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Sample records for deficiency syndrome vaccine

  1. Genetics Home Reference: GLUT1 deficiency syndrome

    Science.gov (United States)

    ... Facebook Twitter Home Health Conditions GLUT1 deficiency syndrome GLUT1 deficiency syndrome Enable Javascript to view the expand/ ... boxes. Download PDF Open All Close All Description GLUT1 deficiency syndrome is a disorder affecting the nervous ...

  2. Cryptosporidiosis in the acquired immune deficiency syndrome.

    Science.gov (United States)

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

    1984-10-01

    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.

  3. Iron Deficiency in Autism and Asperger Syndrome.

    Science.gov (United States)

    Latif, A.; Heinz, P.; Cook, R.

    2002-01-01

    Retrospective analysis of the full blood count and, when available, serum ferritin measurements of 96 children (52 with autism and 44 with Asperger syndrome) found six autistic children had iron deficiency and 12 of the 23 autistic children with serum ferritin measures were iron deficient. Far fewer Asperger children were iron deficient. Results…

  4. New Data on Vaccine Antigen Deficient Bordetella pertussis Isolates

    Directory of Open Access Journals (Sweden)

    Valérie Bouchez

    2015-09-01

    Full Text Available Evolution of Bordetella pertussis is driven by natural and vaccine pressures. Isolates circulating in regions with high vaccination coverage present multiple allelic and antigenic variations as compared to isolates collected before introduction of vaccination. Furthermore, during the last epidemics reported in regions using pertussis acellular vaccines, isolates deficient for vaccine antigens, such as pertactin (PRN, were reported to reach high proportions of circulating isolates. More sporadic filamentous hemagglutinin (FHA or pertussis toxin (PT deficient isolates were also collected. The whole genome of some recent French isolates, deficient or non-deficient in vaccine antigens, were analyzed. Transcription profiles of the expression of the main virulence factors were also compared. The invasive phenotype in an in vitro human tracheal epithelial (HTE cell model of infection was evaluated. Our genomic analysis focused on SNPs related to virulence genes known to be more likely to present allelic polymorphism. Transcriptomic data indicated that isolates circulating since the introduction of pertussis vaccines present lower transcription levels of the main virulence genes than the isolates of the pre-vaccine era. Furthermore, isolates not producing FHA present significantly higher expression levels of the entire set of genes tested. Finally, we observed that recent isolates are more invasive in HTE cells when compared to the reference strain, but no multiplication occurs within cells.

  5. Androgen deficiency and metabolic syndrome in men

    OpenAIRE

    Winter, Ashley G; Zhao, Fujun; Lee, Richard K.

    2014-01-01

    Metabolic syndrome (MetS) is a growing health concern worldwide. Initially a point of interest in cardiovascular events, the cluster of HTN, obesity, dyslipidemia, and insulin resistance known as MetS has become associated with a variety of other disease processes, including androgen deficiency and late-onset hypogonadism (LOH). Men with MetS are at a higher risk of developing androgen deficiency, and routine screening of testosterone (T) is advised in this population. The pathophysiology of ...

  6. Sneddon syndrome associated with Protein S deficiency.

    Science.gov (United States)

    Sayin, Refah; Bilgili, Serap Gunes; Karadag, Ayse Serap; Tombul, Temel

    2012-01-01

    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.

  7. [Testosterone deficiency, metabolic syndrome and diabetes mellitus].

    Science.gov (United States)

    Fernández-Miró, Mercè; Chillarón, Juan J; Pedro-Botet, Juan

    2016-01-15

    Testosterone deficiency in adult age is associated with a decrease in libido, energy, hematocrit, muscle mass and bone mineral density, as well as with depression. More recently, testosterone deficiency has also been associated with various components of the metabolic syndrome, which in turn is associated with a five-fold increase in the risk of cardiovascular disease. Low testosterone levels are associated with increased insulin resistance, increase in fat mass, low HDL cholesterol, higher triglyceride levels and hypertension. Testosterone replacement therapy in patients with testosterone deficiency and type 2 diabetes mellitus and/or metabolic syndrome has shown reductions in insulin resistance, total cholesterol, LDL cholesterol and triglycerides and improvement in glycemic control and anthropometric parameters. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

  8. Sneddon syndrome associated with Protein S deficiency

    Directory of Open Access Journals (Sweden)

    Refah Sayin

    2012-01-01

    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.

  9. Atypical Manifestations in Glut1 Deficiency Syndrome.

    Science.gov (United States)

    De Giorgis, V; Varesio, C; Baldassari, C; Piazza, E; Olivotto, S; Macasaet, J; Balottin, U; Veggiotti, P

    2016-08-01

    Glucose transporter type 1 deficiency syndrome is a genetically determined, treatable, neurologic disorder that is caused by an insufficient transport of glucose into the brain. It is caused by a mutation in the SCL2A1 gene, which is so far the only known to be associated with this condition. Glucose transporter type 1 deficiency syndrome consists of a wide clinical spectrum that usually presents with cognitive impairment, epilepsy, paroxysmal exercise-induced dyskinesia, acquired microcephaly, hemolytic anemia, gait disturbance, and dyspraxia in different combinations. However, there are other clinical manifestations that we consider equally peculiar but that have so far been poorly described in literature. In this review, supported by a video contribution, we will accurately describe this type of clinical manifestation such as oculogyric crises, weakness, paroxysmal kinesigenic and nonkinesigenic dyskinesia in order to provide an additional instrument for a correct, rapid diagnosis. © The Author(s) 2016.

  10. Acquired immune deficiency syndrome: review.

    Science.gov (United States)

    Scully, C; Cawson, R A; Porter, S R

    1986-07-19

    Acquired immunodeficiency syndrome (AIDS) is reviewed for dental practitioners, with an emphasis on oral findings; the clinical course, diagnosis, reporting, treatment, prognosis, transmission, and epidemiology are also covered. HIV infection has an incubation period that may be associated with glandular fever, a prodrome called AIDS-Related Complex (ARC) characterized by lymphadenopathy, low fever, weight loss, night sweats, diarrhea, oral candidosis, nonproductive cough and recurrent infections. AIDS is characterized by opportunistic infections. Over 50% present with pneumocystis carinii pneumonia, 21% with Kaposi's sarcoma, and 6% have both. The AIDS virus causes direct neurological symptoms in some cases. Oral candidosis (thrush) in a young male without a local cause such as xerostomia or immune suppression is strongly suggestive of AIDS. Other oral manifestations are severe herpes simplex, varicella-zoster, Epstein-Barr virus, cytomegalovirus, venereal warts, aphthous ulceration, mycobacterial oral ulcers, oral histoplasmosis, sinusitis and osteomyelitis of the jaw. Hairy leukoplakia, usually seen on the lateral border of the tongue, is probably caused by Epstein-Barr virus. Kaposi's sarcoma, an endothelial cell tumor, is characteristic of AIDS, and in 50% of patients is oral or perioral. Cervical lymph node enlargement will be seen in those with ARC as well as AIDS. No guidelines have been issued by the Department of Health and Social Security for dental surgeons in the UK for reporting AIDS cases. Although HIV virions have been isolated from saliva, there are no known incidents of transmission via saliva. HIV is less likely to be transmitted by needle stick injuries than, for example hepatitis B (25% risk), especially if the blood is from a carrier rather than a full blown AIDS case.

  11. Development of replication-deficient adenovirus malaria vaccines.

    Science.gov (United States)

    Hollingdale, Michael R; Sedegah, Martha; Limbach, Keith

    2017-03-01

    Malaria remains a major threat to endemic populations and travelers, including military personnel to these areas. A malaria vaccine is feasible, as radiation attenuated sporozoites induce nearly 100% efficacy. Areas covered: This review covers current malaria clinical trials using adenoviruses and pre-clinical research. Heterologous prime-boost regimens, including replication-deficient human adenovirus 5 (HuAd5) carrying malaria antigens, are efficacious. However, efficacy appears to be adversely affected by pre-existing anti-HuAd5 antibodies. Current strategies focus on replacing HuAd5 with rarer human adenoviruses or adenoviruses isolated from non-human primates (NHPs). The chimpanzee adenovirus ChAd63 is undergoing evaluation in clinical trials including infants in malaria-endemic areas. Key antigens have been identified and are being used alone, in combination, or with protein subunit vaccines. Gorilla adenoviruses carrying malaria antigens are also currently being evaluated in preclinical models. These replacement adenovirus vectors will be successfully used to develop vaccines against malaria, as well as other infectious diseases. Expert commentary: Simplified prime-boost single shot regimens, dry-coated live vector vaccines or silicon microneedle arrays could be developed for malaria or other vaccines. Replacement vectors with similar or superior immunogenicity have rapidly advanced, and several are now in extensive Phase 2 and beyond in malaria as well as other diseases, notably Ebola.

  12. Analysis of Gait Disturbance in Glut 1 Deficiency Syndrome.

    Science.gov (United States)

    Blumenschine, Michelle; Montes, Jacqueline; Rao, Ashwini K; Engelstad, Kristin; De Vivo, Darryl C

    2016-11-01

    Anticipating potential therapies for Glut 1 deficiency syndrome (Glut1DS) emphasizes the need for effective clinical outcome measures. The 6-minute walk test is a well-established outcome measure that evaluates walking ability in neurological diseases. Twenty-one children with Glut 1 deficiency syndrome and 21 controls performed the 6-minute walk test. Fatigue was determined by comparing distance walked in the first and sixth minutes. Gait was analyzed by stride length, velocity, cadence, base of support, and percentage time in double support. Independent sample t-tests examined differences between group. Repeated-measures analysis of variance evaluated gait parameters over time. Glut 1 deficiency syndrome patients walked less (P Glut 1 deficiency syndrome patients have impaired motor performance, walk more slowly, and have poor balance. The 6-minute walk test with gait analysis may serve as a useful outcome measure in clinical trials in Glut 1 deficiency syndrome.

  13. Hyperthyroidism caused by acquired immune deficiency syndrome.

    Science.gov (United States)

    Wang, J-J; Zhou, J-J; Yuan, X-L; Li, C-Y; Sheng, H; Su, B; Sheng, C-J; Qu, S; Li, H

    2014-01-01

    Acquired immune deficiency syndrome (AIDS) is an immune deficiency disease. The etiology of hyperthyroidism, which can also be immune-related, is usually divided into six classical categories, including hypophyseal, hypothalamic, thyroid, neoplastic, autoimmune and inflammatory hyperthyroidism. Hyperthyroidism is a rare complication of highly active antimicrobial therapy (HAART) for human immunodeficiency virus (HIV). Hyperthyroidism caused directly by AIDS has not been previously reported. A 29-year-old man who complained of dyspnea and asthenia for 1 month, recurrent fever for more than 20 days, and breathlessness for 1 week was admitted to our hospital. The thyroid function test showed that the level of free thyroxine (FT4) was higher than normal and that the level of thyroid-stimulating hormone (TSH) was below normal. He was diagnosed with hyperthyroidism. Additional investigations revealed a low serum albumin level and chest infection, along with diffuse lung fibrosis. Within 1 month, he experienced significant weight loss, no hand tremors, intolerance of heat, and perspiration proneness. We recommended an HIV examination; subsequently, AIDS was diagnosed based on the laboratory parameters. This is the first reported case of hyperthyroidism caused by AIDS. AIDS may cause hyperthyroidism by immunization regulation with complex, atypical, and easily ignored symptoms. Although hyperthyroidism is rare in patients with AIDS, clinicians should be aware of this potential interaction and should carefully monitor thyroid function in HIV-positive patients.

  14. Sudden Infant Death Syndrome (SIDS) and Vaccines

    Science.gov (United States)

    ... Vaccine Safety Shingles (Herpes Zoster) Vaccine Safety Smallpox Vaccine Safety Common Concerns Adjuvants Autism CDC Statement: 2004 Pediatrics Paper on MMR and Autism Fainting (Syncope) Febrile ...

  15. Inactivated and subunit vaccines against porcine reproductive and respiratory syndrome: Current status and future direction.

    Science.gov (United States)

    Renukaradhya, Gourapura J; Meng, Xiang-Jin; Calvert, Jay G; Roof, Michael; Lager, Kelly M

    2015-06-17

    Within a few years of its emergence in the late 1980s, the PRRS virus had spread globally to become the foremost infectious disease concern for the pork industry. Since 1994, modified live-attenuated vaccines against porcine reproductive and respiratory syndrome virus (PRRSV-MLV) have been widely used, but have failed to provide complete protection against emerging and heterologous field strains of the virus. Moreover, like many other MLVs, PRRSV-MLVs have safety concerns including vertical and horizontal transmission of the vaccine virus and several documented incidences of reversion to virulence. Thus, the development of efficacious inactivated vaccines is warranted for the control and eradication of PRRS. Since the early 1990s, researchers have been attempting to develop inactivated PRRSV vaccines, but most of the candidates have failed to elicit protective immunity even against homologous virus challenge. Recent research findings relating to both inactivated and subunit candidate PRRSV vaccines have shown promise, but they need to be pursued further to improve their heterologous efficacy and cost-effectiveness before considering commercialization. In this comprehensive review, we provide information on attempts to develop PRRSV inactivated and subunit vaccines. These includes various virus inactivation strategies, adjuvants, nanoparticle-based vaccine delivery systems, DNA vaccines, and recombinant subunit vaccines produced using baculovirus, plant, and replication-deficient viruses as vector vaccines. Finally, future directions for the development of innovative non-infectious PRRSV vaccines are suggested. Undoubtedly there remains a need for novel PRRSV vaccine strategies targeted to deliver cross-protective, non-infectious vaccines for the control and eradication of PRRS.

  16. Diagnostic criteria for constitutional mismatch repair deficiency syndrome

    DEFF Research Database (Denmark)

    Wimmer, Katharina; Kratz, Christian P; Vasen, Hans F A;

    2014-01-01

    Constitutional mismatch repair deficiency (CMMRD) syndrome is a distinct childhood cancer predisposition syndrome that results from biallelic germline mutations in one of the four MMR genes, MLH1, MSH2, MSH6 or PMS2. The tumour spectrum is very broad, including mainly haematological, brain...

  17. Mumps, measles and rubella vaccination in children with PFAPA syndrome.

    Science.gov (United States)

    Kraszewska-G Omba, Barbara; Matkowska-Kocjan, Agnieszka; Mi Kiewicz, Katarzyna; Szyma Ska-Toczek, Zofia; Wójcik, Marta; Bany, Dorota; Szenborn, Leszek

    2016-11-21

    There is no published data regarding immunologic response to vaccinations in children with PFAPA syndrome (periodic fever, aphthous stomatitis, pharyngitis and cervical adenitis). The aim of this study was to evaluate mumps, measles and rubella immunity in children with PFAPA. 31 children with PFAPA syndrome and 22 healthy children (control group - CG) were recruited to the study. All children were previously vaccinated with one dose of MMR vaccine according to the Polish obligatory vaccination schedule. The patients from both groups were evaluated for anti-measles, anti-mumps and anti-rubella IgG antibodies concentrations (ELISA tests; the reference values for protective antibody levels were 150IU/L, 16RU/L and 11IU/ml respectively). The percentage of patients with protective antibodies levels was as follows: measles - 93.55% of PFAPA and 95.45% of CG patients (p=0.77); mumps - 74.19% of PFAPA and 95.45% of CG patients (p=0.02); rubella - 80.65% of PFAPA and 90.9% of CG patients (p=0.30). Children with PFAPA syndrome present a good response to the measles and rubella component of the MMR vaccine, however immunity against mumps after one dose of MMR may not be sufficient. Further investigation concerning immunity against vaccine-preventable diseases and the safety of vaccinations in children with periodic fever syndromes is required. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Glut1 deficiency syndrome and novel ketogenic diets.

    Science.gov (United States)

    Klepper, Joerg; Leiendecker, Baerbel

    2013-08-01

    The classical ketogenic diet has been used for refractory childhood epilepsy for decades. It is also the treatment of choice for disorders of brain energy metabolism, such as Glut1 deficiency syndrome. Novel ketogenic diets such as the modified Atkins diet and the low glycemic index treatment have significantly improved the therapeutic options for dietary treatment. Benefits of these novel diets are increased palatability, practicability, and thus compliance-at the expense of lower ketosis. As high ketones appear essential to meet the brain energy deficit caused by Glut1 deficiency syndrome, the use of novel ketogenic diets in this entity may be limited. This article discusses the current data on novel ketogenic diets and the implications on the use of these diets in regard to Glut1 deficiency syndrome.

  19. Guillain-Barré Syndrome (GBS) and Flu Vaccine

    Science.gov (United States)

    ... and Flu Vaccines Vaccine Effectiveness Types of Flu Vaccine Flu Shot Quadrivalent Influenza Vaccine Intradermal Influenza (Flu) Vaccination ... Cell-Based Flu Vaccines Flublok Seasonal Influenza (Flu) Vaccine Flu Vaccination by Jet Injector Adjuvant Vaccine Vaccine Virus ...

  20. Exceptional Association Between Klinefelter Syndrome and Growth Hormone Deficiency

    OpenAIRE

    Sana Doubi; Zoubida Amrani; Hanan El Ouahabi; Saïd Boujraf; Farida Ajdi

    2015-01-01

    Klinefelter syndrome (KS) is characterized in adults by the combination of a tall stature, small testes, gynecomastia, and azoospermia. This case is described in a North African population of the Mediterranean region of North Africa. We report the case of a male 16 years old, of Arab ethnic origin, and diagnosed with this syndrome, who had a small height in relation to a growth hormone (GH) deficiency and a history of absence seizures (generalized myoclonic epilepsy). The patient′s size was

  1. West syndrome due to vitamin B12 deficiency.

    Science.gov (United States)

    Serin, Hepsen Mine; Kara, Aslıhan Oruçoğlu; Oğuz, Baran

    2015-12-01

    Vitamin B12 is one of the essential vitamins affecting various systems of the body. Vitamin B12 deficiency in infants often produces haematological and neurological deficits including macrocyticanaemia, neurodevelopmental delay or regression, irritability, weakness, hypotonia, ataxia, apathy, tremor andseizures. In this article, we report the case of a six-month-old male patient diagnosed with West syndrome associated with vitamin B12 deficiency. Although the patient had no evidence of macrocytic anemia in complete blood count, we measured the level of vitamin B12 because the patient had hypotonicity and found it to be low. No other problem was found in the other investigations directed to the etiology of West syndrome. He was being exclusively breast-fed and vitamin B12 deficiency was related with nutritional inadequacy of his mother. Vitamin B12 deficiency should be considered in the differential diagnosis of patients presenting with different neurological findings. In addition, vitamin B12 deficiency should be considered as a rare cause in West syndrome which has a heterogeneous etiology.

  2. Growth hormone deficiency in a Nigerian child with Turner's syndrome

    African Journals Online (AJOL)

    IRORO YARHERE

    Keywords: Turner's syndrome, short stature, growth hormone deficiency, ... CD is a 15-year-old female who presented to the consultant paediatric .... system thus promoting growth.4,7,8 Randomised controlled trials have ... improve non-verbal processing speed, motor performance and verbal and non-verbal memory.

  3. An unusual ocular presentation of acquired immune deficiency syndrome

    Directory of Open Access Journals (Sweden)

    Arunachalam Cynthia

    2008-01-01

    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.

  4. Augmented cell death with Bloom syndrome helicase deficiency.

    Science.gov (United States)

    Kaneko, Hideo; Fukao, Toshiyuki; Kasahara, Kimiko; Yamada, Taketo; Kondo, Naomi

    2011-01-01

    Bloom syndrome (BS) is a rare autosomal genetic disorder characterized by lupus-like erythematous telangi-ectasias of the face, sun sensitivity, infertility, stunted growth, upper respiratory infection, and gastrointestinal infections commonly associated with decreased immuno-globulin levels. The syndrome is associated with immuno-deficiency of a generalized type, ranging from mild and essentially asympto-matic to severe. Chromosomal abnormalities are hallmarks of the disorder, and high frequencies of sister chromatid exchanges and quadriradial configurations in lymphocytes and fibroblasts are diagnostic features. BS is caused by mutations in BLM, a member of the RecQ helicase family. We determined whether BLM deficiency has any effects on cell growth and death in BLM-deficient cells and mice. BLM-deficient EB-virus-transformed cell lines from BS patients and embryonic fibroblasts from BLM-/- mice showed slower growth than wild-type cells. BLM-deficient cells showed abnormal p53 protein expression after irradiation. In BLM-/- mice, small body size, reduced number of fetal liver cells and increased cell death were observed. BLM deficiency causes the up-regulation of p53, double-strand break and apoptosis, which are likely observed in irradiated control cells. Slow cell growth and increased cell death may be one of the causes of the small body size associated with BS patients.

  5. Exceptional Association Between Klinefelter Syndrome and Growth Hormone Deficiency.

    Science.gov (United States)

    Doubi, Sana; Amrani, Zoubida; Ouahabi, Hanan El; Boujraf, Saïd; Ajdi, Farida

    2015-01-01

    Klinefelter syndrome (KS) is characterized in adults by the combination of a tall stature, small testes, gynecomastia, and azoospermia. This case is described in a North African population of the Mediterranean region of North Africa. We report the case of a male 16 years old, of Arab ethnic origin, and diagnosed with this syndrome, who had a small height in relation to a growth hormone (GH) deficiency and a history of absence seizures (generalized myoclonic epilepsy). The patient's size was Klinefelter syndrome - on the contrary, the presence of any associated sign (brain maturation, delay in puberty, aggressiveness) should encourage one to request a karyotype for the diagnosis and appropriate care of any case of KS that can be associated with GH deficiency, or which is in a variant form (isochromosome Xq, 49,XXXXY).

  6. The spectrum of post-vaccination inflammatory CNS demyelinating syndromes.

    Science.gov (United States)

    Karussis, Dimitrios; Petrou, Panayiota

    2014-03-01

    A wide variety of inflammatory diseases temporally associated with the administration of various vaccines, has been reported in the literature. A PubMed search from 1979 to 2013 revealed seventy one (71) documented cases. The most commonly reported vaccinations that were associated with CNS demyelinating diseases included influenza (21 cases), human papilloma virus (HPV) (9 cases), hepatitis A or B (8 cases), rabies (5 cases), measles (5 cases), rubella (5 cases), yellow fever (3 cases), anthrax (2 cases),meningococcus (2 cases) and tetanus (2 cases). The vast majority of post-vaccination CNS demyelinating syndromes, are related to influenza vaccination and this could be attributed to the high percentage of the population that received the vaccine during the HI1N1 epidemia from 2009 to 2012. Usually the symptoms of the CNS demyelinating syndrome appear few days following the immunization (mean: 14.2 days) but there are cases where the clinical presentation was delayed (more than 3 weeks or even up to 5 months post-vaccination) (approximately a third of all the reported cases). In terms of the clinical presentation and the affected CNS areas, there is a great diversity among the reported cases of post-vaccination acute demyelinating syndromes. Optic neuritis was the prominent clinical presentation in 38 cases, multifocal disseminated demyelination in 30, myelitis in 24 and encephalitis in 17. Interestingly in a rather high proportion of the patients (and especially following influenza and human papiloma virus vaccination-HPV) the dominant localizations of demyelination were the optic nerves and the myelon, presenting as optic neuritis and myelitis (with or without additional manifestations of ADEM), reminiscent to neuromyelitic optica (or, more generally, the NMO-spectrum of diseases). Seven patients suffered an NMO-like disease following HPV and we had two similar cases in our Center. One patient with post-vaccination ADEM, subsequently developed NMO. Overall, the

  7. Correction of Iron Deficiency in the Cardiorenal Syndrome

    Directory of Open Access Journals (Sweden)

    Donald S. Silverberg

    2011-01-01

    Full Text Available Impaired energy metabolism is a feature of Congestive Heart Failure (CHF. Iron deficiency has been shown to reduce energy production in the cell in animals and humans. Iron deficiency is common in both Chronic Kidney Disease (CKD and in CHF. Recent studies suggest that iron deficiency is an independent risk factor for mortality in CHF. Studies of correction of the anemia with intravenous (IV iron in both CKD and CHF have shown an improvement in the anemia and, in some cases, in the renal function as well. Some CHF studies of correction of the iron deficiency have shown an improvement in cardiac function and structure as well as in exercise capacity and quality of life. This occurred independent of whether or not they had anemia, suggesting that the iron deficiency itself may be independently contributing to the worsening of the CHF and CKD. If future long-term studies confirm the safety and efficacy of IV iron in the treatment of iron deficiency in CKD and CHF, this will become a new addition to the therapeutic armamentarium of the cardiorenal syndrome, and parameters of iron deficiency will become part of the routine measurements performed in both CKD and CHF whether or not the patient is anemic.

  8. Vaccination with non-toxic mutant toxic shock syndrome toxin-1 induces IL-17-dependent protection against Staphylococcus aureus infection.

    Science.gov (United States)

    Narita, Kouji; Hu, Dong-Liang; Asano, Krisana; Nakane, Akio

    2015-06-01

    Toxic shock syndrome toxin-1 (TSST-1) is one of superantigens produced by Staphylococcus aureus. We have previously demonstrated that vaccination with non-toxic mutant TSST-1 (mTSST-1) develops host protection to lethal S. aureus infection in mice. However, the detailed mechanism underlying this protection is necessary to elucidate because the passive transfer of antibodies against TSST-1 fails to provide complete protection against S. aureus infection. In this study, the results showed that interleukin-17A (IL-17A)-producing cells were increased in the spleen cells of mTSST-1-vaccinated mice. The main source of IL-17A in mTSST-1-vaccinated mice was T-helper 17 (Th17) cells. The protective effect of vaccination was induced when the vaccinated wild type but not IL-17A-deficient mice were challenged with S. aureus. Gene expression of chemokines, CCL2 and CXCL1, and infiltration of neutrophils and macrophages were increased in spleens and livers of vaccinated mice after infection. The IL-17A-dependent immune response was TSST-1 specific because TSST-1-deficient S. aureus failed to induce the response. The present study suggests that mTSST-1 vaccination is able to provide the IL-17A-dependent host defense against S. aureus infection which promotes chemokine-mediated infiltration of phagocytes into the infectious foci.

  9. SCN1A-related Dravet syndrome : Vaccinations and seizure precipitants in disease course and diagnosis

    OpenAIRE

    2015-01-01

    Febrile seizures are well known adverse events following childhood vaccinations. If a seizure following vaccination is the first of an evolving epilepsy syndrome, the vaccination might be misinterpreted as the primary cause of the epilepsy. Dravet syndrome (formerly known as severe myoclonic epilepsy of infancy, or SMEI) is a rare epilepsy syndrome with seizure onset in the first year of life often triggered by fever or vaccinations, in a previously healthy child. In the second year or later,...

  10. HIV-2 and its role in conglutinated approach towards Acquired Immunodeficiency Syndrome (AIDS) Vaccine Development.

    Science.gov (United States)

    Diwan, Batul; Saxena, Rupali; Tiwari, Archana

    2013-12-01

    Acquired Immunodeficiency Syndrome (AIDS) is one of the most critically acclaimed endemic diseases, caused by two lentiviruses HIV-1 and 2. HIV-2 displays intimate serological and antigenic resemblance to Simian Immunodeficiency Virus (SIV) along with less pathogenicity, lower infectivity and appreciable cross reactivity with HIV-1 antigens. The present era is confronted with the challenge to fabricate a vaccine effective against all clades of both the species of HIV. But vaccine development against HIV-1 has proven highly intricate, moreover the laborious and deficient conventional approaches has slackened the pace regarding the development of new vaccines. These concerns may be tackled with the development of HIV-2 vaccine as a natural control of HIV-1 that has been found in ancestors of HIV-2 i.e. African monkeys, mangabeys and macaques. Thereby, suggesting the notion of cross protection among HIV-2 and HIV-1. Assistance of bioinformatics along with vaccinomics strategy can bring about a quantum leap in this direction for surpassing the bottleneck in conventional approaches. These specifics together can add to our conception that HIV-2 vaccine design by in silico strategy will surely be a constructive approach for HIV-1 targeting.

  11. Guillain-Barre syndrome following quadrivalent human papillomavirus vaccination among vaccine-eligible individuals in the United States.

    Science.gov (United States)

    Ojha, Rohit P; Jackson, Bradford E; Tota, Joseph E; Offutt-Powell, Tabatha N; Singh, Karan P; Bae, Sejong

    2014-01-01

    Post-marketing surveillance studies provide conflicting evidence about whether Guillain-Barre syndrome occurs more frequently following quadrivalent human papillomavirus (HPV4) vaccination. We aimed to assess whether Guillain-Barre syndrome is reported more frequently following HPV4 vaccination than other vaccinations among females and males aged 9 to 26 y in the United States. We used adverse event reports received by the United States Vaccine Adverse Event Reporting System (VAERS) between January 1, 2010 and December 31, 2012 to estimate overall, age-, and sex-specific proportional reporting ratios (PRRs) and corresponding Χ2 values for reports of Guillain-Barre syndrome between 5 and 42 d following HPV vaccination. Minimum criteria for a signal using this approach are 3 or more cases, PRR≥2, and Χ2≥4. Guillain-Barre syndrome was listed as an adverse event in 45 of 14,822 reports, of which 9 reports followed HPV4 vaccination and 36 reports followed all other vaccines. The overall, age-, and sex-specific PRR estimates were uniformly below 1. In addition, the overall, age-, and sex-specific Χ2 values were uniformly below 3. Our analysis of post-marketing surveillance data does not suggest that Guillain-Barre syndrome is reported more frequently following HPV4 vaccination than other vaccinations among vaccine-eligible females or males in the United States. Our findings may be useful when discussing the risks and benefits of HPV4 vaccination.

  12. Guillain–Barre syndrome following quadrivalent human papillomavirus vaccination among vaccine-eligible individuals in the United States

    Science.gov (United States)

    Ojha, Rohit P; Jackson, Bradford E; Tota, Joseph E; Offutt-Powell, Tabatha N; Singh, Karan P; Bae, Sejong

    2014-01-01

    Post-marketing surveillance studies provide conflicting evidence about whether Guillain–Barre syndrome occurs more frequently following quadrivalent human papillomavirus (HPV4) vaccination. We aimed to assess whether Guillain–Barre syndrome is reported more frequently following HPV4 vaccination than other vaccinations among females and males aged 9 to 26 y in the United States. We used adverse event reports received by the United States Vaccine Adverse Event Reporting System (VAERS) between January 1, 2010 and December 31, 2012 to estimate overall, age-, and sex-specific proportional reporting ratios (PRRs) and corresponding Χ2 values for reports of Guillain–Barre syndrome between 5 and 42 d following HPV vaccination. Minimum criteria for a signal using this approach are 3 or more cases, PRR ≥2, and Χ2 ≥ 4. Guillain–Barre syndrome was listed as an adverse event in 45 of 14 822 reports, of which 9 reports followed HPV4 vaccination and 36 reports followed all other vaccines. The overall, age-, and sex-specific PRR estimates were uniformly below 1. In addition, the overall, age-, and sex-specific Χ2 values were uniformly below 3. Our analysis of post-marketing surveillance data does not suggest that Guillain–Barre syndrome is reported more frequently following HPV4 vaccination than other vaccinations among vaccine-eligible females or males in the United States. Our findings may be useful when discussing the risks and benefits of HPV4 vaccination. PMID:24013368

  13. Deficiency of Bloom syndrome helicase activity is radiomimetic.

    Science.gov (United States)

    Horowitz, David P; Topaloglu, Ozlem; Zhang, Yonggang; Bunz, Fred

    2008-11-01

    Bloom syndrome is caused by homozygous mutations in BLM, which encodes a RecQ DNA helicase. Patient-derived cells deficient in BLM helicase activity exhibit genetic instability--apparent cytogenetically as sister chromatid exchanges--and activated DNA damage signaling. In this report, we show that BLM-knockout colorectal cancer cells exhibited endogenous, ATM-dependent double-strand DNA break responses similar to those recently observed in Bloom syndrome patient-derived cells. Xenograft tumors established from BLM-deficient cancer cells were not radiosensitive, but exhibited growth impairment that was comparable to that of wild type tumors treated with a single, high dose of ionizing radiation. These results suggest that pharmacological inhibitors of BLM would have a radiomimetic effect and that transient inhibition of BLM activity might be a viable strategy for anticancer therapy.

  14. Refeeding syndrome in a young woman with argininosuccinate lyase deficiency

    Directory of Open Access Journals (Sweden)

    M. Stuy

    2015-09-01

    Full Text Available A severely chronically protein and calorie restricted young woman with argininosuccinate lyase deficiency developed transient refeeding syndrome (RFS and hyperammonemia after modest diet liberalization following initiation of glycerol phenylbutyrate (GPB. The patient required IV supportive care and supplementation with potassium, magnesium and calcium. She is now doing well on GPB and an appropriate maintenance diet. Susceptibility to RFS should be considered in chronically nutritionally restricted patients with metabolic disorders after liberalization of diet.

  15. Refeeding syndrome in a young woman with argininosuccinate lyase deficiency.

    Science.gov (United States)

    Stuy, M; Chen, G-F; Masonek, J M; Scharschmidt, B F

    2015-09-01

    A severely chronically protein and calorie restricted young woman with argininosuccinate lyase deficiency developed transient refeeding syndrome (RFS) and hyperammonemia after modest diet liberalization following initiation of glycerol phenylbutyrate (GPB). The patient required IV supportive care and supplementation with potassium, magnesium and calcium. She is now doing well on GPB and an appropriate maintenance diet. Susceptibility to RFS should be considered in chronically nutritionally restricted patients with metabolic disorders after liberalization of diet.

  16. Refractory absence epilepsy associated with GLUT-1 deficiency syndrome.

    LENUS (Irish Health Repository)

    Byrne, Susan

    2011-05-01

    GLUT-1 deficiency syndrome (GLUT-1 DS) is a disorder of cerebral glucose transport associated with early infantile epilepsy and microcephaly. We report two boys who presented with refractory absence epilepsy associated with hypoglycorrhachia, both of whom have genetically confirmed GLUT-1 DS. We propose that these children serve to expand the phenotype of GLUT-1 DS and suggest that this condition should be considered as a cause of refractory absence seizures in childhood.

  17. Dopamine and glucose, obesity, and reward deficiency syndrome

    OpenAIRE

    Kenneth eBlum; Thanos, Panayotis K.; Mark Stephen Gold

    2014-01-01

    Obesity as a result of overeating as well as a number of well described eating disorders has been accurately considered to be a world-wide epidemic. Recently a number of theories backed by a plethora of scientifically sound neurochemical and genetic studies provide strong evidence that food addiction is similar to psychoactive drug addiction. Our laboratory has published on the concept known as Reward Deficiency Syndrome (RDS) which is a genetic and epigenetic phenomena leading to impairment ...

  18. [Vitamin D deficiency rickets complicating Dorfman-Chanarin syndrome].

    Science.gov (United States)

    Barraud, C; Cano, A; Boulay, C; Milh, M; Bollini, G; Chabrol, B

    2015-04-01

    Vitamin D deficiency rickets remains a public health issue in many parts of the world. In France, this diagnosis has almost disappeared since 1992 with routine vitamin D supplementation for children. Therefore, it is more difficult for doctors to identify risk factors and early signs of this disease. In this article, we report a rickets diagnosis acquired by vitamin D deficiency in a child who presented with the onset of a genu valgum and difficulty walking at the age of 9½ years. This patient was a Comorian child followed up from his birth for Dorfman-Chanarin syndrome. Dorfman-Chanarin syndrome is a rare disease, with about 80 cases reported in the literature. It belongs to the group of neutral lipid storage diseases (NLSD) characterized especially on the skin by ichthyosis. This child presented risk factors for vitamin D deficiency (dark skin color, prolonged and exclusive breastfeeding, premature end of supplementation, and particularly severe ichthyosis) that should have alerted us to the risk of vitamin D deficiency and the need for supplementation. This case highlights the importance of vitamin D, especially if there are risk factors such as ichthyosis, and the need to remain watchful in monitoring all chronic diseases.

  19. Pertactin deficient Bordetella pertussis present a better fitness in mice immunized with an acellular pertussis vaccine.

    Science.gov (United States)

    Hegerle, N; Dore, G; Guiso, N

    2014-11-20

    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.

  20. Defective anti-polysaccharide IgG vaccine responses in IgA deficient mice.

    Science.gov (United States)

    Furuya, Yoichi; Kirimanjeswara, Girish S; Roberts, Sean; Racine, Rachael; Wilson-Welder, Jennifer; Sanfilippo, Alan M; Salmon, Sharon L; Metzger, Dennis W

    2017-09-05

    We report that IgA(-/-) mice exhibit specific defects in IgG antibody responses to various polysaccharide vaccines (Francisella tularensis LPS and Pneumovax), but not protein vaccines such as Fluzone. This defect further included responses to polysaccharide-protein conjugate vaccines (Prevnar and Haemophilus influenzae type b-tetanus toxoid vaccine). In agreement with these findings, IgA(-/-) mice were protected from pathogen challenge with protein- but not polysaccharide-based vaccines. Interestingly, after immunization with live bacteria, IgA(+/+) and IgA(-/-) mice were both resistant to lethal challenge and their IgG anti-polysaccharide antibody responses were comparable. Immunization with live bacteria, but not purified polysaccharide, induced production of serum B cell-activating factor (BAFF), a cytokine important for IgG class switching; supplementing IgA(-/-) cell cultures with BAFF enhanced in vitro polyclonal IgG production. Taken together, these findings show that IgA deficiency impairs IgG class switching following vaccination with polysaccharide antigens and that live bacterial immunization can overcome this defect. Since IgA deficient patients also often show defects in antibody responses following immunization with polysaccharide vaccines, our findings could have relevance to the clinical management of this population. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. [The frequency and development of tissue iron deficiency in 6 iron deficiency anemia patients with plummer-vinson syndrome].

    Science.gov (United States)

    Uchida, T; Matsuno, M; Ide, M; Kawachi, Y

    1998-11-01

    The physical signs of tissue iron deficiency include smooth and red tongue, angular stomatitis, koilonychia, and pica. The incidence of these conditions is unknown in Japan. We evaluated the frequency and development of tissue iron deficiency in 353 patients with iron deficiency anemia. The frequency of tissue iron deficiency was 6.8%; papillary atrophy of the tongue, 5.4%; abnormal nails, 5.4%; angular stomatitis, 1.1%; Plummer-Vinson syndrome, 1.7%; and pica, 0.06%. These findings were compared with the date collected by Wintrobe and Beveridge. The development and incidence of tissue iron deficiency correlated significantly with the severity of iron deficiency anemia.

  2. SCN1A-related Dravet syndrome : Vaccinations and seizure precipitants in disease course and diagnosis

    NARCIS (Netherlands)

    Verbeek, N.E.

    2015-01-01

    Febrile seizures are well known adverse events following childhood vaccinations. If a seizure following vaccination is the first of an evolving epilepsy syndrome, the vaccination might be misinterpreted as the primary cause of the epilepsy. Dravet syndrome (formerly known as severe myoclonic

  3. SCN1A-related Dravet syndrome : Vaccinations and seizure precipitants in disease course and diagnosis

    NARCIS (Netherlands)

    Verbeek, N.E.

    2015-01-01

    Febrile seizures are well known adverse events following childhood vaccinations. If a seizure following vaccination is the first of an evolving epilepsy syndrome, the vaccination might be misinterpreted as the primary cause of the epilepsy. Dravet syndrome (formerly known as severe myoclonic epileps

  4. HPV vaccination syndrome. A questionnaire-based study.

    Science.gov (United States)

    Martínez-Lavín, Manuel; Martínez-Martínez, Laura-Aline; Reyes-Loyola, Paola

    2015-11-01

    Isolated cases and small series have described the development of complex regional pain syndrome, postural orthostatic tachycardia, and fibromyalgia after human papillomavirus (HPV) vaccination. These illnesses are difficult to diagnose and have overlapping clinical features. Small fiber neuropathy and dysautonomia may play a major role in the pathogenesis of these entities. We used the following validated questionnaires to appraise the chronic illness that might appear after HPV vaccination: The 2010 American College of Rheumatology Fibromyalgia Diagnostic Criteria, COMPASS 31 dysautonomia questionnaire, and S-LANSS neuropathic pain form. These questionnaires and a "present illness" survey were e-mailed to persons who had the onset of a chronic ailment soon after HPV vaccination. Forty-five filled questionnaires from individuals living in 13 different countries were collected in a month's period. Mean (±SD) age at vaccination time was 14 ± 5 years. Twenty-nine percent of the cases had immediate (within 24 h) post-vaccination illness onset. The most common presenting complaints were musculoskeletal pain (66%), fatigue (57%), headache (57%), dizziness/vertigo (43%), and paresthesias/allodynia (36%). Fifty-three percent of affected individuals fulfill the fibromyalgia criteria. COMPASS-31 score was 43 ± 21, implying advanced autonomic dysfunction. Eighty-three percent of the patients who had ongoing pain displayed S-LANSS values >12, suggesting a neuropathic component in their pain experience. After a mean period of 4.2 ± 2.5 years post-vaccination, 93% of patients continue to have incapacitating symptoms and remain unable to attend school or work. In conclusion, a disabling syndrome of chronic neuropathic pain, fatigue, and autonomic dysfunction may appear after HPV vaccination.

  5. Replication-Deficient Particles: New Insights into the Next Generation of Bluetongue Virus Vaccines

    Science.gov (United States)

    Celma, Cristina C.; Stewart, Meredith; Wernike, Kerstin; Eschbaumer, Michael; Gonzalez-Molleda, Lorenzo; Breard, Emmanuel; Schulz, Claudia; Hoffmann, Bernd; Haegeman, Andy; De Clercq, Kris; Zientara, Stephan; van Rijn, Piet A.; Beer, Martin

    2016-01-01

    ABSTRACT Bluetongue virus (BTV) is endemic in many parts of the world, often causing severe hemorrhagic disease in livestock. To date, at least 27 different serotypes have been recognized. Vaccination against all serotypes is necessary to protect susceptible animals and to prevent onward spread of the virus by insect vectors. In our previous studies, we generated replication-deficient (disabled infectious single-cycle [DISC]) virus strains for a number of serotypes and reported preliminary data on their protective efficacy in animals. In this report, to advance the DISC vaccines to the marketplace, we investigated different parameters of these DISC vaccines. First, we demonstrated the genetic stabilities of these vaccine strains and also the complementing cell line. Subsequently, the optimal storage conditions of vaccines, including additives, temperature, and desiccation, were determined and their protective efficacies in animals confirmed. Furthermore, to test if mixtures of different vaccine strains could be tolerated, we tested cocktails of DISC vaccines in combinations of three or six different serotypes in sheep and cattle, the two natural hosts of BTV. Groups of sheep vaccinated with a cocktail of six different vaccines were completely protected from challenge with individual virulent serotypes, both in early challenge and after 5 months of challenge without any clinical disease. There was no interference in protection between the different vaccines. Protection was also achieved in cattle with a mixture of three vaccine strains, albeit at a lesser level than in sheep. Our data support and validate the suitability of these virus strains as the next-generation vaccines for BTV. IMPORTANCE Bluetongue (BT) is a debilitating and in many cases lethal disease that affects ruminants of economic importance. Classical vaccines that afford protection against bluetongue virus, the etiological agent, are not free from secondary and undesirable effects. A surge in new

  6. Fetal Syndrome of Endocannabinoid Deficiency (FSECD) In Maternal Obesity.

    Science.gov (United States)

    Schlabritz-Loutsevitch, Natalia; German, Nadezhda; Ventolini, Gary; Larumbe, Eneko; Samson, Jacques

    2016-11-01

    The theory of a fetal origin of adult diseases links many pathological conditions to very early life events and is known as a "developmental programming" phenomenon. The mechanisms of this phenomenon are not quite understood and have been explained by inflammation, stress, etc. In particular the epidemic of obesity, with more than 64% of women being overweight or obese, has been associated with conditions in later life such as mental disorders, diabetes, asthma, and irritable bowel syndrome. Interestingly, these diseases were classified a decade ago as Clinical Syndrome of Endocannabinoid Deficiency (CECD), which was first described by Russo in 2004. Cannabinoids have been used for the treatment of chronic pain for millenniums and act through the mechanism of "kick-starting" the components of the endogenous cannabinoid system (ECS). ECS is a pharmacological target for the treatment of obesity, inflammation, cardiovascular and neuronal damage, and pain. We hypothesize that the deteriorating effect of maternal obesity on offspring health is explained by the mechanism of Fetal Syndrome of Endocannabinoid Deficiency (FSECD), which accompanies maternal obesity. Here we provide support for this hypothesis. Copyright © 2016 Elsevier Ltd. All rights reserved.

  7. [Molecular genetic studies of mitochondrial ornithine transporter deficiency (HHH syndrome)].

    Science.gov (United States)

    Tsujino, S; Miyamoto, T; Kanazawa, N

    2001-11-01

    Mitochondrial ornithine transporter deficiency has been called HHH syndrome, because this disorder is characterized by three biochemical abnormalities; hyperornithinemia, hyperammonemia, and homocitrullinuria, and presents with various neurological symptoms; mental retardation, spastic paraparesis with pyramidal signs, cerebellar ataxia and episodic disturbance of consciousness or coma due to hyperammonemia. We identified four mutations in the mitochondrial ornithine transporter gene (ORNT1) of Japanese patients with HHH syndrome. These include a nonsense mutation (R179X), associated with exon skipping, missense mutations (G27E, P126R), and an insertion of AAC between codons 228 and 229, leading to an insertion of amino acid Asn. Especially, R179X was detected 4 of 7 Japanese patients (8 of 14 alleles), implying that this is a common mutation in Japanese population.

  8. The Change-Over of Yin-yang and Gene Regulation in Kidney Deficiency Syndromes

    Institute of Scientific and Technical Information of China (English)

    DONG Fei-xia; HE Li-qun

    2009-01-01

    The present paper studies gene regulation in kidney deficiency syndromes from the simple Nephrotic Syndrome and with the principle of positive-negative regulation to control the change-over ofyin-yang, the modern molecular biological techniques can be used, such as gene chip, representational difference analysis (RDA) and gene sequence analysis, so as to investigate the inner relationship between the genes and kidney deficiency syndromes and prove the effect given by these genes on the pathophysiological status of change-over ofyin-yang in kidney deficiency syndromes.This philosophical approach and method can also be adopted for studies of the related genes in other TCM syndromes.

  9. Induction of protective CTL immunity against peptide transporter TAP-deficient tumors through dendritic cell vaccination.

    Science.gov (United States)

    Chambers, Benedict; Grufman, Per; Fredriksson, Vanoohi; Andersson, Kenth; Roseboom, Marjet; Laban, Sandra; Camps, Marcel; Wolpert, Elisabeth Z; Wiertz, Emmanuel J H J; Offringa, Rienk; Ljunggren, Hans-Gustaf; van Hall, Thorbald

    2007-09-15

    A large proportion of human cancers show deficiencies in the MHC class I antigen-processing machinery. Such defects render tumors resistant to immune eradication by tumoricidal CTLs. We recently identified a unique population of CTL that selectively targets tumor immune-escape variants through recognition of MHC-presented peptides, termed TEIPP (T cell epitopes associated with impaired peptide processing), expressed on cells lacking functional TAP-peptide transporters. Previously, we showed that vaccination with TEIPP peptides mediates protection against TAP-deficient tumors. Here, we further explored the concept of TEIPP-targeted therapy using a dendritic cell (DC)-based cellular vaccine. Impairment of TAP function in DC induced the presentation of endogenous TEIPP antigens by MHC class I molecules, and immunization with these DCs protected mice against the outgrowth of TAP-deficient lymphomas and fibrosarcomas. Immune analysis of vaccinated mice revealed strong TEIPP-specific CTL responses, and a crucial role for CD8(+) cells in tumor resistance. Finally, we show that TEIPP antigens could be successfully induced in wild-type DC by introducing the viral TAP inhibitor UL49.5. Our results imply that immune intervention strategies with TAP-inhibited DC could be developed for the treatment of antigen processing-deficient cancers in humans.

  10. Vaccination against lymphocytic choriomeningitis virus infection in MHC class II-deficient mice

    DEFF Research Database (Denmark)

    Holst, Peter Johannes; Christensen, Jan Pravsgaard; Thomsen, Allan Randrup

    2011-01-01

    response could be elicited in MHC class II-deficient mice by vaccination with adenovirus encoding lymphocytic choriomeningitis virus (LCMV) glycoprotein tethered to MHC class II-associated invariant chain. Moreover, the response induced conferred significant cytolytic CD8(+) T cell-mediated protection...... against challenge with a high dose of the invasive clone 13 strain of LCMV. In contrast, vaccination with adenovirus encoding unlinked LCMV glycoprotein induced weak virus control in the absence of CD4(+) T cells, and mice may die of increased immunopathology associated with incomplete protection. Acute...

