes, Marianne; van Montfrans, Joris M


    Paediatric patients with antibody deficiency may either be delayed in development of humoral immunity or may be persistently deficient in antibody production. To differentiate between these entities, we examined the 23-valent pneumococcal polysaccharide (PnPS) vaccine-induced IgM-, IgG- and IgA anti

  17. 7 CFR 926.10 - Acquire. (United States)



  18. Hospital-Acquired Condition Reduction Program (United States)

    U.S. Department of Health & Human Services — In October 2014, CMS began reducing Medicare payments for subsection (d) hospitals that rank in the worst performing quartile with respect to hospital-acquired...

  19. Enhancing Medicares Hospital Acquired Conditions Policy (United States)

    U.S. Department of Health & Human Services — The current Medicare policy of non-payment to hospitals for Hospital Acquired Conditions (HAC) seeks to avoid payment for preventable complications identified within...

  20. Orchestration of angiogenesis by immune cells

    Directory of Open Access Journals (Sweden)

    Antonino eBruno


    Full Text Available It is widely accepted that the tumor microenvironment plays a major role in cancer and is indispensable for tumor progression. The tumor microenvironment involves many players going well beyond the malignant-transformed cells, including stromal, immune and endothelial cells. The non-malignant cells can acquire tumor-promoting functions during carcinogenesis. In particular, these cells can orchestrate the symphony of the angiogenic switch, permitting the creation of new blood vessels that allows rapid expansion and progression toward malignancy.Considerable attention within the context of tumor angiogenesis should focus not only on the endothelial cells, representing a fundamental unit, but also on immune cells and on the inflammatory tumor infiltrate. Immune cells infiltrating tumors typically show a tumor-induced polarization associated with attenuation of anti-tumor functions and generation of pro-tumor activities, among these angiogenesis. Here we propose a scenario suggesting that the angiogenic switch is an immune switch arising from the pro-angiogenic polarization of immune cells. This view links immunity, inflammation and angiogenesis to tumor progression. Here we review the data in the literature and seek to identify the conductors of this orchestra. We also suggest that interrupting the immune -> inflammation -> angiogenesis -> tumor progression process can delay or prevent tumor insurgence and malignant disease.