  11. Possible association between vitamin D deficiency and restless legs syndrome

    Directory of Open Access Journals (Sweden)

    Oran M

    2014-05-01

    Full Text Available Mustafa Oran,1 Cuneyt Unsal,2 Yakup Albayrak,2 Feti Tulubas,3 Keriman Oguz,4 Okan Avci,1 Nilda Turgut,4 Recep Alp,4 Ahmet Gurel3 1Department of Internal Medicine, 2Department of Psychiatry, 3Department of Biochemistry, 4Department of Neurology, Namik Kemal University, Faculty of Medicine, Tekirdağ, Turkey Background and aim: Restless legs syndrome (RLS is a distressing sleep disorder that occurs worldwide. Although there have been recent developments in understanding the pathophysiology of RLS, the exact mechanism of the disease has not been well elucidated. An increased prevalence of neurologic and psychiatric diseases involving dopaminergic dysfunction in vitamin D-deficient patients led us to hypothesize that vitamin D deficiency might result in dopaminergic dysfunction and consequently, the development of RLS (in which dopaminergic dysfunction plays a pivotal role. Thus, the aim of this study was to evaluate the relationship between vitamin D deficiency and RLS. Methods: One hundred and fifty-five consecutive patients, 18–65 years of age, who were admitted to the Department of Internal Medicine with musculoskeletal symptoms and who subsequently underwent neurological and electromyography (EMG examination by the same senior neurologist, were included in this study. The patients were divided into two groups according to serum 25-hydroxyvitamin D (25(OHD (a vitamin D metabolite used as a measure of vitamin D status level: 36 patients with serum 25(OHD levels ≥20 ng/mL comprised the normal vitamin D group, and 119 patients with serum 25(OHD levels <20 ng/mL comprised the vitamin D deficiency group. The two groups were compared for the presence of RLS and associated factors. Results: The two groups were similar in terms of mean age, sex, mean body mass index (BMI, and serum levels of calcium, phosphate, alkaline phosphatase (ALP, and ferritin. The presence of RLS was significantly higher in the vitamin D deficiency group (χ2=12.87, P<0

  12. An OTC deficiency 'phenocopy' in association with Klinefelter syndrome.

    Science.gov (United States)

    Swarts, L; Leisegang, F; Owen, E P; Henderson, H E

    2007-02-01

    Late-onset urea cycle disorder in a 20-month-old boy is unusually associated with Klinefelter syndrome with a 47XXY karyotype. We record the typical clinical and biochemical findings of ornithine transcarbamylase (OTC) deficiency in a young boy with a short history of recurrent vomiting, self mutilating behaviour, lethargy, ataxia and seizures. Laboratory studies showed hyperammonaemia and orotic aciduria, with normal citrulline and other urea cycle amino acids. Unfortunately, a liver biopsy for OTC activity measurement was refused by the parents. A rapid reversal of phenotype was seen on the introduction of a low-protein diet with accompanying benzoate and phenylbutyrate administration. Linkage studies suggested the inheritance of two X chromosomes, which was confirmed by karyotype analysis. Sequencing of all exons and immediate splice site regions revealed no sequence alterations in these sections of the OTC gene. A search for skewing of X-inactivation in the liver was not possible but we did show a random pattern of X-inactivation in leukocytes. The possibility of maternal X chromosome iso-disomy in our patient was discounted by microsatellite analysis, which revealed the inheritance of two independent X chromosomes. Mutation analysis in the OTC gene has shown that approximately 20% of patients with liver biopsy confirmed OTC deficiency do not have mutations in the coding or immediate splice-site sequences of this gene. Their classification as OTC phenocopies remains speculative, awaiting clarification of the underlying DNA alteration. We report on the novel association of OTC deficiency and Klinefelter syndrome with the additional interest of a probable unusual genetic defect underlying the OTC abnormality.

  13. Human immunodeficiency virus/acquired immune deficiency syndrome: Using drug from mathematical perceptive.

    Science.gov (United States)

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

    2015-11-12

    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.

  14. [Salmonella typhi vaccination response study reveals defective antibody production selective IgA deficiency patient].

    Science.gov (United States)

    Pleguezuelo, Daniel E; Gianelli, Carla

    2015-01-01

    Selective IgA deficiency (SIgAD) is the most prevalent immunodeficiency worldwide, progressing to common variable immunodeficiency only in few reported cases. We report the case of a Spanish female aged 22 and diagnosed of selective IgA deficiency, a long history of bronchitis, several episodes of pneumonia, bilateral bronchiectasis, normal IgG, IgM, IgG subclasses, and detectable pre-vaccination IgG antibodies against tetanus toxoid and Streptococcus pneumoniae. She was evaluated in our clinic in order to rule out common variable immunodeficiency. We observed good antibody response to tetanus toxoid, absence of circulating switched memory B cells, decreased response to pneumococcal polysaccharide antigens and a lack of response to Salmonella typhi vaccine. Most SIgAD patients presents with upper respiratory tract infections or mild diarrhea. Those with lower tract infections, pneumonia or untreatable diarrhea should follow B-cell subpopulations' study and antibody response to vaccines. Absence of response to Salmonella typhi vaccine allowed us to expose the defective antibody production.

  15. Kleine–Levin syndrome with comorbid iron deficiency anemia

    Science.gov (United States)

    Jain, Rajendra Singh; Kumar, Sunil; Srivastava, Trilochan; Sannegowda, Raghavendra Bakki

    2015-01-01

    Kleine–Levin syndrome (KLS) is a rare chronic sleep disorder of unknown etiopathology, which typically occurs in adolescent males. Although the severity of symptoms and disease course varies between the KLS patients, it usually resolves spontaneously, but sometime comorbid conditions may worsen the symptoms. Herein, we report a case of KLS who presented with severe episodic hypersomnia. During episodes, the patient used to sleep as long as 20 h in a day, affecting his daily living activities. All the relevant investigations including electroencephalography, magnetic resonance imaging of brain and cerebrospinal fluid analysis were normal except for severe iron deficiency anemia (IDA). In our patient, the severity of symptoms worsened due to coexistent IDA. The treatment of IDA along with modafinil decreased the severity of symptoms and shortened the hospital stay during episodes. This might be the first case report of KLS with comorbid IDA. PMID:26634130

  16. Hypoxanthine-guanine phosophoribosyltransferase (HPRT) deficiency: Lesch-Nyhan syndrome.

    Science.gov (United States)

    Torres, Rosa J; Puig, Juan G

    2007-12-08

    Deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity is an inborn error of purine metabolism associated with uric acid overproduction and a continuum spectrum of neurological manifestations depending on the degree of the enzymatic deficiency. The prevalence is estimated at 1/380,000 live births in Canada, and 1/235,000 live births in Spain. Uric acid overproduction is present inall HPRT-deficient patients and is associated with lithiasis and gout. Neurological manifestations include severe action dystonia, choreoathetosis, ballismus, cognitive and attention deficit, and self-injurious behaviour. The most severe forms are known as Lesch-Nyhan syndrome (patients are normal at birth and diagnosis can be accomplished when psychomotor delay becomes apparent). Partial HPRT-deficient patients present these symptoms with a different intensity, and in the least severe forms symptoms may be unapparent. Megaloblastic anaemia is also associated with the disease. Inheritance of HPRT deficiency is X-linked recessive, thus males are generally affected and heterozygous female are carriers (usually asymptomatic). Human HPRT is encoded by a single structural gene on the long arm of the X chromosome at Xq26. To date, more than 300 disease-associated mutations in the HPRT1 gene have been identified. The diagnosis is based on clinical and biochemical findings (hyperuricemia and hyperuricosuria associated with psychomotor delay), and enzymatic (HPRT activity determination in haemolysate, intact erythrocytes or fibroblasts) and molecular tests. Molecular diagnosis allows faster and more accurate carrier and prenatal diagnosis. Prenatal diagnosis can be performed with amniotic cells obtained by amniocentesis at about 15-18 weeks' gestation, or chorionic villus cells obtained at about 10-12 weeks' gestation. Uric acid overproduction can be managed by allopurinol treatment. Doses must be carefully adjusted to avoid xanthine lithiasis. The lack of precise

  17. Hypoxanthine-guanine phosophoribosyltransferase (HPRT deficiency: Lesch-Nyhan syndrome

    Directory of Open Access Journals (Sweden)

    Puig Juan G

    2007-12-01

    Full Text Available Abstract Deficiency of hypoxanthine-guanine phosphoribosyltransferase (HPRT activity is an inborn error of purine metabolism associated with uric acid overproduction and a continuum spectrum of neurological manifestations depending on the degree of the enzymatic deficiency. The prevalence is estimated at 1/380,000 live births in Canada, and 1/235,000 live births in Spain. Uric acid overproduction is present inall HPRT-deficient patients and is associated with lithiasis and gout. Neurological manifestations include severe action dystonia, choreoathetosis, ballismus, cognitive and attention deficit, and self-injurious behaviour. The most severe forms are known as Lesch-Nyhan syndrome (patients are normal at birth and diagnosis can be accomplished when psychomotor delay becomes apparent. Partial HPRT-deficient patients present these symptoms with a different intensity, and in the least severe forms symptoms may be unapparent. Megaloblastic anaemia is also associated with the disease. Inheritance of HPRT deficiency is X-linked recessive, thus males are generally affected and heterozygous female are carriers (usually asymptomatic. Human HPRT is encoded by a single structural gene on the long arm of the X chromosome at Xq26. To date, more than 300 disease-associated mutations in the HPRT1 gene have been identified. The diagnosis is based on clinical and biochemical findings (hyperuricemia and hyperuricosuria associated with psychomotor delay, and enzymatic (HPRT activity determination in haemolysate, intact erythrocytes or fibroblasts and molecular tests. Molecular diagnosis allows faster and more accurate carrier and prenatal diagnosis. Prenatal diagnosis can be performed with amniotic cells obtained by amniocentesis at about 15–18 weeks' gestation, or chorionic villus cells obtained at about 10–12 weeks' gestation. Uric acid overproduction can be managed by allopurinol treatment. Doses must be carefully adjusted to avoid xanthine lithiasis. The

  18. A replication-deficient rabies virus vaccine expressing Ebola virus glycoprotein is highly attenuated for neurovirulence

    Energy Technology Data Exchange (ETDEWEB)

    Papaneri, Amy B. [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702 (United States); Wirblich, Christoph [Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Cann, Jennifer A.; Cooper, Kurt [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick MD, 21702 (United States); Jahrling, Peter B. [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702 (United States); Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick MD, 21702 (United States); Schnell, Matthias J., E-mail: matthias.schnell@jefferson.edu [Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Jefferson Vaccine Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Blaney, Joseph E., E-mail: jblaney@niaid.nih.gov [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702 (United States)

    2012-12-05

    We are developing inactivated and live-attenuated rabies virus (RABV) vaccines expressing Ebola virus (EBOV) glycoprotein for use in humans and endangered wildlife, respectively. Here, we further characterize the pathogenesis of the live-attenuated RABV/EBOV vaccine candidates in mice in an effort to define their growth properties and potential for safety. RABV vaccines expressing GP (RV-GP) or a replication-deficient derivative with a deletion of the RABV G gene (RV{Delta}G-GP) are both avirulent after intracerebral inoculation of adult mice. Furthermore, RV{Delta}G-GP is completely avirulent upon intracerebral inoculation of suckling mice unlike parental RABV vaccine or RV-GP. Analysis of RV{Delta}G-GP in the brain by quantitative PCR, determination of virus titer, and immunohistochemistry indicated greatly restricted virus replication. In summary, our findings indicate that RV-GP retains the attenuation phenotype of the live-attenuated RABV vaccine, and RV{Delta}G-GP would appear to be an even safer alternative for use in wildlife or consideration for human use.

  19. 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

    2015-01-01

    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

  20. Prevalence of iron deficiency in children with Down syndrome.

    Science.gov (United States)

    Dixon, Natalia E; Crissman, Blythe G; Smith, P Brian; Zimmerman, Sherri A; Worley, Gordon; Kishnani, Priya S

    2010-12-01

    To determine the prevalence of iron deficiency (ID) and iron deficiency anemia (IDA) in a sample of children with Down syndrome (DS) and to evaluate the effect of macrocytosis on the diagnosis of ID/IDA in these children. Children with DS ≥ 12 months of age who were followed at the Duke University Medical Center Comprehensive DS Clinic from December 2004 to March 2007 were screened for ID/IDA with a complete blood count, reticulocyte count, iron panel, and erythrocytic protoporphyrins. A total of 114 children were enrolled, with a median age of 4.7 years. ID was identified in 12 subjects (10%), and IDA was identified in 3 subjects (3%). ID/IDA would not have been accurately diagnosed in 13 of 15 subjects (86%) if red blood cell (RBC) indices alone had been used for screening. Abnormal RBC indices with low transferrin saturation were 100% sensitive for ID/ IDA screening. Prevalence of ID/IDA in children with DS was comparable with that in the general pediatric population. Macrocytosis had implications for screening of ID/IDA with only RBC indices. We suggest ID/IDA screening in DS children be done with a laboratory panel at least including complete blood count, reticulocyte count, transferrin saturation, and serum ferritin. Copyright © 2010 Mosby, Inc. All rights reserved.

  1. Safety of vaccinations in patients with cryopyrin-associated periodic syndromes: a prospective registry based study.

    Science.gov (United States)

    Jaeger, Veronika K; Hoffman, Hal M; van der Poll, Tom; Tilson, Hugh; Seibert, Julia; Speziale, Antonio; Junge, Guido; Franke, Kristina; Vritzali, Eleni; Hawkins, Philip N; Kuemmerle-Deschner, Jasmin; Walker, Ulrich A

    2017-09-01

    Pneumococcal, tetanus and influenza vaccinations are recommended for patients with cryopyrin-associated periodic syndromes (CAPS) when treated with immunosuppressive medication. The aim of this publication is to report the safety of pneumococcal and other vaccinations in CAPS patients. All CAPS patients followed in the β-CONFIDENT (Clinical Outcomes and Safety Registry study of Ilaris patients) registry were analysed if they had received a vaccination. The β-CONFIDENT registry is a global, long-term, prospective, observational registry, capturing and monitoring patients treated with canakinumab. Sixty-eight CAPS patients had received a total of 159 vaccine injections, 107 injections against influenza, 19 pneumococcal vaccinations, 12 against tetanus/diphtheria antigens and 21 other vaccinations. Fourteen per cent of injections had elicited at least one vaccine reaction. All five vaccine-related serious adverse events were associated with pneumococcal vaccination. Vaccine reactions were observed in 70% of pneumococcal vaccinations, compared with 7% in influenza and 17% in tetanus/diphtheria vaccinations. The odds ratios to react to the pneumococcal vaccines compared with influenza and tetanus/diphtheria vaccines were 31.0 (95% CI: 8, 119) and 10.8 (95% CI: 2, 74). Vaccine reactions after pneumococcal vaccinations were more severe and lasted significantly longer (up to 3 weeks) compared with other vaccinations. In two patients, pneumococcal vaccination also elicited symptoms consistent with systemic inflammation due to CAPS reactivation. Pneumococcal vaccines, unlike other vaccines, frequently trigger severe local and systemic inflammation in CAPS patients. Clinicians must balance potential benefits of pneumococcal immunization against safety concerns. The 13-valent pneumococcal conjugate vaccine might be favourable over the polysaccharide vaccine in CAPS patients.

  2. Severe acute respiratory syndrome vaccine development: experiences of vaccination against avian infectious bronchitis coronavirus.

    Science.gov (United States)

    Cavanagh, Dave

    2003-12-01

    Vaccines against infectious bronchitis of chickens (Gallus gallus domesticus) have arguably been the most successful, and certainly the most widely used, of vaccines for diseases caused by coronaviruses, the others being against bovine, canine, feline and porcine coronaviruses. Infectious bronchitis virus (IBV), together with the genetically related coronaviruses of turkey (Meleagris gallopovo) and ring-necked pheasant (Phasianus colchicus), is a group 3 coronavirus, severe acute respiratory syndrome (SARS) coronavirus being tentatively in group 4, the other known mammalian coronaviruses being in groups 1 and 2. IBV replicates not only in respiratory tissues (including the nose, trachea, lungs and airsacs, causing respiratory disease), but also in the kidney (associated with minor or major nephritis), oviduct, and in many parts of the alimentary tract--the oesophagus, proventriculus, duodenum, jejunum, bursa of Fabricius, caecal tonsils (near the distal end of the tract), rectum and cloaca (the common opening for release of eggs and faeces), usually without clinical effects. The virus can persist, being re-excreted at the onset of egg laying (4 to 5 months of age), believed to be a consequence of the stress of coming into lay. Genetic lines of chickens differ in the extent to which IBV causes mortality in chicks, and in respect of clearance of the virus after the acute phase. Live attenuated (by passage in chicken embryonated eggs) IBV strains were introduced as vaccines in the 1950s, followed a couple of decades later by inactivated vaccines for boosting protection in egg-laying birds. Live vaccines are usually applied to meat-type chickens at 1 day of age. In experimental situations this can result in sterile immunity when challenged by virulent homologous virus. Although 100% of chickens may be protected (against clinical signs and loss of ciliary activity in trachea), sometimes 10% of vaccinated chicks do not respond with a protective immune response

  3. Severe acute respiratory syndrome: vaccine on the way

    Institute of Scientific and Technical Information of China (English)

    ZHANG Ding-mei; WANG Guo-ling; LU Jia-hai

    2005-01-01

    @@ In November 2002, a new disease-severe acute respiratory syndrome, or SARS-first emerged in Guangdong Province, China. Subsequently, it spread to more than 30 countries worldwide.1 The causative agent was identified to be a previously unknown member of the coronaviridae family, and was named SARS coronavirus (SARS-CoV). SARS coronavirus is a large, enveloped, positive-sense RNA virus. The genome is about 30 kb, which is predicted to contain 14 functional open reading frames (ORFs). Two large 5'-terminal ORFs (1a and 1b) encode the polymerases that are required for viral RNA synthesis. The remaining twelve ORFs encode four structural proteins [spike protein (S), envelope protein (E), membrane protein (M) and nucleocapsid protein (N)] and eight accessory proteins.2 Though the SARS-CoV genome is clear, a great deal more work will be required to develop an efficient vaccine and effective drugs. Neutralizing antibodies were detectable in the convalescent sera of SARS patients, and sera from recovered patients could be used to treat newly infected individuals.3 The data suggest that protective humoral immunity is achievable and that vaccines can be developed for prevention of SARS. In this article, we review and discuss progress towards development of a SARS vaccine.

  4. Varicella vaccination in children with nephrotic syndrome: a report of the Southwest Pediatric Nephrology Study Group.

    Science.gov (United States)

    Furth, Susan L; Arbus, Gerald S; Hogg, Ronald; Tarver, Joyce; Chan, Christina; Fivush, Barbara A

    2003-02-01

    To evaluate the safety and immunogenicity of varicella vaccine in children with nephrotic syndrome, including those taking low-dose, alternate-day prednisone. Prospective, open-label, multicenter clinical trial of varicella vaccine in a 2-dose regimen in US and Canadian children (12 months to or=5 gpELISA units) after 2 doses. At 2-year follow-up, all patients retained detectable antibody, and 91% (21 of 23) had levels >or=5 gpELISA units. There were no adverse events associated with vaccination. Varicella vaccine was generally well tolerated and highly immunogenic in children with nephrotic syndrome, including those on low-dose, alternate-day prednisone.

  5. Dopamine and glucose, obesity and Reward Deficiency Syndrome

    Directory of Open Access Journals (Sweden)

    Kenneth eBlum

    2014-09-01

    Full Text Available Obesity and many well described eating disorders are accurately considered a global epidemic. The consequences of Reward Deficiency Syndrome, a genetic and epigenetic phenomena that involves the interactions of powerful neurotransmitters, are impairments of brain reward circuitry, hypodopaminergic function and abnormal craving behavior. Numerous sound neurochemical and genetic studies provide strong evidence that food addiction is similar to psychoactive drug addiction. Important facts which could translate to potential therapeutic targets espoused in this review include: 1 brain dopamine (DA production and use is stimulated by consumption of alcohol in large quantities or carbohydrates bingeing; 2 in the mesolimbic system the enkephalinergic neurons are in close proximity, to glucose receptors; 3 highly concentrated glucose activates the calcium channel to stimulate dopamine release from P12 cells; 4 blood glucose and cerebrospinal fluid concentrations of homovanillic acid, the dopamine metabolite, are significantly correlated and 5 2-deoxyglucose the glucose analogue, in pharmacological doses associates with enhanced dopamine turnover and causes acute glucoprivation. Evidence from animal studies and human fMRI support the hypothesis that multiple, but similar brain circuits are disrupted in obesity and drug dependence and DA-modulated reward circuits are involved in pathologic eating behaviors. Treatment for addiction to glucose and drugs alike, based on a consensus of neuroscience research, should incorporate dopamine agonist therapy, in contrast to current theories and practices that use dopamine antagonists. Until now, powerful dopamine-D2 agonists have failed clinically, due to chronic down regulation of D2 receptors instead, consideration of novel less powerful D2 agonists that up-regulate D2 receptors seems prudent. We encourage new strategies targeted at improving DA function in the treatment and prevention of obesity a subtype of

  6. Protection from hemolytic uremic syndrome by eyedrop vaccination with modified enterohemorrhagic E. coli outer membrane vesicles.

    Directory of Open Access Journals (Sweden)

    Kyoung Sub Choi

    Full Text Available We investigated whether eyedrop vaccination using modified outer membrane vesicles (mOMVs is effective for protecting against hemolytic uremic syndrome (HUS caused by enterohemorrhagic E. coli (EHEC O157:H7 infection. Modified OMVs and waaJ-mOMVs were prepared from cultures of MsbB- and Shiga toxin A subunit (STxA-deficient EHEC O157:H7 bacteria with or without an additional waaJ mutation. BALB/c mice were immunized by eyedrop mOMVs, waaJ-mOMVs, and mOMVs plus polymyxin B (PMB. Mice were boosted at 2 weeks, and challenged peritoneally with wild-type OMVs (wtOMVs at 4 weeks. As parameters for evaluation of the OMV-mediated immune protection, serum and mucosal immunoglobulins, body weight change and blood urea nitrogen (BUN/Creatinin (Cr were tested, as well as histopathology of renal tissue. In order to confirm the safety of mOMVs for eyedrop use, body weight and ocular histopathological changes were monitored in mice. Modified OMVs having penta-acylated lipid A moiety did not contain STxA subunit proteins but retained non-toxic Shiga toxin B (STxB subunit. Removal of the polymeric O-antigen of O157 LPS was confirmed in waaJ-mOMVs. The mice group vaccinated with mOMVs elicited greater humoral and mucosal immune responses than did the waaJ-mOMVs and PBS-treated groups. Eyedrop vaccination of mOMVs plus PMB reduced the level of humoral and mucosal immune responses, suggesting that intact O157 LPS antigen can be a critical component for enhancing the immunogenicity of the mOMVs. After challenge, mice vaccinated with mOMVs were protected from a lethal dose of wtOMVs administered intraperitoneally, conversely mice in the PBS control group were not. Collectively, for the first time, EHEC O157-derived mOMV eyedrop vaccine was experimentally evaluated as an efficient and safe means of vaccine development against EHEC O157:H7 infection-associated HUS.

  7. Necrotizing Ulcer After BCG Vaccination in a Girl With Leukocyte-adhesion Deficiency Type 1.

    Science.gov (United States)

    Kurosawa, Hidemitsu; Mizukami, Tomoyuki; Nunoi, Hiroyuki; Kato, Masaya; Sato, Yuya; Okuya, Mayuko; Fukushima, Keitaro; Katsuyama, Yoshihiko; Arisaka, Osamu

    2017-05-22

    Leukocyte-adhesion deficiency-1 is a recessively inherited disorder associated with recurrent bacterial infections, severe periodontitis, peripheral leukocytosis, and impaired wound healing. We diagnosed moderate-type leukocyte-adhesion deficiency-1 in a 7-year-old girl who developed a necrotizing ulcer after Bacillus Calmette-Guerin vaccination. The patient showed moderate expression of CD18 in neutrophils with a homozygous splice mutation with c.41_c.58+2dup20 of ITGB2 and experienced recurrent severe infections complicated with systemic lupus erythematosus. She received hematopoietic stem cell transplantation from a matched elder brother with heterozygous mutation of ITGB2, and has since remained free of infection and systemic lupus erythematosus symptoms without immunosuppression therapy.

  8. Egg drop syndrome 1976 (EDS-76) virus infection in inadequately vaccinated chickens.

    Science.gov (United States)

    Cook, J K

    1983-01-01

    Experiments were carried out to study the epizootiology of the egg drop syndrome 1976 virus infection in chickens that were not adequately protected by vaccination. Virus excretion was demonstrated when chickens vaccinated at the recommended level were challenged within 10 days of vaccination and when chickens were challenged 6 weeks after administration of low doses of vaccine. In the latter experiment, those chickens which shed virus had all shown a poor haemagglutination inhibition antibody response to vaccination but had high serum neutralisation antibody titres when challenged.

  9. Complications of bariatric surgery: dumping syndrome, reflux and vitamin deficiencies.

    Science.gov (United States)

    Tack, Jan; Deloose, Eveline

    2014-08-01

    Bariatric surgical procedure are increasingly and successfully applied in the treatment of morbid obesity. Nevertheless, these procedures are not devoid of potential long-term complications. Dumping syndrome may occur after procedures involving at least partial gastric resection or bypass, including Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy. Diagnosis is based on clinical alertness and glucose tolerance testing. Treatment may involve dietary measures, acarbose and somatostatin analogues, or surgical reintervention for refractory cases. Gastro-esophageal reflux disease (GERD) can be aggravated by vertical banded gastroplasty and sleeve gastrectomy procedures, but pre-existing GERD may improve after RYGB and with adjustable gastric banding. Nutrient deficiencies constitute the most important long-term complications of bariatric interventions, as they may lead to haematological, metabolic and especially neurological disorders which are not always reversible. Malabsorptive procedures, poor postoperative nutrient intake, recurrent vomiting and poor compliance with vitamin supplement intake and regular follow-up are important risk factors. Preoperative nutritional assessment and rigourous postoperative follow-up plan with administration of multi-vitamin supplements and assessment of serum levels is recommended in all patients.

  10. Cernunnos/XLF Deficiency: A Syndromic Primary Immunodeficiency

    Directory of Open Access Journals (Sweden)

    Funda Erol Çipe

    2014-01-01

    Full Text Available Artemis, DNA ligase IV, DNA protein kinase catalytic subunit, and Cernunnos/XLF genes in nonhomologous end joining pathways of DNA repair mechanisms have been identified as responsible for radiosensitive SCID. Here, we present a 3-year-old girl patient with severe growth retardation, bird-like face, recurrent perianal abscess, pancytopenia, and polydactyly. Firstly, she was thought as Fanconi anemia and spontaneous DNA breaks were seen on chromosomal analysis. After that DEB test was found to be normal and Fanconi anemia was excluded. Because of that she had low IgG and IgA levels, normal IgM level, and absence of B cells in peripheral blood; she was considered as primary immunodeficiency, Nijmegen breakage syndrome. A mutation in NBS1 gene was not found; then Cernunnos/XLF deficiency was investigated due to clinical similarities with previously reported cases. Homozygous mutation in Cernunnos/XLF gene (NHEJ1 was identified. She is now on regular IVIG prophylaxis and has no new infection. Fully matched donor screening is in progress for bone marrow transplantation which is curative treatment of the disease. In conclusion, the patients with microcephaly, bird-like face, and severe growth retardation should be evaluated for hypogammaglobulinemia and primary immunodeficiency diseases.

  11. Concomitant occurrence of Turner syndrome and growth hormone deficiency.

    Science.gov (United States)

    Yu, Jung; Shin, Ha Young; Lee, Chong Guk; Kim, Jae Hyun

    2016-11-01

    Turner syndrome (TS) is a genetic disorder in phenotypic females that has characteristic physical features and presents as partial or complete absence of the second sex chromosome. Growth hormone deficiency (GHD) is a condition caused by insufficient release of growth hormone from the pituitary gland. The concomitant occurrence of TS and GHD is rare and has not yet been reported in Korea. Here we report 2 cases of TS and GHD. In case 1, GHD was initially diagnosed. Karyotyping was performed because of the presence of the typical phenotype and poor response to growth hormone therapy, which revealed 45,X/45,X+mar. The patient showed increased growth velocity after the growth hormone dose was increased. In case 2, a growth hormone provocation test and chromosomal analysis were performed simultaneously because of decreased growth velocity and the typical TS phenotype, which showed GHD and a mosaic karyotype of 45,X/46,XX. The patient showed spontaneous pubertal development. In female patients with short stature, it is important to perform a throughout physical examination and test for hormonal and chromosomal abnormalities because diagnostic accuracy is important for treatment and prognosis.

  12. Motor hyperactivity of the iron-deficient rat - an animal model of restless legs syndrome.

    Science.gov (United States)

    Lai, Yuan-Yang; Cheng, Yu-Hsuan; Hsieh, Kung-Chiao; Nguyen, Darian; Chew, Keng-Tee; Ramanathan, Lalini; Siegel, Jerome M

    2017-08-26

    Abnormal striatal dopamine transmission has been hypothesized to cause restless legs syndrome. Dopaminergic drugs are commonly used to treat restless legs syndrome. However, they cause adverse effects with long-term use. An animal model would allow the systematic testing of potential therapeutic drugs. A high prevalence of restless legs syndrome has been reported in iron-deficient anemic patients. We hypothesized that the iron-deficient animal would exhibit signs similar to those in restless legs syndrome patients. After baseline polysomnographic recordings, iron-deficient rats received pramipexole injection. Then, iron-deficient rats were fed a standard rodent diet, and polysomnographic recording were performed for 2 days each week for 4 weeks. Iron-deficient rats have low hematocrit levels and show signs of restless legs syndrome: sleep fragmentation and periodic leg movements in wake and in slow-wave sleep. Iron-deficient rats had a positive response to pramipexole treatment. After the iron-deficient rats were fed the standard rodent diet, hematocrit returned to normal levels, and sleep quality improved, with increased average duration of wake and slow-wave sleep episodes. Periodic leg movements decreased during both waking and sleep. Hematocrit levels positively correlated with the average duration of episodes in wake and in slow-wave sleep and negatively correlated with periodic leg movements in wake and in sleep. Western blot analysis showed that striatal dopamine transporter levels were higher in iron-deficient rats. The iron-deficient rat is a useful animal model of iron-deficient anemic restless legs syndrome. © 2017 International Parkinson and Movement Disorder Society. © 2017 International Parkinson and Movement Disorder Society.

  13. Paroxysmal Exercise-induced Dyskinesias Caused by GLUT1 Deficiency Syndrome

    Science.gov (United States)

    Mongin, Marie; Mezouar, Nicolas; Dodet, Pauline; Vidailhet, Marie; Roze, Emmanuel

    2016-01-01

    Background Glucose transporter type 1 deficiency syndrome is due to de novo mutations in the SLC2A1 gene encoding the glucose transporter type 1. Phenomenology Shown Paroxysmal motor manifestations induced by exercise or fasting may be the main manifestations of glucose transporter type 1 deficiency syndrome. Educational Value Proper identification of the paroxysmal events and early diagnosis is important since the disease is potentially treatable. PMID:27351150

  14. Diagnosis of growth hormone (GH deficiency: comparison of pituitary stalk interruption syndrome and transient GH deficiency

    Directory of Open Access Journals (Sweden)

    Brauner Raja

    2009-05-01

    Full Text Available Abstract Background Most patients with childhood non-organic growth hormone (GH deficiency (GHD produce a normal GH peak as young adults. Our objectives were to better define this transient GHD and evaluate the factors influencing the growth response of patients with pituitary stalk interruption syndrome (PSIS. Methods We studied 72 prepubertal patients with a GH peak Results At diagnosis, 64% of Group 1 and one Group 2 were During the first year of GH treatment, the growth rate was ≥ 2 SDS in 81% Group 1 and 37% Group 2 patients. In Group 1, it was negatively correlated with the GH peak before treatment (P The height gain SDSs between diagnosis and adult height were 1.7 ± 1.2 in Group 1 (n = 30 and 1.08 ± 0.8 in Group 2 (n = 12, P = 0.05. Conclusion The factors of the growth response to GH treatment should be analysed separately for each population: with and without PSIS or other markers.

  15. Cortical sinovenous thrombosis in a child with nephrotic syndrome and iron deficiency anaemia.

    Directory of Open Access Journals (Sweden)

    Meena A

    2000-07-01

    Full Text Available Cortical sinovenous thrombosis in a child with nephrotic syndrome and iron deficiency anaemia is described. The most probable mechanism for the hypercoagulable state was thrombocytosis associated with iron deficiency anaemia. The other possible contributing factor might have been the diuretic therapy during the phase of relapse.

  16. Effect of vaccinations on seizure risk and disease course in Dravet syndrome.

    Science.gov (United States)

    Verbeek, Nienke E; van der Maas, Nicoline A T; Sonsma, Anja C M; Ippel, Elly; Vermeer-de Bondt, Patricia E; Hagebeuk, Eveline; Jansen, Floor E; Geesink, Huibert H; Braun, Kees P; de Louw, Anton; Augustijn, Paul B; Neuteboom, Rinze F; Schieving, Jolanda H; Stroink, Hans; Vermeulen, R Jeroen; Nicolai, Joost; Brouwer, Oebele F; van Kempen, Marjan; de Kovel, Carolien G F; Kemmeren, Jeanet M; Koeleman, Bobby P C; Knoers, Nine V; Lindhout, Dick; Gunning, W Boudewijn; Brilstra, Eva H

    2015-08-18

    To study the effect of vaccination-associated seizure onset on disease course and estimate the risk of subsequent seizures after infant pertussis combination and measles, mumps, and rubella (MMR) vaccinations in Dravet syndrome (DS). We retrospectively analyzed data from hospital medical files, child health clinics, and the vaccination register for children with DS and pathogenic SCN1A mutations. Seizures within 24 hours after infant whole-cell, acellular, or nonpertussis combination vaccination or within 5 to 12 days after MMR vaccination were defined as "vaccination-associated." Risks of vaccination-associated seizures for the different vaccines were analyzed in univariable and in multivariable logistic regression for pertussis combination vaccines and by a self-controlled case series analysis using parental seizure registries for MMR vaccines. Disease courses of children with and without vaccination-associated seizure onset were compared. Children who had DS (n = 77) with and without vaccination-associated seizure onset (21% and 79%, respectively) differed in age at first seizure (median 3.7 vs 6.1 months, p vaccination-associated seizures was significantly lower for acellular pertussis (9%; odds ratio 0.18, 95% confidence interval [CI] 0.05-0.71) and nonpertussis (8%; odds ratio 0.11, 95% CI 0.02-0.59) than whole-cell pertussis (37%; reference) vaccines. Self-controlled case series analysis showed an increased incidence rate ratio of seizures of 2.3 (95% CI 1.5-3.4) within the risk period of 5 to 12 days following MMR vaccination. Our results suggest that vaccination-associated earlier seizure onset does not alter disease course in DS, while the risk of subsequent vaccination-associated seizures is probably vaccine-specific. © 2015 American Academy of Neurology.

  17. Dopamine and glucose, obesity, and reward deficiency syndrome.

    Science.gov (United States)

    Blum, Kenneth; Thanos, Panayotis K; Gold, Mark S

    2014-01-01

    Obesity as a result of overeating as well as a number of well described eating disorders has been accurately considered to be a world-wide epidemic. Recently a number of theories backed by a plethora of scientifically sound neurochemical and genetic studies provide strong evidence that food addiction is similar to psychoactive drug addiction. Our laboratory has published on the concept known as Reward Deficiency Syndrome (RDS) which is a genetic and epigenetic phenomena leading to impairment of the brain reward circuitry resulting in a hypo-dopaminergic function. RDS involves the interactions of powerful neurotransmitters and results in abnormal craving behavior. A number of important facts which could help translate to potential therapeutic targets espoused in this focused review include: (1) consumption of alcohol in large quantities or carbohydrates binging stimulates the brain's production of and utilization of dopamine; (2) in the meso-limbic system the enkephalinergic neurons are in close proximity, to glucose receptors; (3) highly concentrated glucose activates the calcium channel to stimulate dopamine release from P12 cells; (4) a significant correlation between blood glucose and cerebrospinal fluid concentrations of homovanillic acid the dopamine metabolite; (5) 2-deoxyglucose (2DG), the glucose analog, in pharmacological doses is associated with enhanced dopamine turnover and causes acute glucoprivation. Evidence from animal studies and fMRI in humans support the hypothesis that multiple, but similar brain circuits are disrupted in obesity and drug dependence and for the most part, implicate the involvement of DA-modulated reward circuits in pathologic eating behaviors. Based on a consensus of neuroscience research treatment of both glucose and drug like cocaine, opiates should incorporate dopamine agonist therapy in contrast to current theories and practices that utilizes dopamine antagonistic therapy. Considering that up until now clinical utilization

  18. Effect of vaccinations on seizure risk and disease course in Dravet syndrome

    NARCIS (Netherlands)

    Verbeek, Nienke E.; van der Maas, Nicoline A. T.; Sonsma, Anja C. M.; Ippel, Elly; Bondt, Patricia E. Vermeer-de; Hagebeuk, Eveline; Jansen, Floor E.; Geesink, Huibert H.; Braun, Kees P.; de Louw, Anton; Augustijn, Paul B.; Neuteboom, Rinze F.; Schieving, Jolanda H.; Stroink, Hans; Vermeulen, R. Jeroen; Nicolai, Joost; Brouwer, Oebele F.; Van Kempen, Marjan; de Kovel, Carolien G. F.; Kemmeren, Jeanet M.; Koeleman, Bobby P. C.; Knoers, Nine V.; Lindhout, Dick; Gunning, W. Boudewijn; Brilstra, Eva H.

    2015-01-01

    Objective: To study the effect of vaccination-associated seizure onset on disease course and estimate the risk of subsequent seizures after infant pertussis combination and measles, mumps, and rubella (MMR) vaccinations in Dravet syndrome (DS). Methods: We retrospectively analyzed data from hospital

  19. Effect of vaccinations on seizure risk and disease course in Dravet syndrome

    NARCIS (Netherlands)

    Verbeek, Nienke E.; van der Maas, Nicoline A. T.; Sonsma, Anja C. M.; Ippel, Elly; Bondt, Patricia E. Vermeer-de; Hagebeuk, Eveline; Jansen, Floor E.; Geesink, Huibert H.; Braun, Kees P.; de Louw, Anton; Augustijn, Paul B.; Neuteboom, Rinze F.; Schieving, Jolanda H.; Stroink, Hans; Vermeulen, R. Jeroen; Nicolai, Joost; Brouwer, Oebele F.; Van Kempen, Marjan; de Kovel, Carolien G. F.; Kemmeren, Jeanet M.; Koeleman, Bobby P. C.; Knoers, Nine V.; Lindhout, Dick; Gunning, W. Boudewijn; Brilstra, Eva H.

    2015-01-01

    Objective: To study the effect of vaccination-associated seizure onset on disease course and estimate the risk of subsequent seizures after infant pertussis combination and measles, mumps, and rubella (MMR) vaccinations in Dravet syndrome (DS). Methods: We retrospectively analyzed data from hospital

  20. Complex regional pain syndrome treated with intravenous immunoglobulin in a patient with common variable immune deficiency.

    Science.gov (United States)

    Tachdjian, Raffi

    2013-12-01

    Common variable immunodeficiency (CVID) represents a large heterogeneous group of antibody-deficiency syndromes associated with a wide range of clinical features and a lack of defined causes in the realm of primary immunodeficiencies. Here, we present a case of CVID in a 62-year-old white male patient with a history of longstanding complex regional pain syndrome (CRPS). His medical history included multiple sinus infections per year and several pneumonias requiring antibiotics. He has had various back surgeries, including a laminectomy at the L4 level 1 year prior to his diagnosis. Thereafter, he underwent four sympathetic nerve blocks with minimal pain relief. Blood chemistries showed a normal white blood cell count with a normal differential, but increased erythrocyte sedimentation rate and C-reactive protein levels. Total Ig (Immunoglobulin)G was 611 mg/dL (normal 700-1,600), IgG1 was 425 mg/dL (341-894), IgG2 was 114 mg/dL (171-632), IgG3 was 14.4 mg/dL (18.4-106), and IgG4 was 7.4 mg/dL (2.4-121). IgA was 47 mg/dL (normal 70-400), IgM was 131 mg/dL (40-230), and IgE was 4.5 kU/L (<4.0). He only had 10 of 23 pneumococcal titers in the protective range post-vaccination. Upon treatment of the CVID with intravenous immunoglobulin, the patient's pain levels were significantly decreased and have been maintained for more than 2 years. Therefore, immunoglobulin therapy appears to have been beneficial in the treatment of the patient's symptoms of CRPS, including pain. Additional studies investigating the mechanism by which immunoglobulin therapy may reduce the inflammation and pain of CRPS are needed.

  1. Attention-deficit-hyperactivity disorder and reward deficiency syndrome

    Directory of Open Access Journals (Sweden)

    Kenneth Blum

    2008-11-01

    form of a gene (DRD2 A1 allele that prevents the expression of the normal laying down of dopamine receptors in brain reward sites. This gene, and others involved in neurophysiological processing of specific neurotransmitters, have been associated with defi cient functions and predispose individuals to have a high risk for addictive, impulsive, and compulsive behavioral propensities. It has been proposed that genetic variants of dopaminergic genes and other “reward genes” are important common determinants of reward deficiency syndrome (RDS, which we hypothesize includes ADHD as a behavioral subtype. We further hypothesize that early diagnosis through genetic polymorphic identification in combination with DNA-based customized nutraceutical administration to young children may attenuate behavioral symptoms associated with ADHD. Moreover, it is concluded that dopamine and serotonin releasers might be useful therapeutic adjuncts for the treatment of other RDS behavioral subtypes, including addictions.Keywords: attention deficit hyperactivity disorder (ADHD, genes, reward dependence, reward deficiency syndrome, treatment, neuropsychological deficits

  2. Paroxysmal eye-head movements in Glut1 deficiency syndrome.

    Science.gov (United States)

    Pearson, Toni S; Pons, Roser; Engelstad, Kristin; Kane, Steven A; Goldberg, Michael E; De Vivo, Darryl C

    2017-04-25

    To describe a characteristic paroxysmal eye-head movement disorder that occurs in infants with Glut1 deficiency syndrome (Glut1 DS). We retrospectively reviewed the medical charts of 101 patients with Glut1 DS to obtain clinical data about episodic abnormal eye movements and analyzed video recordings of 18 eye movement episodes from 10 patients. A documented history of paroxysmal abnormal eye movements was found in 32/101 patients (32%), and a detailed description was available in 18 patients, presented here. Episodes started before age 6 months in 15/18 patients (83%), and preceded the onset of seizures in 10/16 patients (63%) who experienced both types of episodes. Eye movement episodes resolved, with or without treatment, by 6 years of age in 7/8 patients with documented long-term course. Episodes were brief (usually <5 minutes). Video analysis revealed that the eye movements were rapid, multidirectional, and often accompanied by a head movement in the same direction. Eye movements were separated by clear intervals of fixation, usually ranging from 200 to 800 ms. The movements were consistent with eye-head gaze saccades. These movements can be distinguished from opsoclonus by the presence of a clear intermovement fixation interval and the association of a same-direction head movement. Paroxysmal eye-head movements, for which we suggest the term aberrant gaze saccades, are an early symptom of Glut1 DS in infancy. Recognition of the episodes will facilitate prompt diagnosis of this treatable neurodevelopmental disorder. Copyright © 2017 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.

  3. An Interview with AIDS Vaccine Researcher Chris Parks

    Science.gov (United States)

    Sullivan, Megan

    2010-01-01

    The search for an AIDS (acquired immune deficiency syndrome) vaccine is truly a global effort, with university laboratories, biotech firms, pharmaceutical companies, nonprofit research organizations, hospitals, and clinics all working together to develop an effective vaccine as quickly as possible. The International AIDS Vaccine Initiative (IAVI)…

  4. A three-year-old boy with glucose transporter type 1 deficiency syndrome presenting with episodic ataxia.

    Science.gov (United States)

    Ohshiro-Sasaki, Akiko; Shimbo, Hiroko; Takano, Kyoko; Wada, Takahito; Osaka, Hitoshi

    2014-01-01

    Glucose transporter type 1 deficiency syndrome is a metabolic encephalopathy that results from impaired glucose transport into the brain as the result of a mutation of the SLC2A1 gene. It has been recognized recently that these patients can present with a much broader clinical spectrum than previously thought. We describe a 3-year-old boy presenting with episodic ataxia. Our patient exhibited periodic abnormal eye movements, including opsoclonus, since he was 4 months of age. At 2 years of age, he experienced acute cerebellar ataxia after a vaccination. Since then, he has had periodic attacks of ataxic gait, repeated vomiting, and abnormal eye movement. He was diagnosed as having episodic ataxia type 2 because the administration of acetazolamide seemed effective. By 3 years and 10 months of age, he exhibited mild mental retardation and mild trunk ataxia. The attacks were more likely to occur when he was hungry. Molecular analysis revealed that the SLC2A1 gene had a de novo mutation of heterozygous seven nucleotide insertion within exon 7, resulting in a frameshift. He has recently begun a modified Atkins diet; the frequency of attacks has been reduced, and his psychomotor and language skills have begun to develop. Glucose transporter type 1 deficiency syndrome should be considered in the differential diagnosis in children with episodic ataxia, even if acetazolamide is effective. Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Pyrimidine pool imbalance induced by BLM helicase deficiency contributes to genetic instability in Bloom syndrome.

    Science.gov (United States)

    Chabosseau, Pauline; Buhagiar-Labarchède, Géraldine; Onclercq-Delic, Rosine; Lambert, Sarah; Debatisse, Michelle; Brison, Olivier; Amor-Guéret, Mounira

    2011-06-28

    Defects in DNA replication are associated with genetic instability and cancer development, as illustrated in Bloom syndrome. Features of this syndrome include a slowdown in replication speed, defective fork reactivation and high rates of sister chromatid exchange, with a general predisposition to cancer. Bloom syndrome is caused by mutations in the BLM gene encoding a RecQ helicase. Here we report that BLM deficiency is associated with a strong cytidine deaminase defect, leading to pyrimidine pool disequilibrium. In BLM-deficient cells, pyrimidine pool normalization leads to reduction of sister chromatid exchange frequency and is sufficient for full restoration of replication fork velocity but not the fork restart defect, thus identifying the part of the Bloom syndrome phenotype because of pyrimidine pool imbalance. This study provides new insights into the molecular basis of control of replication speed and the genetic instability associated with Bloom syndrome. Nucleotide pool disequilibrium could be a general phenomenon in a large spectrum of precancerous and cancer cells.

  6. 阳虚生风论%Theory of Feng-Syndrome Caused by Yang Deficiency

    Institute of Scientific and Technical Information of China (English)

    潘远根

    2016-01-01

    The treatment of Feng-syndrome in TCM frequently focused on the wind syndromes caused by the strong hot, the hyperactivity of Yang, the Yin deficiency and the blood deficiency, but the Feng syndrome rarely deals with Yang deficiency. In this paper, we puts forward the Feng syndromes also caused by Yang deficiency and briefly discusses on it in the theory, the type of diseases and the syndrome differentiation, and then, to break down the syndrome differentiating keys with some clinical cases.%中医论风证的辨证治疗,向来仅注重火热、阳亢、阴虚、血虚等引起的风证,绝少论及阳虚动风。本文从阳虚生风的理论、病证类型、辨证要点等方面简要论述了阳虚阴盛同样引起动风证,并例举临床病例以详解辨证关键。

  7. [Severe deglutition disorders and iron deficiency; Plummer-Vinson syndrome].

    Science.gov (United States)

    Geerlings, S E; Statius van Eps, L W

    1991-11-01

    At oesophagogastroscopy a web was seen in the upper oesophagus in a female of 73 years with dysphagia. Because she also had a smooth tongue, a low serum iron level and anaemia, the syndrome of Plummer-Vinson was diagnosed. After treatment with ferrous fumarate the dysphagia, the web and the anaemia disappeared and the serum iron rose. The symptomatology of this syndrome is discussed. Remarkably, the pathogenesis is not completely known. There are indications that this uncommon syndrome is a premalignant disorder.

  8. [Cornelia de Lange Syndrome and multiple hormonal deficiency, an unusual association. Clinical case].

    Science.gov (United States)

    Mora-Bautista, Víctor M; Mendoza-Rojas, Víctor; Contreras-García, Gustavo A

    2017-06-01

    Cornelia de Lange syndrome is a genetic disease characterized by distinctive facial features, failure to thrive, microcephaly and several malformations associated. Its main endocrinological features are anomalies of the genitalia. We present a 13-year-old boy, who suffered from complicated aspiration pneumonia and showed Cornelia de Lange syndrome phenotype, with global developmental delay, suction-swallowing abnormalities, short stature and abnormal genitalia associated. His bone age was delayed, so he underwent full endocrinological panel. Central hypothyroidism, growth hormone deficiency and low luteinizing hormone-follicle-stimulating hormone levels were observed and multiple pituitary hormone deficiencies diagnosis was made. Basal cortisol, adrenocorticotropic hormone and prolactin levels were normal. He received thyroid hormonal substitution. Multiple pituitary hormone deficiencies are an unusual feature of De Lange syndrome. We suggest evaluating all different endocrine axes in these patients. Sociedad Argentina de Pediatría.

  9. Reversible white matter lesions during ketogenic diet therapy in glucose transporter 1 deficiency syndrome.

    Science.gov (United States)

    Shiohama, Tadashi; Fujii, Katsunori; Takahashi, Satoru; Nakamura, Fumito; Kohno, Yoichi

    2013-12-01

    Glucose transporter type 1 deficiency syndrome is caused by brain energy failure resulting from a disturbance in glucose transport. We describe a 4-year-old boy with classical type glucose transporter type 1 deficiency syndrome with a heterozygous splice acceptor site mutation (c.517-2A>G) in the SLCA2A1 gene. We initiated a ketogenic diet at 4 months of age. However, even though his condition was good during ketogenic diet therapy, multiple cerebral white matter and right cerebellum lesions appeared at 9 months of age. The lesions in the cerebral white matter subsequently disappeared, indicating that white matter lesions during diet therapy may be reversible and independent of the ketogenic diet. This is the first report of reversible white matter lesions during ketogenic diet therapy in glucose transporter type 1 deficiency syndrome. Copyright © 2013 Elsevier Inc. All rights reserved.

  10. Low hepatitis B vaccine response in children with Down syndrome from Brazil.

    Science.gov (United States)

    Nisihara, R; De Bem, R S; Negreiros, P H R; Utiyama, S R R; Oliveira, N P; Amarante, H

    2014-07-01

    It has been reported that vaccination against hepatitis B is less effective among people with Down syndrome than in the general population. We aimed to evaluate the rate of seroconversion to hepatitis B vaccine in children with Down syndrome from Brazil. A total of 120 people with Down syndrome were included. All of them received the vaccine at intervals of 0, 30 and 180 days and serum samples were tested for the presence of antibodies to the hepatitis B surface antigen (anti-HBs) 30 days after the last dose. In the studied group, 58.3% (70/120) were male and 41.7% (50/120) female, with the median age of 5 years (range 2-15 years). Fifty-eight of 120 (48.3%) developed anti-HBs after vaccination. No association was found between gender and/or age and vaccine response. The low rate of seroconversion in response to hepatitis B vaccine suggests that all patients with Down syndrome immunized against hepatitis B should be followed and monitored by clinicians. © 2013 John Wiley & Sons Ltd.

  11. Acute bilateral useless hand syndrome: a rare presenting manifestation of vitamin B12 deficiency.

    Science.gov (United States)

    Biyani, Sumant; Jha, Sneh Kumar; Pandey, Suchit; Shukla, Rakesh

    2015-10-16

    We report a case of bilateral useless hand syndrome, a rare presenting manifestation of vitamin B12 deficiency. A 38-year-old man, a strict vegetarian and a teacher by occupation, presented with acute onset clumsiness of both hands while performing fine movements. Detailed history-taking, examination of the patient and relevant investigations (complete blood count, serum vitamin B12 and MRI of the cervical spinal cord) were carried out. Laboratory analysis was suggestive of vitamin B12 deficiency and MRI demonstrated a lesion involving the posterior columns of the cervical cord. The patient was diagnosed as a case of non-compressive cervical myelopathy predominantly involving the posterior column due to vitamin B12 deficiency. Acute bilateral useless hand syndrome can be a rare presenting feature of vitamin B12 deficiency.

  12. Taurine deficiency and MELAS are closely related syndromes.

    Science.gov (United States)

    Schaffer, Stephen W; Jong, Chian Ju; Warner, Danielle; Ito, Takashi; Azuma, Junichi

    2013-01-01

    MELAS (mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes) is a mitochondrial disease caused by one or more mutations of tRNA(Leu(UUR)). These mutations reduce both the aminoacylation of tRNA(Leu(UUR)) and a posttranslational modification in the wobble position of tRNA(Leu(UUR)). Both changes result in reduced transcription of mitochondria-encoded proteins; however, reduced aminoacylation affects the decoding of both UUG and UUA while the wobble defect specifically diminishes UUG decoding. Because 12 out of the 13 mitochondria-encoded proteins are more dependent on UUA decoding than UUG decoding, the aminoacylation defect should have a more profound effect on protein synthesis than the wobble defect, which more specifically alters the expression of one mitochondria-encoded protein, ND6. Taurine serves as a substrate in the formation of 5-taurinomethyluridine-tRNA(Leu(UUR)); therefore, taurine deficiency should mimic 5-taurinomethyluridine-tRNA(Leu(UUR)) deficiency. Hence, the wobble hypothesis predicts that the symptoms of MELAS mimic those of taurine deficiency, provided that the dominant defect in MELAS is wobble modification deficiency. On the other hand, if the aminoacylation defect dominates, significant differences should exist between taurine deficiency and MELAS. The present review tests this hypothesis by comparing the symptoms of MELAS and taurine deficiency.

  13. Charles Bonnet syndrome and vitamin B12 deficiency: a case report.

    Science.gov (United States)

    Bourgeois, Valérie; Desbordes, Marie; Follet, Mathieu; Haouzir, Sadeq; Guillin, Olivier

    2010-01-01

    The Charles Bonnet syndrome (CBS) is a condition associated with complex visual hallucinations occurring in the elderly in patients with visual impairment and normal mental health. Here, we report the case of a 78-year-old woman who has a limited visual acuity with a CBS that we postulated to be in relationship to a vitamin B12 deficiency. This case is the first report of vitamin B12 deficiency-associated CBS.

  14. Bovine Neonatal Pancytopenia: is this alloimmune syndrome caused by vaccine-induced alloreactive antibodies?

    Science.gov (United States)

    Bastian, Max; Holsteg, Mark; Hanke-Robinson, Heidrun; Duchow, Karin; Cussler, Klaus

    2011-07-18

    Bovine Neonatal Pancytopenia (BNP) is a new emerging disease observed since 2007 in Germany and neighbouring countries. The syndrome affects newborn calves and is characterized by pancytopenia, severe bleeding and high lethality. So far, a causative role of infectious or toxic agents has been ruled out. Instead, the syndrome is induced after ingestion of colostrum, the first milk that supplies the calf with maternal antibodies. In analogy to similar diseases in humans it has therefore been postulated that BNP is caused by alloreactive, maternal antibodies. There is a striking association between BNP and a previous vaccination of the respective dams with a particular vaccine against Bovine Virus Diarrhoea (BVD). This association has led to a suspension of the marketing authorisation for the vaccine, by the European Commission. The current study investigates the role of this vaccine in the pathogenesis of BNP. By flow cytometry we were able to demonstrate that sera of BNP dams (dams that gave birth to a BNP calf) harbour alloreactive antibodies binding to surface antigens on bovine leukocytes. A significantly weaker alloreactivity was observed with sera of non-BNP dams that have been vaccinated with the same vaccine but delivered healthy calves. No binding was seen with non-BVD-vaccinated control cows and animals that were vaccinated with other inactivated BVD vaccines so far not associated with BNP. The binding is functionally relevant, because opsonization of bovine leukocytes with alloantibodies led to an elevated cytophagocytosis by bovine macrophages. To test whether the vaccine induces alloreactive antibodies two strategies were employed: Guinea pigs were vaccinated with a panel of commercially available BVD-vaccines. Only the incriminated vaccine induced antibodies binding surface antigens on bovine leukocytes. Additionally, two calves were repeatedly vaccinated with the suspected vaccine and the development of alloreactivity was monitored. In dependence of

  15. Severe chronic iron deficiency anaemia secondary to Trichuris dysentery syndrome - a case report.

    Science.gov (United States)

    Azira N, M S; Zeehaida, M

    2012-12-01

    Trichuris dysentery syndrome is caused by Trichuris trichiura which contributes to one of the most common helminthic infections in the world. It is associated with heavy colonic infection that manifests as mucoid diarrhoea, rectal bleeding, rectal prolapse, iron deficiency anaemia, and finger clubbing. Here, we report a case of trichuris dysentery syndrome complicated with severe chronic iron deficiency anaemia in a 4-year-old girl who required blood transfusion. The nematode was visualized on stool microscopic and colonoscopic examination. A longer duration of anti-helminthic treatment is required to achieve effective and better outcome.

  16. Anti-thrombin III, Protein C, and Protein S deficiency in acute coronary syndrome

    Directory of Open Access Journals (Sweden)

    Dasnan Ismail

    2002-06-01

    Full Text Available The final most common pathway for the majority of coronary artery disease is occlusion of a coronary vessel. Under normal conditions, antithrombin III (AT III, protein C, and protein S as an active protein C cofactor, are natural anticoagulants (hemostatic control that balances procoagulant activity (thrombin antithrombin complex balance to prevent thrombosis. If the condition becomes unbalanced, natural anticoagulants and the procoagulants can lead to thrombosis. Thirty subjects with acute coronary syndrome (ACS were studied for the incidence of antithrombin III (AT III, protein C, and protein S deficiencies, and the result were compare to the control group. Among patients with ACS, the frequency of distribution of AT-III with activity < 75% were 23,3% (7 of 30, and only 6,7% ( 2 of 30 in control subject. No one of the 30 control subject have protein C activity deficient, in ACS with activity < 70% were 13,3% (4 of 30. Fifteen out of the 30 (50% control subjects had protein S activity deficiency, while protein S deficiency activity < 70% was found 73.3.% (22 out of 30. On linear regression, the deterministic coefficient of AT-III activity deficiency to the development ACS was 13,25 %, and the deterministic coefficient of protein C activity deficient to the development of ACS was 9,06 %. The cut-off point for AT-III without protein S deficiency expected to contribute to the development of vessel disease was 45%. On discriminant analysis, protein C activity deficiency posed a risk for ACS of 4,5 greater than non deficient subjects, and AT-III activity deficiency posed a risk for ACS of 3,5 times greater than non deficient subjects. On binary logistic regression, protein S activity acted only as a reinforcing factor of AT-III activity deficiency in the development of ACS. Protein C and AT III deficiency can trigger ACS, with determinant coefficients of 9,06% and 13,25% respectively. Low levels of protein C posed a greater risk of

  17. [The role of inositol deficiency in the etiology of polycystic ovary syndrome disorders].

    Science.gov (United States)

    Jakimiuk, Artur J; Szamatowicz, Jacek

    2014-01-01

    Inositol acts as a second messenger in insulin signaling pathway Literature data suggest inositol deficiency in insulin-resistant women with the polycystic ovary syndrome. Supplementation of myo-inisitol decreases insulin resistance as it works as an insulin sensitizing agent. The positive role of myo-inositol in the treatment of polycystic ovary syndrome has been of increased evidence recently The present review presents the effects of myo-inositol on the ovarian, hormonal and metabolic parameters in women with PCOS.

  18. PORCINE RESPIRATORY AND REPRODUCTIVE SYNDROME VIRUS VACCINOLOGY: A REVIEW FOR COMMERCIAL VACCINES

    Directory of Open Access Journals (Sweden)

    V. G. Papatsiros

    2012-01-01

    Full Text Available Porcine Reproductive and Respiratory Syndrome (PRRS since its appearance in Europe in the early 1990’s has resulted in tremendous economic losses. Under field conditions vaccination is one of the most efficient strategies for the prevention and control of PRRS. The aim of this study is to perform the PRRSV vaccinology regarding current status of commercial vaccines in Europe. There are two types of PRRSV commercial available vaccines in Europe: Killed Virus (KV or inactivated vaccines and Modified-Live Virus (MLV or attenuated vaccines. EU KV commercial vaccines provide limited efficacy due to the weak stimulation of the immune system and no effective induction of neutralizing antibodies. However, KV vaccines can induce a strong Cell Mediated Immune (CMI response. One the other hand, commercial EU MLV vaccines provide effective strain-specific protection, only partial protection against genetically heterologous PRRSV and elicit relatively late humoral and CMI responses which lead to delayed protection. In Europe, the KV vaccination prove to reduce the negative effects of PRRSV in breeding herds, improving their reproductive performance, e.g., increase of farrowing rate and number of live or weaned pigs, reduction of premature farrowing rate, abortion rate and number of mummified and stillborn piglets. The use of commercial MLV vaccines in PRRSV-infected breeding herds leads to improvement of: (a reproductive performance e.g., reduction of the abortion and return to oestrus rate and increase of the farrowing rate and number of weaners, ( b the viraemic status, morbidity and mortality rate of piglets and (c the growth performance of vaccinated pigs. In conclusion, nowadays the use of MLV or KV vaccines in Europe is the most economical tool to control the economic losses of PRRSV infection. However, the development of more efficacious PRRSV vaccines is the significant future goal for PRRSV vaccinology.

  19. Interleukin-10 Genotype Correlated to Deficiency Syndrome in Hepatitis B Cirrhosis

    Directory of Open Access Journals (Sweden)

    Qing-Ya Li

    2012-01-01

    Full Text Available Traditional Chinese medicine (TCM syndrome is an important basis for TCM diagnosis and treatment. As Child-Pugh classification as well as compensation and decompensation phase in liver cirrhosis, it is also an underlying clinical classification. In this paper, we investigated the correlation between single nucleotide polymorphisms (SNPs of Interleukin-10 (IL-10 and TCM syndromes in patients with hepatitis B cirrhosis (HBC. Samples were obtained from 343 HBC patients in China. Three SNPs of IL-10 (−592A/C, −819C/T, and −1082A/G were detected with polymerase chain-reaction-ligase detection reaction (PCR-LDR. The result showed the SNP-819C/T was significantly correlated with Deficiency syndrome (P=0.031, but none of the 3 loci showed correlation either with Child-Pugh classification and phase in HBC patients. The logistic regression analysis showed that the Excess syndrome was associated with dizzy and spider nevus, and the Deficiency syndrome was associated with dry eyes, aversion to cold, IL-10-819C/T loci, and IL-10-1082A/G loci. The odds ratio (OR value at IL-10-819C/T was 4.022. The research results suggested that IL-10-819C/T locus (TC plus CC genotype is probably a risk factor in the occurrence of Deficiency syndrome in HBC patients.

  20. A Metabolomics Approach to Stratify Patients Diagnosed with Diabetes Mellitus into Excess or Deficiency Syndromes

    Directory of Open Access Journals (Sweden)

    Tao Wu

    2015-01-01

    Full Text Available The prevalence of type 2 diabetes continuously increases globally. The traditional Chinese medicine (TCM can stratify the diabetic patients based on their different TCM syndromes and, thus, allow a personalized treatment. Metabolomics is able to provide metabolite biomarkers for disease subtypes. In this study, we applied a metabolomics approach using an ultraperformance liquid chromatography (UPLC coupled with quadruple-time-of-flight (QTOF mass spectrometry system to characterize the metabolic alterations of different TCM syndromes including excess and deficiency in patients diagnosed with diabetes mellitus (DM. We obtained a snapshot of the distinct metabolic changes of DM patients with different TCM syndromes. DM patients with excess syndrome have higher serum 2-indolecarboxylic acid, hypotaurine, pipecolic acid, and progesterone in comparison to those patients with deficiency syndrome. The excess patients have more oxidative stress as demonstrated by unique metabolite signatures than the deficiency subjects. The results provide an improved understanding of the systemic alteration of metabolites in different syndromes of DM. The identified serum metabolites may be of clinical relevance for subtyping of diabetic patients, leading to a personalized DM treatment.

  1. Implications of spatially heterogeneous vaccination coverage for the risk of congenital rubella syndrome in South Africa

    OpenAIRE

    Metcalf, C. J. E.; C. Cohen; Lessler, J; McAnerney, J M; G.M. Ntshoe; Puren, A; Klepac, P.; TATEM, A.; Grenfell, B. T.; O.N. Bjørnstad

    2013-01-01

    Rubella is generally a mild childhood disease, but infection during early pregnancy may cause spontaneous abortion or congenital rubella syndrome (CRS), which may entail a variety of birth defects. Since vaccination at levels short of those necessary to achieve eradication may increase the average age of infection, and thus potentially the CRS burden, introduction of the vaccine has been limited to contexts where coverage is high. Recent work suggests that spatial heterogeneity in coverage sh...

  2. HIV-2 and its role in conglutinated approach towards Acquired Immunodeficiency Syndrome (AIDS) Vaccine Development

    OpenAIRE

    Diwan, Batul; Saxena, Rupali; Tiwari, Archana

    2013-01-01

    Acquired Immunodeficiency Syndrome (AIDS) is one of the most critically acclaimed endemic diseases, caused by two lentiviruses HIV-1 and 2. HIV-2 displays intimate serological and antigenic resemblance to Simian Immunodeficiency Virus (SIV) along with less pathogenicity, lower infectivity and appreciable cross reactivity with HIV-1 antigens. The present era is confronted with the challenge to fabricate a vaccine effective against all clades of both the species of HIV. But vaccine development ...

  3. Deficiencies

    Data.gov (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,...

  4. Lack of homozygotes for the most frequent disease allele in carbohydrate-deficient glycoprotein syndrome type 1A.

    OpenAIRE

    MATTHIJS, G; Schollen, E.; van Schaftingen, E; Cassiman, J. J.; Jaeken, J.

    1998-01-01

    Carbohydrate-deficient-glycoprotein syndrome type 1 (CDG1; also known as "Jaeken syndrome") is an autosomal recessive disorder characterized by defective glycosylation. Most patients show a deficiency of phosphomannomutase (PMM), the enzyme that converts mannose 6-phosphate to mannose 1-phosphate in the synthesis of GDP-mannose. The disease is linked to chromosome 16p13, and mutations have recently been identified in the PMM2 gene in CDG1 patients with a PMM deficiency (CDG1A). The availabili...

  5. A recombinant DNA vaccine protects mice deficient in the alpha/beta interferon receptor against lethal challenge with Usutu virus.

    Science.gov (United States)

    Martín-Acebes, Miguel A; Blázquez, Ana-Belén; Cañas-Arranz, Rodrigo; Vázquez-Calvo, Ángela; Merino-Ramos, Teresa; Escribano-Romero, Estela; Sobrino, Francisco; Saiz, Juan-Carlos

    2016-04-19

    Usutu virus (USUV) is a mosquito-borne flavivirus whose circulation had been confined to Africa since it was first detected in 1959. However, in the last decade USUV has emerged in Europe causing episodes of avian mortality and sporadic severe neuroinvasive infections in humans. Remarkably, adult laboratory mice exhibit limited susceptibility to USUV infection, which has impaired the analysis of the immune responses, thus complicating the evaluation of virus-host interactions and of vaccine candidates against this pathogen. In this work, we showed that mice deficient in the alpha/beta interferon receptor (IFNAR (-/-) mice) were highly susceptible to USUV infection and provided a lethal challenge model for vaccine testing. To validate this infection model, a plasmid DNA vaccine candidate encoding the precursor of membrane (prM) and envelope (E) proteins of USUV was engineered. Transfection of cultured cells with this plasmid resulted in expression of USUV antigens and the assembly and secretion of small virus-like particles also known as recombinant subviral particles (RSPs). A single intramuscular immunization with this plasmid was sufficient to elicit a significant level of protection against challenge with USUV in IFNAR (-/-) mice. The characterization of the humoral response induced revealed that DNA vaccination primed anti-USUV antibodies, including neutralizing antibodies. Overall, these results probe the suitability of IFNAR (-/-) mice as an amenable small animal model for the study of USUV host virus interactions and vaccine testing, as well as the feasibility of DNA-based vaccine strategies for the control of this pathogen.

  6. Influenza vaccination is safe and effective in patients suffering from fibromyalgia syndrome

    Directory of Open Access Journals (Sweden)

    J. N. Ablin

    2015-09-01

    Full Text Available The fibromyalgia syndrome (FMS is considered to result from the exposure of a genetically susceptible individual to various triggers, such as physical trauma, stress, viral infections etc. A possible role of vaccination in FMS etiology has been suspected. Our objective was to evaluate the efficacy and safety of influenza vaccination in FMS patients. Nineteen FMS patients underwent physical and dolorimetric examinations and answered the fibromyalgia impact questionnaire (FIQ, the widespread pain index (WPI checklist and the symptoms severity scale (SSS, which are part of the 2010 diagnostic criteria. Thirty-eight healthy subjects were recruited as controls. All participants were vaccinated with the inactivated split virion influenza vaccine. Serum was collected for antibody titration. Six weeks after vaccination, sera were tested by hemagglutination (HI against A/California (H1N1, A/Perth (H3N2 and B/Brisbane. Humoral response was defined as either a fourfold or greater increase in titer, or an increase from a non-protective baseline level of <1/40 to a level of 1/40. No severe vaccination reactions were observed. No significant change was observed between WPI, SSS and FIQ values before and after vaccination, indicating no worsening of FMS symptoms. Vaccine immunogenicity: Six weeks after vaccination, FMS patients showed a significant increase in geometric mean titers of HI antibody. The rates of sero-protection increased from 22.9% for H1N1 to 89.5% post-vaccination. A significant increase in HI antibody titers was also demonstrated among healthy controls. Influenza vaccination was both safe and effective in FMS patients. In view of these results, FMS patients should be encouraged to undergo influenza vaccination according to the standard WHO recommendations.

  7. Glucose transporter-1 deficiency syndrome: The expanding clinical and genetic spectrum of a treatable disorder

    NARCIS (Netherlands)

    W.G. Leen (Wilhelmina); J. Klepper (Joerg); M.M. Verbeek (Marcel); M. Leferink (Maike); T. Hofste (Tom); B.G.M. van Engelen (Baziel); R.A. Wevers (Ron); T. Arthur (Todd); N. Bahi-Buisson (Nadia); D. Ballhausen (Diana); J. Bekhof (Jolita); P. van Bogaert (Patrick); I. Carrilho (Inês); B. Chabrol (Brigitte); M.P. Champion (Michael); J. Coldwell (James); P. Clayton (Peter); E. Donner (Elizabeth); A. Evangeliou (Athanasios); F. Ebinger (Friedrich); K. Farrell (Kevin); R.J. Forsyth (Rob); C.G.E.L. de Goede (Christian); S. Gross (Stephanie); S. Grünewald (Sonja); H. Holthausen (Hans); S. Jayawant (Sandeep); K. Lachlan (Katherine); V. Laugel (Vincent); K. Leppig (Kathy); M.J. Lim (Ming); G.M.S. Mancini (Grazia); A.D. Marina; L. Martorell (Loreto); J. McMenamin (Joe); M.E.C. Meuwissen (Marije); H. Mundy (Helen); N.O. Nilsson (Nils); A. Panzer (Axel); B.T. Poll-The; C. Rauscher (Christian); C.M.R. Rouselle (Christophe); I. Sandvig (Inger); T. Scheffner (Thomas); E. Sheridan (Eamonn); N. Simpson (Neil); P. Sykora (Parol); R. Tomlinson (Richard); J. Trounce (John); D.W.M. Webb (David); B. Weschke (Bernhard); H. Scheffer (Hans); M.A. Willemsen (Michél)

    2010-01-01

    textabstractGlucose transporter-1 deficiency syndrome is caused by mutations in the SLC2A1 gene in the majority of patients and results in impaired glucose transport into the brain. From 2004-2008, 132 requests for mutational analysis of the SLC2A1 gene were studied by automated Sanger sequencing an

  8. A Milk-Free Diet Downregulates Folate Receptor Autoimmunity in Cerebral Folate Deficiency Syndrome

    Science.gov (United States)

    Ramaekers, Vincent T.; Sequeira, Jeffrey M.; Blau, Nenad; Quadros, Edward V.

    2008-01-01

    In cerebral folate deficiency syndrome, the presence of autoantibodies against the folate receptor (FR) explains decreased folate transport to the central nervous system and the clinical response to folinic acid. Autoantibody crossreactivity with milk FR from different species prompted us to test the effect of a milk-free diet. Intervention with a…

  9. Acquired Immune Deficiency Syndrome: A Preliminary Examination of the Effects on Gay Couples and Coupling.

    Science.gov (United States)

    Carl, Douglas

    1986-01-01

    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…

  10. Posterior fossa syndrome in a patient with an ornithine transcarbamylase deficiency

    NARCIS (Netherlands)

    Nedermeijer, S. C M; Van Den Hout, J.; Geleijns, C.; De Klerk, H.; Catsman-Berrevoets, C. E.

    2015-01-01

    The posterior fossa syndrome (PFS) is a well-known clinical entity and mainly occurs in children. Ornithine transcarbamylase deficiency (OTC) is the most common urea cycle disorder, which occurs in an estimated 1 per 50.000 live births in Japan. Symptoms are mostly due to hyperammonemia and include

  11. Upstream SLC2A1 translation initiation causes GLUT1 deficiency syndrome

    NARCIS (Netherlands)

    Willemsen, M.A.A.P.; Vissers, L.E.L.M.; Verbeek, M.M.; Bon, B.W.M. van; Geuer, S.; Gilissen, C.F.; Klepper, J.; Kwint, M.P.; Leen, W.G.; Pennings, M.; Wevers, R.A.; Veltman, J.A.; Kamsteeg, E.J.

    2017-01-01

    Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a neurometabolic disorder with a complex phenotypic spectrum but simple biomarkers in cerebrospinal fluid. The disorder is caused by impaired glucose transport into the brain resulting from variants in SCL2A1. In 10% of GLUT1DS patients, a

  12. Cerebrospinal Fluid Analysis in the Workup of GLUT1 Deficiency Syndrome: A Systematic Review

    NARCIS (Netherlands)

    Leen, W.G.; Wevers, R.A.; Kamsteeg, E.J.; Scheffer, H.; Verbeek, M.M.; Willemsen, Marjolein

    2013-01-01

    IMPORTANCE GLUT1 deficiency syndrome is a treatable neurometabolic disorder, characterized by a low concentration of glucose in cerebrospinal fluid (CSF) and a decreased CSF to blood glucose ratio. Reports of patients with apparently normal CSF glucose levels, however, have raised the question wheth

  13. GLUT1 deficiency syndrome into adulthood: a follow-up study

    NARCIS (Netherlands)

    Leen, W.G.; Taher, M.; Verbeek, M.M.; Kamsteeg, E.J.; Warrenburg, B.P.C. van de; Willemsen, M.A.

    2014-01-01

    GLUT1 deficiency syndrome (GLUT1DS) is a treatable neurometabolic disorder in which glucose transport into the brain is disturbed. Besides the classic phenotype of intellectual disability, epilepsy, and movement disorders, other phenotypes are increasingly recognized. These include, for example, idi

  14. Glucose transporter-1 (GLUT1) deficiency syndrome: diagnosis and treatment in late childhood.

    NARCIS (Netherlands)

    Gramer, G.; Wolf, N.I.; Vater, D.; Bast, T.; Santer, R.; Kamsteeg, E.J.; Wevers, R.A.; Ebinger, F.

    2012-01-01

    BACKGROUND: Typical cases of glucose transporter-1 deficiency syndrome (GLUT1-DS) present with early-onset epilepsy. We report symptoms, diagnostic results, and effects of therapy in two patients diagnosed with GLUT1-DS at the age of 10 and 15 years, respectively. PATIENTS: Patient 1: After four cer

  15. TSP-1 Deficiency Alters Ocular Microbiota: Implications for Sjögren's Syndrome Pathogenesis

    OpenAIRE

    Terzulli, Marielle; Ruiz, Laura Contreras; Kugadas, Abirami; Masli, Sharmila; Gadjeva, Mihaela

    2015-01-01

    Purpose: The potential role of commensals as triggering factors that promote inflammation in dry eye disease has not been explored. The objective of this study was to evaluate whether ocular microbiota changes with the onset of dry eye disease in thrombospondin-1-deficient (TSP-1−/−) mice, a strain that develops Sjögren's syndrome-like disease.

  16. Movement disorders in GLUT1 deficiency syndrome respond to the modified Atkins diet

    NARCIS (Netherlands)

    Leen, W.G.; Mewasingh, L.; Verbeek, M.M.; Kamsteeg, E.J.; Warrenburg, B.P.C. van de; Willemsen, M.A.A.P.

    2013-01-01

    BACKGROUND: Movement disorders are a prominent feature of glucose transporter-1 (GLUT1) deficiency syndrome (GLUT1DS). First-choice treatment is a ketogenic diet, but compliance is poor. We have investigated the effect of the modified Atkins diet as an alternative treatment for movement disorders in

  17. Glucose transporter-1 (GLUT1) deficiency syndrome: diagnosis and treatment in late childhood.

    NARCIS (Netherlands)

    Gramer, G.; Wolf, N.I.; Vater, D.; Bast, T.; Santer, R.; Kamsteeg, E.J.; Wevers, R.A.; Ebinger, F.

    2012-01-01

    BACKGROUND: Typical cases of glucose transporter-1 deficiency syndrome (GLUT1-DS) present with early-onset epilepsy. We report symptoms, diagnostic results, and effects of therapy in two patients diagnosed with GLUT1-DS at the age of 10 and 15 years, respectively. PATIENTS: Patient 1: After four cer

  18. Movement disorders in GLUT1 deficiency syndrome respond to the modified Atkins diet

    NARCIS (Netherlands)

    Leen, W.G.; Mewasingh, L.; Verbeek, M.M.; Kamsteeg, E.J.; Warrenburg, B.P.C. van de; Willemsen, M.A.A.P.

    2013-01-01

    BACKGROUND: Movement disorders are a prominent feature of glucose transporter-1 (GLUT1) deficiency syndrome (GLUT1DS). First-choice treatment is a ketogenic diet, but compliance is poor. We have investigated the effect of the modified Atkins diet as an alternative treatment for movement disorders in

  19. Glucose transporter-1 deficiency syndrome : the expanding clinical and genetic spectrum of a treatable disorder

    NARCIS (Netherlands)

    Leen, Wilhelmina G.; Klepper, Joerg; Verbeek, Marcel M.; Leferink, Maike; Hofste, Tom; van Engelen, Baziel G.; Wevers, Ron A.; Arthur, Todd; Bahi-Buisson, Nadia; Ballhausen, Diana; Bekhof, Jolita; van Bogaert, Patrick; Carrilho, Ines; Chabrol, Brigitte; Champion, Michael P.; Coldwell, James; Clayton, Peter; Donner, Elizabeth; Evangeliou, Athanasios; Ebinger, Friedrich; Farrell, Kevin; Forsyth, Rob J.; de Goede, Christian G. E. L.; Gross, Stephanie; Grunewald, Stephanie; Holthausen, Hans; Jayawant, Sandeep; Lachlan, Katherine; Laugel, Vincent; Leppig, Kathy; Lim, Ming J.; Mancini, Grazia; Della Marina, Adela; Martorell, Loreto; McMenamin, Joe; Meuwissen, Marije E. C.; Mundy, Helen; Nilsson, Nils O.; Panzer, Axel; Poll-The, Bwee T.; Rauscher, Christian; Rouselle, Christophe M. R.; Sandvig, Inger; Scheffner, Thomas; Sheridan, Eamonn; Simpson, Neil; Sykora, Parol; Tomlinson, Richard; Trounce, John; Webb, David; Weschke, Bernhard; Scheffer, Hans; Willemsen, Michel A.

    2010-01-01

    Glucose transporter-1 deficiency syndrome is caused by mutations in the SLC2A1 gene in the majority of patients and results in impaired glucose transport into the brain. From 2004-2008, 132 requests for mutational analysis of the SLC2A1 gene were studied by automated Sanger sequencing and multiplex

  20. A Milk-Free Diet Downregulates Folate Receptor Autoimmunity in Cerebral Folate Deficiency Syndrome

    Science.gov (United States)

    Ramaekers, Vincent T.; Sequeira, Jeffrey M.; Blau, Nenad; Quadros, Edward V.

    2008-01-01

    In cerebral folate deficiency syndrome, the presence of autoantibodies against the folate receptor (FR) explains decreased folate transport to the central nervous system and the clinical response to folinic acid. Autoantibody crossreactivity with milk FR from different species prompted us to test the effect of a milk-free diet. Intervention with a…

  1. Glucose Transporter Type 1 Deficiency Syndrome with Carbohydrate-Responsive Symptoms but without Epilepsy

    Science.gov (United States)

    Koy, Anne; Assmann, Birgit; Klepper, Joerg; Mayatepek, Ertan

    2011-01-01

    Glucose transporter type 1 deficiency syndrome (GLUT1-DS) is caused by a defect in glucose transport across the blood-brain barrier. The main symptoms are epilepsy, developmental delay, movement disorders, and deceleration of head circumference. A ketogenic diet has been shown to be effective in controlling epilepsy in GLUT1-DS. We report a female…

  2. Acquired Immune Deficiency Syndrome: A Preliminary Examination of the Effects on Gay Couples and Coupling.

    Science.gov (United States)

    Carl, Douglas

    1986-01-01

    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…

  3. Posterior fossa syndrome in a patient with an ornithine transcarbamylase deficiency

    NARCIS (Netherlands)

    Nedermeijer, S. C M; Van Den Hout, J.; Geleijns, C.; De Klerk, H.; Catsman-Berrevoets, C. E.

    2015-01-01

    The posterior fossa syndrome (PFS) is a well-known clinical entity and mainly occurs in children. Ornithine transcarbamylase deficiency (OTC) is the most common urea cycle disorder, which occurs in an estimated 1 per 50.000 live births in Japan. Symptoms are mostly due to hyperammonemia and include

  4. Glucose transporter-1 (GLUT1) deficiency syndrome: diagnosis and treatment in late childhood.

    NARCIS (Netherlands)

    Gramer, G.; Wolf, N.I.; Vater, D.; Bast, T.; Santer, R.; Kamsteeg, E.J.; Wevers, R.A.; Ebinger, F.

    2012-01-01

    BACKGROUND: Typical cases of glucose transporter-1 deficiency syndrome (GLUT1-DS) present with early-onset epilepsy. We report symptoms, diagnostic results, and effects of therapy in two patients diagnosed with GLUT1-DS at the age of 10 and 15 years, respectively. PATIENTS: Patient 1: After four

  5. Vitamin D deficiency is prevalent in girls and women with rett syndrome

    Science.gov (United States)

    The aim of the study was to determine the prevalence of vitamin D deficiency and identify the relation between 25-hydroxyvitamin D (25-(OH)D) levels and the consumption of dietary sources of vitamin D or exposure to anticonvulsants in girls and women with Rett syndrome (RTT). Retrospective review of...

  6. Beyond the cardiorenal anaemia syndrome : recognizing the role of iron deficiency

    NARCIS (Netherlands)

    Macdougall, Iain C.; Canaud, Bernard; de Francisco, Angel L. M.; Filippatos, Gerasimos; Ponikowski, Piotr; Silverberg, Donald; van Veldhuisen, Dirk J.; Anker, Stefan D.

    2012-01-01

    Growing awareness that heart failure, renal impairment, and anaemia are frequent co-morbidities which can exacerbate one another in a vicious circle of clinical deterioration has led to the concept of the cardiorenal anaemia syndrome (CRAS). The role of iron deficiency within this complex interplay

  7. Multiple endocrinopathies (growth hormone deficiency, autoimmune hypothyroidism and diabetes mellitus in Kearns-Sayre syndrome

    Directory of Open Access Journals (Sweden)

    A. Berio

    2013-06-01

    Full Text Available Kearns-Sayre syndrome is characterized by onset before 20 years, chronic progressive external opthalmoplegia, pigmentary retinal degeneration, and ataxia (and/or hearth block, and/or high protein content in the cerebrospinal fluid in the presence of mtDNA rearrangements. Multiple endocrine dysfunction associated with this syndrome was rarely reported. In this paper, the Authors report on a female patient with Kearns-Sayre syndrome with large heteroplasmic mtDNA deletion, absence of cytochrome c oxidase in many muscle fibers, partial GH deficiency, hypothyroidism and subsequently insulin dependent diabetes mellitus (IDDM. Anti-thyroid peroxidase and antithyreoglobulin antibodies were present in high titer in serum while anti-islet cell antibodies were absent. The patient developed thyroiditis with Hashimoto encephalopathy. The presence of GH deficiency, autoimmune thyroiditis with hypothyroidism and IDDM distinguishes this case from others and confirms the association of Kearns-Sayre syndrome with multiple endocrine dysfunction. Hashimoto encephalopathy and anti-thyroideal antibodies suggest that in this patient, predisposed by a genetic factor (a mitochondrial deletion anti-thyroideal antibodies may have contributed to the hypothyroidism and, by interfering with cerebral mitochondrial function, may have caused the encephalopathy. GH deficiency and IDDM can be attributed to oxidative phosphorylation deficiency but the autoimmunity may also have played a role in the production of glandular insufficiencies. It seems important to search for endocrine autoimmunity in every case of KSS.

  8. Isolated Vitamin D Deficiency Is Not Associated with Nonthyroidal Illness Syndrome, but with Thyroid Autoimmunity

    Directory of Open Access Journals (Sweden)

    Muyesser Sayki Arslan

    2015-01-01

    Full Text Available Aim. This study aimed to compare thyroid functions, thyroid autoantibodies, and the existence of nonthyroidal illness syndrome (NTIS according to vitamin D level. Materials and Methods. The study included age- and BMI-matched healthy volunteers with and without vitamin D deficiency. In addition, the nonthyroidal illness syndrome status was evaluated. Results. Anti-TPO positivity was significantly more common in those with severe and moderate vitamin D deficiency, as compared to those with a normal 25(OHD level. Furthermore, TSH levels were significantly lower in those with severe and moderate vitamin D deficiency than in those with a normal 25(OHD level. In addition, there was a significant weak inverse correlation between anti-TPO positivity and the 25(OHD level and a positive correlation between the TSH level and 25(OHD level. Only 1 thyroid function test result was compatible with NTIS among the participants with moderate vitamin D deficiency; therefore the difference was not significant. Conclusions. The prevalence of thyroid autoantibody positivity was higher in those with severe and moderate vitamin D deficiency than in those with a normal 25(OHD level. Additional large-scale studies must be conducted to determine if vitamin D deficiency plays a causal role in the pathogenesis of Hashimoto’s thyroiditis and NTIS.

  9. Intervention effect of traditional Chinese medicine Yi Tang Kang on metabolic syndrome of spleen deficiency

    Institute of Scientific and Technical Information of China (English)

    Xiao-Xi Liu; Yan Shi

    2015-01-01

    Objective:To investigate effects of herbal compoundYiTangKang on the spleen deficiency metabolic syndrome.Methods:Forty maleWistar rats were randomly divided into two groups: the normal control group and theMS spleen deficiency syndrome group.The control group rats were fed with standard diet and water, whileMS spleen deficiency syndrome group with high fat diet and low dose intraperitoneal injection ofstreptozocin, which swam to the endurance limit. After12 weeks, theMS spleen deficiency syndrome group was randomly divided into two groups, with13 rats in each group.Rats in model group were fed with high fat diet and continuouly administered with daily saline, and rats in intervention group with high fat diet were trated with traditionalChinese medicinesYiTangKang by gavage,2 mL/200 g at the same time every day.10 weeks later, the expression of serum proteomics was investigated through abdominal aortic puncture and separation of serum, using isotope labeling technique, high performance liquid chromatography and four bar-Orbitrap mass spectrometer.Results:After treatment with traditionalChinese medicine yitangkang, in the model group, important carboxylesterase and retinal guanylatecyclase2 precursor were upregulated.As for intervention group, these indesxes were raised, but immunoglobulinIgG, carnitine acetyltransferase, tubulin beta -5, andGanLu sugar binding proteinC were down-regulated.At the same time, some new biological active substances, such as protein tyrosine kinase, beta glucosidase were also found.Conclusions:TraditionalChinese medicinesYiTangKang could regulate glucose and lipid metabolism in rats with spleen deficiency syndrome.

  10. [Strategies to promote testosterone deficiency syndrome: a paradigm of disease mongering].

    Science.gov (United States)

    Gavilán, Enrique; Jiménez de Gracia, Laura; Gérvas, Juan

    2014-01-01

    The so-called «testosterone deficiency syndrome» is a blend of nonspecific symptoms typical of the physiological process of aging. This syndrome has been the subject of intense promotional activity that has presented the phenomenon as highly prevalent and with a major public health impact. This strategy has been accompanied by the emergence of new and easy to administer testosterone devices into the pharmaceutical market and has generated significant sales for drug companies. The commercial promotion of testosterone deficiency syndrome and its remedies has exploited cultural stereotypes of aging and sexuality through awareness campaigns promoted by the laboratories involved and has been disseminated by media with the participation of numerous experts and with the support of scientific associations, representing a paradigmatic case of disease mongering. This example might be of use in the response to disease mongering activities from the clinical and public health fields. Copyright © 2013 SESPAS. Published by Elsevier Espana. All rights reserved.

  11. Unusual phenotype of glucose transport protein type 1 deficiency syndrome: A case report and literature review

    Directory of Open Access Journals (Sweden)

    Annio Posar

    2014-01-01

    Full Text Available The glucose transport protein type 1 (GLUT1 deficit causes a chronic brain energy failure. The classic phenotype of GLUT1 deficiency syndrome is characterized by: Mild to severe motor delay and mental retardation; infantile-onset epilepsy; head growth deceleration; movement disorders (ataxia, dystonia, spasticity; and non-epileptic paroxysmal events (intermittent ataxia, periodic confusion, recurrent headaches. During last years the classic phenotype of this syndrome, as originally reported, has expanded. We report the atypical phenotype of a boy with GLUT1 deficiency syndrome, characterized by mild mental retardation and drug-resistant absence seizures with onset at the age of 6 years, without movement disorders nor decrease of head circumference. A prompt diagnosis of this disorder is mandatory since the ketogenic diet might represent an effective treatment.

  12. The immune response in SAPHO syndrome: deficiency, hyper- responsiveness, or both?

    Science.gov (United States)

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

    2013-01-01

    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.

  13. Recombinant egg drop syndrome subunit vaccine offers an alternative to virus propagation in duck eggs.

    Science.gov (United States)

    Gutter, B; Fingerut, E; Gallili, G; Eliahu, D; Perelman, B; Finger, A; Pitcovski, J

    2008-02-01

    Egg drop syndrome (EDS) virus vaccines are routinely produced in embryonated duck eggs (Solyom et al., 1982). This procedure poses the risk of dissemination of pathogens, such as avian influenza virus, as the eggs used are not from specific pathogen free birds. To address this problem, the knob and part of the shaft domain of the fibre protein of the EDS virus (termed knob-s) were expressed in Escherichia coli and assessed as a subunit vaccine. A single vaccination with the recombinant protein induced the production of anti-EDS virus antibodies, as detected by haemagglutination inhibition, enzyme-linked immunosorbent assay and virus neutralization tests, for at least 20 weeks. A positive correlation was demonstrated between these three assays. A dose-response assessment showed that the vaccine was effective over the range of 2 to 64 microg protein per dose. Two vaccinations with the recombinant protein, administered before the onset of lay, induced high haemagglutination inhibition antibody titres, comparable with those induced by an inactivated whole-virus vaccine. The vaccine did not have any adverse effects on egg production, quality or weight. The present study has shown that two vaccinations with the recombinant knob-s protein elicited high neutralizing antibody titres that persisted for more than 50 weeks of lay.

  14. Osteomyelitis in leukocyte adhesion deficiency type 1 syndrome

    DEFF Research Database (Denmark)

    Jabbari Azad, Farahzad; Ardalan, Maryam; H.Rafati, Ali;

    2010-01-01

    Leukocyte adhesion deficiency type 1 (LAD-1) is a rare, inherited immunodeficiency that affects one per million people yearly and usually presents with recurrent, indolent bacterial infections of the skin, mouth, and respiratory tract and impaired pus formation and wound healing. A 13-year-old gi......(10.60%). A plain radiography of the left leg revealed osteomyelitis. It is highly suggested that patients diagnosed mild to moderate LAD-1 with recurrent skin infection and simultaneous weak response to conventional therapy undergo (BMT) marrow transplant to prohibit subsequent life...

  15. Osteomyelitis in leukocyte adhesion deficiency type 1 syndrome

    DEFF Research Database (Denmark)

    Jabbari Azad, Farahzad; Ardalan, Maryam; H.Rafati, Ali

    2010-01-01

    Leukocyte adhesion deficiency type 1 (LAD-1) is a rare, inherited immunodeficiency that affects one per million people yearly and usually presents with recurrent, indolent bacterial infections of the skin, mouth, and respiratory tract and impaired pus formation and wound healing. A 13-year-old girl......(10.60%). A plain radiography of the left leg revealed osteomyelitis. It is highly suggested that patients diagnosed mild to moderate LAD-1 with recurrent skin infection and simultaneous weak response to conventional therapy undergo (BMT) marrow transplant to prohibit subsequent life...

  16. Immunological efficacy of Vaccination against Measles in Children with Down syndrome

    Directory of Open Access Journals (Sweden)

    S. P. Kaplina

    2011-01-01

    Full Text Available The data of current vaccination process of cellular, humoral immunity and specific antibody formation in 41 children with Down syndrome at the age of 1 year to 6 years old is observed. To prevent easles used measles vaccine (n=12, divaccine -measles-mumps (n=21 and or Priorix vaccine (n=8. The comparison group consisted of 63 children without Down syndrome. The post-vaccination period in 97,6% of children with Down syndrome cases are asymptomatic, only 2,4% of children mentioned layering of intercurrent diseases. The immunological status in children with Down syndrome is characterized by a significant decrease in the  umber leucocytes, lymphocytes, CD3+, CD4+, CD8+ and absolute number of CD20+, but functional activity of the cells is preserved. By 30 days after immunization they have increased leucocytes, lymphocytes, CD 95+cells. The number of antibodies significantly increased (6,63±0,33 compared to 5,79±0,32 log2, р < 0,05.

  17. Vaccinations

    Science.gov (United States)

    ... vaccinated? For many years, a set of annual vaccinations was considered normal and necessary for dogs and ... to protect for a full year. Consequently, one vaccination schedule will not work well for all pets. ...

  18. Glucose transporter type 1 deficiency syndrome effectively treated with modified Atkins diet.

    Science.gov (United States)

    Haberlandt, Edda; Karall, Daniela; Jud, Veronika; Baumgartner, Sara Sigl; Zotter, Sibylle; Rostasy, Kevin; Baumann, Matthias; Scholl-Buergi, Sabine

    2014-04-01

    This is a report on the successful treatment of a 6-year-old girl with genetically proven glucose transporter type 1 deficiency syndrome (GLUT1-DS) with modified Atkins diet (MAD). GLUT1-DS is an inborn disorder of glucose transport across the blood-brain barrier, which leads to energy deficiency of the brain with a broad spectrum of neurological symptoms including therapy-resistant epilepsy. Usually classical ketogenic diet (KD) is the standard treatment for patients with GLUT1-DS. Treatment with MAD, a variant of KD, for an observation period of 17 months resulted in improvement of seizures, alertness, cognitive abilities, and electroencephalography in this patient.

  19. Comparison of the efficacy of autogenous inactivated Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) vaccines with that of commercial vaccines against homologous and heterologous challenges.

    Science.gov (United States)

    Geldhof, Marc F; Vanhee, Merijn; Van Breedam, Wander; Van Doorsselaere, Jan; Karniychuk, Uladzimir U; Nauwynck, Hans J

    2012-10-03

    The porcine reproductive and respiratory syndrome virus (PRRSV) is a rapidly evolving pathogen of swine. At present, there is a high demand for safe and more effective vaccines that can be adapted regularly to emerging virus variants. A recent study showed that, by the use of a controlled inactivation procedure, an experimental BEI-inactivated PRRSV vaccine can be developed that offers partial protection against homologous challenge with the prototype strain LV. At present, it is however not known if this vaccine can be adapted to currently circulating virus variants. In this study, two recent PRRSV field isolates (07 V063 and 08 V194) were used for BEI-inactivated vaccine production. The main objective of this study was to assess the efficacy of these experimental BEI-inactivated vaccines against homologous and heterologous challenge and to compare it with an experimental LV-based BEI-inactivated vaccine and commercial inactivated and attenuated vaccines. In addition, the induction of challenge virus-specific (neutralizing) antibodies by the different vaccines was assessed. In a first experiment (challenge with 07 V063), vaccination with the experimental homologous (07 V063) inactivated vaccine shortened the viremic phase upon challenge with approximately 2 weeks compared to the mock-vaccinated control group. Vaccination with the commercial attenuated vaccines reduced the duration of viremia with approximately one week compared to the mock-vaccinated control group. In contrast, the experimental heterologous (LV) inactivated vaccine and the commercial inactivated vaccine did not influence viremia. Interestingly, both the homologous and the heterologous experimental inactivated vaccine induced 07 V063-specific neutralizing antibodies upon vaccination, while the commercial inactivated and attenuated vaccines failed to do so.In the second experiment (challenge with 08 V194), use of the experimental homologous (08 V194) inactivated vaccine shortened viremia upon

  20. Bordetella pertussis and pertactin-deficient clinical isolates: lessons for pertussis vaccines.

    Science.gov (United States)

    Hegerle, Nicolas; Guiso, Nicole

    2014-09-01

    Bordetella pertussis causes whooping cough in humans, a highly transmissible respiratory disease life threatening for unvaccinated infants. Vaccination strategies were thus introduced worldwide with great success in developed countries reaching high vaccine coverage with efficacious vaccines. In the late 20th/early 21st century, acellular pertussis vaccines replaced whole cell pertussis vaccines but B. pertussis still circulates and evolves in humans, its only known reservoir. The latest transformation of this pathogen, and of its close relative Bordetella parapertussis, is the loss of pertactin production, a virulence factor included in different acellular pertussis vaccines. The real impact of this evolution on acellular pertussis vaccines efficacy and effectiveness should be assessed through standardized surveillance and isolation of B. pertussis and B. parapertussis worldwide.

  1. Congenital rubella syndrome and autism spectrum disorder prevented by rubella vaccination - United States, 2001-2010

    Directory of Open Access Journals (Sweden)

    Omer Saad B

    2011-05-01

    Full Text Available Abstract Background Congenital rubella syndrome (CRS is associated with several negative outcomes, including autism spectrum disorders (ASDs. The objective of this study was to estimate the numbers of CRS and ASD cases prevented by rubella vaccination in the United States from 2001 through 2010. Methods Prevention estimates were calculated through simple mathematical modeling, with values of model parameters determined from published literature. Model parameters included pre-vaccine era CRS incidence, vaccine era CRS incidence, the number of live births per year, and the percentage of CRS cases presenting with an ASD. Results Based on our estimates, 16,600 CRS cases (range: 8300-62,250 were prevented by rubella vaccination from 2001 through 2010 in the United States. An estimated 1228 ASD cases were prevented by rubella vaccination in the United States during this time period. Simulating a slight expansion in ASD diagnostic criteria in recent decades, we estimate that a minimum of 830 ASD cases and a maximum of 6225 ASD cases were prevented. Conclusions We estimate that rubella vaccination prevented substantial numbers of CRS and ASD cases in the United States from 2001 through 2010. These findings provide additional incentive to maintain high measles-mumps-rubella (MMR vaccination coverage.

  2. Severe somatoform and dysautonomic syndromes after HPV vaccination: case series and review of literature.

    Science.gov (United States)

    Palmieri, Beniamino; Poddighe, Dimitri; Vadalà, Maria; Laurino, Carmen; Carnovale, Carla; Clementi, Emilio

    2016-08-09

    Human papilloma virus (HPV) is recognized as a major cause for cervical cancer among women worldwide. Two HPV vaccines are currently available: Gardasil(®) and Cervarix(®). Both vaccines enclose viral antigenic proteins, but differ as to the biological systems of culture and the adjuvant components. Recently, a collection of symptoms, indicating nervous system dysfunction, has been described after HPV vaccination. We retrospectively described a case series including 18 girls (aged 12-24 years) referred to our "Second Opinion Medical Network" for the evaluation of "neuropathy with autonomic dysfunction" after HPV vaccination. All girls complained of long-lasting and invalidating somatoform symptoms (including asthenia, headache, cognitive dysfunctions, myalgia, sinus tachycardia and skin rashes) that have developed 1-5 days (n = 11), 5-15 days (n = 5) and 15-20 days (n = 2) after the vaccination. These cases can be included in the recently described immune dysfunction named autoimmune/inflammatory syndrome induced by adjuvants (ASIA). HPV vaccine, through its adjuvant component, is speculated to induce an abnormal activation of the immune system, involving glia cells in the nervous system too. Further researches should aim at defining the pathological and clinical aspects of these post-vaccination diseases and identifying a genetic background predisposing to these adverse reactions.

  3. Clinical and radiologic review of uncommon cause of profound iron deficiency anemia: Median arcuate ligament syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Gunduz, Yasemin; Asil, Kiyasrttin; Aksoy, Yakup Ersel; Ayhan, Lacin Tatli [Dept. of Radiology, Sakarya University Medical Faculty, Sakarya (Turkmenistan)

    2014-08-15

    Median arcuate ligament syndrome is an anatomic and clinical entity characterized by dynamic compression of the proximal celiac artery by the median arcuate ligament, which leads to postprandial epigastric pain, vomiting, and weight loss. These symptoms are usually nonspecific and are easily misdiagnosed as functional dyspepsia, peptic ulcer disease, or gastropathy. In this report, we presented a 72-year-old male patient with celiac artery compression syndrome causing recurrent abdominal pain associated with gastric ulcer and iron deficiency anemia. This association is relatively uncommon and therefore not well determined. In addition, we reported the CT angiography findings and three-dimensional reconstructions of this rare case.

  4. Testosterone deficiency syndrome: benefits, risks, and realities associated with testosterone replacement therapy.

    Science.gov (United States)

    Hassan, Jacob; Barkin, Jack

    2016-02-01

    Testosterone deficiency syndrome, which has sometimes been termed age-related or late-onset hypogonadism, is a syndrome characterized by both clinical manifestations as well as a biochemical deficiency of testosterone. This condition is associated with considerable morbidity and mortality, accounting for billions of dollars in health care costs. There is some evidence that suggests that restoring testosterone levels in these individuals may help to manage or delay progression of the associated morbidities. Furthermore, despite controversies in the literature and media, testosterone replacement has proven to be quite safe in most men with minimal if any adverse effects when dosing to achieve the eugonadal range. It is nevertheless very important for clinicians to be aware of the possible risks and contraindications of treatment to ensure proper patient selection and appropriate monitoring.

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

    Directory of Open Access Journals (Sweden)

    Naidoo P

    2013-09-01

    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

  6. Yang/Qi Invigoration: An Herbal Therapy for Chronic Fatigue Syndrome with Yang Deficiency?

    Directory of Open Access Journals (Sweden)

    Pou Kuan Leong

    2015-01-01

    Full Text Available According to traditional Chinese medicine (TCM theory, Yang and Qi are driving forces of biological activities in the human body. Based on the crucial role of the mitochondrion in energy metabolism, we propose an extended view of Yang and Qi in the context of mitochondrion-driven cellular and body function. It is of interest that the clinical manifestations of Yang/Qi deficiencies in TCM resemble those of chronic fatigue syndrome in Western medicine, which is pathologically associated with mitochondrial dysfunction. By virtue of their ability to enhance mitochondrial function and its regulation, Yang- and Qi-invigorating tonic herbs, such as Cistanches Herba and Schisandrae Fructus, may therefore prove to be beneficial in the treatment of chronic fatigue syndrome with Yang deficiency.

  7. Netherton Syndrome in a Neonate with Possible Growth Hormone Deficiency and Transient Hyperaldosteronism

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    Chatziioannidis Ilias

    2015-01-01

    Full Text Available Netherton syndrome, a rare autosomal recessive genetic disorder, is classified as an ichthyosiform syndrome. In this report we present the case of a neonate with erythroderma shortly after birth, accompanied by severe hypernatremia, recurrent infections, transient hyperaldosteronism, and signs of growth hormone (GH deficiency. DNA molecular analysis in the SPINK5 gene revealed heterozygosity in our index patient for 238insG and 2468delA frameshift mutations in exons 4 and 26, respectively, in the maternal allele and 1431-12G>A splice-site mutation in intron 15 in the paternal allele as well as the missense variation E420K in homozygous state. Combination of the identified mutations along with transient hyperaldosteronism and possible GH deficiency have not been described before. Accordingly, the importance of early multidisciplinary approach is highlighted, in order to reach accurate diagnosis, initiate prompt treatment, and ensure survival with fewer disease complications.

  8. Creatine Deficiency Syndrome could be Missed Easily: A Case Report of Guanidinoacetate Methyltransferase Deficiency Presented with Neurodevelopmental Delay, Seizures, and Behavioral Changes, but Normal Structural MRI.

    Science.gov (United States)

    Pacheva, Iliyana; Ivanov, Ivan; Penkov, Marin; Kancheva, Daliya; Jordanova, Albena; Ivanova, Mariya

    2016-09-01

    A case with GAMT deficiency (homozygous c.64dupG mutation) presented with neurodevelopmental delay, rare seizures, behavioral disturbances, and mild hypotonia, posing diagnostic challenges. Metabolic investigations showed low creatinine in plasma and urine (guanidinoacetate couldn't be investigated) and slightly elevated lactate. MRI was normal. Correct diagnosis was possible only after MR spectroscopy was performed at age 5½ years. A homozygous c.64dupG mutation of the GAMT gene was identified in the proband. In conclusion, every case with neurodevelopmental delay or arrest, especially when accompanied by seizures, behavioral impairment, muscle hypotonia or extrapyramidal symptoms should undergo MRI with MR spectroscopy. Normal structural MRI doesn't exclude a creatine deficiency syndrome. Biochemical investigations of guanidinoacetate, creatine, and creatinine in body fluid should be done to diagnose cerebral creatine deficiency syndromes and to specify the deficient enzyme. Thus, a treatable disease will not be missed.

  9. Serum-free microcarrier based production of replication deficient Influenza vaccine candidate virus lacking NS1 using Vero cells

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    Yan Mylene L

    2011-08-01

    Full Text Available Abstract Background Influenza virus is a major health concern that has huge impacts on the human society, and vaccination remains as one of the most effective ways to mitigate this disease. Comparing the two types of commercially available Influenza vaccine, the live attenuated virus vaccine is more cross-reactive and easier to administer than the traditional inactivated vaccines. One promising live attenuated Influenza vaccine that has completed Phase I clinical trial is deltaFLU, a deletion mutant lacking the viral Nonstructural Protein 1 (NS1 gene. As a consequence of this gene deletion, this mutant virus can only propagate effectively in cells with a deficient interferon-mediated antiviral response. To demonstrate the manufacturability of this vaccine candidate, a batch bioreactor production process using adherent Vero cells on microcarriers in commercially available animal-component free, serum-free media is described. Results Five commercially available animal-component free, serum-free media (SFM were evaluated for growth of Vero cells in agitated Cytodex 1 spinner flask microcarrier cultures. EX-CELL Vero SFM achieved the highest cell concentration of 2.6 × 10^6 cells/ml, whereas other SFM achieved about 1.2 × 10^6 cells/ml. Time points for infection between the late exponential and stationary phases of cell growth had no significant effect in the final virus titres. A virus yield of 7.6 Log10 TCID50/ml was achieved using trypsin concentration of 10 μg/ml and MOI of 0.001. The Influenza vaccine production process was scaled up to a 3 liter controlled stirred tank bioreactor to achieve a cell density of 2.7 × 10^6 cells/ml and virus titre of 8.3 Log10 TCID50/ml. Finally, the bioreactor system was tested for the production of the corresponding wild type H1N1 Influenza virus, which is conventionally used in the production of inactivated vaccine. High virus titres of up to 10 Log10 TCID50/ml were achieved. Conclusions We describe for the

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

    Directory of Open Access Journals (Sweden)

    Farzaneh Vadoudfam

    2001-05-01

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1987-06-01

    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.

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

    Science.gov (United States)

    Drane, W E; Tipler, B M

    1987-06-01

    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.

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

    OpenAIRE

    Naidoo P; Pillay D; Saman S

    2013-01-01

    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...

  14. Pseudo-Foster Kennedy Syndrome as a Rare Presentation of Vitamin B12 Deficiency

    OpenAIRE

    Petramfar, Peyman; Hosseinzadeh, Farideh; Mohammadi, S. Saeed

    2016-01-01

    Introduction Pseudo-Foster Kennedy syndrome is a triad consisting of ipsilateral optic atrophy, contralateral optic disc edema, and ipsilateral anosmia in the absence of an intracranial mass. Vitamin B12 plays an important role in DNA synthesis, and its deficiency causes peripheral neuropathy, myeloneuropathy, and, very rarely, optic neuropathy. Case Presentation In this study, we describe a 34-year-old male who presented with progressive loss of visual acuity and field. Fundoscopy showed opt...

  15. Severe transient ADAMTS13 deficiency in pneumococcal-associated hemolytic uremic syndrome.

    Science.gov (United States)

    Pelras, Sybille; Delmas, Yahsou; Lamireau, Delphine; Villega, Frédéric; Nolent, Paul; Ryman, Anne; Llanas, Brigitte; Brissaud, Olivier; Harambat, Jérôme

    2011-04-01

    Thrombotic microangiopathies comprise different entities, including hemolytic uremic syndrome (HUS), thrombotic thrombocytopenic purpura (TTP), and several other conditions. TTP is characterized by hemolytic anemia, thrombocytopenia, and multiorgan failure. TTP is the result of severe von Willebrand factor multimer cleaving protease (ADAMTS13) deficiency that is either inherited or the result of acquired autoantibodies. We report a critically ill 2-year-old girl with invasive pneumococcal disease associated HUS (p-HUS) whose condition was complicated by severe ADAMTS13 deficiency, without detectable inhibitor, in a context of multiple organ failure. The patient recovered with supportive treatment, and ADAMTS13 activity normalized without plasmatherapy. Severe ADAMTS13 deficiency appears to be a manifestation of transient endothelial cell injury in the context of severe sepsis, including invasive p-HUS. The choice of appropriate therapy should not be based on this finding.

  16. Heterologous challenge with porcine reproductive and respiratory syndrome (PRRS) vaccine virus: no evidence of reactivation of previous European-type PRRS virus infection

    DEFF Research Database (Denmark)

    Bøtner, Anette; Nielsen, Jens; Oleksiewicz, M.B.

    1999-01-01

    In Denmark, a porcine reproductive and respiratory syndrome virus (PRRSV) control programme, comprising vaccination of seropositive herds with a live American type PRRSV vaccine, was started in 1996. In several of these herds, spread of vaccine virus from vaccinated 3-18 week old pigs to non-vacc...

  17. The impact of the vaccination program for hemorrhagic fever with renal syndrome in Hu County, China.

    Science.gov (United States)

    Xiao, Dan; Wu, Kejian; Tan, Xin; Yan, Tiecheng; Li, Haitao; Yan, Yongping

    2014-02-03

    The incidence of hemorrhagic fever with renal syndrome (HFRS) in Hu County ranked third of all counties in China in 2010. Although this county has provided a HFRS vaccination program freely since 1994, the impact of HFRS remains quite substantial. In order to continue the vaccination program effectively and control HFRS, a detailed understanding of the effect of the vaccination program should be undertaken. The Cochran-Armitage trend test was employed to examine the temporal trends of HFRS incidences, mortality rate and vaccination compliance. Temporal cluster analysis was performed to detect time periods of high HFRS risk. Cross correlation analysis was conducted to detect the correlation between HFRS incidence and vaccination compliance. Wavelet analysis was employed to detect the shift of the periodicity of HFRS. Between 1971 and 2011, the HFRS incidence and mortality rate ranged from 9.53/100,000 to 300.57/100,000 and 0 to 24.91/100,000, respectively, with a fluctuating but distinctly declining trend (incidence: Z=-34.38, P1994. In conclusion, the increase in vaccination compliance may play an important role in HFRS control and prevention in Hu County, China.

  18. Ferric carboxymaltose in patients with restless legs syndrome and nonanemic iron deficiency: A randomized trial.

    Science.gov (United States)

    Trenkwalder, Claudia; Winkelmann, Juliane; Oertel, Wolfgang; Virgin, Garth; Roubert, Bernard; Mezzacasa, Anna

    2017-06-23

    Compromised iron status is important in restless legs syndrome pathophysiology. We compared the efficacy and tolerability of ferric carboxymaltose (single intravenous dose) versus placebo for restless legs syndrome treatment in iron-deficient nonanemic patients. Patients with moderate to severe restless legs syndrome and serum ferritin Restless Legs Syndrome Severity Scale score from baseline to week 4 was the primary end point; week 12 was a secondary end point. Ferric carboxymaltose treatment (n = 59) led to nonsignificant improvement over placebo (n = 51) in International Restless Legs Syndrome Severity Scale score at week 4 (difference [95% confidence interval], -2.5 [-5.93 to 1.02], P = 0.163), reaching significance by week 12 (-4.66 [-8.59 to -0.73], P = 0.021). In patients who responded to treatment, ferric carboxymaltose may require more time to stabilize restless legs syndrome than previously assumed. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society. © 2017 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

  19. 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.

    Science.gov (United States)

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

    2016-01-06

    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.

  20. Small for Gestational Age and Magnesium: Intrauterine magnesium deficiency may induce metabolic syndrome in later life

    Directory of Open Access Journals (Sweden)

    Junji Takaya

    2015-12-01

    Full Text Available Magnesium deficiency during pregnancy as a result of insufficient or low intake of magnesium is common in developing and developed countries. Previous reports have shown that intracellular magnesium of cord blood platelets is lower among small for gestational age (SGA groups than that of appropriate for gestational age (AGA groups, suggesting that intrauterine magnesium deficiency may result in SGA. Additionally, the risk of adult-onset diseases such as insulin resistance syndrome is greater among children whose mothers were malnourished during pregnancy, and who consequently had a low birth weight. In a number of animal models, poor nutrition during pregnancy leads to offspring that exhibit pathophysiological changes similar to human diseases. The offspring of pregnant rats fed a magensium restricted diet have developed hypermethylation in the hepatic 11β-hydroxysteroid dehydrogenase-2 promoter. These findings indicate that maternal magnesium deficiencies during pregnancy influence regulation of non-imprinted genes by altering the epigenetic regulation of gene expression, thereby inducing different metabolic phenotypes. Magnesium deficiency during pregnancy may be responsible for not only maternal and fetal nutritional problems, but also lifelong consequences that affect the offspring throughout their life. Epidemiological, clinical, and basic research on the effects of magnesium deficiency now indicates underlying mechanisms, especially epigenetic processes.

  1. Influenza vaccination and the endurance against air pollution among elderly with acute coronary syndrome.

    Science.gov (United States)

    Huang, Ching-Hui; Chao, Day-Yu; Wu, Chao-Chun; Hsu, Shu-Yun; Soon, Maw-Soan; Chang, Chia-Chu; Kor, Chew-Teng; Chang, Wan-Tzu; Lian, Ie-Bin

    2016-12-07

    Air pollution, weather condition and influenza are known risk factors of acute coronary syndrome (ACS) among elderly people. The influenza vaccine (IV) has been shown to reduce major cardiovascular events. The purpose of this study was to compare resistance to air pollution and weather factors causing ACS between vaccinated and less-vaccinated elderly people. A case-crossover design was applied to 1835 elderly ACS patients who were obtained from the 1-million sample of Taiwan National Health Insurance Research Data with inclusion criteria: (1) the first diagnosis of ACS was in cold season and at age 68 or more, (2) had received the free IV program at least once during the period 3years before the ACS. They were stratified into two groups: 707 had received flu vaccinations for all the 3years and the remaining 1128 had not. The measurements of air pollutants, temperature, and humidity corresponding to each of the 3days prior to the ACS diagnosis date were retrieved from the data banks of the Taiwan Environmental Protection Administration and Central Weather Bureau. Increases in air pollution concentrations of CO, NO2, PM10 or PM2.5 and decreases in temperature significantly influenced the risk of ACS for the non-continuously vaccinated elderly population; however, less significant effects were observed for the continuously vaccinated population. Consecutive influenza vaccination may potentially offer resistance against the detrimental effects of air pollution and changes in temperature in frail elderly adults with ACS. Future studies are needed to directly assess the interaction effect between the vaccination and environmental factors on ACS. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Vitamin A deficiency impairs adaptive B and T cell responses to a prototype monovalent attenuated human rotavirus vaccine and virulent human rotavirus challenge in a gnotobiotic piglet model.

    Directory of Open Access Journals (Sweden)

    Kuldeep S Chattha

    Full Text Available Rotaviruses (RV are a major cause of gastroenteritis in children. Widespread vitamin A deficiency is associated with reduced efficacy of vaccines and higher incidence of diarrheal infections in children in developing countries. We established a vitamin A deficient (VAD gnotobiotic piglet model that mimics subclinical vitamin A deficiency in children to study its effects on an oral human rotavirus (HRV vaccine and virulent HRV challenge. Piglets derived from VAD and vitamin A sufficient (VAS sows were orally vaccinated with attenuated HRV or mock, with/without supplemental vitamin A and challenged with virulent HRV. Unvaccinated VAD control piglets had significantly lower hepatic vitamin A, higher severity and duration of diarrhea and HRV fecal shedding post-challenge as compared to VAS control pigs. Reduced protection coincided with significantly higher innate (IFNα cytokine and CD8 T cell frequencies in the blood and intestinal tissues, higher pro-inflammatory (IL12 and 2-3 fold lower anti-inflammatory (IL10 cytokines, in VAD compared to VAS control pigs. Vaccinated VAD pigs had higher diarrhea severity scores compared to vaccinated VAS pigs, which coincided with lower serum IgA HRV antibody titers and significantly lower intestinal IgA antibody secreting cells post-challenge in the former groups suggesting lower anamnestic responses. A trend for higher serum HRV IgG antibodies was observed in VAD vs VAS vaccinated groups post-challenge. The vaccinated VAD (non-vitamin A supplemented pigs had significantly higher serum IL12 (PID2 and IFNγ (PID6 compared to vaccinated VAS groups suggesting higher Th1 responses in VAD conditions. Furthermore, regulatory T-cell responses were compromised in VAD pigs. Supplemental vitamin A in VAD pigs did not fully restore the dysregulated immune responses to AttHRV vaccine or moderate virulent HRV diarrhea. Our findings suggest that that VAD in children in developing countries may partially contribute to more

  3. Diagnosis of Constitutional Mismatch Repair-Deficiency Syndrome Based on Microsatellite Instability and Lymphocyte Tolerance to Methylating Agents

    DEFF Research Database (Denmark)

    Bodo, Sahra; Colas, Chrystelle; Buhard, Olivier

    2015-01-01

    BACKGROUND & AIMS: Patients with bi-allelic germline mutations in mismatch repair (MMR) genes (MLH1, MSH2, MSH6, or PMS2) develop a rare but severe variant of Lynch syndrome called constitutional MMR deficiency (CMMRD). This syndrome is characterized by early-onset colorectal cancers, lymphomas o...

  4. Human papillomavirus vaccines, complex regional pain syndrome, postural orthostatic tachycardia syndrome, and autonomic dysfunction - a review of the regulatory evidence from the European Medicines Agency

    DEFF Research Database (Denmark)

    Jefferson, Tom; Jørgensen, Lars

    2017-01-01

    Recent concerns about a possible association between exposure of young women to human papillomavirus (HPV) vaccines and two "dysautonomic syndromes" (a collection of signs and symptoms thought to be caused by autoimmunity) - complex regional pain syndrome (CRPS) and postural orthostatic tachycardia...

  5. Identification of a novel mutation in an Indian patient with CAII deficiency syndrome

    Directory of Open Access Journals (Sweden)

    Shivaprasad C

    2010-01-01

    Full Text Available Carbonic anhydrase II (CAII deficiency syndrome characterized by osteopetrosis (OP, renal tubular acidosis (RTA, and cerebral calcifications is caused by mutations in the carbonic anhydrase 2 (CA2 gene. Severity of this disorder varies depending on the nature of the mutation and its effect on the protein. We present here, the clinical and radiographic details along with, results of mutational analysis of the CA2 gene in an individual clinically diagnosed with renal tubular acidosis, osteopetrosis and mental retardation and his family members to establish genotype-phenotype correlation. A novel homozygous deletion mutation c.251delT was seen in the patient resulting in a frameshift and a premature stop codon at amino acid position 90 generating a truncated protein leading to a complete loss of function and a consequential deficiency of the enzyme making this a pathogenic mutation. Confirmation of clinical diagnosis by molecular methods is essential as the clinical features of the CAII deficiency syndrome are similar to other forms of OP but the treatment modalities are different. Genetic confirmation of the diagnosis at an early age leads to the timely institution of therapy improving the growth potential, reduces other complications like fractures, and aids in providing prenatal testing and genetic counseling to the parents planning a pregnancy.

  6. 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

    2010-12-01

    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.

  7. Small for Gestational Age and Magnesium in Cord Blood Platelets: Intrauterine Magnesium Deficiency May Induce Metabolic Syndrome in Later Life

    Directory of Open Access Journals (Sweden)

    Junji Takaya

    2011-01-01

    Full Text Available Magnesium deficiency in pregnancy frequently occurs because of inadequate or low intake of magnesium. Magnesium deficiency during pregnancy can induce not only maternal and fetal nutritional problems, but also consequences that might last in offspring throughout life. Many epidemiological studies have disclosed that small for gestational age (SGA is associated with an increased risk of insulin resistance in adult life. We reported that intracellular magnesium of cord blood platelets is lower in SGA groups than that in appropriate for gestational age groups, suggesting that intrauterine magnesium deficiency may result in SGA. Taken together, intrauterine magnesium deficiency in the fetus may lead to or at least program insulin resistance after birth. In this review, we propose that intrauterine magnesium deficiency may induce metabolic syndrome in later life. We discuss the potential contribution of aberrant magnesium regulation to SGA and to the pathogenesis of metabolic syndrome.

  8. On the vaccination of shrimp against white spot syndrome virus

    NARCIS (Netherlands)

    Witteveldt, J.

    2006-01-01

    More than a decade after its discovery inSouth-East Asia, White Spot Syndrome Virus (WSSV) is still the most important (viral) pathogen in the shrimp culture industry. Despite the shift from culturingPenaeusmonodon

  9. Evolution of specific immunity in shrimp - a vaccination perspective against white spot syndrome virus.

    Science.gov (United States)

    Syed Musthaq, Syed Khader; Kwang, Jimmy

    2014-10-01

    Invertebrates lack true adaptive immunity and it solely depends on the primitive immunity called innate immunity. However, various innate immune molecules and mechanisms are identified in shrimp that plays potential role against invading bacterial, fungal and viral pathogens. Perceiving the shrimp innate immune mechanisms will contribute in developing effective vaccine strategies against major shrimp pathogens. Hence this review intends to explore the innate immune molecules of shrimp with suitable experimental evidences together with the evolution of "specific immune priming" of invertebrates. In addition, we have emphasized on the development of an effective vaccine strategy against major shrimp pathogen, white spot syndrome virus (WSSV). The baculovirus displayed rVP28 (Bac-VP28), a major envelope protein of WSSV was utilized to study its vaccine efficacy by oral route. A significant advantage of this baculovirus expression cassette is the use of WSSV-immediate early 1 (ie1) promoter that derived the abundant expression of rVP28 protein at the early stage of the infection in insect cell. The orally vaccinated shrimp with Bac-VP28 transduced successfully in the shrimp cells as well as provided highest survival rate. In support to our vaccine efficacy we analysed Pattern Recognition Proteins (PRPs) β-1,3 glucan lipopolysaccharides (LGBP) and STAT gene profiles in the experimental shrimp. Indeed, the vaccination of shrimp with Bac-VP28 demonstrated some degree of specificity with enhanced survival rate when compared to control vaccination with Bac-wt. Hence it is presumed that the concept of "specific immune priming" in relevant to shrimp immunity is possible but may not be common to all shrimp pathogens.

  10. Human TYK2 deficiency: Mycobacterial and viral infections without hyper-IgE syndrome

    Science.gov (United States)

    Kreins, Alexandra Y.; Ciancanelli, Michael J.; Okada, Satoshi; Kong, Xiao-Fei; Ramírez-Alejo, Noé; Kilic, Sara Sebnem; El Baghdadi, Jamila; Nonoyama, Shigeaki; Mahdaviani, Seyed Alireza; Ailal, Fatima; Bousfiha, Aziz; Mansouri, Davood; Nievas, Elma; Ma, Cindy S.; Rao, Geetha; Bernasconi, Andrea; Sun Kuehn, Hye; Niemela, Julie; Stoddard, Jennifer; Deveau, Paul; Cobat, Aurelie; El Azbaoui, Safa; Sabri, Ayoub; Lim, Che Kang; Sundin, Mikael; Avery, Danielle T.; Halwani, Rabih; Grant, Audrey V.; Boisson, Bertrand; Bogunovic, Dusan; Itan, Yuval; Moncada-Velez, Marcela; Martinez-Barricarte, Ruben; Migaud, Melanie; Deswarte, Caroline; Alsina, Laia; Kotlarz, Daniel; Klein, Christoph; Muller-Fleckenstein, Ingrid; Fleckenstein, Bernhard; Cormier-Daire, Valerie; Rose-John, Stefan; Picard, Capucine; Hammarstrom, Lennart; Puel, Anne; Al-Muhsen, Saleh; Abel, Laurent; Chaussabel, Damien; Rosenzweig, Sergio D.; Minegishi, Yoshiyuki; Tangye, Stuart G.; Bustamante, Jacinta; Casanova, Jean-Laurent

    2015-01-01

    Autosomal recessive, complete TYK2 deficiency was previously described in a patient (P1) with intracellular bacterial and viral infections and features of hyper-IgE syndrome (HIES), including atopic dermatitis, high serum IgE levels, and staphylococcal abscesses. We identified seven other TYK2-deficient patients from five families and four different ethnic groups. These patients were homozygous for one of five null mutations, different from that seen in P1. They displayed mycobacterial and/or viral infections, but no HIES. All eight TYK2-deficient patients displayed impaired but not abolished cellular responses to (a) IL-12 and IFN-α/β, accounting for mycobacterial and viral infections, respectively; (b) IL-23, with normal proportions of circulating IL-17+ T cells, accounting for their apparent lack of mucocutaneous candidiasis; and (c) IL-10, with no overt clinical consequences, including a lack of inflammatory bowel disease. Cellular responses to IL-21, IL-27, IFN-γ, IL-28/29 (IFN-λ), and leukemia inhibitory factor (LIF) were normal. The leukocytes and fibroblasts of all seven newly identified TYK2-deficient patients, unlike those of P1, responded normally to IL-6, possibly accounting for the lack of HIES in these patients. The expression of exogenous wild-type TYK2 or the silencing of endogenous TYK2 did not rescue IL-6 hyporesponsiveness, suggesting that this phenotype was not a consequence of the TYK2 genotype. The core clinical phenotype of TYK2 deficiency is mycobacterial and/or viral infections, caused by impaired responses to IL-12 and IFN-α/β. Moreover, impaired IL-6 responses and HIES do not appear to be intrinsic features of TYK2 deficiency in humans. PMID:26304966

  11. An evaluation of sleep quality and the prevalence of restless leg syndrome in vitamin D deficiency.

    Science.gov (United States)

    Çakır, Tuncay; Doğan, Gülsüm; Subaşı, Volkan; Filiz, Meral Bilgilisoy; Ülker, Nur; Doğan, Şebnem Koldaş; Toraman, Naciye Füsun

    2015-12-01

    Vitamin D is known to increase levels of dopamine and its metabolites in the brain and also protects dopaminergic neurons against dopaminergic toxins. The aims of the study were to assess the frequency and symptom severity of restless leg syndrome (RLS) and sleep quality in vitamin D deficiency. A total of 102 patients were enrolled in this cross-sectional study, comprising 57 vitamin D deficient patients as Group 1 and 45 patients with normal levels of vitamin D as Group 2. RLS was diagnosed according to the International RLS Study Group (IRLSSG) diagnostic criteria. Symptom severity was assessed using the IRLSSG rating scale and sleep quality was measured with the Pittsburgh sleep quality index (PSQI). RLS incidence was higher in Group 1 (p = 0.034). The PSQI scores were higher in Group 1 and the difference between the groups was determined as statistically significant (p 0.05). The findings of this study support the hypothesis that RLS is more frequent and more severe in vitamin D deficiency and indicate a negative effect of vitamin deficiency on sleep parameters.

  12. Early-onset Evans syndrome, immunodeficiency, and premature immunosenescence associated with tripeptidyl-peptidase II deficiency.

    Science.gov (United States)

    Stepensky, Polina; Rensing-Ehl, Anne; Gather, Ruth; Revel-Vilk, Shoshana; Fischer, Ute; Nabhani, Schafiq; Beier, Fabian; Brümmendorf, Tim H; Fuchs, Sebastian; Zenke, Simon; Firat, Elke; Pessach, Vered Molho; Borkhardt, Arndt; Rakhmanov, Mirzokhid; Keller, Bärbel; Warnatz, Klaus; Eibel, Hermann; Niedermann, Gabriele; Elpeleg, Orly; Ehl, Stephan

    2015-01-29

    Autoimmune cytopenia is a frequent manifestation of primary immunodeficiencies. Two siblings presented with Evans syndrome, viral infections, and progressive leukopenia. DNA available from one patient showed a homozygous frameshift mutation in tripeptidyl peptidase II (TPP2) abolishing protein expression. TPP2 is a serine exopeptidase involved in extralysosomal peptide degradation. Its deficiency in mice activates cell death programs and premature senescence. Similar to cells from naïve, uninfected TPP2-deficient mice, patient cells showed increased major histocompatibility complex I expression and most CD8(+) T-cells had a senescent CCR7-CD127(-)CD28(-)CD57(+) phenotype with poor proliferative responses and enhanced staurosporine-induced apoptosis. T-cells showed increased expression of the effector molecules perforin and interferon-γ with high expression of the transcription factor T-bet. Age-associated B-cells with a CD21(-) CD11c(+) phenotype expressing T-bet were increased in humans and mice, combined with antinuclear antibodies. Moreover, markers of senescence were also present in human and murine TPP2-deficient fibroblasts. Telomere lengths were normal in patient fibroblasts and granulocytes, and low normal in lymphocytes, which were compatible with activation of stress-induced rather than replicative senescence programs. TPP2 deficiency is the first primary immunodeficiency linking premature immunosenescence to severe autoimmunity. Determination of senescent lymphocytes should be part of the diagnostic evaluation of children with refractory multilineage cytopenias.

  13. Pseudo-Foster Kennedy Syndrome as a Rare Presentation of Vitamin B12 Deficiency

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    Petramfar, Peyman; Hosseinzadeh, Farideh; Mohammadi, S. Saeed

    2016-01-01

    Introduction Pseudo-Foster Kennedy syndrome is a triad consisting of ipsilateral optic atrophy, contralateral optic disc edema, and ipsilateral anosmia in the absence of an intracranial mass. Vitamin B12 plays an important role in DNA synthesis, and its deficiency causes peripheral neuropathy, myeloneuropathy, and, very rarely, optic neuropathy. Case Presentation In this study, we describe a 34-year-old male who presented with progressive loss of visual acuity and field. Fundoscopy showed optic disc edema with telangiectasia in the right eye, while the left eye had optic disc atrophy. We ruled out nearly all possible and common causes of optic neuropathy, and vitamin B12 deficiency was finally diagnosed. After treatment with vitamin B12, the patient improved. Conclusions Demyelinating disease, anterior ischemic optic neuropathy, non-arteritic anterior ischemic optic neuropathy, autoimmune disease, and hereditary optic neuropathy could cause optic neuropathy. Normal CBC parameters and the absence of clinical manifestations of vitamin B12 deficiency could not rule out its diagnosis. Careful physical examinations and history-taking with a classical approach led us to the diagnosis of vitamin B12 deficiency and its treatment. PMID:27621919

  14. Deficient auditory processing in children with Asperger Syndrome, as indexed by event-related potentials.

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    Jansson-Verkasalo, Eira; Ceponiene, Rita; Kielinen, Marko; Suominen, Kalervo; Jäntti, Ville; Linna, Sirkka Liisa; Moilanen, Irma; Näätänen, Risto

    2003-03-06

    Asperger Syndrome (AS) is characterized by normal language development but deficient understanding and use of the intonation and prosody of speech. While individuals with AS report difficulties in auditory perception, there are no studies addressing auditory processing at the sensory level. In this study, event-related potentials (ERP) were recorded for syllables and tones in children with AS and in their control counterparts. Children with AS displayed abnormalities in transient sound-feature encoding, as indexed by the obligatory ERPs, and in sound discrimination, as indexed by the mismatch negativity. These deficits were more severe for the tone stimuli than for the syllables. These results indicate that auditory sensory processing is deficient in children with AS, and that these deficits might be implicated in the perceptual problems encountered by children with AS.

  15. Histidine decarboxylase deficiency causes Tourette syndrome: parallel findings in humans and mice

    Science.gov (United States)

    Baldan, Lissandra Castellan; Rapanelli, Maximiliano; Crowley, Michael; Anderson, George M.; Loring, Erin; Gorczyca, Roxanne; Billingslea, Eileen; Wasylink, Suzanne; Panza, Kaitlyn E.; Ercan-Sencicek, A. Gulhan; Krusong, Kuakarun; Leventhal, Bennett L.; Ohtsu, Hiroshi; Bloch, Michael H.; Hughes, Zoë A.; Krystal, John H.; Mayes, Linda; de Araujo, Ivan; Ding, Yu-Shin; State, Matthew W.; Pittenger, Christopher

    2013-01-01

    Tourette syndrome (TS) is characterized by tics, sensorimotor gating deficiencies, and abnormalities of cortico-basal ganglia circuits. A mutation in histidine decarboxylase (Hdc), the key enzyme for the biosynthesis of histamine (HA), has been implicated as a rare genetic cause. Hdc knockout mice exhibited potentiated tic-like stereotypies, recapitulating core phenomenology of TS; these were mitigated by the dopamine D2 antagonist haloperidol, a proven pharmacotherapy, and by HA infusion into the brain. Prepulse inhibition was impaired in both mice and humans carrying Hdc mutations. HA infusion reduced striatal dopamine (DA) levels; in Hdc knockout mice, striatal DA was increased and the DA-regulated immediate early gene Fos was upregulated. Dopamine D2/D3 receptor binding was altered both in mice and in humans carrying the Hdc mutation. These data confirm HDC deficiency as a rare cause of TS and identify histamine-dopamine interactions in the basal ganglia as an important locus of pathology. PMID:24411733

  16. Importance of donor history of restless leg syndrome and pica to asses iron deficiency.

    Science.gov (United States)

    Singh, Ashutosh; Chaudhary, Rajendra; Sonker, Atul; Pandey, Hem Chandra

    2016-04-01

    Iron deficiency is associated with neuropsychological changes such as restless leg syndrome (RLS), pica, hair loss, etc. Our objective was to assess usefulness of history of RLS and pica in relation with iron stores in blood donors. During medical examination, apart from routine questionnaires specific history of RLS and pica was elicited. Along with hemoglobin markers of iron deficiency such as s. iron, s. ferritin and mean corpuscular volume were analyzed. Out of 400 blood donors 41 had h/o pica/RLS/pagophagia. Positive and negative predictive value of above history is 73.17% and 80.5% respectively. We recommend the use of a screening question for pica and/or RLS in blood donor questionnaire.

  17. A novel Sin Nombre virus DNA vaccine and its inclusion in a candidate pan-hantavirus vaccine against hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS).

    Science.gov (United States)

    Hooper, Jay W; Josleyn, Matthew; Ballantyne, John; Brocato, Rebecca

    2013-09-13

    Sin Nombre virus (SNV; family Bunyaviridae, genus Hantavirus) causes a hemorrhagic fever known as hantavirus pulmonary syndrome (HPS) in North America. There have been approximately 200 fatal cases of HPS in the United States since 1993, predominantly in healthy working-age males (case fatality rate 35%). There are no FDA-approved vaccines or drugs to prevent or treat HPS. Previously, we reported that hantavirus vaccines based on the full-length M gene segment of Andes virus (ANDV) for HPS in South America, and Hantaan virus (HTNV) and Puumala virus (PUUV) for hemorrhagic fever with renal syndrome (HFRS) in Eurasia, all elicited high-titer neutralizing antibodies in animal models. HFRS is more prevalent than HPS (>20,000 cases per year) but less pathogenic (case fatality rate 1-15%). Here, we report the construction and testing of a SNV full-length M gene-based DNA vaccine to prevent HPS. Rabbits vaccinated with the SNV DNA vaccine by muscle electroporation (mEP) developed high titers of neutralizing antibodies. Furthermore, hamsters vaccinated three times with the SNV DNA vaccine using a gene gun were completely protected against SNV infection. This is the first vaccine of any kind that specifically elicits high-titer neutralizing antibodies against SNV. To test the possibility of producing a pan-hantavirus vaccine, rabbits were vaccinated by mEP with an HPS mix (ANDV and SNV plasmids), or HFRS mix (HTNV and PUUV plasmids), or HPS/HFRS mix (all four plasmids). The HPS mix and HFRS mix elicited neutralizing antibodies predominantly against ANDV/SNV and HTNV/PUUV, respectively. Furthermore, the HPS/HFRS mix elicited neutralizing antibodies against all four viruses. These findings demonstrate a pan-hantavirus vaccine using a mixed-plasmid DNA vaccine approach is feasible and warrants further development. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. A novel Sin Nombre virus DNA vaccine and its inclusion in a candidate pan-hantavirus vaccine against hantavirus pulmonary syndrome (HPS) and hemorrhagic fever with renal syndrome (HFRS)☆

    Science.gov (United States)

    Hooper, Jay W.; Josleyn, Matthew; Ballantyne, John; Brocato, Rebecca

    2014-01-01

    Sin Nombre virus (SNV; family Bunyaviridae, genus Hantavirus) causes a hemorrhagic fever known as hantavirus pulmonary syndrome (HPS) in North America. There have been approximately 200 fatal cases of HPS in the United States since 1993, predominantly in healthy working-age males (case fatality rate 35%). There are no FDA-approved vaccines or drugs to prevent or treat HPS. Previously, we reported that hantavirus vaccines based on the full-length M gene segment of Andes virus (ANDV) for HPS in South America, and Hantaan virus (HTNV) and Puumala virus (PUUV) for hemorrhagic fever with renal syndrome (HFRS) in Eurasia, all elicited high-titer neutralizing antibodies in animal models. HFRS is more prevalent than HPS (>20,000 cases per year) but less pathogenic (case fatality rate 1–15%). Here, we report the construction and testing of a SNV full-length M gene-based DNA vaccine to prevent HPS. Rabbits vaccinated with the SNV DNA vaccine by muscle electroporation (mEP) developed high titers of neutralizing antibodies. Furthermore, hamsters vaccinated three times with the SNV DNA vaccine using a gene gun were completely protected against SNV infection. This is the first vaccine of any kind that specifically elicits high-titer neutralizing antibodies against SNV. To test the possibility of producing a pan-hantavirus vaccine, rabbits were vaccinated by mEP with an HPS mix (ANDV and SNV plasmids), or HFRS mix (HTNV and PUUV plasmids), or HPS/HFRS mix (all four plasmids). The HPS mix and HFRS mix elicited neutralizing antibodies predominantly against ANDV/SNV and HTNV/PUUV, respectively. Furthermore, the HPS/HFRS mix elicited neutralizing antibodies against all four viruses. These findings demonstrate a pan-hantavirus vaccine using a mixed-plasmid DNA vaccine approach is feasible and warrants further development. PMID:23892100

  19. First Association of Interleukin 12 Receptor Beta 1 Deficiency with Sjögren’s Syndrome

    Directory of Open Access Journals (Sweden)

    Georgios Sogkas

    2017-07-01

    Full Text Available IntroductionInterleukin 12 receptor beta 1 (IL12Rβ1 deficiency is a primary immunodeficiency resulting mainly in susceptibility to opportunistic infection by non-tuberculous, environmental mycobacteria and severe infection caused by Salmonella spp. Till now, less than 300 patients with IL12Rβ1 deficiency have been reported. Among them, only three have been described to develop autoimmunity.Case presentationWe present the case of a 50-year-old male with IL12Rβ1 deficiency due to compound heterozygosity [c. 1623_1624delGCinsTT (pGln542Stop and c.1791 + 2T > C (donor splice site], who—18 months after diagnosis of disseminated BCGitis—presented with recurrent fever and sicca syndrome. No indication of an infectious origin of these symptoms could be found at that point. The diagnosis of a Sjögren’s syndrome (SS was made on the basis of fulfilled American-European consensus classification criteria, including a positive minor salivary gland biopsy.ConclusionApart from persistent antigenic stimulation, which may drive autoimmune inflammation in primary immunodeficiency, evidence on the involvement of interleukin 12 in pathogenesis of SS suggests that the same immunological mechanism may underlie both defense against infection and the maintenance of tolerance. To our knowledge, this is the first report of a case of autoimmunity in the form of SS in a patient with a primary immunodeficiency and one of the rare cases of IL12Rβ1 deficiency with manifested autoimmunity.

  20. An unusual combination of Klinefelter syndrome and growth hormone deficiency in a prepubertal child.

    Science.gov (United States)

    Ramesh, Jayanthy; Nagasatyavani, Mudiganti; Venkateswarlu, Javvadii; Nagender, Jakka

    2014-09-01

    Klinefelter syndrome (KS) is the most common chromosomal aneuploidy in males. It is very difficult to diagnose this disorder in childhood due to absence of significant manifestations before puberty. These patients usually present with tall stature. We report a case of KS with short stature due to growth hormone deficiency. The boy's height was below the 3rd centile with significant delay in bone age. He responded well to growth hormone injections. In view of mental subnormality karyotyping was done, which revealed KS (47XXY).

  1. Severe hypophosphatemic osteomalacia with Fanconi syndrome, renal tubular acidosis, vitamin D deficiency and primary biliary cirrhosis.

    Science.gov (United States)

    Bando, Hironori; Hashimoto, Naoko; Hirota, Yushi; Sakaguchi, Kazuhiko; Hisa, Itoko; Inoue, Yoshifumi; Imanishi, Yasuo; Seino, Susumu; Kaji, Hiroshi

    2009-01-01

    A 49-year-old woman was admitted to our hospital for back pain with marked thoracic and extremity deformities leading to bed-rest for three years. She was diagnosed with hypophosphatemic osteomalacia based on her symptoms, X-ray and bone scintigram, high serum alkaline phosphatase level, and low serum levels of both phosphorus and 1,25 dihydroxyvitamin D(3) with inhibition of phosphorus reabsorption. Fanconi syndrome with renal tubular acidosis, vitamin D deficiency and primary biliary cirrhosis were related to the pathogenesis of osteomalacia in this case. Several causal diseases may be concomitantly responsible for acceleration of the severity of osteomalacia in this patient.

  2. Hypocretin Deficiency Associated with Narcolepsy Type 1 and Central Hypoventilation Syndrome in Neurosarcoidosis of the Hypothalamus.

    Science.gov (United States)

    Mayo, Mary Catherine; Deng, Jane C; Albores, Jeffrey; Zeidler, Michelle; Harper, Ronald M; Avidan, Alon Y

    2015-09-15

    We report a case of a 53-year-old man presenting with depressed alertness and severe excessive sleepiness in the setting of neurosarcoidosis. Neuroimaging demonstrated hypothalamic destruction due to sarcoidosis with a CSF hypocretin level of 0 pg/mL. The patient also experienced respiratory depression that presumably resulted from hypocretin-mediated hypothalamic dysfunction as a result of extensive diencephalic injury. This is a novel case, demonstrating both hypocretin deficiency syndrome, as well as respiratory dysfunction from destruction of hypocretin neurons and extensive destruction of key diencephalic structures secondary to the underlying neurosarcoidosis.

  3. Carnitine Deficiency and Oxidative Stress Provoke Cardiotoxicity in an Ifosfamide-Induced Fanconi Syndrome Rat Model

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    Mohamed M. Sayed-Ahmed

    2010-01-01

    Full Text Available In addition to hemorrhagic cystitis, Fanconi Syndrome is a serious clinical side effect during ifosfamide (IFO therapy. Fanconi syndrome is a generalized dysfunction of the proximal tubule which is characterized by excessive urinary excretion of glucose, phosphate, bicarbonate, amino acids and other solutes excreted by this segment of the nephron including L-carnitine. Carnitine is essential cofactor for β-oxidation of long-chain fatty acids in the myocardium. IFO therapy is associated with increased urinary carnitine excretion with subsequent secondary deficiency of the molecule. Cardiac abnormalities in IFO-treated cancer patients were reported as isolated clinical cases. This study examined whether carnitine deficiency and oxidative stress, secondary to Fanconi Syndrome, provoke IFO-induced cardiomyopathy as well as exploring if carnitine supplementation using Propionyl-L-carnitine (PLC could offer protection against this toxicity. In the current study, an animal model of carnitine deficiency was developed in rats by D-carnitine-mildronate treatment Adult male Wistar albino rats were assigned to one of six treatment groups: the first three groups were injected intraperitoneally with normal saline, D-carnitine (DC, 250 mg/kg/day combined with mildronate (MD, 200 mg/kg/day and PLC (250 mg/kg/day, respectively, for 10 successive days. The 4th, 5th and 6th groups were injected with the same doses of normal saline, DC-MD and PLC, respectively for 5 successive days before and 5 days concomitant with IFO (50 mg/kg/day. IFO significantly increased serum creatinine, blood urea nitrogen (BUN, urinary carnitine excretion and clearance, creatine phosphokinase isoenzyme (CK-MB, lactate dehydrogenase (LDH, intramitochondrial acetyl-CoA/CoA-SH and thiobarbituric acid reactive substances (TBARS in cardiac tissues and significantly decreased adenosine triphosphate (ATP and total carnitine and reduced glutathione (GSH content in cardiac tissues. In carnitine

  4. Tenascin-x deficiency mimics ehlers-danlos syndrome in mice through alteration of collagen deposition

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    Mao, J.R.; Taylor, G.; Dean, W.B.; Wagner, D.R.; Afzal, V.; Lotz, J.C.; Rubin, E.M.; Bristow, J.

    2002-03-01

    Tenascin-X is a large extracellular matrix protein of unknown function1-3. Tenascin-X deficiency in humans is associated with Ehlers-Danlos syndrome4,5, a generalized connective tissue disorder resulting from altered metabolism of the fibrillar collagens6. Because TNXB is the first Ehlers-Danlos syndrome gene that does not encode a fibrillar collagen or collagen-modifying enzyme7-14, we suggested that tenascin-X might regulate collagen synthesis or deposition15. To test this hypothesis, we inactivated Tnxb in mice. Tnxb-/- mice showed progressive skin hyperextensibility, similar to individuals with Ehlers-Danlos syndrome. Biomechanical testing confirmed increased deformability and reduced tensile strength of their skin. The skin of Tnxb-/- mice was histologically normal, but its collagen content was significantly reduced. At the ultrastructural level, collagen fibrils of Tnxb-/- mice were of normal size and shape, but the density of fibrils in their skin was reduced, commensurate with the reduction in collagen content. Studies of cultured dermal fibroblasts showed that although synthesis of collagen I by Tnxb-/- and wildtype cells was similar, Tnxb-/- fibroblasts failed to deposit collagen I into cell-associated matrix. This study confirms a causative role for TNXB in human Ehlers-Danlos syndrome and suggests that tenascin-X is an essential regulator of collagen deposition by dermal fibroblasts.

  5. Serum antibody-negative Goodpasture syndrome with delta granule pool storage deficiency and eosinophilia.

    Science.gov (United States)

    Kussman, Ashleigh; Gohara, Amira

    2012-12-01

    Goodpasture syndrome is a rare, life-threatening autoimmune disease characterized by a triad of rapidly progressive glomerulonephritis, a hemorrhagic pulmonary condition and the presence of anti-glomerular basement membrane (anti-GBM) antibodies. The antibodies initiate destruction of the kidney glomeruli, resulting in a focal necrotizing glomerulitis, which may progress rapidly to renal failure. Autoantibody-mediated damage of alveolar basement membranes leads to diffuse pulmonary hemorrhage, which in some cases may be severe enough to cause respiratory failure. Many clinicians use a variety of assays to detect serum anti-GBM antibodies; however, these tests may be falsely negative in up to 15% of patients with Goodpasture syndrome. Here, we report an unusual case of a 40-year-old man with clinical evidence of Goodpasture syndrome, a negative anti-GBM antibody serum result, eosinophilia and delta granule pool storage deficiency. After a 14-day hospital stay and extensive workup, as well as treatment with antibiotics, steroids and ventilator support for respiratory failure, the patient continued to deteriorate and entered multisystem organ failure. The family decided to withdraw ventilator support, and the patient expired. Immunofluorescence testing for anti-GBM autoantibodies on lung and kidney tissues during an autopsy confirmed the diagnosis of Goodpasture syndrome.

  6. Adenosine receptors as markers of brain iron deficiency: Implications for Restless Legs Syndrome.

    Science.gov (United States)

    Quiroz, César; Gulyani, Seema; Ruiqian, Wan; Bonaventura, Jordi; Cutler, Roy; Pearson, Virginia; Allen, Richard P; Earley, Christopher J; Mattson, Mark P; Ferré, Sergi

    2016-12-01

    Deficits of sensorimotor integration with periodic limb movements during sleep (PLMS) and hyperarousal and sleep disturbances in Restless Legs Syndrome (RLS) constitute two pathophysiologically distinct but interrelated clinical phenomena, which seem to depend mostly on alterations in dopaminergic and glutamatergic neurotransmission, respectively. Brain iron deficiency is considered as a main pathogenetic mechanism in RLS. Rodents with brain iron deficiency represent a valuable pathophysiological model of RLS, although they do not display motor disturbances. Nevertheless, they develop the main neurochemical dopaminergic changes found in RLS, such as decrease in striatal dopamine D2 receptor density. On the other hand, brain iron deficient mice exhibit the characteristic pattern of hyperarousal in RLS, providing a tool to find the link between brain iron deficiency and sleep disturbances in RLS. The present study provides evidence for a role of the endogenous sleep-promoting factor adenosine. Three different experimental preparations, long-term (22 weeks) severe or moderate iron-deficient (ID) diets (3- or 7-ppm iron diet) in mice and short-term (3 weeks) severe ID diet (3-ppm iron diet) in rats, demonstrated a significant downregulation (Western blotting in mouse and radioligand binding saturation experiments in rat brain tissue) of adenosine A1 receptors (A1R) in the cortex and striatum, concomitant to striatal D2R downregulation. On the other hand, the previously reported upregulation of adenosine A2A receptors (A2AR) was only observed with severe ID in both mice and rats. The results suggest a key role for A1R downregulation in the PLMS and hyperarousal in RLS. Published by Elsevier Ltd.

  7. The assessment of efficacy of porcine reproductive respiratory syndrome virus inactivated vaccine based on the viral quantity and inactivation methods.

    Science.gov (United States)

    Kim, Hyunil; Kim, Hye Kwon; Jung, Jung Ho; Choi, Yoo Jung; Kim, Jiho; Um, Chang Gyu; Hyun, Su Bin; Shin, Sungho; Lee, Byeongchun; Jang, Goo; Kang, Bo Kyu; Moon, Hyoung Joon; Song, Dae Sub

    2011-06-27

    There have been many efforts to develop efficient vaccines for the control of porcine reproductive and respiratory syndrome virus (PRRSV). Although inactivated PRRSV vaccines are preferred for their safety, they are weak at inducing humoral immune responses and controlling field PRRSV infection, especially when heterologous viruses are involved. In all groups, the sample to positive (S/P) ratio of IDEXX ELISA and the virus neutralization (VN) titer remained negative until challenge. While viremia did not reduce in the vaccinated groups, the IDEXX-ELISA-specific immunoglobulin G increased more rapidly and to significantly greater levels 7 days after the challenge in all the vaccinated groups compared to the non-vaccinated groups (p vaccine-inoculated and binary ethylenimine (BEI)-inactivated groups 22 days after challenge (p inactivated vaccines tested in this study provided weak memory responses with sequential challenge without any obvious active immune responses in the vaccinated pigs. The inactivated vaccine failed to show the humoral immunity, but it showed different immune response after the challenge compared to mock group. Although the 106 PFU/mL-vaccinated and BEI-inactivated groups showed significantly greater VN titers 22 days after challenge, all the groups were already negative for viremia.

  8. Effect of Testosterone Replacement Therapy on Cognitive Performance and Depression in Men with Testosterone Deficiency Syndrome

    Science.gov (United States)

    Jung, Hyun Jin

    2016-01-01

    Purpose We aimed to evaluate the effect of testosterone replacement therapy (TRT) on cognitive function and depression in men with testosterone deficiency syndrome. Materials and Methods We carried out a prospective, placebo-controlled trial involving 106 men with total testosterone levels testosterone undecanoate) or a placebo (advice to modify lifestyle), the study population was divided into a TRT group (n=54) and a control group (n=52). Results The age among patients in the TRT and control groups was 56.7±12.6 years and 57.8±11.4 years, respectively (p> 0.05). At baseline, no significant differences between the TRT and control groups were noted regarding serum testosterone or prostate-specific antigen levels, or regarding the scores for aging symptoms (Aging Males' Symptoms scale), erectile function (5-item International Index of Erectile Function questionnaire), cognitive function (Korean Mini-Mental State Examination), and depression (Beck Depression Inventory). At 8 months after intervention total serum testosterone levels and erectile function scores had significantly increased (ptestosterone deficiency syndrome if low testosterone levels are associated with depression or cognitive impairment. PMID:28053949

  9. Vaccination with Replication Deficient Adenovectors Encoding YF-17D Antigens Induces Long-Lasting Protection from Severe Yellow Fever Virus Infection in Mice.

    Science.gov (United States)

    Bassi, Maria R; Larsen, Mads A B; Kongsgaard, Michael; Rasmussen, Michael; Buus, Søren; Stryhn, Anette; Thomsen, Allan R; Christensen, Jan P

    2016-02-01

    The live attenuated yellow fever vaccine (YF-17D) has been successfully used for more than 70 years. It is generally considered a safe vaccine, however, recent reports of serious adverse events following vaccination have raised concerns and led to suggestions that even safer YF vaccines should be developed. Replication deficient adenoviruses (Ad) have been widely evaluated as recombinant vectors, particularly in the context of prophylactic vaccination against viral infections in which induction of CD8+ T-cell mediated immunity is crucial, but potent antibody responses may also be elicited using these vectors. In this study, we present two adenobased vectors targeting non-structural and structural YF antigens and characterize their immunological properties. We report that a single immunization with an Ad-vector encoding the non-structural protein 3 from YF-17D could elicit a strong CD8+ T-cell response, which afforded a high degree of protection from subsequent intracranial challenge of vaccinated mice. However, full protection was only observed using a vector encoding the structural proteins from YF-17D. This vector elicited virus-specific CD8+ T cells as well as neutralizing antibodies, and both components were shown to be important for protection thus mimicking the situation recently uncovered in YF-17D vaccinated mice. Considering that Ad-vectors are very safe, easy to produce and highly immunogenic in humans, our data indicate that a replication deficient adenovector-based YF vaccine may represent a safe and efficient alternative to the classical live attenuated YF vaccine and should be further tested.

  10. Immunogenicity and efficacy of chimeric dengue vaccine (DENVax) formulations in interferon-deficient AG129 mice.

    Science.gov (United States)

    Brewoo, Joseph N; Kinney, Richard M; Powell, Tim D; Arguello, John J; Silengo, Shawn J; Partidos, Charalambos D; Huang, Claire Y-H; Stinchcomb, Dan T; Osorio, Jorge E

    2012-02-14

    Formulations of chimeric dengue vaccine (DENVax) viruses containing the pre-membrane (prM) and envelope (E) genes of serotypes 1-4 expressed in the context of the attenuated DENV-2 PDK-53 genome were tested for safety, immunogenicity and efficacy in interferon receptor knock-out mice (AG129). Monovalent formulations were safe and elicited robust neutralizing antibody responses to the homologous virus and only limited cross-reactivity to other serotypes. A single dose of monovalent DENVax-1, -2, or -3 vaccine provided eighty or greater percent protection against both wild-type (wt) DENV-1 (Mochizuki strain) and DENV-2 (New Guinea C strain) challenge viruses. A single dose of monovalent DENVax-4 also provided complete protection against wt DENV-1 challenge and significantly increased the survival times after challenge with wt DENV-2. In studies using tetravalent mixtures, DENVax ratios were identified that: (i) caused limited viremia, (ii) induced serotype-specific neutralizing antibodies to all four DENV serotypes with different hierarchies, and (iii) conferred full protection against clinical signs of disease following challenge with either wt DENV-1 or DENV-2 viruses. Overall, these data highlight the immunogenic profile of DENVax, a novel candidate tetravalent dengue vaccine and the advantage of sharing a common attenuated genomic backbone among the DENVax monovalent vaccines that confer protection against homologous or heterologous virus challenge.

  11. The Modification Effect of Influenza Vaccine on Prognostic Indicators for Cardiovascular Events after Acute Coronary Syndrome: Observations from an Influenza Vaccination Trial

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    Apirak Sribhutorn

    2016-01-01

    Full Text Available Introduction. The prognosis of acute coronary syndrome (ACS patients has been improved with several treatments such as antithrombotics, beta-blockers, and angiotensin-converting enzyme inhibitors (ACEI as well as coronary revascularization. Influenza vaccination has been shown to reduce adverse outcomes in ACS, but no information exists regarding the interaction of other treatments. Methods. This study included 439 ACS patients from Phrommintikul et al. A single dose of inactivated influenza vaccine was given by intramuscular injection in the vaccination group. The cardiovascular outcomes were described as major cardiovascular events (MACEs which included mortality, hospitalization due to ACS, and hospitalization due to heart failure (HF. The stratified and multivariable Cox’s regression analysis was performed. Results. The stratified Cox’s analysis by influenza vaccination for each cardiovascular outcome and discrimination of hazard ratios showed that beta-blockers had an interaction with influenza vaccination. Moreover, the multivariable hazard ratios disclosed that influenza vaccine is associated with a significant reduction of hospitalization due to HF in patients who received beta-blockers (HR = 0.05, 95% CI = 0.004–0.71, P=0.027, after being adjusted for prognostic indicators (sex, dyslipidemia, serum creatinine, and left ventricular ejection fraction. Conclusions. The influenza vaccine was shown to significantly modify the effect of beta-blockers in ACS patients and to reduce the hospitalization due to HF. However, further study of a larger population and benefits to HF patients should be investigated.

  12. A rare outcome of iron deficiency and pica: Rapunzel syndrome in a 5-year-old child iron deficiency and pica.

    Science.gov (United States)

    Islek, Ali; Sayar, Ersin; Yılmaz, Aygen; Boneval, Cem; Artan, Reha

    2014-02-01

    Bezoar is defined as the accumulation of organic or nonbiological substances inside the gastrointestinal system. Trichobezoars are the most frequently detected ones and are mostly present in patients with neuropsychiatric disorders. The continuance of the trichobezoar tail-shaped extension over the duodenum and jejunum is described in Rapunzel syndrome. Both conditions are rarely reported in children. The present case submitted here is related to a 5-year-old girl referred with an abdominal mass and anemia, diagnosed with Rapunzel syndrome and developing trichobezoar due to iron deficiency and pica.

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

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    Moreno-Reyes Rodrigo

    2009-04-01

    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.

  14. Gray platelet syndrome and defective thrombo-inflammation in Nbeal2-deficient mice.

    Science.gov (United States)

    Deppermann, Carsten; Cherpokova, Deya; Nurden, Paquita; Schulz, Jan-Niklas; Thielmann, Ina; Kraft, Peter; Vögtle, Timo; Kleinschnitz, Christoph; Dütting, Sebastian; Krohne, Georg; Eming, Sabine A; Nurden, Alan T; Eckes, Beate; Stoll, Guido; Stegner, David; Nieswandt, Bernhard

    2013-07-01

    Platelets are anuclear organelle-rich cell fragments derived from bone marrow megakaryocytes (MKs) that safeguard vascular integrity. The major platelet organelles, α-granules, release proteins that participate in thrombus formation and hemostasis. Proteins stored in α-granules are also thought to play a role in inflammation and wound healing, but their functional significance in vivo is unknown. Mutations in NBEAL2 have been linked to gray platelet syndrome (GPS), a rare bleeding disorder characterized by macrothrombocytopenia, with platelets lacking α-granules. Here we show that Nbeal2-knockout mice display the characteristics of human GPS, with defective α-granule biogenesis in MKs and their absence from platelets. Nbeal2 deficiency did not affect MK differentiation and proplatelet formation in vitro or platelet life span in vivo. Nbeal2-deficient platelets displayed impaired adhesion, aggregation, and coagulant activity ex vivo that translated into defective arterial thrombus formation and protection from thrombo-inflammatory brain infarction following focal cerebral ischemia. In a model of excisional skin wound repair, Nbeal2-deficient mice exhibited impaired development of functional granulation tissue due to severely reduced differentiation of myofibroblasts in the absence of α-granule secretion. This study demonstrates that platelet α-granule constituents are critically required not only for hemostasis but also thrombosis, acute thrombo-inflammatory disease states, and tissue reconstitution after injury.

  15. Mechanism of choline deficiency and membrane alteration in postural orthostatic tachycardia syndrome primary skin fibroblasts.

    Science.gov (United States)

    Schenkel, Laila C; Singh, Ratnesh K; Michel, Vera; Zeisel, Steven H; da Costa, Kerry-Ann; Johnson, Amy R; Mudd, Harvey S; Bakovic, Marica

    2015-05-01

    Fibroblasts from a patient with postural orthostatic tachycardia syndrome (POTS), who presented with low plasma choline and betaine, were studied to determine the metabolic characteristics of the choline deficiency. Choline is required for the synthesis of the phospholipid phosphatidylcholine (PC) and for betaine, an important osmoregulator. Here, choline transport, lipid homeostasis, and mitochondria function were analyzed in skin fibroblasts from POTS and compared with control cells. The choline transporter-like protein 1/solute carrier 44A1 (CTL1/SLC44A1) and mRNA expression were 2-3 times lower in POTS fibroblasts, and choline uptake was reduced 60% (P < 0.05). Disturbances of membrane homeostasis were observed by reduced ratios between PC:phosphatidylethanolamine and sphingomyelin:cholesterol, as well as by modified phospholipid fatty acid composition. Choline deficiency also impaired mitochondria function, which was observed by a reduction in oxygen consumption, mitochondrial potential, and glycolytic activity. When POTS cells were treated with choline, transporter was up-regulated, and uptake of choline increased, offering an option for patient treatment. The characteristics of the POTS fibroblasts described here represent a first model of choline and CTL1/SLC44A1 deficiency, in which choline transport, membrane homeostasis, and mitochondrial function are impaired.

  16. Orthostatic intolerance and postural tachycardia syndrome as suspected adverse effects of vaccination against human papilloma virus

    DEFF Research Database (Denmark)

    Brinth, Louise S; Pors, Kirsten; Theibel, Ann C

    2015-01-01

    intolerance, headache, fatigue, cognitive dysfunction, and neuropathic pain starting in close relation to HPV vaccination. METHODS: Patients were referred for orthostatic intolerance following HPV vaccination. Symptoms of autonomic dysfunction were quantified by standardised questionnaire. The diagnosis...... of postural orthostatic tachycardia syndrome (POTS) rested on finding a sustained heart rate increment of >30min(-1) (>40min(-1) in adolescents) or to levels >120min(-1) during orthostatic challenge. RESULTS: 35 women aged 23.3±7.1 years participated. Twenty-five had a high level of physical activity before...... intolerance, 94% nausea, 82% chronic headache, 82% fatigue, 77% cognitive dysfunction, 72% segmental dystonia, 68% neuropathic pain. CONCLUSIONS: In a population referred for symptoms of orthostatic intolerance and other symptoms consistent with autonomic dysfunction that began in close temporal association...

  17. Clinical problems of colorectal cancer and endometrial cancer cases with unknown cause of tumor mismatch repair deficiency (suspected Lynch syndrome

    Directory of Open Access Journals (Sweden)

    Buchanan DD

    2014-10-01

    Full Text Available Daniel D Buchanan,1,2 Christophe Rosty,1,3,4 Mark Clendenning,1 Amanda B Spurdle,5 Aung Ko Win2 1Oncogenomics Group, Genetic Epidemiology Laboratory, Department of Pathology, The University of Melbourne, Parkville, VIC, Australia; 2Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, VIC, Australia; 3Envoi Specialist Pathologists, Herston, QLD, Australia; 4School of Medicine, University of Queensland, Herston, QLD, Australia; 5Molecular Cancer Epidemiology Laboratory, Genetics and Computational Biology Division, QIMR Berghofer Medical Research Institute, Herston, QLD, AustraliaAbstract: Carriers of a germline mutation in one of the DNA mismatch repair (MMR genes have a high risk of developing numerous different cancers, predominantly colorectal cancer and endometrial cancer (known as Lynch syndrome. MMR gene mutation carriers develop tumors with MMR deficiency identified by tumor microsatellite instability or immunohistochemical loss of MMR protein expression. Tumor MMR deficiency is used to identify individuals most likely to carry an MMR gene mutation. However, MMR deficiency can also result from somatic inactivation, most commonly methylation of the MLH1 gene promoter. As tumor MMR testing of all incident colorectal and endometrial cancers (universal screening is becoming increasingly adopted, a growing clinical problem is emerging for individuals who have tumors that show MMR deficiency who are subsequently found not to carry an MMR gene mutation after genetic testing using the current diagnostic approaches (Sanger sequencing and multiplex ligation-dependent probe amplification and who also show no evidence of MLH1 methylation. The inability to determine the underlying cause of tumor MMR deficiency in these "Lynch-like" or "suspected Lynch syndrome" cases has significant implications on the clinical management of these individuals and their relatives. When the

  18. A case of juvenile idiopathic polyarticular arthritis complicated by IgA deficiency in 22q11 deletion syndrome.

    Science.gov (United States)

    Sato, Satoshi; Kawashima, Hisashi; Suzuki, Kazunori; Nagao, Ryuhei; Tsuyuki, Kazumitsu; Hoshika, Akinori

    2011-08-01

    Chronic arthritis may occur in association with antibody deficiency and chromosomal aberrations. This report presents the case of a 6-year-old girl with chromosome 22q11 deletion syndrome and chronic arthritis. The onset of arthritis occurred at 4 years of age. The chronic arthritis course has been the polyarticular type. Neither antinuclear antibody nor rheumatoid factor was detected. Serum IgA was extremely low. She was diagnosed with juvenile idiopathic polyarticular arthritis (JIA) complicated by IgA deficiency in the 22q11 deletion syndrome. There is an increased prevalence of chronic arthritis in association with 22q11 deletion syndrome with IgA deficiency, but the reasons for this association are unknown. This study evaluated the possible correlation between cytokines and the susceptibility to chronic arthritis in the 22q11 deletion syndrome with IgA deficiency. The expression of pro-inflammatory cytokines such as IL-8, IL-6, MIP-1β, and MCP-1 suggests that T and B cells, macrophages and neutrophils modulate joint inflammation by an immune response. And the presence of IL-10 and IL-5 might suggest that the synovitis is associated with JIA and IgA deficiency.

  19. Correlation Study of PtfV1 with Heart-Qi Deficiency Syndrome in Patients with Hypertensive Left Ventricular Hypertrophy

    Institute of Scientific and Technical Information of China (English)

    杨传华; 陆峰

    2002-01-01

    @@ It is generally believed that the change of p-wave terminal force in lead V1 (PtfV1) is associated with the inner diameter of left atrium, left ventricular compliance,and ventricular diastolic function. The increase of negative value of PtfV1 in essential hypertensive (EH) patients with left ventricular hypertrophy (LVH) indicates the cardiac function may be damaged. In order to explore the relationship between Heart-Qi Deficiency Syndrome (HQDS) of TCM and PtfV1 level in hypertensive LVH patients, correlation analysis of scores of Heart-Qi Deficiency Syndrome and negative value of PtfV1 was made by the authors.

  20. Derivative chromosome 1 and GLUT1 deficiency syndrome in a sibling pair

    Directory of Open Access Journals (Sweden)

    Akarsu Nurten

    2010-05-01

    Full Text Available Abstract Background Genomic imbalances constitute a major cause of congenital and developmental abnormalities. GLUT1 deficiency syndrome is caused by various de novo mutations in the facilitated human glucose transporter 1 gene (1p34.2 and patients with this syndrome have been diagnosed with hypoglycorrhachia, mental and developmental delay, microcephaly and seizures. Furthermore, 1q terminal deletions have been submitted in the recent reports and the absence of corpus callosum has been related to the deletion between C1orf100 and C1orf121 in 1q44. Results This study reports on a sibling pair with developmental delay, mental retardation, microcephaly, hypotonia, epilepsy, facial dysmorphism, ataxia and impaired speech. Chromosome analysis revealed a derivative chromosome 1 in both patients. FISH and MCB analysis showed two interstitial deletions at 1p34.2 and 1q44. SNP array and array-CGH analysis also determined the sizes of deletions detailed. The deleted region on 1p34.2 encompasses 33 genes, among which is GLUT1 gene (SLC2A1. However, the deleted region on 1q44 includes 59 genes and distal-proximal breakpoints were located in the ZNF672 gene and SMYD3 gene, respectively. Conclusion Haploinsufficiency of GLUT1 leads to GLUT1 deficiency syndrome, consistent with the phenotype in patients of this study. Conversely, in the deleted region on 1q44, none of the genes are related to findings in these patients. Additionally, the results confirm previous reports on that corpus callosal development may depend on the critical gene(s lying in 1q44 proximal to the SMYD3 gene.

  1. A role for the body burden of aluminium in vaccine-associated macrophagic myofasciitis and chronic fatigue syndrome.

    Science.gov (United States)

    Exley, Christopher; Swarbrick, Louise; Gherardi, Rhomain K; Authier, Francois-Jérôme

    2009-02-01

    Macrophagic myofasciitis and chronic fatigue syndrome are severely disabling conditions which may be caused by adverse reactions to aluminium-containing adjuvants in vaccines. While a little is known of disease aetiology both conditions are characterised by an aberrant immune response, have a number of prominent symptoms in common and are coincident in many individuals. Herein, we have described a case of vaccine-associated chronic fatigue syndrome and macrophagic myofasciitis in an individual demonstrating aluminium overload. This is the first report linking the latter with either of these two conditions and the possibility is considered that the coincident aluminium overload contributed significantly to the severity of these conditions in this individual. This case has highlighted potential dangers associated with aluminium-containing adjuvants and we have elucidated a possible mechanism whereby vaccination involving aluminium-containing adjuvants could trigger the cascade of immunological events which are associated with autoimmune conditions including chronic fatigue syndrome and macrophagic myofasciitis.

  2. Mutations in NFKB2 and potential genetic heterogeneity in patients with DAVID syndrome, having variable endocrine and immune deficiencies

    OpenAIRE

    Brue, Thierry; Quentien, Marie-Hélène; Khetchoumian, Konstantin; Bensa, Marco; Capo-Chichi, José-Mario; Delemer, Brigitte; Balsalobre, Aurelio; Nassif, Christina; Papadimitriou, Dimitris T; Pagnier, Anne; Hasselmann, Caroline; Patry, Lysanne; Schwartzentruber, Jeremy; Souchon, Pierre-François; Takayasu, Shinobu

    2014-01-01

    Background DAVID syndrome is a rare condition combining anterior pituitary hormone deficiency with common variable immunodeficiency. NFKB2 mutations have recently been identified in patients with ACTH and variable immunodeficiency. A similar mutation was previously found in Nfkb2 in the immunodeficient Lym1 mouse strain, but the effect of the mutation on endocrine function was not evaluated. Methods We ascertained six unrelated DAVID syndrome families. We performed whole exome and traditional...

  3. Predictive genetic testing in children: constitutional mismatch repair deficiency cancer predisposing syndrome.

    Science.gov (United States)

    Bruwer, Zandrè; Algar, Ursula; Vorster, Alvera; Fieggen, Karen; Davidson, Alan; Goldberg, Paul; Wainwright, Helen; Ramesar, Rajkumar

    2014-04-01

    Biallelic germline mutations in mismatch repair genes predispose to constitutional mismatch repair deficiency syndrome (CMMR-D). The condition is characterized by a broad spectrum of early-onset tumors, including hematological, brain and bowel and is frequently associated with features of Neurofibromatosis type 1. Few definitive screening recommendations have been suggested and no published reports have described predictive testing. We report on the first case of predictive testing for CMMR-D following the identification of two non-consanguineous parents, with the same heterozygous mutation in MLH1: c.1528C > T. The genetic counseling offered to the family, for their two at-risk daughters, is discussed with a focus on the ethical considerations of testing children for known cancer-causing variants. The challenges that are encountered when reporting on heterozygosity in a child younger than 18 years (disclosure of carrier status and risk for Lynch syndrome), when discovered during testing for homozygosity, are addressed. In addition, the identification of CMMR-D in a three year old, and the recommended clinical surveillance that was proposed for this individual is discussed. Despite predictive testing and presymptomatic screening, the sudden death of the child with CMMR-D syndrome occurred 6 months after her last surveillance MRI. This report further highlights the difficulty of developing guidelines, as a result of the rarity of cases and diversity of presentation.

  4. Investigating Reports of Complex Regional Pain Syndrome: An Analysis of HPV-16/18-Adjuvanted Vaccine Post-Licensure Data.

    Science.gov (United States)

    Huygen, Frank; Verschueren, Kristin; McCabe, Candida; Stegmann, Jens-Ulrich; Zima, Julia; Mahaux, Olivia; Van Holle, Lionel; Angelo, Maria-Genalin

    2015-09-01

    Complex regional pain syndrome (CRPS) is a chronic pain disorder that typically follows trauma or surgery. Suspected CRPS reported after vaccination with human papillomavirus (HPV) vaccines led to temporary suspension of proactive recommendation of HPV vaccination in Japan. We investigated the potential CRPS signal in relation to HPV-16/18-adjuvanted vaccine (Cervarix®) by database review of CRPS cases with independent expert confirmation; a disproportionality analysis and analyses of temporality; an observed versus expected analysis using published background incidence rates; systematic reviews of aggregate safety data, and a literature review. The analysis included 17 case reports of CRPS: 10 from Japan (0.14/100,000 doses distributed) and seven from the United Kingdom (0.08/100,000). Five cases were considered by independent experts to be confirmed CRPS. Quantitative analyses did not suggest an association between CRPS and HPV-16/18-adjuvanted vaccine. Observed CRPS incidence after HPV-16/18 vaccination was statistically significantly below expected rates. Systematic database reviews using search terms varying in specificity and sensitivity did not identify new cases. No CRPS was reported during clinical development and no unexpected results found in the literature. There is not sufficient evidence to suggest an increased risk of developing CRPS following vaccination with HPV-16/18-adjuvanted vaccine. Post-licensure safety surveillance confirms the acceptable benefit-risk of HPV-16/18 vaccination.

  5. Stevens-johnson syndrome associated with drugs and vaccines in children: a case-control study.

    Directory of Open Access Journals (Sweden)

    Umberto Raucci

    Full Text Available OBJECTIVE: Stevens-Johnson Syndrome (SJS is one of the most severe muco-cutaneous diseases and its occurrence is often attributed to drug use. The aim of the present study is to quantify the risk of SJS in association with drug and vaccine use in children. METHODS: A multicenter surveillance of children hospitalized through the emergency departments for acute conditions of interest is currently ongoing in Italy. Cases with a diagnosis of SJS were retrieved from all admissions. Parents were interviewed on child's use of drugs and vaccines preceding the onset of symptoms that led to the hospitalization. We compared the use of drugs and vaccines in cases with the corresponding use in a control group of children hospitalized for acute neurological conditions. RESULTS: Twenty-nine children with a diagnosis of SJS and 1,362 with neurological disorders were hospitalized between 1(st November 1999 and 31(st October 2012. Cases were more frequently exposed to drugs (79% vs 58% in the control group; adjusted OR 2.4; 95% CI 1.0-6.1. Anticonvulsants presented the highest adjusted OR: 26.8 (95% CI 8.4-86.0. Significantly elevated risks were also estimated for antibiotics use (adjusted OR 3.3; 95% CI 1.5-7.2, corticosteroids (adjusted OR 4.2; 95% CI 1.8-9.9 and paracetamol (adjusted OR 3.2; 95% CI 1.5-6.9. No increased risk was estimated for vaccines (adjusted OR: 0.9; 95% CI 0.3-2.8. DISCUSSION: Our study provides additional evidence on the etiologic role of drugs and vaccines in the occurrence of SJS in children.

  6. Minimal change nephrotic syndrome in an 82 year old patient following a tetanus-diphteria-poliomyelitis-vaccination

    Directory of Open Access Journals (Sweden)

    Clajus Christian

    2009-08-01

    Full Text Available Abstract Background The most common cause of idiopathic nephrotic syndrome in children and younger adults is the minimal change nephrotic syndrome (MCNS. In the elderly MCNS is relatively uncommon. Over the last decade some reports suggest a rare but possible association with the administration of various vaccines. Case presentation A 82-year old Caucasian female presented with pronounced nephrotic syndrome (proteinuria of 7.1 g/d, hypoproteinemia of 47 g/l. About six weeks prior to admission, she had received a combination vaccination for tetanus, diphtheria and poliomyelitis as a booster-vaccination from her general practitioner. The renal biopsy revealed typical minimal change lesions. She responded well to the initiated steroid treatment. As through physical examination as well as extensive laboratory and imaging studies did neither find any evidence for malignancies nor infections we suggest that the minimal change nephrotic syndrome in this patient might be related to the activation of the immune system triggered by the vaccination. Conclusion Our case as well as previous anecdotal reports suggests that vaccination and the resulting stimulations of the immune system might cause MCNS and other severe immune-reactions. Increased awareness in that regard might help to expand the database of those cases.

  7. Successful vaccination strategies that protect aged mice from lethal challenge from influenza virus and heterologous severe acute respiratory syndrome coronavirus.

    Science.gov (United States)

    Sheahan, Timothy; Whitmore, Alan; Long, Kristin; Ferris, Martin; Rockx, Barry; Funkhouser, William; Donaldson, Eric; Gralinski, Lisa; Collier, Martha; Heise, Mark; Davis, Nancy; Johnston, Robert; Baric, Ralph S

    2011-01-01

    Newly emerging viruses often circulate as a heterogeneous swarm in wild animal reservoirs prior to their emergence in humans, and their antigenic identities are often unknown until an outbreak situation. The newly emerging severe acute respiratory syndrome coronavirus (SARS-CoV) and reemerging influenza virus cause disproportionate disease in the aged, who are also notoriously difficult to successfully vaccinate, likely due to immunosenescence. To protect against future emerging strains, vaccine platforms should induce broad cross-reactive immunity that is sufficient to protect from homologous and heterologous challenge in all ages. From initial studies, we hypothesized that attenuated Venezuelan equine encephalitis virus (VEE) replicon particle (VRP) vaccine glycoproteins mediated vaccine failure in the aged. We then compared the efficacies of vaccines bearing attenuated (VRP(3014)) or wild-type VEE glycoproteins (VRP(3000)) in young and aged mice within novel models of severe SARS-CoV pathogenesis. Aged animals receiving VRP(3000)-based vaccines were protected from SARS-CoV disease, while animals receiving the VRP(3014)-based vaccines were not. The superior protection for the aged observed with VRP(3000)-based vaccines was confirmed in a lethal influenza virus challenge model. While the VRP(3000) vaccine's immune responses in the aged were sufficient to protect against lethal homologous and heterologous challenge, our data suggest that innate defects within the VRP(3014) platform mediate vaccine failure. Exploration into the mechanism(s) of successful vaccination in the immunosenescent should aid in the development of successful vaccine strategies for other viral diseases disproportionately affecting the elderly, like West Nile virus, influenza virus, norovirus, or other emerging viruses of the future.

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

    Directory of Open Access Journals (Sweden)

    April Kaur Randhawa

    2011-08-01

    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

  9. COPPER AND MAGNESIUM DEFICIENCIES IN PATIENTS WITH SHORT BOWEL SYNDROME RECEIVING PARENTERAL NUTRITION OR ORAL FEEDING

    Directory of Open Access Journals (Sweden)

    Camila Bitu Moreno BRAGA

    2015-06-01

    Full Text Available Background Patients with short bowel syndrome have significant fluid and electrolytes loss. Objective Evaluate the mineral and electrolyte status in short bowel syndrome patients receiving intermittent parenteral nutrition or oral feeding. Methods Twenty two adults with short bowel syndrome, of whom 11 were parenteral nutrition dependent (PN group, and the 11 remaining had been weaned off parenteral nutrition for at least 1 year and received all nutrients by oral feeding (OF group. The study also included 14 healthy volunteers paired by age and gender (control group. Food ingestion, anthropometry, serum or plasma levels of sodium, potassium, phosphorus, magnesium, calcium, zinc, iron and copper were evaluated. PN group subjects were evaluated before starting a new parenteral nutrition cycle. Results The levels of sodium, potassium, phosphorus, calcium and zinc were similar between the groups. The magnesium value was lower in the PN group (1.0 ± 0.4 mEq /L than other groups. Furthermore, this electrolyte was lower in the OF group (1.4 ± 0.3 mEq /L when compared to the Control group (1.8 ± 0.1 mEq/L. Lower values of copper (69±24 vs 73±26 vs 109±16 µg/dL were documented, respectively, for the PN and OF groups when compared to the control group. Conclusion Hypomagnesemia and hypocupremia are electrolyte disturbances commonly observed in short bowel syndrome. Patients with massive intestinal resection require monitoring and supplementation in order to prevent magnesium and copper deficiencies.

  10. Deficiency in N-acetylgalactosamine-6-sulfate sulfatase results in collagen perturbations in cartilage of Morquio syndrome A patients

    NARCIS (Netherlands)

    Bank, R.A.; Groener, J.E.M.; van Gemund, J.J.; Maaswinkel, P.D.; Hoeben, K.A.; Schut, H.A.; Everts, V.

    2009-01-01

    Aim: To investigate extracellular matrix (ECM) characteristics of cortical bone and articular cartilage of patients with Morquio syndrome A, a lysosomal storage disease caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase. Patients and methods: Cartilage, bone, and fibroblasts from 2

  11. Deficiency of acyl-CoA: Dihydroxyacetone phosphate acyltransferase in patients with Zellweger (cerebro-hepato-renal) syndrome

    NARCIS (Netherlands)

    Bosch, H. van den; Schutgens, R.B.H.; Romeyn, G.J.; Wanders, R.J.A.; Schrakamp, G.; Heymans, H.S.A.

    1984-01-01

    We have recently reported on plasmalogen deficiency in tissues and fibroblasts from patients with Zellweger syndrome. In this paper we have analyzed the activity of the first enzyme in the pathway leading to plasmalogen biosynthesis, i.e. acyl-CoA: dihydroxyacetone phosphate acyltransferase in

  12. Respiratory chain complex I deficiency due to NDUFA12 mutations as a new cause of Leigh syndrome

    DEFF Research Database (Denmark)

    Ostergaard, Elsebet; Rodenburg, Richard J; van den Brand, Mariël;

    2011-01-01

    This study investigated a girl with Leigh syndrome born to first-cousin parents of Pakistani descent with an isolated respiratory chain complex I deficiency in muscle and fibroblasts. Her early development was delayed, and from age 2 years she started losing motor abilities. Cerebral MRI showed...

  13. Coping Strategies of Patients with Haemophilia as a Risk Group for AIDS (Acquired Immune Deficiency Syndrome). Brief Research Report.

    Science.gov (United States)

    Naji, Simon; And Others

    1986-01-01

    Plans are described for a 2-year project whose major focus is the identification of ways in which patients with hemophilia and their families assimilate, interpret, and act on information about Acquired Immune Deficiency Syndrome (AIDS). Findings will be related to perceived risk, anxiety levels, and the development of coping strategies.…

  14. AIDS: Acquired Immune Deficiency Syndrome, Information and Procedural Guidelines for Providing Services to Persons with AIDS/HTLV-III.

    Science.gov (United States)

    Montana State Dept. of Health and Environmental Sciences, Helena.

    This manual presents information about the disease, Acquired Immune Deficiency Syndrome (AIDS), and guidelines for service delivery to Montana residents who have been diagnosed with AIDS or related disorders. The first section describes the disease's causes, symptoms, and transmission; risk factors; high-risk populations; prevention suggestions;…

  15. Deficiency of acyl-CoA: Dihydroxyacetone phosphate acyltransferase in patients with Zellweger (cerebro-hepato-renal) syndrome

    NARCIS (Netherlands)

    Bosch, H. van den; Schutgens, R.B.H.; Romeyn, G.J.; Wanders, R.J.A.; Schrakamp, G.; Heymans, H.S.A.

    1984-01-01

    We have recently reported on plasmalogen deficiency in tissues and fibroblasts from patients with Zellweger syndrome. In this paper we have analyzed the activity of the first enzyme in the pathway leading to plasmalogen biosynthesis, i.e. acyl-CoA: dihydroxyacetone phosphate acyltransferase in liver

  16. Social capital of Iranian patients living with acquired immune deficiency syndrome and associated factors.

    Science.gov (United States)

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

    2015-12-13

    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.

  17. The Bloom syndrome protein limits the lethality associated with RAD51 deficiency.

    Science.gov (United States)

    Lahkim Bennani-Belhaj, Kenza; Rouzeau, Sébastien; Buhagiar-Labarchède, Géraldine; Chabosseau, Pauline; Onclercq-Delic, Rosine; Bayart, Emilie; Cordelières, Fabrice; Couturier, Jérôme; Amor-Guéret, Mounira

    2010-03-01

    Little is known about the functional interaction between the Bloom's syndrome protein (BLM) and the recombinase RAD51 within cells. Using RNA interference technology, we provide the first demonstration that RAD51 acts upstream from BLM to prevent anaphase bridge formation. RAD51 downregulation was associated with an increase in the frequency of BLM-positive anaphase bridges, but not of BLM-associated ultrafine bridges. Time-lapse live microscopy analysis of anaphase bridge cells revealed that BLM promoted cell survival in the absence of Rad51. Our results directly implicate BLM in limiting the lethality associated with RAD51 deficiency through the processing of anaphase bridges resulting from the RAD51 defect. These findings provide insight into the molecular basis of some cancers possibly associated with variants of the RAD51 gene family.

  18. Upstream SLC2A1 translation initiation causes GLUT1 deficiency syndrome.

    Science.gov (United States)

    Willemsen, Michèl A; Vissers, Lisenka Elm; Verbeek, Marcel M; van Bon, Bregje W; Geuer, Sinje; Gilissen, Christian; Klepper, Joerg; Kwint, Michael P; Leen, Wilhelmina G; Pennings, Maartje; Wevers, Ron A; Veltman, Joris A; Kamsteeg, Erik-Jan

    2017-06-01

    Glucose transporter type 1 deficiency syndrome (GLUT1DS) is a neurometabolic disorder with a complex phenotypic spectrum but simple biomarkers in cerebrospinal fluid. The disorder is caused by impaired glucose transport into the brain resulting from variants in SCL2A1. In 10% of GLUT1DS patients, a genetic diagnosis can not be made. Using whole-genome sequencing, we identified a de novo 5'-UTR variant in SLC2A1, generating a novel translation initiation codon, severely compromising SLC2A1 function. This finding expands our understanding of the disease mechanisms underlying GLUT1DS and encourages further in-depth analysis of SLC2A1 non-coding regions in patients without variants in the coding region.

  19. Diagnosis and treatment of GH deficiency in Prader-Willi syndrome.

    Science.gov (United States)

    Grugni, Graziano; Marzullo, Paolo

    2016-12-01

    Prader-Willi syndrome (PWS) results from under-expression of the paternally-derived chromosomal region 15q11-13. Growth failure is a recognized feature of PWS, and both quantitative and qualitative defects of the GH/IGF-I axis revealing GH deficiency (GHD) have been demonstrated in most children with PWS. In PWS adults, criteria for GHD are biochemically fulfilled in 8-38% of the studied cohorts. Published data support benefits of early institution of GH therapy (GHT) in PWS children, with positive effects on statural growth, body composition, metabolic homeostasis, and neurocognitive function. Like in pediatric PWS, GHT also yields beneficial effects on lean and body fat, exercise capacity, and quality of life of PWS adults. Although GHT has been generally administered safely in PWS children and adults, careful surveillance of risks is mandatory during prolonged GH replacement for all PWS individuals.

  20. Fibromyalgia syndrome: is it related to vitamin D deficiency in premenopausal female patients?

    Science.gov (United States)

    Okumus, Muyesser; Koybası, Mine; Tuncay, Figen; Ceceli, Esma; Ayhan, Figen; Yorgancioglu, Rezan; Borman, Pinar

    2013-12-01

    There are a number of studies that have evaluated the relationship between fibromyalgia (FM) and vitamin D deficiency with conflicting results. The aim of this study was to assess vitamin D deficiency in patients with FM and to evaluate the relationship with the common symptoms of FM and levels of serum vitamin D. Forty premenopausal female fibromyalgia patients and 40 age- and sex-matched control subjects were included in the study. The demographic characteristics of all subjects, including age, sex, and body mass index, were recorded. The number of tender points was recorded, and the intensity of the widespread pain of the subjects was measured by the visual analog scale. The activities of daily living component of the Fibromyalgia Impact Questionnaire (FIQ-ADL), was used to assess physical functional capacity. Serum vitamin D was measured in both groups, and vitamin D levels vitamin D deficiency. The vitamin D levels and clinical and laboratory characteristics of the patient and control groups were comparatively analyzed. The relationship between vitamin D levels and clinical findings of the FM patients were also determined. The mean age was 41.23 ± 4.8 and 39.48 ± 4.08 years for the patient and control groups, respectively. The pain intensity, number of tender points, and FIQ-ADL scores were higher in FM patients than in control subjects. The mean levels of vitamin D in the patient and control groups were determined to be 31.97 ± 15.50 and 28.97 ± 13.31 nmol/L, respectively (p > .05). The incidence of vitamin D deficiency was similar between the patient and control groups (67.5% vs. 70%). Vitamin D levels significantly correlated with pain intensity (r = -0.653; p = .001) and FIQ-ADL scores in the FM group (r = -0.344; p = .030). In conclusion, the results of this study indicate that deficiency of vitamin D is not more common in premenopausal female patients with FM than in control subjects without FM. However, the association between pain and vitamin D

  1. The assessment of efficacy of porcine reproductive respiratory syndrome virus inactivated vaccine based on the viral quantity and inactivation methods

    Directory of Open Access Journals (Sweden)

    Lee Byeongchun

    2011-06-01

    Full Text Available Abstract Background There have been many efforts to develop efficient vaccines for the control of porcine reproductive and respiratory syndrome virus (PRRSV. Although inactivated PRRSV vaccines are preferred for their safety, they are weak at inducing humoral immune responses and controlling field PRRSV infection, especially when heterologous viruses are involved. Results In all groups, the sample to positive (S/P ratio of IDEXX ELISA and the virus neutralization (VN titer remained negative until challenge. While viremia did not reduce in the vaccinated groups, the IDEXX-ELISA-specific immunoglobulin G increased more rapidly and to significantly greater levels 7 days after the challenge in all the vaccinated groups compared to the non-vaccinated groups (p 6 PFU/mL PRRSV vaccine-inoculated and binary ethylenimine (BEI-inactivated groups 22 days after challenge (p Conclusions The inactivated vaccine failed to show the humoral immunity, but it showed different immune response after the challenge compared to mock group. Although the 106 PFU/mL-vaccinated and BEI-inactivated groups showed significantly greater VN titers 22 days after challenge, all the groups were already negative for viremia.

  2. Growth hormone deficiency and central precocious puberty in Klinefelter syndrome: report of a case and review of KIGS database.

    Science.gov (United States)

    Gonzales-Ellis, Bryn A; Pingul, Mia M; Reddy, Sujana; Boney, Charlotte M; Wajnrajch, Michael P; Quintos, Jose Bernarto

    2013-01-01

    Growth hormone deficiency (GHD) and central precocious puberty (CPP) have each, individually, been described in patients with Klinefelter syndrome. However, the combination of GHD, CPP, and Klinefelter syndrome has never been reported. We described a Klinefelter syndrome patient who developed GHD at age 2 10/12 years and CPP at 8 6/12 years. Despite CPP, GnRH agonist therapy was not initiated because of his excellent predicted adult height. At 11 8/12 years, his height was 164.6 cm, close to his mid-parental target height of 165 cm. We report an additional nine patients with Klinefelter syndrome and GHD from the Pfizer International Growth Study (KIGS) database, none of whom had CPP. We conclude that the combination of GHD and CPP is very rare in Klinefelter syndrome and that CPP is unlikely to compromise final adult height.

  3. Fatal adult-onset antibody deficiency syndrome in a patient with cartilage hair hypoplasia.

    Science.gov (United States)

    Horn, Julia; Schlesier, Michael; Warnatz, Klaus; Prasse, Antje; Superti-Furga, Andrea; Peter, Hans-Hartmut; Salzer, Ulrich

    2010-09-01

    Cartilage hair hypoplasia (CHH) is an autosomal recessive disorder caused by mutations in the ribonuclease mitochondrial RNA-processing (RMRP) gene. Although its most constant feature is metaphyseal dysplasia with short stature, CHH is associated with extraskeletal defects such as thin hair, anemia, immunodeficiency, and increased incidence of lymphomas. The spectrum of immunologic phenotypes in CHH translates into clinical severity. Whereas T-cell deficiency may remain subclinical or may result in severe combined immunodeficiency or Omenn syndrome, humoral immunodeficiency has only rarely been noted in these patients. Here we report the diagnosis of CHH in a woman who presented with severe short stature and a full-blown antibody deficiency, clinically resembling common variable immunodeficiency. Sequencing of the RMRP gene revealed compound heterozygosity for two novel mutations (g.68_69delinsTT and g.76C>T). Despite the late onset of immunodeficiency in the patient, its clinical course was severe, and the patient died 3 years after the first diagnosis.

  4. Mutations in the SURF1 gene associated with Leigh syndrome and cytochrome C oxidase deficiency.

    Science.gov (United States)

    Péquignot, M O; Dey, R; Zeviani, M; Tiranti, V; Godinot, C; Poyau, A; Sue, C; Di Mauro, S; Abitbol, M; Marsac, C

    2001-05-01

    Cytochrome c oxidase (COX) deficiency is one of the major causes of Leigh Syndrome (LS), a fatal encephalopathy of infancy or childhood, characterized by symmetrical lesions in the basal ganglia and brainstem. Mutations in the nuclear genes encoding COX subunits have not been found in patients with LS and COX deficiency, but mutations have been identified in SURF1. SURF1 encodes a factor involved in COX biogenesis. To date, 30 different mutations have been reported in 40 unrelated patients. We aim to provide an overview of all known mutations in SURF1, and to propose a common nomenclature. Twelve of the mutations were insertion/deletion mutations in exons 1, 4, 6, 8, and 9; 10 were missense/nonsense mutations in exons 2, 4, 5, 7, and 8; and eight were detected at splicing sites in introns 3 to 7. The most frequent mutation was 312_321del 311_312insAT which was found in 12 patients out of 40. Twenty mutations have been described only once. We also list all polymorphisms discovered to date.

  5. Mismatch repair-deficient crypt foci in Lynch syndrome--molecular alterations and association with clinical parameters.

    Directory of Open Access Journals (Sweden)

    Laura Staffa

    Full Text Available Lynch syndrome is caused by germline mutations of DNA mismatch repair (MMR genes, most frequently MLH1 and MSH2. Recently, MMR-deficient crypt foci (MMR-DCF have been identified as a novel lesion which occurs at high frequency in the intestinal mucosa from Lynch syndrome mutation carriers, but very rarely progress to cancer. To shed light on molecular alterations and clinical associations of MMR-DCF, we systematically searched the intestinal mucosa from Lynch syndrome patients for MMR-DCF by immunohistochemistry. The identified lesions were characterised for alterations in microsatellite-bearing genes with proven or suspected role in malignant transformation. We demonstrate that the prevalence of MMR-DCF (mean 0.84 MMR-DCF per 1 cm2 mucosa in the colorectum of Lynch syndrome patients was significantly associated with patients' age, but not with patients' gender. No MMR-DCF were detectable in the mucosa of patients with sporadic MSI-H colorectal cancer (n = 12. Microsatellite instability of at least one tested marker was detected in 89% of the MMR-DCF examined, indicating an immediate onset of microsatellite instability after MMR gene inactivation. Coding microsatellite mutations were most frequent in the genes HT001 (ASTE1 with 33%, followed by AIM2 (17% and BAX (10%. Though MMR deficiency alone appears to be insufficient for malignant transformation, it leads to measurable microsatellite instability even in single MMR-deficient crypts. Our data indicate for the first time that the frequency of MMR-DCF increases with patients' age. Similar patterns of coding microsatellite instability in MMR-DCF and MMR-deficient cancers suggest that certain combinations of coding microsatellite mutations, including mutations of the HT001, AIM2 and BAX gene, may contribute to the progression of MMR-deficient lesions into MMR-deficient cancers.

  6. Prediabetes is associated with an increased risk of testosterone deficiency, independent of obesity and metabolic syndrome.

    Directory of Open Access Journals (Sweden)

    Chen-Hsun Ho

    Full Text Available OBJECTIVE: The association between type 2 diabetes and low testosterone has been well recognized. However, testosterone levels in men with prediabetes have been rarely reported. We aimed to investigate whether prediabetes was associated with an increased risk of testosterone deficiency. METHODS: This study included 1,306 men whose sex hormones was measured during a medical examination. Serum total testosterone and sex hormone-binding globulin were measured; free and bioavailable testosterone concentrations were calculated by Vermeulen's formula. Prediabetes was defined by impaired fasting glucose (IFG, impaired postprandial glucose (IPG, or glycated hemoglobin (HbA1c 5.7%-6.4%. Logistic regression was performed to obtain the odds ratios (OR for subnormal total testosterone (<300 ng/dL or free testosterone (<6 ng/dL in prediabetic and diabetic men compared with normoglycemic individuals, while adjusting for age, BMI, waist circumference, and metabolic syndrome (MetS. RESULTS: Normoglycemia, prediabetes, and diabetes were diagnosed in 577 (44.2%, 543 (41.6%, and 186 (14.2% men, respectively. Prediabetes was associated with an increased risk of subnormal total testosterone compared to normoglycemic individuals (age-adjusted OR=1.87; 95%CI=1.38-2.54. The risk remained significant in all multivariate analyses. After adjusting for MetS, the OR in prediabetic men equals that of diabetic patients (1.49 versus 1.50. IFG, IPG, and HbA1c 5.7%-6.4% were all associated with an increased risk of testosterone deficiency, with different levels of significance in multivariate analyses. However, neither prediabetes nor diabetes was associated with subnormal free testosterone in multivariate analyses. CONCLUSIONS: Prediabetes is associated with an increased risk of testosterone deficiency, independent of obesity and MetS. After adjusting for MetS, the risk equals that of diabetes. Our data suggest that testosterone should be measured routinely in men with

  7. High Density Lipoprotein Phospholipids as a Marker of Coronary Heart Disease of Shen-Yang Deficiency Syndrome

    Institute of Scientific and Technical Information of China (English)

    GUO Ping-qing (郭平清); LIN Qiu-cheng (林求诚); GUO Yin-geng (郭银庚); SHEN Zong-guo (沈宗国)

    2003-01-01

    Objective: To seek a new biochemical index for diagnosis of coronary heart disease (CHD)of shen-Yang deficiency syndrom (CHD-SYD). Methods: Sixty-one patients with CHD were divided into 3 groups according to their TCM Syndrome type, 10 patients in the group without Xin-Qi deficiency (Group A), 25 in the group with Xin-Qi deficiency but without Shen-Yang deficiency (Group B) and 26 in the group both with Xin-Qi deficiency and Shen-Yang deficiency (Group C). Levels of 17-hydroxy-corticosteroid in urine (urinary 17-OHCS) per 24 hrs, and serum level of high density lipoprotein cholesterol (HDL-C) and high density lipoprotein phospholipid (HDL-PL) in them were determined in synchrostep and compared with those in the control group of 23 healthy aged persons. urinary 17-OHCS per 24 hrs was taken as the diagnostic standard to screen a new index for diagnosis of Shen-Yang deficiency Syndrome, and preliminary appraisal to the index was made. Results: Serum HDL-PL in the CHD-SYD patients( Group C) was 616±157 mg/L, which was obviously lower than that in the patients of Group A and B. With low HDL-PL (<650 mg/L) used as the index to diagnose CHD-SYD, the sensitivity was 73%, the specificity 86% and the accuracy 80%. Conclusion: HDL-PL <650 mg/L could be adopted as an index for CHD-SYD diagnosis, which is simple and practical.

  8. Deficiency for the ubiquitin ligase UBE3B in a blepharophimosis-ptosis-intellectual-disability syndrome.

    Science.gov (United States)

    Basel-Vanagaite, Lina; Dallapiccola, Bruno; Ramirez-Solis, Ramiro; Segref, Alexandra; Thiele, Holger; Edwards, Andrew; Arends, Mark J; Miró, Xavier; White, Jacqueline K; Désir, Julie; Abramowicz, Marc; Dentici, Maria Lisa; Lepri, Francesca; Hofmann, Kay; Har-Zahav, Adi; Ryder, Edward; Karp, Natasha A; Estabel, Jeanne; Gerdin, Anna-Karin B; Podrini, Christine; Ingham, Neil J; Altmüller, Janine; Nürnberg, Gudrun; Frommolt, Peter; Abdelhak, Sonia; Pasmanik-Chor, Metsada; Konen, Osnat; Kelley, Richard I; Shohat, Mordechai; Nürnberg, Peter; Flint, Jonathan; Steel, Karen P; Hoppe, Thorsten; Kubisch, Christian; Adams, David J; Borck, Guntram

    2012-12-07

    Ubiquitination plays a crucial role in neurodevelopment as exemplified by Angelman syndrome, which is caused by genetic alterations of the ubiquitin ligase-encoding UBE3A gene. Although the function of UBE3A has been widely studied, little is known about its paralog UBE3B. By using exome and capillary sequencing, we here identify biallelic UBE3B mutations in four patients from three unrelated families presenting an autosomal-recessive blepharophimosis-ptosis-intellectual-disability syndrome characterized by developmental delay, growth retardation with a small head circumference, facial dysmorphisms, and low cholesterol levels. UBE3B encodes an uncharacterized E3 ubiquitin ligase. The identified UBE3B variants include one frameshift and two splice-site mutations as well as a missense substitution affecting the highly conserved HECT domain. Disruption of mouse Ube3b leads to reduced viability and recapitulates key aspects of the human disorder, such as reduced weight and brain size and a downregulation of cholesterol synthesis. We establish that the probable Caenorhabditis elegans ortholog of UBE3B, oxi-1, functions in the ubiquitin/proteasome system in vivo and is especially required under oxidative stress conditions. Our data reveal the pleiotropic effects of UBE3B deficiency and reinforce the physiological importance of ubiquitination in neuronal development and function in mammals.

  9. Impaired telomere maintenance in Alazami syndrome patients with LARP7 deficiency

    Directory of Open Access Journals (Sweden)

    Brody Holohan

    2016-10-01

    Full Text Available Abstract Background Loss of function in genes required for telomere maintenance result in disorders known as telomeropathies, which are characterized by a pattern of symptoms including generalized and specific lymphocytopenias as well as very short telomere length and disease anticipation. Methods Because human LARP7 is the most likely ortholog of the Tetrahymena p65 protein, which is required for telomerase activity in that organism, we investigated the effects of LARP7 silencing in human cells as well as in two distinct families with Alazami syndrome (loss of function of LARP7. Results Depletion of LARP7 caused a reduction in telomerase enzymatic activity and progressively shorter telomeres in human cancer cell lines. Alazami syndrome patients from two separate cohorts exhibited very short lymphocyte telomeres. Further, wild-type offspring of LARP7 mutant individuals also had very short telomeres, comparable to what is observed in telomerase (hTERT mutant cohorts. Conclusions Together, these experiments demonstrate that in addition to the readily apparent developmental disorder associated with LARP7 deficiency, an underlying telomeropathy exists even in unaffected siblings of these individuals.

  10. International collaboration to assess the risk of Guillain Barre Syndrome following Influenza A (H1N1) 2009 monovalent vaccines

    NARCIS (Netherlands)

    Dodd, Caitlin N.; Romio, Silvana A.; Black, Steven; Vellozzi, Claudia; Andrews, Nick; Sturkenboom, Miriam; Zuber, Patrick; Hua, Wei; Bonhoeffer, Jan; Buttery, Jim; Crawford, Nigel; Deceuninck, Genevieve; de Vries, Corinne; De Wals, Philippe; Gutierrez-Gimeno, M. Victoria; Heijbel, Harald; Hughes, Hayley; Hur, Kwan; Hviid, Anders; Kelman, Jeffrey; Kilpi, Tehri; Chuang, S. K.; Macartney, Kristine; Rett, Melisa; Lopez-Callada, Vesta Richardson; Salmon, Daniel; Sanchez, Francisco Gimenez; Sanz, Nuria; Silverman, Barbara; Storsaeter, Jann; Thirugnanam, Umapathi; van der Maas, Nicoline; Yih, Katherine; Zhang, Tao; Izurieta, Hector

    2013-01-01

    Background: The global spread of the 2009 novel pandemic influenza A (H1N1) virus led to the accelerated production and distribution of monovalent 2009 Influenza A (H1N1) vaccines (pH1N1). This pandemic provided the opportunity to evaluate the risk of Guillain-Barre syndrome (GBS), which has been an

  11. Properdin deficiency associated with recurrent otitis media and pneumonia, and identification of male carrier with Klinefelter syndrome.

    Science.gov (United States)

    Schejbel, Lone; Rosenfeldt, Vibeke; Marquart, Hanne; Valerius, Niels Henrik; Garred, Peter

    2009-06-01

    Properdin is an initiator and stabilizer of the alternative complement activation pathway (AP). Deficiency of properdin is a rare X-linked condition characterized by increased susceptibility to infection with Neisseria meningitidis associated with a high mortality rate. We report properdin deficiency in a large Pakistani family. The index cases were found by screening for immunodeficiency due to a history of recurrent infections. This revealed absent AP activity, but normal classical and lectin pathway activity. Sequencing of the properdin gene (PFC) revealed a novel frameshift mutation. When all available relatives (n=24) were screened for the mutation, four affected males, four female carriers and a male heterozygous carrier were identified. He was subsequently diagnosed with Klinefelter syndrome. A questionnaire revealed a striking association between properdin deficiency and recurrent otitis media (P=0.0012), as well as recurrent pneumonia (P=0.0017). This study is the first to show a significant association between properdin deficiency and recurrent infections.

  12. A rare cause of congenital adrenal hyperplasia : Antley-Bixler syndrome due to POR deficiency

    NARCIS (Netherlands)

    Herkert, J. C.; Blaauwwiekel, E. E.; Hoek, A.; Veenstra-Knol, H. E.; Kema, I. P.; Arlt, W.; Kerstens, M. N.

    Cytochrome P(450) oxidoreductase (POR) deficiency is a recently discovered new variant of congenital adrenal hyperplasia. Distinctive features of POR deficiency are the presence of disorders of sexual development in both sexes, glucocorticoid deficiency and skeletal malformations similar to those

  13. Guillain-Barré syndrome and adjuvanted pandemic influenza A (H1N1) 2009 vaccine: Multinational case-control study in Europe

    NARCIS (Netherlands)

    J.P. Dieleman (Jeanne); S. Romio (Silvana); K. Johansen (Kari); D.M. Weibel (Daniel); J. Bonhoeffer (Jan); M.C.J.M. Sturkenboom (Miriam)

    2011-01-01

    textabstractObjective: To assess the association between pandemic influenza A (H1N1) 2009 vaccine and Guillain-Barré syndrome. Design: Case-control study. Setting: Five European countries. Participants: 104 patients with Guillain-Barré syndrome and its variant Miller-Fisher syndrome matched to one

  14. Medical Management of Acute Radiation Syndromes : Comparison of Antiradiation Vaccine and Antioxidants radioprotection potency.

    Science.gov (United States)

    Maliev, Slava; Popov, Dmitri; Lisenkov, Nikolai

    Introduction: This experimental study of biological effects of the Antiradiation Vaccine and Antioxidants which were used for prophylaxis and treatment of the Acute Radiation Syndromes caused by high doses of the low-LET radiation. An important role of Reactive Oxyden Species (Singlet oxygen, hydroxyl radicals, superoxide anions and bio-radicals)in development of the Acute Radiation Syndromes could be defined as a "central dogma" of radiobiology. Oxida-tion and damages of lipids, proteins, DNA, and RNA are playing active role in development of postradiation apoptosis. However, the therapeutic role of antioxidants in modification of a postradiation injury caused by high doses of radiation remains controversial.Previous stud-ies had revealed that antioxidants did not increase a survival rate of mammals with severe forms of the Acute Radiation Syndromes caused by High Doses of the low-LET radiation. The Antiradiation Vaccine(ARV) contains toxoid forms of the Radiation Toxins(RT) from the Specific Radiation Determinants Group (SRD). The RT SRD has toxic and antigenic prop-erties at the same time and stimulates a specific antibody elaboration and humoral response form activated acquired immune system. The blocking antiradiation antibodies induce an im-munologically specific effect and have inhibiting effects on radiation induced neuro-toxicity, vascular-toxicity, gastrointestinal toxcity, hematopoietic toxicity, and radiation induced cytol-ysis of selected groups of cells that are sensitive to radiation. Methods and materials: Scheme of experiments: 1. Irradiated animals with development of Cerebrovascular ARS (Cv-ARS), Cardiovascular ARS (Cr-ARS) Gastrointestinal ARS(GI-ARS), Hematopoietic ARS (H-ARS) -control -were treated with placebo administration. 2. Irradiated animals were treated with antioxidants prophylaxisis and treatment of Cv-ARS, Cr-SRS, GI-ARS, Hp-ARS forms of the ARS. 3. irradiated animals were treated with radioprotection by Antiradiation Vaccine

  15. Summary of differentiation and treating on spleen Yin deficiency syndrome%脾阴虚证辨治概要

    Institute of Scientific and Technical Information of China (English)

    王军瑞

    2011-01-01

    针对中医脾病辨证中对脾阴的认识不足,以中医理论为基础,就脾阴的理论源流、病因病机、证候特点、类证鉴别及治疗方药等加以阐述,旨在说明脾阴脾阳同等重要,脾阴虚与脾气虚、胃阴虚不可混淆,并在一定程度上证明脾阴虚的发生确有其病理学基础.%Aiming at the recognition insufficient about spleen yin in the disease syndrome differentiation of TCM and on the basis of TCM theory this article explained the theoretical origin and development, etiology and pathogenesis, syndrome characteristic, similar syndrome differentiation and treating herbs for spleen yin. It was suggested that spleen yin and spleen yang had an equal important role and confusion could not performed between spleen yin deficiency, spleen Qi deficiency and stomach yin deficiency. In some extent, demonstration the occurrence of spleen yin deficiency had its pathologic foundation indeed.

  16. Effects of dietary threonine and tryptophan supplementation on growing pigs induced by porcine respiratory and reproductive syndrome vaccination.

    Science.gov (United States)

    Xu, Shengyu; Shen, Jie; Fang, Zhengfeng; Zhao, Yingfei; Lin, Yan; Che, Lianqiang; Wu, De

    2014-01-01

    A total of 32 growing pigs were used in a 2 × 2 factorial arrangement of treatments with two different diets (conventional [CON] diet vs. threonine [Thr]- and tryptophan [Trp]-rich [TTR] diet) and two immunological challenge regimens (porcine respiratory and reproductive syndrome [PRRS] vaccine vs. phosphate buffer solution [PBS]) to study the hypothesis that dietary supplementation with Trp and Thr would benefit for growing pigs vaccinated with PRRS vaccine. After feeding the experimental diets for 21 d, the pigs were intramuscularly vaccinated with PRRS or PBS. Performance data were recorded over a period of 10 weeks and are presented for the pre-challenge period (3 weeks) and the challenge period (7 weeks, where on day 1, pigs were immunologically challenged). During the pre-challenge period, the growth performance was not different between dietary treatments. PRRS vaccination resulted in increased rectal temperature and decreased feed intake and growth rate (p pigs, diet TTR enhanced the feed intake, especially during the first 2 weeks after the PRRS vaccination compared with diet CON (p pigs had a higher Thr and Trp requirement than non-vaccinated pigs.

  17. Disaccharidase deficiency.

    Science.gov (United States)

    Bayless, T M; Christopher, N L

    1969-02-01

    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.

  18. Properdin deficiency associated with recurrent otitis media and pneumonia, and identification of male carrier with Klinefelter syndrome

    DEFF Research Database (Denmark)

    Schejbel, Lone; Rosenfeldt, Vibeke; Marquart, Hanne

    2009-01-01

    deficiency in a large Pakistani family. The index cases were found by screening for immunodeficiency due to a history of recurrent infections. This revealed absent AP activity, but normal classical and lectin pathway activity. Sequencing of the properdin gene (PFC) revealed a novel frameshift mutation. When...... all available relatives (n=24) were screened for the mutation, four affected males, four female carriers and a male heterozygous carrier were identified. He was subsequently diagnosed with Klinefelter syndrome. A questionnaire revealed a striking association between properdin deficiency and recurrent...

  19. White monkey syndrome and presumptive copper deficiency in wild savannah baboons.

    Science.gov (United States)

    Markham, A Catherine; Gesquiere, Laurence R; Bellenger, Jean-Philippe; Alberts, Susan C; Altmann, Jeanne

    2011-11-01

    In immature wild savannah baboons (Papio cynocephalus), we observed symptoms consistent with copper (Cu) deficiency and, more specifically, with a disorder referred to as white monkey syndrome (WMS) in laboratory primates. The objectives of this study were to characterize this pathology, and test three hypotheses that (1) Cu deficiency may have been induced by zinc (Zn) toxicity, (2) it may have been induced by molybdenum (Mo) toxicity, and (3) cumulative rainfall during the perinatal period and particularly during gestation is an ecological factor distinguishing infants afflicted with WMS from non-WMS infants. During 2001-2009, we observed 22 instances of WMS out of a total 377 live births in the study population. Visible symptoms exhibited by WMS infants included whitening of the animal's fur and/or impaired mobility characterized by an apparent "stiffening" of the hindlimbs. Occurrence of WMS did not vary significantly by gender. However, among individuals that survived at least 180 days, WMS males had a significantly lower survivorship probability than non-WMS males. Zn/Cu ratios assessed from hair samples of adult female baboons were higher in females who had produced at least one WMS offspring relative to females who had not had a WMS offspring. This was true even when the hair sample was collected long after the birth of the female's afflicted infant. We consider this potentially indicative of a robust tendency for low Cu levels induced by elevated Zn intake in some individuals. No significant differences of Mo/Cu ratios were observed. Cumulative rainfall during gestation (∼179 days) was 50% lower for WMS infants relative to non-WMS infants. In contrast, rainfall for the two classes of infants did not differ in the 180 days before conception or in the 180 days following birth. This finding highlights the importance of prenatal ecological conditions in healthy fetal development with regard to WMS.

  20. Thimerosal-Preserved Hepatitis B Vaccine and Hyperkinetic Syndrome of Childhood

    Directory of Open Access Journals (Sweden)

    David A. Geier

    2016-03-01

    Full Text Available (1 Background: Hyperkinetic syndrome of childhood (HKSoC is an International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9 category in which the majority of the children are also diagnosed under the Diagnostic and Statistical Manual of Mental Disorders, 4th Edition, Text Revision (DSM-IV-TR, where the umbrella term is “Attention-Deficit and Disruptive Behavior Disorders”. The diagnostic criteria for HKSoC are developmentally inappropriate inattention, hyperactivity, and impulsivity. Some studies have implicated mercury (Hg exposure as a risk factor. (2 Methods: This hypothesis testing study; using the Vaccine Safety Datalink; assessed the toxicological effects of bolus exposure to organic-Hg from Thimerosal-containing vaccines (TCVs by examining the relationship between Thimerosal-preserved hepatitis B vaccines (TM-HepB given at varying levels and at specific intervals in the first six months after birth and the risk of a child being diagnosed with HKSoC. (3 Results: Children diagnosed with HKSoC were significantly more likely to be exposed to increased organic-Hg from TM-HepB doses given within the first month (odds ratio = 1.45; 95% confidence interval (CI = 1.30–1.62; within the first two months (odds ratio = 1.43; 95% CI = 1.28–1.59; and within the first six months (odds ratio = 4.51; 95% CI = 3.04–6.71 than controls. (4 Conclusion: The results indicate that increasing organic-Hg exposure from TCVs heightens the risk of a HKSoC diagnosis.

  1. A subunit vaccine against the adenovirus egg-drop syndrome using part of its fiber protein.

    Science.gov (United States)

    Fingerut, E; Gutter, B; Gallili, G; Michael, A; Pitcovski, J

    2003-06-20

    In this study, the effectiveness of antibodies against the hexon, fiber or a fiber fragment of an avian adenovirus egg-drop syndrome (EDS), in neutralizing the virus was tested. The fiber protein is responsible for binding the virus to the target cell. The fiber fragment knob-s comprises the carboxy-terminal knob domain and 34 amino acids of the immediately adjacent shaft domain of the adenovirus fiber protein. The hexon, fiber capsid protein and knob-s were produced in E. coli and injected into chickens. Antibodies that were produced against the whole fiber protein showed some hemagglutination inhibition (HI) activity. Antibodies produced against the knob-s protein showed HI activity and serum neutralization (SN) activity similar to the positive control-whole virus vaccine. We assume that production of only part of the fiber enables the protein produced in E. coli to fold correctly. Antibodies produced against the hexon protein showed no SN activity. In summary, knob-s induced SN and HI antibodies against EDS virus at a rate similar to the whole virus and were significantly more efficient than the full-length fiber. The recombinant knob-s protein may be used as a vaccine against pathogenic adenovirus infections.

  2. 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?

    Science.gov (United States)

    Hässig, A; Wen-Xi, L; Stampfli, K

    1996-04-01

    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.

  3. Observation on the Efficiency of the Mongolian Gerbil Kidney Tissue Culture Inactivated Bivalent Vaccine for Hemorrhagic Fever with Renal Syndrome

    Institute of Scientific and Technical Information of China (English)

    董关木; 朱智勇; 安祺; 朱凤才; 刘文雪; 孔艳; 杨立宏; 俞永新

    2004-01-01

    The Z10 and Z37 strains of hemorrhagic fever with renal syndrome (HFRS) virus and the Mongolian gerbil (Merions unguiculatus ) kidney cells were used to prepare the inactivated bivalent vaccine. A phase Ⅱ clinical trial use of this vaccine was made in 750 Chinese volunteers. The results showed that the side reaction rate was 2.5% and the sero-conversion rate of neutralizing antibodies against Hantaan and Seoul viruses in the inoculated volunteers were 87.6% and 96.3% respectively.

  4. DNA mismatch repair deficiency and hereditary syndromes in Latino patients with colorectal cancer.

    Science.gov (United States)

    Ricker, Charité N; Hanna, Diana L; Peng, Cheng; Nguyen, Nathalie T; Stern, Mariana C; Schmit, Stephanie L; Idos, Greg E; Patel, Ravi; Tsai, Steven; Ramirez, Veronica; Lin, Sonia; Shamasunadara, Vinay; Barzi, Afsaneh; Lenz, Heinz-Josef; Figueiredo, Jane C

    2017-10-01

    The landscape of hereditary syndromes and clinicopathologic characteristics among US Latino/Hispanic individuals with colorectal cancer (CRC) remains poorly understood. A total of 265 patients with CRC who were enrolled in the Hispanic Colorectal Cancer Study were included in the current study. Information regarding CRC risk factors was elicited through interviews, and treatment and survival data were abstracted from clinical charts. Tumor studies and germline genetic testing results were collected from medical records or performed using standard molecular methods. The mean age of the patients at the time of diagnosis was 53.7 years (standard deviation, 10.3 years), and 48.3% were female. Overall, 21.2% of patients reported a first-degree or second-degree relative with CRC; 3.4% met Amsterdam I/II criteria. With respect to Bethesda guidelines, 38.5% of patients met at least 1 criterion. Of the 161 individuals who had immunohistochemistry and/or microsatellite instability testing performed, 21 (13.0%) had mismatch repair (MMR)-deficient (dMMR) tumors. dMMR tumors were associated with female sex (61.9%), earlier age at the time of diagnosis (50.4 ± 12.4 years), proximal location (61.9%), and first-degree (23.8%) or second-degree (9.5%) family history of CRC. Among individuals with dMMR tumors, 13 (61.9%) had a germline MMR mutation (MutL homolog 1 [MLH1] in 6 patients; MutS homolog 2 [MSH2] in 4 patients; MutS homolog 6 [MHS6] in 2 patients; and PMS1 homolog 2, mismatch repair system component [PMS2] in 1 patient). The authors identified 2 additional MLH1 mutation carriers by genetic testing who had not received immunohistochemistry/microsatellite instability testing. In total, 5.7% of the entire cohort were confirmed to have Lynch syndrome. In addition, 6 individuals (2.3%) had a polyposis phenotype. The percentage of dMMR tumors noted among Latino individuals (13%) is similar to estimates in non-Hispanic white individuals. In the current study, the majority of

  5. Novel mutation in a patient with late onset GLUT1 deficiency syndrome.

    Science.gov (United States)

    Juozapaite, Sandra; Praninskiene, Ruta; Burnyte, Birute; Ambrozaityte, Laima; Skerliene, Birute

    2017-04-01

    Glucose transporter 1 deficiency syndrome (GLUT1-DS) is an inborn error of metabolism caused by impaired glucose transport through blood brain barrier due to mutation in SLC2A1 gene, encoding transporter protein. Clinical spectrum includes various signs and symptoms, ranging from severe epileptic encephalopathy to movement disorders. The diagnosis of GLUT1-DS requires hypoglycorrhachia in the presence of normoglycaemia with a reduced cerebrospinal fluid (CSF):plasma glucose ratio. The absence of pathogenic mutation in SLC2A1 gene does not exclude the diagnosis. This case report describes a patient with late onset GLUT1-DS with a novel sporadic mutation c.539T>A, p.Met180Lys in exon 5 of the SLC2A1 gene. The dominating clinical features were epilepsy and paroxysmal dyskinesias provoked by infection, emotional stress and fasting. The ictal EEG was characterized by generalized paroxysmal 3-3.5Hz spike-slow wave complexes (absences). Treatment with ketogenic diet showed clinical improvement with the reduction of paroxysmal dyskinesias. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  6. Brain correlates of spike and wave discharges in GLUT1 deficiency syndrome.

    Science.gov (United States)

    Vaudano, Anna Elisabetta; Olivotto, Sara; Ruggieri, Andrea; Gessaroli, Giuliana; De Giorgis, Valentina; Parmeggiani, Antonia; Veggiotti, Pierangelo; Meletti, Stefano

    2017-01-01

    To provide imaging biomarkers of generalized spike-and-wave discharges (GSWD) in patients with GLUT1 deficiency syndrome (GLUT1DS). Eighteen GLUT1DS patients with pathogenetic mutation in SLC2A1 gene were studied by means of Video-EEG simultaneously recorded with functional MRI (VideoEEG-fMRI). A control group of sex and age-matched patients affected by Genetic Generalized Epilepsy (GGE) with GSWD were investigated with the same protocol. Within and between groups comparison was performed as appropriated. For GLUT1DS, correlations analyses between the contrast of interest and the main clinical measurements were provided. EEG during fMRI revealed interictal GSWD in 10 GLUT1DS patients. Group-level analysis showed BOLD signal increases at the premotor cortex and putamen. With respect to GGE, GLUT1DS patients demonstrated increased neuronal activity in the putamen, precuneus, cingulate cortex, SMA and paracentral lobule. Whole-brain correlation analyses disclosed a linear relationship between the GSWD-related BOLD changes and the levels of glycorrhachia at diagnosis over the sensory-motor cortex and superior parietal lobuli. The BOLD dynamics related to GSWD in GLUT1DS are substantially different from typical GGE showing the former an increased activity in the premotor-striatal network and a decrease in the thalamus. The revealed hemodynamic maps might represent imaging biomarkers of GLUT1DS, being potentially useful for a precocious diagnosis of this genetic disorder.

  7. Eculizumab in neonatal hemolytic uremic syndrome with homozygous factor H deficiency.

    Science.gov (United States)

    Michaux, Katell; Bacchetta, Justine; Javouhey, Etienne; Cochat, Pierre; Frémaux-Bacchi, Véronique; Sellier-Leclerc, Anne-Laure

    2014-12-01

    Neonatal atypical hemolytic uremic syndrome (aHUS) is a rare but severe disease that is mainly due to methylmalonic aciduria or genetic complement abnormalities. Traditional management of aHUS includes plasma infusion/exchange, but in small or unstable infants, plasma exchange can be challenging because of high extracorporeal volume and difficulty to obtain an adequate venous access. The C5 complement blocker eculizumab has become a cornerstone of first-line management of aHUS due to complement deregulation in older patients. However, little data are available on its use in neonatal aHUS. We report on an 11-day-old neonate with severe aHUS (myocardial impairment, respiratory failure, acute kidney disease requiring hemodiafiltration) due to homozygous factor-H deficiency. She received early treatment with eculizumab as first-line therapy and completely recovered within 5 days. A second dose of eculizumab was administered 7 days after the first infusion, followed by a dose every 2 weeks for 2 months and then every 3 weeks, at the same dosage (300 mg). With more than 24 months of follow-up, renal function remains normal. We report on the long-term efficacy and safety of eculizumab as first-line therapy in neonatal aHUS. However its use still requires optimization in terms of indications and administration (frequency, dosage).

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

    Institute of Scientific and Technical Information of China (English)

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

    2012-01-01

    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.

  9. Occurrence of GLUT1 deficiency syndrome in patients treated with ketogenic diet.

    Science.gov (United States)

    Ramm-Pettersen, Anette; Nakken, Karl O; Haavardsholm, Kathrine Cammermeyer; Selmer, Kaja Kristine

    2014-03-01

    Glucose transporter 1 deficiency syndrome (GLUT1-DS) is a treatable metabolic encephalopathy caused by a mutation in the SLC2A1 gene. This mutation causes a compromised transport of glucose across the blood-brain barrier. The treatment of choice is ketogenic diet, with which most patients become seizure-free. At the National Centre for Epilepsy, we have, since 2005, offered treatment with ketogenic diet (KD) and modified Atkins diet (MAD) to children with difficult-to-treat epilepsy. As we believe many children with GLUT1-DS are unrecognized, the aim of this study was to search for patients with GLUT1-DS among those who had been responders (>50% reduction in seizure frequency) to KD or MAD. Of the 130 children included, 58 (44%) were defined as responders. Among these, 11 were already diagnosed with GLUT1-DS. No mutations in the SLC2A1 gene were detected in the remaining patients. However, the clinical features of these patients differed considerably from the patients diagnosed with GLUT1-DS. While 9 out of 10 patients with GLUT1-DS became seizure-free with dietary treatment, only 3 out of the 33 remaining patients were seizure-free with KD or MAD treatment. We therefore conclude that a seizure reduction of >50% following dietary treatment is not a suitable criterion for identifying patients with GLUT1-DS, as these patients generally achieve complete seizure freedom shortly after diet initiation.

  10. Modified Atkins diet therapy for a case with glucose transporter type 1 deficiency syndrome.

    Science.gov (United States)

    Ito, Susumu; Oguni, Hirokazu; Ito, Yasushi; Ishigaki, Keiko; Ohinata, Junko; Osawa, Makiko

    2008-03-01

    Glucose transporter type 1 deficiency syndrome (GLUT-1 DS), giving rise to impaired glucose transport across the blood-brain barrier, is characterized by infantile seizures, complex motor disorders, global developmental delay, acquired microcephaly, and hypoglycorrhachia. GLUT-1 DS can be treated effectively with a ketogenic diet because it can provide an alternative fuel for brain metabolism; however, the excessive restriction of food intake involved frequently makes it difficult for patients to initiate or continue the diet. Recently, the modified Atkins diet, which is much less restrictive in terms of the total calorie and protein intake than the classical ketogenic diet, has been shown to be effective and well tolerated in children with intractable epilepsy. We successfully introduced the modified Atkins diet to a 7-year-old boy with GLUT-1 DS, whose caregivers refused ketogenic diet treatment because of strong concerns over restricting the diet. The modified Atkins diet should be considered for patients with GLUT-1 DS as an alternative to the traditional ketogenic diet.

  11. Movement disorders in GLUT1 deficiency syndrome respond to the modified Atkins diet.

    Science.gov (United States)

    Leen, Wilhelmina G; Mewasingh, Leena; Verbeek, Marcel M; Kamsteeg, Erik-Jan; van de Warrenburg, Bart P; Willemsen, Michel A

    2013-09-01

    Movement disorders are a prominent feature of glucose transporter-1 (GLUT1) deficiency syndrome (GLUT1DS). First-choice treatment is a ketogenic diet, but compliance is poor. We have investigated the effect of the modified Atkins diet as an alternative treatment for movement disorders in GLUT1DS. Four patients with GLUT1DS ages 15 to 30 years who had movement disorders as the most prominent feature were prospectively evaluated after initiation of the modified Atkins diet. Movement disorders included dystonia, ataxia, myoclonus, and spasticity, either continuous or paroxysmal, triggered by action or exercise. Duration of treatment ranged from 3 months to 16 months. All patients reached mild to moderate ketosis and experienced remarkable improvement in the frequency and severity of paroxysmal movement disorders. Cognitive function also improved subjectively. The modified Atkins diet is an effective and feasible alternative to the ketogenic diet for the treatment of GLUT1DS-related paroxysmal movement disorders in adolescence and adulthood. © 2013 International Parkinson and Movement Disorder Society.

  12. Effect of Equiguard in Treating Patients with Shen-Yang Deficiency Syndrome

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Objective:To observe the therapeutic effect of Equiguard in old patients with Shen (肾)-yang deficiency syndrome (SYDS).Methods:Twenty old patients with diagnosis matching the criteria of SYDS selected from out-patients were administered with Equiguard capsule 3 times per day,0.70 g each time for 3 successive months.The changes in general condition,peripheral blood picture,function of the liver and kidney,and sex hormones before and after treatment were observed.The changes in the American Urinary Surgery Association (AUA) score of prostatism,urosis and residue urine in the urinary bladder were also estimated.Results:After the 3-month treatment,no significant change was found in the patients' general condition,peripheral blood picture,liver and kidney function and sex hormones,while the symptoms of prostatism and urosis were markedly improved (P<0.01),and the volume of residue urine in the urinary bladder was obviously reduced.Conclusion:Equiguard shows a significant therapeutic effect in treating old patients with SYDS,which could effectively improve the symptoms of prostatism and urosis in patients and is highly safe.

  13. LRPPRC mutations cause a phenotypically distinct form of Leigh syndrome with cytochrome c oxidase deficiency.

    Science.gov (United States)

    Debray, François-Guillaume; Morin, Charles; Janvier, Annie; Villeneuve, Josée; Maranda, Bruno; Laframboise, Rachel; Lacroix, Jacques; Decarie, Jean-Claude; Robitaille, Yves; Lambert, Marie; Robinson, Brian H; Mitchell, Grant A

    2011-03-01

    The natural history of all known patients with French-Canadian Leigh disease (Saguenay-Lac-St-Jean cytochrome c oxidase deficiency, MIM220111, SLSJ-COX), the largest known cohort of patients with a genetically homogeneous, nuclear encoded congenital lactic acidosis, was studied. 55 of 56 patients were homozygous for the A354V mutation in LRPPRC. One was a genetic compound (A354V/C1277Xdel8). Clinical features included developmental delay, failure to thrive, characteristic facial appearance and, in 90% of patients, acute crises that have not previously been detailed, either metabolic (fulminant lactic acidosis) and/or neurological (Leigh syndrome and/or stroke-like episodes). Survival ranged from 5 days to >30 years. 46/56 patients (82%) died, at a median age of 1.6 years. Of 73 crises, 38 (52%) were fatal. The immediate causes of death were multiple organ failure and/or Leigh disease. Major predictors of mortality during crises (pgenetic and/or environmental factors can influence outcome.

  14. Vaccine-associated paralytic poliomyelitis and BCG-osis in an immigrant child with severe combined immunodeficiency syndrome - Texas, 2013.

    Science.gov (United States)

    Trimble, Robert; Atkins, Jane; Quigg, Troy C; Burns, Cara C; Wallace, Gregory S; Thomas, Mary; Mangla, Anil T; Infante, Anthony J

    2014-08-22

    Poliovirus transmission has been eliminated in most of the world through the use of inactivated poliovirus vaccine (IPV) and live, attenuated oral poliovirus vaccine (OPV). In the United States, use of OPV was discontinued by the year 2000 because of the potential for vaccine-associated paralytic polio (VAPP); an average of eight cases were reported each year in the United States during 1980-2000. Polio eradication efforts in other parts of the world continue to rely on OPV to take advantage of transmission of poliovirus vaccine strains to unvaccinated persons in the population, lower cost, and ease of administration. In 2013, an infant aged 7 months who recently immigrated to the United States from India was referred to a hospital in San Antonio, Texas. The infant had fever, an enlarging skin lesion in the deltoid region with axillary lymphadenopathy, decreased activity, and inability to bear weight on the left leg, progressing to paralysis of the left leg over a 6-week period. Recognition of lymphopenia on complete blood count led to immune evaluation, which revealed the presence of severe combined immunodeficiency syndrome (SCIDS), an inherited disorder. A history of OPV and bacille Calmette-Guérin (BCG) vaccination in India led to the diagnoses of VAPP and BCG-osis, which were confirmed microbiologically. This report demonstrates the importance of obtaining a comprehensive clinical history in a child who has recently immigrated to the United States, with recognition that differing vaccine practices in other countries might require additional consideration of potential etiologies.

  15. Free-thiamine is a potential biomarker of thiamine transporter-2 deficiency: a treatable cause of Leigh syndrome.

    Science.gov (United States)

    Ortigoza-Escobar, Juan Darío; Molero-Luis, Marta; Arias, Angela; Oyarzabal, Alfonso; Darín, Niklas; Serrano, Mercedes; Garcia-Cazorla, Angels; Tondo, Mireia; Hernández, María; Garcia-Villoria, Judit; Casado, Mercedes; Gort, Laura; Mayr, Johannes A; Rodríguez-Pombo, Pilar; Ribes, Antonia; Artuch, Rafael; Pérez-Dueñas, Belén

    2016-01-01

    Thiamine transporter-2 deficiency is caused by mutations in the SLC19A3 gene. As opposed to other causes of Leigh syndrome, early administration of thiamine and biotin has a dramatic and immediate clinical effect. New biochemical markers are needed to aid in early diagnosis and timely therapeutic intervention. Thiamine derivatives were analysed by high performance liquid chromatography in 106 whole blood and 38 cerebrospinal fluid samples from paediatric controls, 16 cerebrospinal fluid samples from patients with Leigh syndrome, six of whom harboured mutations in the SLC19A3 gene, and 49 patients with other neurological disorders. Free-thiamine was remarkably reduced in the cerebrospinal fluid of five SLC19A3 patients before treatment. In contrast, free-thiamine was slightly decreased in 15.2% of patients with other neurological conditions, and above the reference range in one SLC19A3 patient on thiamine supplementation. We also observed a severe deficiency of free-thiamine and low levels of thiamine diphosphate in fibroblasts from SLC19A3 patients. Surprisingly, pyruvate dehydrogenase activity and mitochondrial substrate oxidation rates were within the control range. Thiamine derivatives normalized after the addition of thiamine to the culture medium. In conclusion, we found a profound deficiency of free-thiamine in the CSF and fibroblasts of patients with thiamine transporter-2 deficiency. Thiamine supplementation led to clinical improvement in patients early treated and restored thiamine values in fibroblasts and cerebrospinal fluid.

  16. Injected phage-displayed-VP28 vaccine reduces shrimp Litopenaeus vannamei mortality by white spot syndrome virus infection.

    Science.gov (United States)

    Solís-Lucero, G; Manoutcharian, K; Hernández-López, J; Ascencio, F

    2016-08-01

    White spot syndrome virus (WSSV) is the most important viral pathogen for the global shrimp industry causing mass mortalities with huge economic losses. Recombinant phages are capable of expressing foreign peptides on viral coat surface and act as antigenic peptide carriers bearing a phage-displayed vaccine. In this study, the full-length VP28 protein of WSSV, widely known as potential vaccine against infection in shrimp, was successfully cloned and expressed on M13 filamentous phage. The functionality and efficacy of this vaccine immunogen was demonstrated through immunoassay and in vivo challenge studies. In ELISA assay phage-displayed VP28 was bind to Litopenaeus vannamei immobilized hemocyte in contrast to wild-type M13 phage. Shrimps were injected with 2 × 10(10) cfu animal(-1) single dose of VP28-M13 and M13 once and 48 h later intramuscularly challenged with WSSV to test the efficacy of the vaccine against the infection. All dead challenged shrimps were PCR WSSV-positive. The accumulative mortality of the vaccinated and challenged shrimp groups was significantly lower (36.67%) than the unvaccinated group (66.67%). Individual phenoloxidase and superoxide dismutase activity was assayed on 8 and 48 h post-vaccination. No significant difference was found in those immunological parameters among groups at any sampled time evaluated. For the first time, phage display technology was used to express a recombinant vaccine for shrimp. The highest percentage of relative survival in vaccinated shrimp (RPS = 44.99%) suggest that the recombinant phage can be used successfully to display and deliver VP28 for farmed marine crustaceans.

  17. B-cell activating factor receptor deficiency is associated with an adult-onset antibody deficiency syndrome in humans

    OpenAIRE

    Warnatz, Klaus; Salzer, Ulrich; Rizzi, Marta; Fischer, Beate; Gutenberger, Sylvia; Böhm, Joachim; Kienzler, Anne-Kathrin; Pan-Hammarström, Qiang; Hammarström, Lennart; Rakhmanov, Mirzokhid; Schlesier, Michael; Grimbacher, Bodo; Peter, Hans-Hartmut; Eibel, Hermann

    2009-01-01

    B-cell survival depends on signals induced by B-cell activating factor (BAFF) binding to its receptor (BAFF-R). In mice, mutations in BAFF or BAFF-R cause B-cell lymphopenia and antibody deficiency. Analyzing BAFF-R expression and BAFF-binding to B cells in common variable immunodeficiency (CVID) patients, we identified two siblings carrying a homozygous deletion in the BAFF-R gene. Removing most of the BAFF-R transmembrane part, the deletion precludes BAFF-R expression. Without BAFF-R, B-cel...

  18. A rare cause of congenital adrenal hyperplasia : Antley-Bixler syndrome due to POR deficiency

    NARCIS (Netherlands)

    Herkert, J. C.; Blaauwwiekel, E. E.; Hoek, A.; Veenstra-Knol, H. E.; Kema, I. P.; Arlt, W.; Kerstens, M. N.

    2011-01-01

    Cytochrome P(450) oxidoreductase (POR) deficiency is a recently discovered new variant of congenital adrenal hyperplasia. Distinctive features of POR deficiency are the presence of disorders of sexual development in both sexes, glucocorticoid deficiency and skeletal malformations similar to those ob

  19. Roundtable for the Development of Drugs and Vaccines Against Acquired Immuno Deficiency Syndrome (AIDS).

    Science.gov (United States)

    1991-05-01

    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

  20. Communication and education as vaccine against the spread of acquired immune deficiency syndrome (AIDS) in Africa.

    Science.gov (United States)

    Soola, E O

    1991-01-01

    Attention is focused on the segmentation of the audience (urban, rural, urban slum) and messages, and on how appropriate communication and educational strategies can be adopted to create awareness of AIDS among the African population. It is important to determine the scope, nature, and content of the message in addition to the delivery of these messages through proper channels. Channels of communication vary in reach and influence, and different segments of the population vary in the capacity to absorb information. Rural people are considered susceptible because of their penchant for continually using injections for treatment of any ailment; the source of concern is unsterilized needles and syringes. The semantics of AIDs is discussed to emphasize the problem of how to identify AIDs among the multiplicity of languages in individual countries. For instance, in Nigeria there may be 150-400 languages, and these languages lack systematically developed metalanguage and specialized vocabularies. The view that local language use must be one way, linear is accepted, and the difficulties surmounted. Local languages may be used to transmit information of a nontechnical nature. The literate minority should have access to detailed information on causes, modes of transmission, symptoms, treatment or management, but not everyone needs this extent of detail. The rural and urban residents should know about the incurability of the disease, the mode of transmission, its symptoms, and what should be done if someone is suspected of having an HIV infection. Already the Hausa of Nigeria have a term for AIDs, Karya-Garkuwa, which suggests a disease that breaks down the mechanism of the biological functioning of the body. Communicators must be knowledgeable and able to effectively transmit facts not myths. Of the 3 modes of transmission (sex, blood, mother to child), sexual transmission is the most important. Blood routes are through transfusions, contaminated blood products for hemophilia patients, contaminated needles and syringes of intravenous drug users, unsterilized needles and syringes used for medical treatment, knives for circumcision or body marking, razor blades in barber shops, and toothbrushes. All media should be used as well as community based informal and political channels. Traditional communication modes in rural areas are required. A multidisciplinary team of experts in modern and traditional media and instructional communication design and operation is needed.

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

    Science.gov (United States)

    1994-05-06

    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

  2. Vitamin D supplementation has no effect on insulin resistance assessment in women with polycystic ovary syndrome and vitamin D deficiency.

    Science.gov (United States)

    Ardabili, Hania R; Gargari, Bahram P; Farzadi, Laya

    2012-03-01

    Insulin resistance is one of the most common features of polycystic ovary syndrome (PCOS). Some studies suggest that vitamin D deficiency may have a role in insulin resistance; thus, the aim of the current study was to determine the effect of vitamin D supplementation on insulin resistance in women with PCOS and a vitamin D deficiency. We hypothesized that vitamin D supplementation would lower the glucose level and insulin resistance in women with PCOS and a vitamin D deficiency. The current study was a randomized, placebo-controlled, double-blinded trial with 50 women with PCOS and a vitamin D deficiency, 20 to 40 years old, assigned to receive 3 oral treatments consisting of 50,000 IU of vitamin D₃ or a placebo (1 every 20 days) for 2 months (vitamin D, n = 24; placebo, n = 26). The fasting blood glucose, insulin, 25-hydroxyvitamin D, and parathyroid hormone levels, as well as the homeostasis model assessment of insulin resistance and quantitative insulin sensitivity check index were measured at baseline and after treatment. In the vitamin D group, the serum level of 25-hydroxyvitamin D increased (6.9 ± 2.8 to 23.4 ± 6.1 ng/mL, P insulin resistance did not change significantly by the end of the study. We were not able to demonstrate the effect of vitamin D supplementation on insulin sensitivity and insulin resistance in women with PCOS and vitamin D deficiency.

  3. Preliminary molecular basis of Danggui-buxue-tang on Qi deficiency and blood stasis syndrome

    Institute of Scientific and Technical Information of China (English)

    LIU Ya; LI Xiao-hui

    2008-01-01

    Objective To study the molecular biology mechanism of Danggui-buxue-tang on tonifying Qi and controlling blood circulation through modulation the immune functional genes. Methods Rats were randomly divided into control group, model group, and Danggui-buxue-tang group. Effect of Dang-guibuxue-tang on mRNA expressions of IL-1β, TNF-α, HSP-70, NF-kB, p38MAPK and JNK in blood cells of rats with Qi deficiency and blood stasis were measured with real-time fluorescent quantitative-PCR at 5th, 14th and 28th day. And that in artery wall were determined at the 28th day. NF-kB/p65 and p-c-jun protein expressions in rat artery wall were detected by western blotting as well. Results In model group, TNF-α, IL-1β, NF-kB, HSP-70, p38MAPK and JNK mRNA expression in blood cell increased significantly compared with control group. Compared with model group, mRNA expression of IL-1βand JNK decreased significantly; TNF-α decreased at 5th, 14th day;HSP-70, p38MAPK decreased at 14th, 28th day; NF-kB decreased at 28th day. In model group, TNF-α, IL-1β, NF-kB, p38MAPK and JNK mRNA expression in artery increased compared with control group, excluded HSP-70, and that in Danggui-buxue-tang group decreased significantly. In model group, NF-kB/p65 and p-c-jun protein expression in artery increased compared with control group, and that in Danggui-buxue-tang group decreased significantly. Conclusions The effects of Dang-guibuxuetang on Qi deficiency and blood stasis syndrome was brought from the regulating of cytokine network at multi-link and multi-target, NF-kB, p38MAPK and JNK signal transduction pathways included. Through which the immune system and whole body reached to a functional balance status.

  4. The Virosome as a Novel Concept for High Pathogenic Porcine Reproductive and Respiratory Syndrome Virus (HP-PRRSV) Vaccines

    Institute of Scientific and Technical Information of China (English)

    CAO Zheng; Lü Feng-lin

    2013-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) is an envelope, positive, single-strand RNA virus and is a member of the Arteriviridae family, Nidovirales order. PRRSV is the viral pathogen responsible for porcine reproductive and respiratory syndrome (PRRS) and caused reproductive failure and high rate of late abortion and early farrowing in sows and respiratory disease in all age. In 2006, a large scale outbreak of atypical PRRS occurred in China is characterized by high fever (41-42°C), high morbidity (50-100%) and high mortality (20-100%). The disease was caused by a highly pathogenic PRRSV with a 30 amino acid deletions in its Nsp2 coding region. Because the PRRSV strains are genetically heterogeneous, and elicit delayed and weak cell-mediated immune (CMI) and antibody responses after vaccination the current vaccines are failed to provide sustainable disease control. Virosomes are virus-like particles, consisting of reconstituted virus envelopes without genetic material of the native virus. Since the virosomes has being similar to the original virus in terms of morphology and cell entry characteristics. Virosomes provide a vaccine platform that has the capacity to combine the antigen and an adjuvant within a single particle that could activate both the humoral and the cellular arm of the immune system. Furthermore, the virosomes are also providing a novel promising approach for the development of an efficacious vaccine against HP-PRRSV.

  5. Avian hepatitis E virus, vaccines and methods of protecting against avian hepatitis-splenomegaly syndrome and mammalian hepatitis E

    OpenAIRE

    2009-01-01

    The present invention relates to a novel isolated avian hepatitis E virus having a nucleotide sequence set forth in SEQ ID NO:1 or its complementary strand. The invention further concerns immunogenic compositions comprising this new virus or recombinant products such as the nucleic acid and vaccines that protect an avian or mammalian species from viral infection or hepatitis-splenomegaly syndrome caused by the hepatitis E virus. Also included in the scope of the invention is a method for prop...

  6. GH treatment to final height produces similar height gains in patients with SHOX deficiency and turner syndrome: Results of a multicenter trial

    NARCIS (Netherlands)

    W.F. Blum (Werner); J.L. Ross (J.); A.G. Zimmermann (Alan); C.A. Quigley (Charmian); C.J. Child (Christopher); G. Kalifa (Gabriel); C.L. Deal (Cheri Lynn); S.L.S. Drop (Stenvert); G. Rappold (G.); G. Cutler (Gordon)

    2013-01-01

    textabstractContext: Growth impairment in short stature homeobox-containing gene (SHOX) deficiency and Turner syndrome share a similar etiology. Because of the established effect of GH treatment on height in patients with Turner syndrome, we hypothesized that GH therapy would also stimulate growth

  7. GH treatment to final height produces similar height gains in patients with SHOX deficiency and turner syndrome: Results of a multicenter trial

    NARCIS (Netherlands)

    W.F. Blum (Werner); J.L. Ross (J.); A.G. Zimmermann (Alan); C.A. Quigley (Charmian); C.J. Child (Christopher); G. Kalifa (Gabriel); C.L. Deal (Cheri Lynn); S.L.S. Drop (Stenvert); G. Rappold (G.); G. Cutler (Gordon)

    2013-01-01

    textabstractContext: Growth impairment in short stature homeobox-containing gene (SHOX) deficiency and Turner syndrome share a similar etiology. Because of the established effect of GH treatment on height in patients with Turner syndrome, we hypothesized that GH therapy would also stimulate growth i

  8. Risk of sudden infant death syndrome after immunization with the diphtheria-tetanus-pertussis vaccine.

    Science.gov (United States)

    Griffin, M R; Ray, W A; Livengood, J R; Schaffner, W

    1988-09-01

    To evaluate recent immunization against diphtheria, tetanus, and pertussis (DTP) as a possible risk factor for sudden infant death syndrome (SIDS), we studied the rates of SIDS after the administration of DTP vaccine in a cohort of 129,834 children who were born in four urban Tennessee counties during the period from 1974 through 1984. All the children received at least one DTP immunization in the first year of life at county health-department clinics or from Medicaid providers. Computerized immunization records from these sources were linked with Tennessee birth and death certificates to establish the cohort, ascertain the timing of immunization, and identify cases of SIDS. These children represented 42 percent of the births in the four counties. Among these children, 204 deaths occurred at the ages of 29 to 365 days; 109 deaths were classified as due to SIDS. We estimated the risk of SIDS according to the length of time, up to 30 days, since DTP immunization and compared it with the risk 31 days or more after immunization to calculate the relative risk. With control for age, the relative risk from 0 to 3 days after DTP immunization was 0.18 (95 percent confidence interval, 0.04 to 0.8); from 4 to 7 days, 0.17 (95 percent confidence interval, 0.04 to 0.7); from 8 to 14 days, 0.75 (95 percent confidence interval, 0.4 to 1.5); and from 15 to 30 days, 1.0 (95 percent confidence interval, 0.6 to 1.6). A multivariate analysis in which we controlled for age, sex, race, year, birth weight, and Medicaid enrollment, produced similar results. We conclude that in this large population of children there was no increase in the risk of SIDS after immunization with the DTP vaccine.

  9. Guillain-Barre Syndrome, Influenza Vaccination, and Antecedent Respiratory and Gastrointestinal Infections: A Case-Centered Analysis in the Vaccine Safety Datalink, 2009-2011.

    Directory of Open Access Journals (Sweden)

    Sharon K Greene

    Full Text Available Guillain-Barré Syndrome (GBS can be triggered by gastrointestinal or respiratory infections, including influenza. During the 2009 influenza A (H1N1 pandemic in the United States, monovalent inactivated influenza vaccine (MIV availability coincided with high rates of wildtype influenza infections. Several prior studies suggested an elevated GBS risk following MIV, but adjustment for antecedent infection was limited.We identified patients enrolled in health plans participating in the Vaccine Safety Datalink and diagnosed with GBS from July 2009 through June 2011. Medical records of GBS cases with 2009-10 MIV, 2010-11 trivalent inactivated influenza vaccine (TIV, and/or a medically-attended respiratory or gastrointestinal infection in the 1 through 141 days prior to GBS diagnosis were reviewed and classified according to Brighton Collaboration criteria for diagnostic certainty. Using a case-centered design, logistic regression models adjusted for patient-level time-varying sources of confounding, including seasonal vaccinations and infections in GBS cases and population-level controls.Eighteen confirmed GBS cases received vaccination in the 6 weeks preceding onset, among 1.27 million 2009-10 MIV recipients and 2.80 million 2010-11 TIV recipients. Forty-four confirmed GBS cases had infection in the 6 weeks preceding onset, among 3.77 million patients diagnosed with medically-attended infection. The observed-versus-expected odds that 2009-10 MIV/2010-11 TIV was received in the 6 weeks preceding GBS onset was odds ratio = 1.54, 95% confidence interval (CI, 0.59-3.99; risk difference = 0.93 per million doses, 95% CI, -0.71-5.16. The association between GBS and medically-attended infection was: odds ratio = 7.73, 95% CI, 3.60-16.61; risk difference = 11.62 per million infected patients, 95% CI, 4.49-26.94. These findings were consistent in sensitivity analyses using alternative infection definitions and risk intervals for prior

  10. Outcome of ketogenic diets in GLUT1 deficiency syndrome in Japan: A nationwide survey.

    Science.gov (United States)

    Fujii, Tatsuya; Ito, Yasushi; Takahashi, Satoru; Shimono, Kuriko; Natsume, Jun; Yanagihara, Keiko; Oguni, Hirokazu

    2016-08-01

    To evaluate the outcome of ketogenic diets (KDs) in patients with glucose transport type 1 deficiency syndrome (GLUT1DS) in Japan. A nationwide survey for GLUT1DS was conducted by sending questionnaires to board-certified pediatric neurologists nationwide to obtain clinical and laboratory data. Among 39 patients whose diagnosis was confirmed molecularly or by the 3-O-methylglucose uptake assay, 31 were treated with KDs for longer than 1month. Seventeen patients (55%) were on the modified Atkins diet, 11 (35%) were on the classic KD, and 3 were on the medium-chain triglyceride (MCT) diet. The median values and ranges of serum β-hydroxybutyrate levels in patients on the modified Atkins diet, classic KD and MCT diet were 2.5mM (0.75-4.1), 1.7mM (0.23-3.5) and 2.6mM (1.5-3.0), respectively. The KDs were effective on seizures (80%), aggravation after fasting (80%) and ataxia (79%). Thus, ataxia was as responsive as seizures. Two patients on the classic KD with a ketogenic ratio as low as 1:1 showed improvement in neurological symptoms. The development or intelligence quotient measured using the same psychological scales before and after the KDs in 9 patients did not show a significant improvement; the median quotients before and after the diets were 40 (12-91) and 46 (12-67). The KDs were most effective on seizures, transient aggravation after fasting and ataxia. The efficacy on intellectual development was equivocal. The modified Atkins diet was more commonly used for GLUT1DS in this study, and its ketogenicity was equivalent to the classic KD. Copyright © 2016 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

  11. GLUT1-deficiency syndrome: Report of a four-generation Norwegian family with a mild phenotype.

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    Ramm-Pettersen, Anette; Nakken, Karl O; Haavardsholm, Kathrine C; Selmer, Kaja Kristine

    2017-05-01

    Glucose transporter type 1 deficiency syndrome (GLUT1-DS) is a rare metabolic encephalopathy with a wide variation of clinical phenotypes. Familial variants are often milder than de novo cases, and may therefore remain undiagnosed. The aim of this study was to characterize the clinical course of GLUT1-DS in a four-generation Norwegian family where the oldest generations had never received any treatment. Through interviews and clinical investigations, we characterized a family of 26 members, where 11 members had symptoms strongly suggesting GLUT1-DS. All members were offered genetic testing of the SLC2A1 gene. Affected members were offered treatment with ketogenic diet, and the effect of the treatment was registered. We sequenced the SLC2A1 gene in 13 members, and found that 10, all with symptoms, had the c.823G>A (p.Ala275Thr) variant. All affected members had experienced early-onset epilepsy, paroxysmal exercise-induced dyskinesias, and most had mild learning disability. Moreover, some had symptoms and signs of a distal neuropathy in addition to reduced sense of orientation and excessive daytime sleep. Their load of symptoms had decreased over the years, although that they never had received any treatment. Nevertheless, those who started dietary treatment all experienced an improved quality of life. We report a four-generation family with GLUT1-DS where the disease has a mild course, even when untreated. In addition to classical GLUT1-DS features, we also describe symptoms which have never been reported in GLUT1-DS previously. As such, this family extends the phenotypic spectrum of GLUT1-DS and underlines the importance of diagnosing also relatively mildly affected patients, even in adult life, as they also seem to benefit from dietary treatment. Published by Elsevier Inc.

  12. A Rare Combination: Congenital Adrenal Hyperplasia Due To 21 Hydroxylase Deficiency and Turner Syndrome

    Science.gov (United States)

    Peltek Kendirci, Havva Nur; Aycan, Zehra; Çetinkaya, Semra; Baş, Veysel Nijat; Ağladıoğlu, Sebahat Yılmaz; Önder, Aşan

    2012-01-01

    A combination of Turner syndrome (TS) and classical congenital adrenal hyperplasia (CAH) is rare. A one-day-old newborn was referred to our hospital with ambiguous genitalia. The parents were third-degree relatives. The infant’s weight was 3350g (50-75p), and the head circumference was 34.5cm (50p). The gonads were nonpalpable. Presence of a 3 cm phallus, one urogenital opening into the perineum, and incomplete labial fusion were identified. Laboratory tests revealed a classical type of CAH due to 21-hydroxylase deficiency. Karyotyping revealed a 45X0(35)/46XX(22) pattern with negative sex-determining region Y (SRY) on gene analysis. At the most recent follow-up visit, the patient appeared to be in good health - her height was 70.4 cm [-1.5 standard deviation (SD)] and her weight was 9.8 kg (0.3 SD). She was receiving hydrocortisone in a dose of 10 mg/m2/day, fludrocortisone acetate in a dose of 0.075 mg/day, and oral salt of 1 g/day. System examinations were normal. The patient’s electrolyte levels were found to be normal and she was in good metabolic control. The findings of this patient demonstrate that routine karyotyping during investigation of patients with sexual differentiation disorders can reveal TS. Additionally, signs of virilism should always be investigated at diagnosis or during physical examinations for follow-up of TS cases. [i][/i]SRY analysis should be performed primarily when signs of virilism are observed. CAH should also be considered in patients with negative [i]SRY[/i]. Conflict of interest:None declared. PMID:23261864

  13. A pharmacogenomic approach to the treatment of children with GH deficiency or Turner syndrome

    Science.gov (United States)

    Clayton, P; Chatelain, P; Tatò, L; Yoo, H W; Ambler, G R; Belgorosky, A; Quinteiro, S; Deal, C; Stevens, A; Raelson, J; Croteau, P; Destenaves, B; Olivier, C

    2013-01-01

    Objective Individual sensitivity to recombinant human GH (r-hGH) is variable. Identification of genetic factors contributing to this variability has potential use for individualization of treatment. The objective of this study was to identify genetic markers and gene expression profiles associated with growth response on r-hGH therapy in treatment-naïve, prepubertal children with GH deficiency (GHD) or Turner syndrome (TS). Design A prospective, multicenter, international, open-label pharmacogenomic study. Methods The associations of genotypes in 103 growth- and metabolism-related genes and baseline gene expression profiles with growth response to r-hGH (cm/year) over the first year were evaluated. Genotype associations were assessed with growth response as a continuous variable and as a categorical variable divided into quartiles. Results Eleven genes in GHD and ten in TS, with two overlapping between conditions, were significantly associated with growth response either as a continuous variable (seven in GHD, two in TS) or as a categorical variable (four more in GHD, eight more in TS). For example, in GHD, GRB10 was associated with high response (≥Q3; P=0.0012), while SOS2 was associated with low response (≤Q1; P=0.006), while in TS, LHX4 was associated with high response (P=0.0003) and PTPN1 with low response (P=0.0037). Differences in expression were identified for one of the growth response-associated genes in GHD (AKT1) and for two in TS (KRAS and MYOD1). Conclusions Carriage of specific growth-related genetic markers is associated with growth response in GHD and TS. These findings indicate that pharmacogenomics could have a role in individualized management of childhood growth disorders. PMID:23761422

  14. TSP-1 Deficiency Alters Ocular Microbiota: Implications for Sjögren's Syndrome Pathogenesis.

    Science.gov (United States)

    Terzulli, Marielle; Contreras-Ruiz, Laura; Ruiz, Laura Contreras; Kugadas, Abirami; Masli, Sharmila; Gadjeva, Mihaela

    2015-09-01

    The potential role of commensals as triggering factors that promote inflammation in dry eye disease has not been explored. The objective of this study was to evaluate whether ocular microbiota changes with the onset of dry eye disease in thrombospondin-1-deficient (TSP-1(-/-)) mice, a strain that develops Sjögren's syndrome-like disease. Conjunctival swabs were collected from TSP-1(-/-) and C57BL/6 mice and analyzed for bacterial presence. Opsonophagocytosis of the bacterial conjunctival isolates derived from the aged TSP-1(-/-) mice by neutrophils derived from either TSP-1(-/-) or C57BL/6 bone marrow was evaluated. The bactericidal activities of TSP-1-derived peptide were examined. We found that in TSP-1(-/-) mice, the conjunctival colonization with Staphylococcus aureus and coagulase negative staphylococci sp (CNS) species was significantly increased with aging and preceded that of the wild-type C57BL/6 control mice. This correlated with increased neutrophil infiltration into the conjunctiva of the TSP-1(-/-) mice, suggesting that TSP-1 plays a significant role in regulating immunity to commensals. Accordingly, the TSP-1(-/-) PMNs opsonophagocytozed the ocular commensals less efficiently than the TSP-1-sufficient neutrophils. Furthermore, a TSP-1-derived peptide, 4N1K, exhibited significant antimicrobial activity when compared to a control peptide against commensal sp. These studies illustrate that alterations in the commensal frequency occur in the early stages of development of Sjögren's-like pathology and suggest that interventions that limit commensal outgrowth such as the use of TSP-1-derived peptides could be used for treatment during the early stages of the disease to reduce the commensal burden and ensuing inflammation.

  15. Risk assessment of obstructive sleep apnea syndrome in pediatric patients with vitamin D deficiency

    Science.gov (United States)

    Ozgurhan, Gamze; Vehapoglu, Aysel; Vermezoglu, Oznur; Temiz, Rabia Nur; Guney, Asuman; Hacihamdioglu, Bulent

    2016-01-01

    Abstract The aim of the following study is to evaluate the risk of obstructive sleep apnea syndrome (OSAS) in subjects with vitamin D deficiency. Prospective and comparative study. We enrolled 240 subjects into the study. The participants were divided into 2 groups based on 25-hydroxyvitamin D (25[OH]D) levels: low level of 25(OH)D (20 ng/mL) group (n = 120). Subjects were classified as being at a high or low risk of developing OSAS by using the Berlin Questionnaire. Risk of developing OSAS, gender, age, and body mass index (BMI) z-score were assessed by comparing the low level of 25(OH)D group and control group. No statistically significant difference was observed between the low level of 25(OH)D group and control group in terms of gender, age, and BMI z-score distributions; P = 0.323, P = 0.387, and P = 0.093, respectively. There were 24 subjects with high risk of developing OSAS in 2 groups (17 subjects in the low level of 25[OH]D group and 7 subjects in the control group). In the low level of 25(OH)D group, the risk of developing OSAS was found to be significantly higher than the control group (P = 0.030). BMI z-score was found significantly higher in high-risk groups than low-risk groups (P = 0.034 for low-level 25[OH]D group and P = 0.023 for control group). The findings revealed that low level of 25(OH)D increases the risk of developing OSAS. PMID:27684795

  16. Blood donors at high risk of transmitting the acquired immune deficiency syndrome.

    Science.gov (United States)

    Contreras, M; Hewitt, P E; Barbara, J A; Mochnaty, P Z

    1985-03-09

    The acquired immune deficiency syndrome (AIDS) occurs most commonly in homosexual men. This group carries the greatest risk of transmitting AIDS by blood transfusion. Both promiscuous and nonpromiscuous male homosexuals should refrain from giving blood. A leaflet stating this advice was prepared by the Department of Health and Social Security, United Kingdom. In July 1984 a questionnaire was given to all donors attending a blood donor clinic in the west end of London, England. 53% were male. Donors were given a leaflet on AIDS and a questionnaire to complete in private. Those who considered themselves to be in a high risk group were asked to designate their blood for research purposes only. Serum samples from donors who confirmed that they were in the high risk category were tested for antihepatitis B core antigen and anti-human T lymphotropic virus type III (anti-HTLV-III) in addition to the routine screening of donors for hepatitis B surface antigen and syphilis. All high risk donors were men. Homosexuality was the only high risk factor. Of 5000 questionnaires administered between July and October, 614 were not completed or had ambiguous answers. 38 donors who completed the questionnaire beonged to a high risk group. Of these, 7 were positive for antihepatitis B core antigen; none were positive for anti-HTLV-III, T pallidum hemagglatination, or hepatits B surface antigen. Although the homosexual donors had a much lower incidence of sexually transmitted disease than those attending special clinics, this should not encourage complacency. All possible measures must be taken to prevent homosexuals from donating blood.

  17. Reproduction of post-weaning multi-systemic wasting syndrome in an animal disease model as a tool for vaccine testing under controlled conditions.

    Science.gov (United States)

    McKillen, John; McNair, Irene; Lagan, Paula; McKay, Karen; McClintock, Julie; Casement, Veronica; Charreyre, Catherine; Allan, Gordon

    2016-04-01

    Snatch farrowed, colostrum deprived piglets were inoculated with different combinations of porcine circovirus 2, porcine parvovirus and Erysipelothrix rhusiopathiae candidate vaccines. 10 piglets were mock-vaccinated. Following virus challenge with a combined porcine circovirus 2/porcine parvovirus inoculum, all animals were monitored and samples taken for serology, immunohistochemistry and qPCR. At 24 dpc all non-vaccinated animals remaining were exhibiting signs of post-weaning multi-systemic wasting syndrome which was confirmed by laboratory analysis. Details of the study, analysis of samples and performance of the candidate vaccines are described. Copyright © 2016 Elsevier Ltd. All rights reserved.

  18. Prevalence of SCN1A-related dravet syndrome among children reported with seizures following vaccination: a population-based ten-year cohort study.

    Directory of Open Access Journals (Sweden)

    Nienke E Verbeek

    Full Text Available OBJECTIVES: To determine the prevalence of Dravet syndrome, an epileptic encephalopathy caused by SCN1A-mutations, often with seizure onset after vaccination, among infants reported with seizures following vaccination. To determine differences in characteristics of reported seizures after vaccination in children with and without SCN1A-related Dravet syndrome. METHODS: Data were reviewed of 1,269 children with seizures following immunization in the first two years of life, reported to the safety surveillance system of the Dutch national immunization program between 1 January 1997 and 31 December 2006. Selective, prospective follow-up was performed of children with clinical characteristics compatible with a diagnosis of Dravet syndrome. RESULTS: In 21.9% (n = 279 of children, a diagnosis of Dravet syndrome could not be excluded based on available clinical data (median age at follow-up 16 months. Additional follow-up data were obtained in 83.9% (n = 234 of these children (median age 8.5 years. 15 (1.2% of 1,269; 95%CI:0.6 to 1.8% children were diagnosed with SCN1A-related Dravet syndrome. Of all reported seizures following vaccinations in the first year of life, 2.5% (95%CI:1.3 to 3.6% were due to SCN1A-related Dravet syndrome, as were 5.9% of reported seizures (95%CI:3.1 to 8.7% after 2(nd or 3(rd DTP-IPV-Hib vaccination. Seizures in children with SCN1A-related Dravet syndrome occurred more often with a body temperature below 38.5°C (57.9% vs. 32.6%, p = 0.020 and reoccurred more often after following vaccinations (26.7% vs. 4.0%, p = 0.003, than in children without a diagnosis of SCN1A-related Dravet Syndrome. CONCLUSIONS: Although Dravet syndrome is a rare genetic epilepsy syndrome, 2.5% of reported seizures following vaccinations in the first year of life in our cohort occurred in children with this disorder. Knowledge on the specific characteristics of vaccination-related seizures in this syndrome might promote early diagnosis

  19. Antiradiation Vaccine: Immunological neutralization of Radiation Toxins at Acute Radiation Syndromes.

    Science.gov (United States)

    Popov, Dmitri; Maliev, Slava

    Introduction: Current medical management of the Acute Radiation Syndromes (ARS) does not include immune prophylaxis based on the Antiradiation Vaccine. Existing principles for the treatment of acute radiation syndromes are based on the replacement and supportive therapy. Haemotopoietic cell transplantation is recomended as an important method of treatment of a Haemopoietic form of the ARS. Though in the different hospitals and institutions, 31 pa-tients with a haemopoietic form have previously undergone transplantation with stem cells, in all cases(100%) the transplantants were rejected. Lethality rate was 87%.(N.Daniak et al. 2005). A large amount of biological substances or antigens isolated from bacterias (flagellin and derivates), plants, different types of venom (honeybees, scorpions, snakes) have been studied. This biological active substances can produce a nonspecific stimulation of immune system of mammals and protect against of mild doses of irradiation. But their radioprotection efficacy against high doses of radiation were not sufficient. Relative radioprotection characteristics or adaptive properties of antioxidants were expressed only at mild doses of radiation. However antioxidants demonstrated a very low protective efficacy at high doses of radiation. Some ex-periments demonstrated even a harmful effect of antioxidants administered to animals that had severe forms of the ARS. Only Specific Radiation Toxins roused a specific antigenic stim-ulation of antibody synthesis. An active immunization by non-toxic doses of radiation toxins includes a complex of radiation toxins that we call the Specific Radiation Determinant (SRD). Immunization must be provided not less than 24 days before irradiation and it is effective up to three years and more. Active immunization by radiation toxins significantly reduces the mortality rate (100%) and improves survival rate up to 60% compare with the 0% sur-vival rate among the irradiated animals in control groups

  20. DNA vaccine-derived human IgG produced in transchromosomal bovines protect in lethal models of hantavirus pulmonary syndrome.

    Science.gov (United States)

    Hooper, Jay W; Brocato, Rebecca L; Kwilas, Steven A; Hammerbeck, Christopher D; Josleyn, Matthew D; Royals, Michael; Ballantyne, John; Wu, Hua; Jiao, Jin-an; Matsushita, Hiroaki; Sullivan, Eddie J

    2014-11-26

    Polyclonal immunoglobulin-based medical products have been used successfully to treat diseases caused by viruses for more than a century. We demonstrate the use of DNA vaccine technology and transchromosomal bovines (TcBs) to produce fully human polyclonal immunoglobulins (IgG) with potent antiviral neutralizing activity. Specifically, two hantavirus DNA vaccines [Andes virus (ANDV) DNA vaccine and Sin Nombre virus (SNV) DNA vaccine] were used to produce a candidate immunoglobulin product for the prevention and treatment of hantavirus pulmonary syndrome (HPS). A needle-free jet injection device was used to vaccinate TcB, and high-titer neutralizing antibodies (titers >1000) against both viruses were produced within 1 month. Plasma collected at day 10 after the fourth vaccination was used to produce purified α-HPS TcB human IgG. Treatment with 20,000 neutralizing antibody units (NAU)/kg starting 5 days after challenge with ANDV protected seven of eight animals, whereas zero of eight animals treated with the same dose of normal TcB human IgG survived. Likewise, treatment with 20,000 NAU/kg starting 5 days after challenge with SNV protected immunocompromised hamsters from lethal HPS, protecting five of eight animals. Our findings that the α-HPS TcB human IgG is capable of protecting in animal models of lethal HPS when administered after exposure provides proof of concept that this approach can be used to develop candidate next-generation polyclonal immunoglobulin-based medical products without the need for human donors, despeciation protocols, or inactivated/attenuated vaccine antigen. Copyright © 2014, American Association for the Advancement of Science.

  1. Lack of homozygotes for the most frequent disease allele in carbohydrate-deficient glycoprotein syndrome type 1A.

    Science.gov (United States)

    Matthijs, G; Schollen, E; Van Schaftingen, E; Cassiman, J J; Jaeken, J

    1998-03-01

    Carbohydrate-deficient-glycoprotein syndrome type 1 (CDG1; also known as "Jaeken syndrome") is an autosomal recessive disorder characterized by defective glycosylation. Most patients show a deficiency of phosphomannomutase (PMM), the enzyme that converts mannose 6-phosphate to mannose 1-phosphate in the synthesis of GDP-mannose. The disease is linked to chromosome 16p13, and mutations have recently been identified in the PMM2 gene in CDG1 patients with a PMM deficiency (CDG1A). The availability of the genomic sequences of PMM2 allowed us to screen for mutations in 56 CDG1 patients from different geographic origins. By SSCP analysis and by sequencing, we identified 23 different missense mutations and 1 single-base-pair deletion. In total, mutations were found on 99% of the disease chromosomes in CDG1A patients. The R141H substitution is present on 43 of the 112 disease alleles. However, this mutation was never observed in the homozygous state, suggesting that homozygosity for these alterations is incompatible with life. On the other hand, patients were found homozygous for the D65Y and F119L mutations, which must therefore be mild mutations. One particular genotype, R141H/D188G, which is prevalent in Belgium and the Netherlands, is associated with a severe phenotype and a high mortality. Apart from this, there is only a limited relation between the genotype and the clinical phenotype.

  2. An Integrated Epidemiological and Economic Analysis of Vaccination against Highly Pathogenic Porcine Reproductive and Respiratory Syndrome (PRRS in Thua Thien Hue Province, Vietnam

    Directory of Open Access Journals (Sweden)

    Haifeng Zhang

    2014-10-01

    Full Text Available The purposes of this study are to assess pig farmers’ preference for highly pathogenic porcine reproductive and respiratory syndrome (PRRS vaccine, and estimate the cost and benefit of PRRS vaccination in Vietnam. This study employed an integrated epidemiological and economic analysis which combined susceptible-infectious-recovered (SIR model, choice experiment (CE and cost-benefit analysis (CBA together. The result of SIR model showed the basic reproduction number (R0 of PRRS transmission in this study is 1.3, consequently, the optimal vaccination percentage is 26%. The results of CE in this study indicate that Vietnam pig farmers are showing a high preference for the PRRS vaccine. However, their mean willingness to pay is lower than the potential cost of PRRS vaccine. It can be considered to be one of the reasons that the PRRS vaccination ratio is still low in Vietnam. The results of CBA specified from the whole society’s point of view (Social perspective, the benefits of PRRS vaccination are 2.3 to 4.5 times larger than the costs. To support policy making for increasing the PRRS vaccination proportion, this study indicates two ways to increase the vaccination proportion: i decrease vaccine price by providing a subsidy, ii provide compensation of culling only for PRRS vaccinated pigs.

  3. An Integrated Epidemiological and Economic Analysis of Vaccination against Highly Pathogenic Porcine Reproductive and Respiratory Syndrome (PRRS) in Thua Thien Hue Province, Vietnam.

    Science.gov (United States)

    Zhang, Haifeng; Kono, Hiroichi; Kubota, Satoko

    2014-10-01

    The purposes of this study are to assess pig farmers' preference for highly pathogenic porcine reproductive and respiratory syndrome (PRRS) vaccine, and estimate the cost and benefit of PRRS vaccination in Vietnam. This study employed an integrated epidemiological and economic analysis which combined susceptible-infectious-recovered (SIR) model, choice experiment (CE) and cost-benefit analysis (CBA) together. The result of SIR model showed the basic reproduction number (R0) of PRRS transmission in this study is 1.3, consequently, the optimal vaccination percentage is 26%. The results of CE in this study indicate that Vietnam pig farmers are showing a high preference for the PRRS vaccine. However, their mean willingness to pay is lower than the potential cost of PRRS vaccine. It can be considered to be one of the reasons that the PRRS vaccination ratio is still low in Vietnam. The results of CBA specified from the whole society's point of view (Social perspective), the benefits of PRRS vaccination are 2.3 to 4.5 times larger than the costs. To support policy making for increasing the PRRS vaccination proportion, this study indicates two ways to increase the vaccination proportion: i) decrease vaccine price by providing a subsidy, ii) provide compensation of culling only for PRRS vaccinated pigs.

  4. Chart-confirmed guillain-barre syndrome after 2009 H1N1 influenza vaccination among the Medicare population, 2009-2010.

    Science.gov (United States)

    Polakowski, Laura L; Sandhu, Sukhminder K; Martin, David B; Ball, Robert; Macurdy, Thomas E; Franks, Riley L; Gibbs, Jonathan M; Kropp, Garner F; Avagyan, Armen; Kelman, Jeffrey A; Worrall, Christopher M; Sun, Guoying; Kliman, Rebecca E; Burwen, Dale R

    2013-09-15

    Given the increased risk of Guillain-Barré Syndrome (GBS) found with the 1976 swine influenza vaccine, both active surveillance and end-of-season analyses on chart-confirmed cases were performed across multiple US vaccine safety monitoring systems, including the Medicare system, to evaluate the association of GBS after 2009 monovalent H1N1 influenza vaccination. Medically reviewed cases consisted of H1N1-vaccinated Medicare beneficiaries who were hospitalized for GBS. These cases were then classified by using Brighton Collaboration diagnostic criteria. Thirty-one persons had Brighton level 1, 2, or 3 GBS or Fisher Syndrome, with symptom onset 1-119 days after vaccination. Self-controlled risk interval analyses estimated GBS risk within the 6-week period immediately following H1N1 vaccination compared with a later control period, with additional adjustment for seasonality. Our results showed an elevated risk of GBS with 2009 monovalent H1N1 vaccination (incidence rate ratio = 2.41, 95% confidence interval: 1.14, 5.11; attributable risk = 2.84 per million doses administered, 95% confidence interval: 0.21, 5.48). This observed risk was slightly higher than that seen with previous seasonal influenza vaccines; however, additional results that used a stricter case definition (Brighton level 1 or 2) were not statistically significant, and our ability to account for preceding respiratory/gastrointestinal illness was limited. Furthermore, the observed risk was substantially lower than that seen with the 1976 swine influenza vaccine.

  5. Therapeutic vaccination with a trivalent T-cell receptor (TCR) peptide vaccine restores deficient FoxP3 expression and TCR recognition in subjects with multiple sclerosis.

    Science.gov (United States)

    Vandenbark, Arthur A; Culbertson, Nicole E; Bartholomew, Richard M; Huan, Jianya; Agotsch, Marci; LaTocha, Dorian; Yadav, Vijayshree; Mass, Michele; Whitham, Ruth; Lovera, Jesus; Milano, June; Theofan, Georgia; Chou, Yuan K; Offner, Halina; Bourdette, Dennis N

    2008-01-01

    Therapeutic vaccination using T-cell receptor (TCR) peptides from V genes commonly expressed by potentially pathogenic T cells remains an approach of interest for treatment of multiple sclerosis (MS) and other autoimmune diseases. We developed a trivalent TCR vaccine containing complementarity determining region (CDR) 2 peptides from BV5S2, BV6S5 and BV13S1 emulsified in incomplete Freund's adjuvant that reliably induced high frequencies of TCR-specific T cells. To evaluate induction of regulatory T-cell subtypes, immunological and clinical parameters were followed in 23 treatment-naïve subjects with relapsing-remitting or progressive MS who received 12 monthly injections of the trivalent peptide vaccine over 1 year in an open-label study design. Prior to vaccination, subjects had reduced expression of forkhead box (Fox) P3 message and protein, and reduced recognition of the expressed TCR repertoire by TCR-reactive cells compared with healthy control donors. After three or four injections, most vaccinated MS subjects developed high frequencies of circulating interleukin (IL)-10-secreting T cells specific for the injected TCR peptides and significantly enhanced expression of FoxP3 by regulatory T cells present in both 'native' CD4+ CD25+ and 'inducible' CD4+ CD25- peripheral blood mononuclear cells (PBMC). At the end of the trial, PBMC from vaccinated MS subjects retained or further increased FoxP3 expression levels, exhibited significantly enhanced recognition of the TCR V gene repertoire apparently generated by perturbation of the TCR network, and significantly suppressed neuroantigen but not recall antigen responses. These findings demonstrate that therapeutic vaccination using only three commonly expressed BV gene determinants can induce an expanded immunoregulatory network in vivo that may optimally control complex autoreactive responses that characterize the inflammatory phase of MS.

  6. Loss-of-function mutations of SURF-1 are specifically associated with Leigh syndrome with cytochrome c oxidase deficiency.

    Science.gov (United States)

    Tiranti, V; Jaksch, M; Hofmann, S; Galimberti, C; Hoertnagel, K; Lulli, L; Freisinger, P; Bindoff, L; Gerbitz, K D; Comi, G P; Uziel, G; Zeviani, M; Meitinger, T

    1999-08-01

    Mutations of SURF-1, a gene located on chromosome 9q34, have recently been identified in patients affected by Leigh syndrome (LS), associated with deficiency of cytochrome c oxidase (COX), the terminal component of the mitochondrial respiratory chain. To investigate to what extent SURF-1 is responsible for human disorders because of COX deficiency, we undertook sequence analysis of the SURF-1 gene in 46 unrelated patients. We analyzed 24 COX-defective patients classified as having typical Leigh syndrome (LS(COX)), 6 patients classified as Leigh-like (LL(COX)) cases, and 16 patients classified as non-LS(COX) cases. Frameshift, stop, and splice mutations of SURF-1 were detected in 18 of 24 (75%) of the LS(COX) cases. No mutations were found in the LL(COX) and non-LS(COX) group of patients. Rescue of the COX phenotype was observed in transfected cells from patients harboring SURF-1 mutations, but not in transfected cell lines from 2 patients in whom no mutations were detected by sequence analysis. Loss of function of SURF-1 protein is specifically associated with LS(COX), although a proportion of LS(COX) cases must be the result of abnormalities in genes other than SURF-1. SURF-1 is the first nuclear gene to be consistently mutated in a major category of respiratory chain defects. DNA analysis can now be used to accurately diagnose LS(COX), a common subtype of Leigh syndrome.

  7. The Relationship between Iron Deficiency and Restless Legs Syndrome in Hemodialysis Patients

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    R Ghanei Gheshlagh

    2012-10-01

    Full Text Available Introduction: Restless legs syndrome is a neurological disorder; hemodialysis patients seem to suffer more from this syndrome. Although the pathophysiology of restless legs syndrome is still unknown, assessment of factors associated with this syndrome can help to develop medical knowledge in this field. The present study assessed the relationship between restless legs syndrome, serum iron, and serum ferritin levels in patients on hemodialysis. Methods: This descriptive study was carried out with purposive sampling method on 168 hemodialysis patients who referred to the Urmia Taleghani Hospital Hemodialysis Unit. Data were gathered using restless legs syndrome questionnaire and laboratory Index of serum iron and ferritin. Data were analyzed using descriptive and inferential statistical tests. Results: The study results revealed that 38.7 percent of samples complained from restless legs syndrome whose average score serum iron was 78±29.3 μg. Results showed in hemodialysis patients with restless legs syndrome, serum iron and serum ferritin levels were significantly lower than hemodialysis patients without restless legs syndrome (p=0. 02, p=0.005. Conclusion: Considering the high prevalence of restless legs syndrome in patients with hemodialysis, identification of factors associated with this syndrome and providing the necessary solutions for modifying or eliminating the factors, seem to be necessary. Since the relationship between indicators of iron and ferritin and restless legs syndrome in hemodialysis patients is confirmed, the results can be helpful in the treatment and management of these patients.

  8. [FEATURES OF CLINICAL COURSE AND MORPHOMETRIC PARAMETERS OF BENIGN PROSTATIC HYPERPLASIA IN MEN WITH METABOLIC SYNDROME AND ANDROGEN DEFICIENCY].

    Science.gov (United States)

    Tyuzikov, I A; Grekov, E A; Kalinchenko, S Yu

    2015-01-01

    The study was aimed to the evaluation of the effect of the components of the metabolic syndrome (obesity, insulin resistance (IR)) and androgen deficiency on the clinical course of lower urinary tract symptoms against the background of benign prostatic hyperplasia (LUTS/BPH) and nocturia, as well as on some of the parameters of BPH (prostate volume, residual urine volume, total prostate-specific antigen (PSA) blood level). The comprehensive survey of 160 men with LUTS/BPH (mean age 56.7 ± 3.3 years) was performed; based on the results of survey, three comparison groups were formed: Group 1 (n = 70)--patients with isolated obesity; Group 2 (n = 36)--patients with obesity and insulin resistance; and Group 3 (n = 54)--patients with obesity, insulin resistance and androgen deficiency. The control group consisted of 30 patients with LUTS/BPH without these metabolic and hormonal disorders. In patients with LUTS/BPH and obesity, higher frequency of nocturia compared with the control group was revealed (63.7% vs 23.3%; P resistance and androgen deficiency had the highest average prostate volume and residual urine volume compared with those of other groups (P resistance, androgen deficiency are associated pathological conditions, greatly aggravating the clinical course of LUTS/BPH due to adverse impact on the BPH parameters, acting both together and separately. The most severe LUTS/BPH were associated with the presence of all three of the above systemic disorders.

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

    Institute of Scientific and Technical Information of China (English)

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

    2002-01-01

    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.

  10. Development and biological function of the female gonads and genitalia in IGF-I deficiency -- Laron syndrome as a model.

    Science.gov (United States)

    Laron, Zvi

    2006-01-01

    Laron syndrome (LS) or primary GH insensitivity is a unique human model to study the effects of congenital IGF-I deficiency. Within our cohort of 63 patients with LS, 15 female patients were regularly followed since birth or infancy, throughout puberty. We observed that they were short at birth, with small genitalia and gonads -- during puberty, developed delayed puberty but eventually reached between 16 and 19 1/2 years full sexual development. Reproduction is unaffected at a young adult age. It is concluded that IGF-I in concert with the sex hormones has a modulatory but not essential function on female sexual development and maturation.

  11. Acquired immune deficiency syndrome (AIDS) in the United States in 1986: etiology, epidemiology, clinical manifestations, and dental implications.

    Science.gov (United States)

    Anneroth, G; Anneroth, I; Lynch, D P

    1986-12-01

    The acquired immune deficiency syndrome (AIDS) results from a lymphotropic retrovirus (HTLV-III) infection and is characterized by specific opportunistic infections and malignancies. The virus is transmitted primarily by semen and blood. Infection is limited principally to defined risk groups, i.e., homosexual men and intravenous drug users. Head and neck manifestations include cervical lymphadenopathy and Kaposi's sarcoma. Oral manifestations include Kaposi's sarcoma, candidiasis, hairy leukoplakia, precocious periodontal disease, xerostomia, herpes simplex, recurrent aphthae, erythema multiforme, and venereal warts. Although HTLV-III is present in saliva, there are no reported cases of transmission secondary to dental procedures. Appropriate precautions and techniques are recommended in treating patients at risk for AIDS.

  12. Blue rubber bleb naevus syndrome: a rare cause of chronic occult blood loss and iron deficiency anaemia.

    Science.gov (United States)

    Lybecker, Martin Bell; Stawowy, Marek; Clausen, Niels

    2016-12-20

    Blue rubber bleb naevus syndrome (BRBNS) is a rare vascular disorder with malformed veins, or blebs, appearing in the skin or internal organs. Gastrointestinal tract involvement is the most common feature and often subject to bleeding, potentially resulting in chronic occult blood loss and iron deficiency anaemia. We present the case of a 10-year-old boy with venous malformations on the feet and severe anaemia. Although massive sudden haemorrhage rarely occurs, awareness of the illness is necessary to prevent complications. 2016 BMJ Publishing Group Ltd.

  13. "Prepandemic" immunization for novel influenza viruses, "swine flu" vaccine, Guillain-Barré syndrome, and the detection of rare severe adverse events.

    Science.gov (United States)

    Evans, David; Cauchemez, Simon; Hayden, Frederick G

    2009-08-01

    The availability of immunogenic, licensed H5N1 vaccines and the anticipated development of vaccines against "swine" influenza A(H1N1) have stimulated debate about the possible use of these vaccines for protection of those exposed to potential pandemic influenza viruses and for immunization or "priming" of populations in the so-called "prepandemic" (interpandemic) era. However, the safety of such vaccines is a critical issue in policy development for wide-scale application of vaccines in the interpandemic period. For example, wide-scale interpandemic use of H5N1 vaccines could lead to millions of persons receiving vaccines of uncertain efficacy potentially associated with rare severe adverse events and against a virus that may not cause a pandemic. Here, we first review aspects of the 1976 National Influenza Immunization Programme against "swine flu" and its well-documented association with Guillain-Barré syndrome as a case study illustration of a suspected vaccine-associated severe adverse event in a mass interpandemic immunization setting. This case study is especially timely, given the recent spread of a novel influenza A(H1N1) virus in humans in Mexico and beyond. Following this, we examine available safety data from clinical trials of H5N1 vaccines and briefly discuss how vaccine safety could be monitored in a postmarketing surveillance setting.

  14. 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

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    Yang Gong

    2015-01-01

    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.

  15. Development of a vaccine vector based on a subgenomic replicon of porcine reproductive and respiratory syndrome virus.

    Science.gov (United States)

    Huang, Qinfeng; Yao, Qingxia; Fan, Huiying; Xiao, Shaobo; Si, Youhui; Chen, Huanchun

    2009-09-01

    In this study, a DNA-launched subgenomic replicon of porcine reproductive and respiratory syndrome virus (PRRSV) was developed for use as a vaccine vector. This replicon plasmid contained a PRRSV subgenome without structural genes ORF2-ORF6, and was under the transcriptional control of the immediate-early promoter of cytomegalovirus (CMV). Using enhanced green fluorescent protein (EGFP) as a reporter gene, the DNA-launched subgenomic replicon of PRRSV, named pOK-Clone20-rep, could express heterologous genes in vitro. After direct inoculation of pOK-Clone20-rep, mice developed antibody responses that were specific for both the EGFP and the N gene in a dose-dependent manner. Furthermore, mice immunized with pOK-Clone20-rep at a dose of 100microg showed significantly enhanced levels of IFN-gamma compared with those inoculated with 100microg of pcD-EGFP, a conventional DNA vaccine that encodes EGFP. In summary, the results show that the DNA-launched subgenomic replicon of PRRSV could not only mediate foreign gene expression in vitro but also induced an immune response in vivo. Similarly, expression and immunogenicity of the N gene also strengthened the potential of the replicon to serve as a vaccine vector expressing multiple genes. It therefore provides a useful tool for vaccine development and the study of the transcription and replication of PRRSV.

  16. Protein profiling in the gut of Penaeus monodon gavaged with oral WSSV-vaccines and live white spot syndrome virus.

    Science.gov (United States)

    Kulkarni, Amod D; Kiron, Viswanath; Rombout, Jan H W M; Brinchmann, Monica F; Fernandes, Jorge M O; Sudheer, Naduvilamuriparampu S; Singh, Bright I S

    2014-07-01

    White spot syndrome virus (WSSV) is a pathogen that causes considerable mortality of the farmed shrimp, Penaeus monodon. Candidate 'vaccines', WSSV envelope protein VP28 and formalin-inactivated WSSV, can provide short-lived protection against the virus. In this study, P. monodon was orally intubated with the aforementioned vaccine candidates, and protein expression in the gut of immunised shrimps was profiled. The alterations in protein profiles in shrimps infected orally with live-WSSV were also examined. Seventeen of the identified proteins in the vaccine and WSSV-intubated shrimps varied significantly compared to those in the control shrimps. These proteins, classified under exoskeletal, cytoskeletal, immune-related, intracellular organelle part, intracellular calcium-binding or energy metabolism, are thought to directly or indirectly affect shrimp's immunity. The changes in the expression levels of crustacyanin, serine proteases, myosin light chain, and ER protein 57 observed in orally vaccinated shrimp may probably be linked to immunoprotective responses. On the other hand, altered expression of proteins linked to exoskeleton, calcium regulation and energy metabolism in WSSV-intubated shrimps is likely to symbolise disturbances in calcium homeostasis and energy metabolism.

  17. Impaired signaling via the high-affinity IgE receptor in Wiskott-Aldrich syndrome protein-deficient mast cells.

    Science.gov (United States)

    Pivniouk, Vadim I; Snapper, Scott B; Kettner, Alexander; Alenius, Harri; Laouini, Dhafer; Falet, Hervé; Hartwig, John; Alt, Frederick W; Geha, Raif S

    2003-12-01

    Wiskott-Aldrich syndrome protein (WASP) is the product of the gene deficient in boys with X-linked Wiskott-Aldrich syndrome. We assessed the role of WASP in signaling through the high-affinity IgE receptor (FcepsilonRI) using WASP-deficient mice. IgE-dependent degranulation and cytokine secretion were markedly diminished in bone marrow-derived mast cells from WASP-deficient mice. Upstream signaling events that include FcepsilonRI-triggered total protein tyrosine phosphorylation, and protein tyrosine phosphorylation of FcepsilonRIbeta and Syk were not affected by WASP deficiency. However, tyrosine phosphorylation of phospholipase Cgamma and Ca(2+) mobilization were diminished. IgE-dependent activation of c-Jun N-terminal kinase, cell spreading and redistribution of cellular F-actin in mast cells were reduced in the absence of WASP. We conclude that WASP regulates FcepsilonRI-mediated granule exocytosis, cytokine production and cytoskeletal changes in mast cells.

  18. Deficient expression of aldehyde dehydrogenase 1A1 is consistent with increased sensitivity of Gorlin syndrome patients to radiation carcinogenesis.

    Science.gov (United States)

    Wright, Aaron T; Magnaldo, Thierry; Sontag, Ryan L; Anderson, Lindsey N; Sadler, Natalie C; Piehowski, Paul D; Gache, Yannick; Weber, Thomas J

    2015-06-01

    Human phenotypes that are highly susceptible to radiation carcinogenesis have been identified. Sensitive phenotypes often display robust regulation of molecular features that modify biological response, which can facilitate identification of the pathways/networks that contribute to pathophysiological outcomes. Here we interrogate primary dermal fibroblasts isolated from Gorlin syndrome patients (GDFs), who display a pronounced inducible tumorigenic response to radiation, in comparison to normal human dermal fibroblasts (NHDFs). Our approach exploits newly developed thiol reactive probes to define changes in protein thiol profiles in live cell studies, which minimizes artifacts associated with cell lysis. Redox probes revealed deficient expression of an apparent 55 kDa protein thiol in GDFs from independent Gorlin syndrome patients, compared with NHDFs. Proteomics tentatively identified this protein as aldehyde dehydrogenase 1A1 (ALDH1A1), a key enzyme regulating retinoic acid synthesis, and ALDH1A1 protein deficiency in GDFs was confirmed by Western blot. A number of additional protein thiol differences in GDFs were identified, including radiation responsive annexin family members and lamin A/C. Collectively, candidates identified in our study have plausible implications for radiation health effects and cancer susceptibility.

  19. Pathological and behavioral manifestations of the “Cayuga syndrome,” a thiamine deficiency in larval landlocked Atlantic salmon

    Science.gov (United States)

    Fisher, Jeffrey P.; Spitsbergen, Jan M.; Iamonte, Tina; Little, Edward E.; DeLonay, Aaron

    1995-01-01

    The “Cayuga syndrome” is a maternally transmitted, naturally occurring thiamine deficiency that causes 100% mortality of larval landlocked Atlantic salmon Salmo salar in several of New York's Finger Lakes, Results of multiyear studies to qualify and quantify the neurobehavioral and gross pathological signs of this condition are described, Affected sac fry became weak and ataxic and responded atypically to stimuli 1–2 weeks before death. Quantitative assays of stimulus-provoked swimming revealed a significant neuropathy whereby the sac fry exhibited abnormal thigmotactic and phototactic behaviors. Gross lesions observed in Cayuga sac fry included yolk-sac opacities, subcutaneous edema, vitelline hemorrhage or congestion, pericardial edema, retrobulbar edema, branchial congestion, foreshortened maxillae, hydrocephalus, and occasional caudal fin deformities, Lesion frequency in progeny differed significantly between dam source. Yolk conversion efficiency was decreased at least 1 week before death, suggesting that the bioenergetics of the fish was compromised and thereby supporting the thiamine residue and treatment data reported elsewhere, Comparisons with coagulated-yolk, blue-sac and swim-up syndromes are presented, The pathological signs of the Cayuga syndrome represent a unique departure from the lesions induced by toxicants or pathogens in other piscine models, and for the first time profile the profound effects of thiamine deficiency on cardiovascular and neurological systems of larval fish.

  20. A severe H7N9 pneumonia with syndrome of inappropriate antidiuresis and vitamin D deficiency

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    Leng Lin

    2014-01-01

    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. Relationship between metabolic syndrome and multinodular non-toxic goiter in an inpatient population from a geographic area with moderate iodine deficiency.

    Science.gov (United States)

    Rendina, D; De Filippo, G; Mossetti, G; Zampa, G; Muscariello, R; Benvenuto, G; Vivona, C L; Ippolito, S; Galante, F; Lombardi, G; Biondi, B; Strazzullo, P

    2012-04-01

    Obesity and insulin resistance predispose individuals to the development of both metabolic syndrome and non-toxic nodular thyroid diseases. The aim of this observational, cross-sectional study is to evaluate the relationship between metabolic syndrome and multinodular nontoxic goiter in an inpatient population from a geographic area with moderate iodine deficiency. We examined 1422 Caucasian euthyroid inpatients. Thyroid volume was determined by ultrasound of the neck. A fine-needle aspiration biopsy was performed to evaluate single thyroid nodules and dominant nodules ≥15 mm in euthyroid multinodular goiter. The diagnosis of metabolic syndrome was made according to the criteria of the American Heart Association/ National Heart, Lung, and Blood Institute. Of the sample, 277 patients had clinical evidence of multinodular nontoxic goiter, 461 met the criteria for the diagnosis of metabolic syndrome, and 132 were found to have both conditions. After adjusting for age, gender, body mass index, nicotinism, parity, alcohol intake, thyroid function, and metabolic syndrome- related pharmacological treatment, metabolic syndrome was found to be an independent risk factor for the occurrence of multinodular non-toxic goiter. The relationship between metabolic syndrome and multi nodular non-toxic goiter was apparent in both men and women. In this study of euthyroid inpatients, we demonstrate that metabolic syndrome is an independent risk factor for the occurrence of multinodular non-toxic goiter in a geographic area with moderate iodine deficiency. We propose that patients meeting the criteria for metabolic syndrome should be screened for the presence of multinodular non-toxic goiter.

  2. Postural Orthostatic Tachycardia With Chronic Fatigue After HPV Vaccination as Part of the "Autoimmune/Auto-inflammatory Syndrome Induced by Adjuvants": Case Report and Literature Review.

    Science.gov (United States)

    Tomljenovic, Lucija; Colafrancesco, Serena; Perricone, Carlo; Shoenfeld, Yehuda

    2014-01-01

    We report the case of a 14-year-old girl who developed postural orthostatic tachycardia syndrome (POTS) with chronic fatigue 2 months following Gardasil vaccination. The patient suffered from persistent headaches, dizziness, recurrent syncope, poor motor coordination, weakness, fatigue, myalgias, numbness, tachycardia, dyspnea, visual disturbances, phonophobia, cognitive impairment, insomnia, gastrointestinal disturbances, and a weight loss of 20 pounds. The psychiatric evaluation ruled out the possibility that her symptoms were psychogenic or related to anxiety disorders. Furthermore, the patient tested positive for ANA (1:1280), lupus anticoagulant, and antiphospholipid. On clinical examination she presented livedo reticularis and was diagnosed with Raynaud's syndrome. This case fulfills the criteria for the autoimmune/auto-inflammatory syndrome induced by adjuvants (ASIA). Because human papillomavirus vaccination is universally recommended to teenagers and because POTS frequently results in long-term disabilities (as was the case in our patient), a thorough follow-up of patients who present with relevant complaints after vaccination is strongly recommended.

  3. [Studies on the possible association between severe neurological syndromes and compulsory vaccination in Milano].

    Science.gov (United States)

    Fara, G M; Signorelli, C

    1987-01-01

    From June 1978 throughout February 1979, 66 children with a mean age of 13 months were admitted to a pediatric intensive care unit in Naples (Santobono Hospital) after a rapid onset of coma or deep stupor of unknown ethiology. The "mystery disease" ("il male oscuro") as somebody in Naples has defined this syndrome, was suspected to be associated with tetanus and diphtheria immunization. Epidemiological investigations and an international symposium of experts agreed not to consider the cases due to immunization. Some of these deaths were related with with Respiratory Syncitial Virus (RSV), evidence which is favored by the poor sanitary situation, evident in many sections of Naples. Although an ad hoc Committee appointed by the Italian Ministry of Health excluded any correlation with immunization, the Ministry of Health invited some Italian groups to carry epidemiological retrospective studies in some Regions of the Country. To obtain comparable results a special protocol was prepared. Two retrospective case-control studies, performed in Genoa and Florence, did not show any association between immunization with anti-diphtheria-tetanus and even anti-poliomyelitis vaccine and severe neurological illness. A retrospective study, performed by us at the Institute of Hygiene of the University of Milan for the years 1983, 1984 and 1985, has included not only the 208 admittances to the only pediatric intensive care unit of Milan (S. Carlo Hospital) but also the other intensive care units of Milan where, sometimes, children are accepted, especially if they were previously admitted to the pediatric wards of the same hospitals.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. Deficiency in origin licensing proteins impairs cilia formation: implications for the aetiology of Meier-Gorlin syndrome.

    Directory of Open Access Journals (Sweden)

    Tom Stiff

    Full Text Available Mutations in ORC1, ORC4, ORC6, CDT1, and CDC6, which encode proteins required for DNA replication origin licensing, cause Meier-Gorlin syndrome (MGS, a disorder conferring microcephaly, primordial dwarfism, underdeveloped ears, and skeletal abnormalities. Mutations in ATR, which also functions during replication, can cause Seckel syndrome, a clinically related disorder. These findings suggest that impaired DNA replication could underlie the developmental defects characteristic of these disorders. Here, we show that although origin licensing capacity is impaired in all patient cells with mutations in origin licensing component proteins, this does not correlate with the rate of progression through S phase. Thus, the replicative capacity in MGS patient cells does not correlate with clinical manifestation. However, ORC1-deficient cells from MGS patients and siRNA-mediated depletion of origin licensing proteins also have impaired centrosome and centriole copy number. As a novel and unexpected finding, we show that they also display a striking defect in the rate of formation of primary cilia. We demonstrate that this impacts sonic hedgehog signalling in ORC1-deficient primary fibroblasts. Additionally, reduced growth factor-dependent signaling via primary cilia affects the kinetics of cell cycle progression following cell cycle exit and re-entry, highlighting an unexpected mechanism whereby origin licensing components can influence cell cycle progression. Finally, using a cell-based model, we show that defects in cilia function impair chondroinduction. Our findings raise the possibility that a reduced efficiency in forming cilia could contribute to the clinical features of MGS, particularly the bone development abnormalities, and could provide a new dimension for considering developmental impacts of licensing deficiency.

  5. Evans syndrome and antibody deficiency: an atypical presentation of chromosome 22q11.2 deletion syndrome

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    Gloria Colarusso

    2010-06-01

    Full Text Available We report a case of an 8-year-old male patient with Evans syndrome and severe hypogammaglobulinemia, subsequently in whom the 22q11.2 deletion syndrome (22q11.2 DS was diagnosed. No other clinical sign of 22q11.2 DS was present with the exception of slight facial dysmorphism. The case is of particular interest because it suggests the need to research chromosome 22q11.2 deletion in patients who present with autoimmune cytopenia and peculiar facial abnormalities, which could be an atypical presentation of an incomplete form of 22q11.2 DS.

  6. Evans syndrome and antibody deficiency: an atypical presentation of chromosome 22q11.2 deletion syndrome.

    Science.gov (United States)

    Colarusso, Gloria; Gambineri, Eleonora; Lapi, Elisabetta; Casini, Tommaso; Tucci, Fabio; Lippi, Francesca; Azzari, Chiara

    2010-09-06

    We report a case of an 8-year-old male patient with Evans syndrome and severe hypogammaglobulinemia, subsequently in whom the 22q11.2 deletion syndrome (22q11.2 DS) was diagnosed. No other clinical sign of 22q11.2 DS was present with the exception of slight facial dysmorphism. The case is of particular interest because it suggests the need to research chromosome 22q11.2 deletion in patients who present with autoimmune cytopenia and peculiar facial abnormalities, which could be an atypical presentation of an incomplete form of 22q11.2 DS.

  7. [Nicolau syndrome induced by intramuscular injection of a hexavalent vaccine in a 6-month-old girl].

    Science.gov (United States)

    Stefano, Paola C; Garello, Mónica; Nolte, María F; Lamy, Patricia; Giglio, Norberto; Castellano, Vanesa; Gentile, Ángela

    2017-02-01

    Nicolau syndrome, also known as embolia cutis medicamentosa or livedo-like dermatitis, is a sudden tissue necrosis, a rare complication of intramuscular injection of some drugs. We report a case of a 6-month-old girl who received intramuscularly the third dose of hexavalent vaccine (DTaP- HVB-IPV/HIb), and immediately presented a livedoid lesion around the injection site, progressing to necrosis. We reinforce the importance of early diagnosis to perform a suitable treatment and clinical follow-up to avoid ischemic secondary complications.

  8. The hyperimmunoglobulin E syndrome - clinical manifestation diversity in primary immune deficiency

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    Szczawinska-Poplonyk Aleksandra

    2011-11-01

    Full Text Available Abstract The hyper-IgE syndromes are rare, complex primary immunodeficiencies characterized by clinical manifestation diversity, by particular susceptibility to staphylococcal and mycotic infections as well as by a heterogeneous genetic origin. Two distinct entities - the classical hyper-IgE syndrome which is inherited in an autosomal dominant pattern and the autosomal recessive hyper-IgE syndrome have been recognized. The autosomal dominant hyper-IgE syndrome is associated with a cluster of facial, dental, skeletal, and connective tissue abnormalities which are not observable in the recessive type. In the majority of affected patients with autosomal dominant hyper-IgE syndrome a mutation in the signal transducer and the activator of the transcription 3 gene has been identified, leading to an impaired Th17 cells differentiation and to a downregulation of an antimicrobial response. A mutation in the dedicator of the cytokinesis 8 gene has been identified as the cause of many cases with autosomal recessive hyper-IgE syndrome and, in one patient, a mutation in tyrosine kinase 2 gene has been demonstrated. In this paper, the authors provide a review of the clinical manifestations in the hyper-IgE syndromes with particular emphasis on the diversity of their phenotypic expression and present current diagnostic guidelines for these diseases.

  9. Effect of Qiju Dihuang pill on serum levels of IFN-γ and IL-4 in pregnant women of Gan-Shen Yin deficiency syndrome

    Institute of Scientific and Technical Information of China (English)

    李艳芳

    2014-01-01

    Objective To observe the effect of Qiju Dihuang Pill(QDP)on changes of Chinese medical syndrome types in pregnant women of Gan-Shen yin deficiency syndrome(GSYDS),and to explore the correlation between imbalanced cytokine levels and GSYDS.Methods This was a random controlled trail.A total of 163 pregnant women of GSYDS at 12-16 gestational weeks were randomly allo-

  10. DNA vaccine-generated duck polyclonal antibodies as a postexposure prophylactic to prevent hantavirus pulmonary syndrome (HPS.

    Directory of Open Access Journals (Sweden)

    Rebecca Brocato

    Full Text Available Andes virus (ANDV is the predominant cause of hantavirus pulmonary syndrome (HPS in South America and the only hantavirus known to be transmitted person-to-person. There are no vaccines, prophylactics, or therapeutics to prevent or treat this highly pathogenic disease (case-fatality 35-40%. Infection of Syrian hamsters with ANDV results in a disease that closely mimics human HPS in incubation time, symptoms of respiratory distress, and disease pathology. Here, we evaluated the feasibility of two postexposure prophylaxis strategies in the ANDV/hamster lethal disease model. First, we evaluated a natural product, human polyclonal antibody, obtained as fresh frozen plasma (FFP from a HPS survivor. Second, we used DNA vaccine technology to manufacture a polyclonal immunoglobulin-based product that could be purified from the eggs of vaccinated ducks (Anas platyrhynchos. The natural "despeciation" of the duck IgY (i.e., Fc removed results in an immunoglobulin predicted to be minimally reactogenic in humans. Administration of ≥ 5,000 neutralizing antibody units (NAU/kg of FFP-protected hamsters from lethal disease when given up to 8 days after intranasal ANDV challenge. IgY/IgYΔFc antibodies purified from the eggs of DNA-vaccinated ducks effectively neutralized ANDV in vitro as measured by plaque reduction neutralization tests (PRNT. Administration of 12,000 NAU/kg of duck egg-derived IgY/IgYΔFc protected hamsters when administered up to 8 days after intranasal challenge and 5 days after intramuscular challenge. These experiments demonstrate that convalescent FFP shows promise as a postexposure HPS prophylactic. Moreover, these data demonstrate the feasibility of using DNA vaccine technology coupled with the duck/egg system to manufacture a product that could supplement or replace FFP. The DNA vaccine-duck/egg system can be scaled as needed and obviates the necessity of using limited blood products obtained from a small number of HPS survivors. This

  11. DNA Vaccine-Generated Duck Polyclonal Antibodies as a Postexposure Prophylactic to Prevent Hantavirus Pulmonary Syndrome (HPS)

    Science.gov (United States)

    Brocato, Rebecca; Josleyn, Matthew; Ballantyne, John; Vial, Pablo; Hooper, Jay W.

    2012-01-01

    Andes virus (ANDV) is the predominant cause of hantavirus pulmonary syndrome (HPS) in South America and the only hantavirus known to be transmitted person-to-person. There are no vaccines, prophylactics, or therapeutics to prevent or treat this highly pathogenic disease (case-fatality 35–40%). Infection of Syrian hamsters with ANDV results in a disease that closely mimics human HPS in incubation time, symptoms of respiratory distress, and disease pathology. Here, we evaluated the feasibility of two postexposure prophylaxis strategies in the ANDV/hamster lethal disease model. First, we evaluated a natural product, human polyclonal antibody, obtained as fresh frozen plasma (FFP) from a HPS survivor. Second, we used DNA vaccine technology to manufacture a polyclonal immunoglobulin-based product that could be purified from the eggs of vaccinated ducks (Anas platyrhynchos). The natural “despeciation" of the duck IgY (i.e., Fc removed) results in an immunoglobulin predicted to be minimally reactogenic in humans. Administration of ≥5,000 neutralizing antibody units (NAU)/kg of FFP-protected hamsters from lethal disease when given up to 8 days after intranasal ANDV challenge. IgY/IgYΔFc antibodies purified from the eggs of DNA-vaccinated ducks effectively neutralized ANDV in vitro as measured by plaque reduction neutralization tests (PRNT). Administration of 12,000 NAU/kg of duck egg-derived IgY/IgYΔFc protected hamsters when administered up to 8 days after intranasal challenge and 5 days after intramuscular challenge. These experiments demonstrate that convalescent FFP shows promise as a postexposure HPS prophylactic. Moreover, these data demonstrate the feasibility of using DNA vaccine technology coupled with the duck/egg system to manufacture a product that could supplement or replace FFP. The DNA vaccine-duck/egg system can be scaled as needed and obviates the necessity of using limited blood products obtained from a small number of HPS survivors. This is the

  12. Functional deficiency of fibroblasts heterozygous for Bloom syndrome as specific manifestation of the primary defect.

    OpenAIRE

    Bartram, C.R.; Rüdiger, H W; Schmidt-Preuss, U; Passarge, E

    1981-01-01

    The effect on the rate of sister chromatid exchanges (SCEs) in Bloom syndrome fibroblasts by cocultivation with Fanconi anemia and xeroderma pigmentosum fibroblasts and with Bloom syndrome heterozygotes was studied. Cells of Fanconi anemia and xeroderma origin reduced the rate of SCEs in Bloom cells by about 45%-50%, just as control cells do. In contrast, heterozygous Bloom cells reduced the rate of SCEs by only 16%-28%. In absolute figures, Fanconi cells reduced the mean rate of SCE in Bloom...

  13. Pulmonary Thromboembolism in Klinefelter%u2019s Syndrome Patient with Deficient of Protein C

    OpenAIRE

    Mehmet Yigit

    2013-01-01

    Klinefelter syndrome (KS) is a common genetic disorder caused by one or more supernumerary X chromosomes. KS poses an increased risk for venous thromboembolic events such as deep venous thrombosis and pulmonary embolism. Klinefelter syndrome is prone to hypercoagulability due to hormonal imbalance and one or more inherited thrombophilic factors. Therefore, patients with KS having a medical history of venous thromboembolism require chest computed tomographic (CT) images and oral anticoagulatio...

  14. A 2020 vision for vaccines against HIV, tuberculosis and malaria.

    Science.gov (United States)

    Rappuoli, Rino; Aderem, Alan

    2011-05-26

    Acquired immune deficiency syndrome (AIDS), malaria and tuberculosis collectively cause more than five million deaths per year, but have nonetheless eluded conventional vaccine development; for this reason they represent one of the major global public health challenges as we enter the second decade of the twenty-first century. Recent trials have provided evidence that it is possible to develop vaccines that can prevent infection by human immunodeficiency virus (HIV) and malaria. Furthermore, advances in vaccinology, including novel adjuvants, prime-boost regimes and strategies for intracellular antigen presentation, have led to progress in developing a vaccine against tuberculosis. Here we discuss these advances and suggest that new tools such as systems biology and structure-based antigen design will lead to a deeper understanding of mechanisms of protection which, in turn, will lead to rational vaccine development. We also argue that new and innovative approaches to clinical trials will accelerate the availability of these vaccines.

  15. Vaccine Associated Myocarditis

    Directory of Open Access Journals (Sweden)

    Johnson Francis

    2017-04-01

    Full Text Available Most of the cases of vaccine associated myocarditis have been following small pox vaccination. Reports have also been there after streptococcal pneumonia vaccine and influenza vaccine. In some cases, autoimmune/inflammatory syndrome induced by adjuvants (ASIA used in the vaccine have been implicated. Exclusion of other causes is very important in the diagnostic process, especially that of acute coronary syndrome. Management is similar to that of other etiologies of myocarditis. These rare instances of myocarditis should not preclude one from taking necessary immunization for vaccine preventable diseases.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2012-01-01

    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. Vaccination and Infection as Causative Factors in Japanese Patients With Rasmussen Syndrome: Molecular Mimicry and HLA Class I

    Directory of Open Access Journals (Sweden)

    Yukitoshi Takahashi

    2006-01-01

    Full Text Available Rasmussen syndrome is an intractable epilepsy with a putative causal relation with cellular and humoral autoimmunity. Almost half of the patients have some preceding causative factors, with infections found in 38.2%, vaccinations in 5.9% and head trauma in 8.9% of Japanese patients. In a patient with seizure onset after influenza A infections, cross-reaction of the patient's lymphocytes with GluRε2 and influenza vaccine components was demonstrated by lymphocyte stimulation test. Database analyses revealed that influenza A virus hemagglutinin and GluRε2 molecules contain peptides with the patient's HLA class I binding motif (HLA ࢤ A*0201. The relative risks of HLA class I genotypes for Rasmussen syndrome are 6.1 (A*2402, 6.4 (A*0201, 6.3 (A*2601 and 11.4 (B*4601. The relative risks of HLA class I-A and B haplotypes are infinity (A*2601+B*5401, 21.1 (A*2402+B*1501, 13.3 (A*2402+B*4801 and 5.1 (A*2402+B*5201. Some alleles and haplotypes of HLA class I may be the risk factors in Japanese patients. Cross-reactivity of cytotoxic T lymphocytes may contribute to the processes leading from infection to the involvement of CNS.

  19. The IGSF1 deficiency syndrome: Characteristics of male and female patients

    NARCIS (Netherlands)

    S.D. Joustra (Sjoerd); N. Schoenmakers (Nadia); L. Persani (Luca); I. Campi (Irene); E. Bonomi (Elisa); G. Radetti (Giorgio); P. Beck-Peccoz (Paolo); H. Zhu (H.); T.M.E. Davis (Timothy M.); Y. Sun (Y.); E.P. Corssmit (Eleonora); N.M. Appelman-Dijkstra (Natasha); C.A. Heinen (C.); A.M. Pereira (Alberto); A.J. Varewijck (Aimee); J.A.M.J.L. Janssen (Joseph); E. Endert (Erik); R.C.M. Hennekam (Raoul); M.P. Lombardi (Paola); M.M.A.M. Mannens (Marcel); B. Bak (Beata); D.J. Bernard (Daniel); M.H. Breuning (Martijn); K. Chatterjee (Krishna); M.T. Dattani (Mehul); W. Oostdijk (Wilma); N.R. Biermasz; J.M. Wit (Jan); A.S.P. van Trotsenburg (Paul)

    2013-01-01

    textabstractContext: Ig superfamily member1 (IGSF1) deficiency was recently discovered as a novel X-linked cause of central hypothyroidism (CeH) and macro-orchidism. However, clinical and biochemical data regarding growth, puberty, and metabolic outcome, as well as features of female carriers, are s

  20. Development of an Inactivated Iridovirus Vaccine Against Turbot Viral Reddish Body Syndrome

    Institute of Scientific and Technical Information of China (English)

    FAN Tingjun; HU Xiuzhong; WANG Liyan; GENG Xiaofen; JIANG Guojian; YANG Xiuxia; YU Miaomiao

    2012-01-01

    Turbot (Scophthalmus maximus L.) reddish body iridovirus (TRBIV) was propagated in turbot fin cells (TF cells) and inactivated as the TRBIV vaccine with its protection efficiency evaluated in this study.TF cells were cultured in 10% bovine calf serum (BCS)-containing MEM medium (pH7.0) at 22 ℃,in which TRBIV propagated to a titer as high as 105.6 TCID50 mL-1.The TRBIV was inactivated with 0.1% formalin and formulated with 0.5% aluminum hydroxide.The inactivated vaccine caused neither cytopathogenic effect (CPE) on TF cells nor pathogenic effect on turbots.After being administered with the vaccine twice via muscle injection,the turbot developed high-tittered TRBIV neutralizing antibodies in a dose-dependent manner.The vaccine protected the turbot from dying with an immunoprotection rate of 83.3% as was determined via subcutaneous vaccination in the laboratory and 90.5% via bath vaccination in turbot farms,respectively.The inactivated vaccine was very immunogenic,efficiently preventing turbot from death.It holds the potential of being applied in aquaculture.

  1. Development of an inactivated iridovirus vaccine against turbot viral reddish body syndrome

    Science.gov (United States)

    Fan, Tingjun; Hu, Xiuzhong; Wang, Liyan; Geng, Xiaofen; Jiang, Guojian; Yang, Xiuxia; Yu, Miaomiao

    2012-03-01

    Turbot ( Scophthalmus maximus L.) reddish body iridovirus (TRBIV) was propagated in turbot fin cells (TF cells) and inactivated as the TRBIV vaccine with its protection efficiency evaluated in this study. TF cells were cultured in 10% bovine calf serum (BCS)-containing MEM medium (pH7.0) at 22°C, in which TRBIV propagated to a titer as high as 105.6 TCID50 mL-1. The TRBIV was inactivated with 0.1% formalin and formulated with 0.5% aluminum hydroxide. The inactivated vaccine caused neither cytopathogenic effect (CPE) on TF cells nor pathogenic effect on turbots. After being administered with the vaccine twice via muscle injection, the turbot developed high-tittered TRBIV neutralizing antibodies in a dose-dependent manner. The vaccine protected the turbot from dying with an immunoprotection rate of 83.3% as was determined via subcutaneous vaccination in the laboratory and 90.5% via bath vaccination in turbot farms, respectively. The inactivated vaccine was very immunogenic, efficiently preventing turbot from death. It holds the potential of being applied in aquaculture.

  2. Seizure control and acceptance of the ketogenic diet in GLUT1 deficiency syndrome: a 2- to 5-year follow-up of 15 children enrolled prospectively.

    NARCIS (Netherlands)

    Klepper, J.; Scheffer, H.; Leiendecker, B.; Gertsen, E.; Binder, S.; Leferink, M.; Hertzberg, C.; Nake, A.; Voit, T.; Willemsen, M.A.A.P.

    2005-01-01

    BACKGROUND: GLUT1 deficiency syndrome is caused by impaired glucose transport into the brain resulting in an epileptic encephalopathy, developmental delay, and a complex motor disorder. A ketogenic diet provides an alternative fuel to the brain and effectively restores brain energy metabolism.

  3. Seizure control and acceptance of the ketogenic diet in GLUT1 deficiency syndrome: a 2- to 5-year follow-up of 15 children enrolled prospectively.

    NARCIS (Netherlands)

    Klepper, J.; Scheffer, H.; Leiendecker, B.; Gertsen, E.; Binder, S.; Leferink, M.; Hertzberg, C.; Nake, A.; Voit, T.; Willemsen, M.A.A.P.

    2005-01-01

    BACKGROUND: GLUT1 deficiency syndrome is caused by impaired glucose transport into the brain resulting in an epileptic encephalopathy, developmental delay, and a complex motor disorder. A ketogenic diet provides an alternative fuel to the brain and effectively restores brain energy metabolism. METHO

  4. Seizure control and acceptance of the ketogenic diet in GLUT1 deficiency syndrome: a 2- to 5-year follow-up of 15 children enrolled prospectively.

    NARCIS (Netherlands)

    Klepper, J.; Scheffer, H.; Leiendecker, B.; Gertsen, E.; Binder, S.; Leferink, M.; Hertzberg, C.; Nake, A.; Voit, T.; Willemsen, M.A.A.P.

    2005-01-01

    BACKGROUND: GLUT1 deficiency syndrome is caused by impaired glucose transport into the brain resulting in an epileptic encephalopathy, developmental delay, and a complex motor disorder. A ketogenic diet provides an alternative fuel to the brain and effectively restores brain energy metabolism. METHO

  5. 肌酸缺乏综合征诊断与治疗%Diagnosis and treatment of creatine deficiency syndrome

    Institute of Scientific and Technical Information of China (English)

    方方; 杨蕾

    2014-01-01

    肌酸缺乏综合征(creatine deficiency syndromes,CDS)是一组影响肌酸合成及转运的先天性遗传代谢性疾病,临床表现为智力缺损、语言发育迟缓、孤独症、癫痫发作、肌张力减退、以锥体外系损害为主的运动障碍和行为问题等.早期诊断并给予肌酸治疗,可改善预后.了解CDS的临床特点,有利于提高临床认识.

  6. Thiamine Deficiency in Self-Induced Refeeding Syndrome, an Undetected and Potentially Lethal Condition

    Directory of Open Access Journals (Sweden)

    Einat Hershkowitz

    2014-01-01

    Full Text Available Rapid restoration of nutrients and electrolytes after prolonged starvation could result in a life threatening condition characterized by sensory and neurological dysfunction and severe metabolic imbalance that has been designated as refeeding syndrome. Its diagnosis is frequently missed resulting in severe complications and even death. We describe a 25-years-old female patient with mental disorders and severe malnutrition who developed severe clinical manifestations and biochemical abnormalities characteristic of the refeeding syndrome, after restarting oral feeding on her own. Schizophrenia was later diagnosed. Increased awareness of this condition and its complications is necessary to prevent its detrimental complications.

  7. Thiamine deficiency in self-induced refeeding syndrome, an undetected and potentially lethal condition.

    Science.gov (United States)

    Hershkowitz, Einat; Reshef, Alon; Munich, Olga; Yosefi, Bracha; Markel, Arie

    2014-01-01

    Rapid restoration of nutrients and electrolytes after prolonged starvation could result in a life threatening condition characterized by sensory and neurological dysfunction and severe metabolic imbalance that has been designated as refeeding syndrome. Its diagnosis is frequently missed resulting in severe complications and even death. We describe a 25-years-old female patient with mental disorders and severe malnutrition who developed severe clinical manifestations and biochemical abnormalities characteristic of the refeeding syndrome, after restarting oral feeding on her own. Schizophrenia was later diagnosed. Increased awareness of this condition and its complications is necessary to prevent its detrimental complications.

  8. Antiviral Biologic Produced in DNA Vaccine/Goose Platform Protects Hamsters Against Hantavirus Pulmonary Syndrome When Administered Post-exposure

    Science.gov (United States)

    Henderson, Thomas; Nilles, Matthew L.; Kwilas, Steve A.; Josleyn, Matthew D.; Hammerbeck, Christopher D.; Schiltz, James; Royals, Michael; Ballantyne, John; Hooper, Jay W.; Bradley, David S.

    2015-01-01

    Andes virus (ANDV) and ANDV-like viruses are responsible for most hantavirus pulmonary syndrome (HPS) cases in South America. Recent studies in Chile indicate that passive transfer of convalescent human plasma shows promise as a possible treatment for HPS. Unfortunately, availability of convalescent plasma from survivors of this lethal disease is very limited. We are interested in exploring the concept of using DNA vaccine technology to produce antiviral biologics, including polyclonal neutralizing antibodies for use in humans. Geese produce IgY and an alternatively spliced form, IgYΔFc, that can be purified at high concentrations from egg yolks. IgY lacks the properties of mammalian Fc that make antibodies produced in horses, sheep, and rabbits reactogenic in humans. Geese were vaccinated with an ANDV DNA vaccine encoding the virus envelope glycoproteins. All geese developed high-titer neutralizing antibodies after the second vaccination, and maintained high-levels of neutralizing antibodies as measured by a pseudovirion neutralization assay (PsVNA) for over 1 year. A booster vaccination resulted in extraordinarily high levels of neutralizing antibodies (i.e., PsVNA80 titers >100,000). Analysis of IgY and IgYΔFc by epitope mapping show these antibodies to be highly reactive to specific amino acid sequences of ANDV envelope glycoproteins. We examined the protective efficacy of the goose-derived antibody in the hamster model of lethal HPS. α-ANDV immune sera, or IgY/IgYΔFc purified from eggs, were passively transferred to hamsters subcutaneously starting 5 days after an IM challenge with ANDV (25 LD50). Both immune sera, and egg-derived purified IgY/IgYΔFc, protected 8 of 8 and 7 of 8 hamsters, respectively. In contrast, all hamsters receiving IgY/IgYΔFc purified from normal geese (n=8), or no-treatment (n=8), developed lethal HPS. These findings demonstrate that the DNA vaccine/goose platform can be used to produce a candidate antiviral biological product

  9. Antiviral Biologic Produced in DNA Vaccine/Goose Platform Protects Hamsters Against Hantavirus Pulmonary Syndrome When Administered Post-exposure.

    Directory of Open Access Journals (Sweden)

    Nicole Haese

    Full Text Available Andes virus (ANDV and ANDV-like viruses are responsible for most hantavirus pulmonary syndrome (HPS cases in South America. Recent studies in Chile indicate that passive transfer of convalescent human plasma shows promise as a possible treatment for HPS. Unfortunately, availability of convalescent plasma from survivors of this lethal disease is very limited. We are interested in exploring the concept of using DNA vaccine technology to produce antiviral biologics, including polyclonal neutralizing antibodies for use in humans. Geese produce IgY and an alternatively spliced form, IgYΔFc, that can be purified at high concentrations from egg yolks. IgY lacks the properties of mammalian Fc that make antibodies produced in horses, sheep, and rabbits reactogenic in humans. Geese were vaccinated with an ANDV DNA vaccine encoding the virus envelope glycoproteins. All geese developed high-titer neutralizing antibodies after the second vaccination, and maintained high-levels of neutralizing antibodies as measured by a pseudovirion neutralization assay (PsVNA for over 1 year. A booster vaccination resulted in extraordinarily high levels of neutralizing antibodies (i.e., PsVNA80 titers >100,000. Analysis of IgY and IgYΔFc by epitope mapping show these antibodies to be highly reactive to specific amino acid sequences of ANDV envelope glycoproteins. We examined the protective efficacy of the goose-derived antibody in the hamster model of lethal HPS. α-ANDV immune sera, or IgY/IgYΔFc purified from eggs, were passively transferred to hamsters subcutaneously starting 5 days after an IM challenge with ANDV (25 LD50. Both immune sera, and egg-derived purified IgY/IgYΔFc, protected 8 of 8 and 7 of 8 hamsters, respectively. In contrast, all hamsters receiving IgY/IgYΔFc purified from normal geese (n=8, or no-treatment (n=8, developed lethal HPS. These findings demonstrate that the DNA vaccine/goose platform can be used to produce a candidate antiviral

  10. Interhomolog recombination and loss of heterozygosity in wild-type and Bloom syndrome helicase (BLM)-deficient mammalian cells.

    Science.gov (United States)

    LaRocque, Jeannine R; Stark, Jeremy M; Oh, Jin; Bojilova, Ekaterina; Yusa, Kosuke; Horie, Kyoji; Takeda, Junji; Jasin, Maria

    2011-07-19

    Genomic integrity often is compromised in tumor cells, as illustrated by genetic alterations leading to loss of heterozygosity (LOH). One mechanism of LOH is mitotic crossover recombination between homologous chromosomes, potentially initiated by a double-strand break (DSB). To examine LOH associated with DSB-induced interhomolog recombination, we analyzed recombination events using a reporter in mouse embryonic stem cells derived from F1 hybrid embryos. In this study, we were able to identify LOH events although they occur only rarely in wild-type cells (≤2.5%). The low frequency of LOH during interhomolog recombination suggests that crossing over is rare in wild-type cells. Candidate factors that may suppress crossovers include the RecQ helicase deficient in Bloom syndrome cells (BLM), which is part of a complex that dissolves recombination intermediates. We analyzed interhomolog recombination in BLM-deficient cells and found that, although interhomolog recombination is slightly decreased in the absence of BLM, LOH is increased by fivefold or more, implying significantly increased interhomolog crossing over. These events frequently are associated with a second homologous recombination event, which may be related to the mitotic bivalent structure and/or the cell-cycle stage at which the initiating DSB occurs.

  11. Intranasal siRNA administration reveals IGF2 deficiency contributes to impaired cognition in Fragile X syndrome mice

    Science.gov (United States)

    Pardo, Marta; Cheng, Yuyan; Velmeshev, Dmitry; Magistri, Marco; Martinez, Ana; Faghihi, Mohammad A.; Jope, Richard S.; Beurel, Eleonore

    2017-01-01

    Molecular mechanisms underlying learning and memory remain imprecisely understood, and restorative interventions are lacking. We report that intranasal administration of siRNAs can be used to identify targets important in cognitive processes and to improve genetically impaired learning and memory. In mice modeling the intellectual deficiency of Fragile X syndrome, intranasally administered siRNA targeting glycogen synthase kinase-3β (GSK3β), histone deacetylase-1 (HDAC1), HDAC2, or HDAC3 diminished cognitive impairments. In WT mice, intranasally administered brain-derived neurotrophic factor (BDNF) siRNA or HDAC4 siRNA impaired learning and memory, which was partially due to reduced insulin-like growth factor-2 (IGF2) levels because the BDNF siRNA– or HDAC4 siRNA–induced cognitive impairments were ameliorated by intranasal IGF2 administration. In Fmr1–/– mice, hippocampal IGF2 was deficient, and learning and memory impairments were ameliorated by IGF2 intranasal administration. Therefore intranasal siRNA administration is an effective means to identify mechanisms regulating cognition and to modulate therapeutic targets. PMID:28352664

  12. Prevalence, Pathophysiology, and Management of Androgen Deficiency in Men with Metabolic Syndrome, Type 2 Diabetes Mellitus, or Both.

    Science.gov (United States)

    Taylor, Shawn Riser; Meadowcraft, Lindsy M; Williamson, Bobbie

    2015-08-01

    The prevalence of type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS) has increased in the United States over the past 40 years. These conditions, long linked with many cardiovascular complications, have recently been linked with androgen or testosterone deficiency in men. Several pathophysiologic hypotheses exist regarding this association, with the most widely reported a relationship to obesity and insulin resistance. Several randomized trials have confirmed that when testosterone replacement therapy is given to patients with T2DM, MetS, or both, metabolic parameters such as waist circumference, hemoglobin A1c , and systolic blood pressure are significantly reduced by up to 11 cm, 1.9%, and 23 mm Hg, respectively. This has not, however, resulted in improved cardiovascular outcomes, as evidenced in studies that found increased rates of cardiovascular events following testosterone replacement therapy. In this review, we summarize the relevant literature regarding the pathophysiology and management of androgen deficiency in men with T2DM, MetS, or both.

  13. Empty sella syndrome associated with hormone deficiency in adults; Silla turca vacia asociada a disfuncion hormonal en adultos

    Energy Technology Data Exchange (ETDEWEB)

    Oleaga, L.; Paja, M.; Goni, F.; Grande, J.; Grande, D. [Hospital de Basurto. Bilbao (Spain); Merino, M. [Hospital General Yague (Spain); Delgado, A. [Hospital Marques de Valdecilla. Santander (Spain)

    1999-07-01

    The objective of this study was to correlate the magnetic resonance (MR) images in patients with hormone deficiencies with the clinical data and the hormonal status. We studied 11 cases ef empty sella with different peripheral pituitary deficiencies. Hormone levels were determined according to standard laboratory methods. All the patients underwent MR imaging. The studies were carried out with a 1 Tesla superconducting magnet, using the cranial cavity for transmission and reception. Segittal and coronal T1-weighted spin-echo sequences (TR/TE: 600/15 ms), axial T2-weighted spin-echo sequences (TR/TE: 3,500/19/93 ms) and gadolinium-enhanced (=.2 cc/kg body weight) sagital and coronal T1-weighted spin-echo sequences (TR/TE: 600/15 ms) were employed. Six of the patients presented partial or total hypopituitarism associated with the syndrome of inappropriate antidiuretic hormone secretion (SIADH); there was one case of panhypopituitarism without SIADH and four cases of primary hypothyroidism, there of which were associated with pituitary deficiency, MR imaging revealed five cases of partially empty sella with residual pituitary gland on the sella floor and six cases in which the sella was completely empty. This study also identified six cases of normally situated neurohypophysis, another four in which the neurohypophysis could not be identified and one case of ectopic neurohypophysis. MR imaging is the technique of choice in the study of abnormal hypothalamic-pituitary activity. Empty and partially empty sella should be included among the frequent causes of hypopituitarism, although there is no clear relationship between the degree of adenohypophyseal insufficiency and the degree of atrophy of this system as viewed in MR images. In some cases, this entity may be the radiological sign of a phase in the development of an autoimmune inflammatory process involving the pituitary gland. (Author) 16 refs.

  14. Study of the serotonin transporter (SLC6A4 and BDNF genes in French patients with non syndromic mental deficiency

    Directory of Open Access Journals (Sweden)

    Mignon Laurence

    2010-02-01

    Full Text Available Abstract Background Mental deficiency has been linked to abnormalities in cortical neuronal network connectivity and plasticity. These mechanisms are in part under the control of two interacting signalling pathways, the serotonergic and the brain-derived neurotrophic (BDNF pathways. The aim of the current paper is to determine whether particular alleles or genotypes of two crucial genes of these systems, the serotonin transporter gene (SLC6A4 and the brain-derived neurotrophic factor gene (BDNF, are associated with mental deficiency (MD. Methods We analyzed four functional polymorphisms (rs25531, 5-HTTLPR, VNTR, rs3813034 of the SLC6A4 gene and one functional polymorphism (Val66 Met of the BDNF gene in 98 patients with non-syndromic mental deficiency (NS-MD and in an ethnically matched control population of 251 individuals. Results We found no significant differences in allele and genotype frequencies in the five polymorphisms studied in the SLC6A4 and BDNF genes of NS-MD patients versus control patients. While the comparison of the patterns of linkage disequilibrium (D' in the control and NS-MD populations revealed a degree of variability it did not, however, reach significance. No significant differences in frequencies of haplotypes and genotypes for VNTR/rs3813034 and rs25531/5-HTTLPR were observed. Conclusion Altogether, results from the present study do not support a role for any of the five functional polymorphisms of SLC6A4 and BDNF genes in the aetiology of NS-RM. Moreover, they suggest no epistatic interaction in NS-MD between polymorphisms in BDNF and SLC6A4. However, we suggest that further studies on these two pathways in NS-MD remain necessary.

  15. Aire-deficient mice provide a model of corneal and lacrimal gland neuropathy in Sjögren's syndrome.

    Science.gov (United States)

    Chen, Feeling Y; Lee, Albert; Ge, Shaokui; Nathan, Sara; Knox, Sarah M; McNamara, Nancy A

    2017-01-01

    Sjögren's syndrome (SS) is a chronic, autoimmune exocrinopathy that leads to severe dryness of the mouth and eyes. Exocrine function is highly regulated by neuronal mechanisms but little is known about the link between chronic inflammation, innervation and altered exocrine function in the diseased eyes and exocrine glands of SS patients. To gain a better understanding of neuronal regulation in the immunopathogenesis of autoimmune exocrinopathy, we profiled a mouse model of spontaneous, autoimmune exocrinopathy that possess key characteristics of peripheral neuropathy experienced by SS patients. Mice deficient in the autoimmune regulator (Aire) gene developed spontaneous, CD4+ T cell-mediated exocrinopathy and aqueous-deficient dry eye that were associated with loss of nerves innervating the cornea and lacrimal gland. Changes in innervation and tear secretion were accompanied by increased proliferation of corneal epithelial basal cells, limbal expansion of KRT19-positive progenitor cells, increased vascularization of the peripheral cornea and reduced nerve function in the lacrimal gland. In addition, we found extensive loss of MIST1+ secretory acinar cells in the Aire -/- lacrimal gland suggesting that acinar cells are a primary target of the disease, Finally, topical application of ophthalmic steroid effectively restored corneal innervation in Aire -/- mice thereby functionally linking nerve loss with local inflammation in the aqueous-deficient dry eye. These data provide important insight regarding the relationship between chronic inflammation and neuropathic changes in autoimmune-mediated dry eye. Peripheral neuropathies characteristic of SS appear to be tightly linked with the underlying immunopathological mechanism and Aire -/- mice provide an excellent tool to explore the interplay between SS-associated immunopathology and peripheral neuropathy.

  16. Guillain-Barré syndrome and adjuvanted pandemic influenza A (H1N1) 2009 vaccines: A multinational self-controlled case series in Europe

    NARCIS (Netherlands)

    S.A. Romio (Silvana); D.M. Weibel (Daniel); J.P. Dieleman (Jeanne); H.K. Olberg (Henning); C.S. de Vries (Corinne); C. Sammon (Cormac); N.J. Andrews (Nick); H. Svanström (Henrik); D. Mølgaard-Nielsen (Ditte); A. Hviid (Anders); M. Lapeyre-Mestre (Maryse); A. Sommet (Agnès); C. Saussier (Christel); A. Castot (Anne); H. Heijbel (Harald); L. Arnheim-Dahlström (Lisen); P. Sparen (Pär); M. Mosseveld (Mees); M.J. Schuemie (Martijn); N.A.T. van der Maas (Nicoline); B.C. Jacobs (Bart); T. Leino (Tuija); T. Kilpi (Terhi); J. Storsaeter (Jann); K. Johansen (Kari); P Kramarz (Piotr); J. Bonhoeffer (Jan); M.C.J.M. Sturkenboom (Miriam)

    2014-01-01

    textabstractBackground: The risk of Guillain-Barré syndrome (GBS) following the United States' 1976 swine flu vaccination campaign in the USA led to enhanced active surveillance during the pandemic influenza (A(H1N1)pdm09) immunization campaign. This study aimed to estimate the risk of GBS following

  17. International collaboration to assess the risk of Guillain Barré Syndrome following Influenza A (H1N1) 2009 monovalent vaccines

    NARCIS (Netherlands)

    C. Dodd (Caitlin); S.A. Romio (Silvana); S. Black (Steve); C. Vellozzi (Claudia); N.J. Andrews (Nick); M.C.J.M. Sturkenboom (Miriam); P. Zuber (Patrick); W. Hua (Wei); J. Bonhoeffer (Jan); J. Buttery (Jim); N. Crawford (Nigel); G. Deceuninck (Genevieve); C.S. de Vries (Corinne); P. de Wals (Philippe); D. Gimeno (David); H. Heijbel (Harald); H. Hughes (Hayley); K. Hur (Kwan); A. Hviid (Anders); J. Kelman (Jeffrey); T. Kilpi (Tehri); S.K. Chuang (S.); T. Macartney (Thomas); M. Rett (Melisa); V.R. Lopez-Callada (Vesta Richardson); D. Salmon (Daniel); F.G. Sanchez (Francisco Gimenez); N. Sanz (Nuria); B. Silverman (Bernard); J. Storsaeter (Jann); U. Thirugnanam (Umapathi); N.A.T. van der Maas (Nicoline); K. Yih (Katherine); T. Zhang (Teng Fei); H.S. Izurieta (Hector); B.J. Addis; A. Akhtar (Aysha); J. Cope (Judith); R.L. Davis (Robert); P. Gargiullo (Paul); X. Kurz (Xavier); B. Law (Barbara); I. Sahinovic (Isabelle); J. Tokars (Jerry); P. Serrano (Pedro); A. Cheng (Aixin); N.J. Andrews (Nick); P. Charles (Pat); H. Clothier (Hazel); B. Day (Bruce); T. Day (Timothy); P. Gates (Peter); R. MacDonnell (Richard); L. Roberts (Les); V. Rodriguez-Casero (Vic-toria); T. Wijeratne (Tissa); H.A.L. Kiers (Henk); C. Blyth (Christopher); R. Booy (Robert); E. Elliott (Elizabeth); M.R. Gold (Michael); H. Marshall; P. McIntyre (Peter); P. Richmond (Peter); J. Royle (Jenny); N.W. Wood (Nicholas); Y. Zurynski (Yvonne); G. Calvo (Gonzalo); M. Campins (Magda); N. Corominas (Nuria); F. Torres (Ferran); V. Valls; A. Vilella (Ángels); A. Dutra (Amalia); A. Eick-Cost (Angelia); H.M. Jackson (Henry); K. Garman (Katherine); Z. Hu (Zheng); J. Rigo; J. Badoo (Judith); D Cho (David); L.L. Polakowski (Laura); S.K. Sandhu (Sukhminder); G. Sun (Guoying); H.-S.S. Chan (Hoi-Shan Sophelia); K.-Y. Chan (Kwok-Yin); R. Cheung (Raymond); Y-F. Cheung (Yuk-Fai); S. Cherk (Sharon); S.K Chuang (S.); D. Fok (Dennis); B.-H. Fung (Bun-Hey); K.-F. Ko (Kwai-Fu); K.W. Lau (Ka Wing); K.-K. Lau (Kwok-Kwong); P. Li (Pulin); H.-T. Liu (Hui-Tung); S.-H. Liu (Shao-Haei); K. Mok (Kin); J. So (Joanna); W. Wong (Winnie); S.-P. Wu (Shun-Ping); V. Avagyan (Vardan); R. Ball (Robert); D. Burwen (Dale); R.L. Franks (Riley); J.M. Gibbs (Jonathan); R.E. Kliman (Rebecca); S. Kropp (Silke); T.E. MaCurdy (Thomas); D.B. Martin (David); S.-D.K. Sandhu (Sukhmin-Der); B.B. Worrall (Bradford B.); D.E.F. Fuentes (Dra. Elvira Fuentes); P.C.O. González (Paola Carolina Ojeda); V.F. Reyna (Valerie ); M. Kulldorff (Martin); G. Lee (Grace); T.A. Lieu (Tracy); S. Platt; G.D. Serres (Gaston De); K. Jabin (Kamilah); B.L.S. Soh (Bee Leng Sally); L. Arnheim-Dahlström (Lisen); A. Castot (Anne); H.E. de Melker (Hester); J.P. Dieleman (Jeanne); J. Hallgren (Jonal); B.C. Jacobs (Bart); K. Johansen (Kari); P Kramarz (Piotr); M. Lapeyre (Maryse); T. Leino (Tuija); D. Mølgaard-Nielsen (Ditte); M. Mosseveld (Mees); H.K. Olberg (Henning K); C.-M. Sammon (Cor-Mac); C. Saussier (Christel); M.J. Schuemie (Martijn); A. Sommet (Agnès); P. Sparen (Pär); H. Svanström (Henrik); A.M. Vanrolleghem (Ann M.); D.M. Weibel (Daniel); J.D. Domingo (Javier Diez); J.L. Esparza (José LuísMicó); R.M.O. Lucas (Rafael M. Ortí); J.B.M. Maseres (Juan B. Mollar); J.L.A. Sánchez (José Luís Alfonso); M.G. Sánchez (Mercedes Garcés); V.Z. Viguer (Vicente Zanón); F. Cunningham (Francesca); B. Thakkar (Bharat); R. Zhang (Rongping)

    2013-01-01

    textabstractBackground: The global spread of the 2009 novel pandemic influenza A (H1N1) virus led to the accelerated production and distribution of monovalent 2009 Influenza A (H1N1) vaccines (pH1N1). This pandemic provided the opportunity to evaluate the risk of Guillain-Barré syndrome (GBS), which

  18. International collaboration to assess the risk of Guillain Barré Syndrome following Influenza A (H1N1) 2009 monovalent vaccines

    NARCIS (Netherlands)

    C. Dodd (Caitlin); S.A. Romio (Silvana); S. Black (Steve); C. Vellozzi (Claudia); N.J. Andrews (Nick); M.C.J.M. Sturkenboom (Miriam); P. Zuber (Patrick); W. Hua (Wei); J. Bonhoeffer (Jan); J. Buttery (Jim); N. Crawford (Nigel); G. Deceuninck (Genevieve); C.S. de Vries (Corinne); P. de Wals (Philippe); D. Gimeno (David); H. Heijbel (Harald); H. Hughes (Hayley); K. Hur (Kwan); A. Hviid (Anders); J. Kelman (Jeffrey); T. Kilpi (Tehri); S.K. Chuang (S.); T. Macartney (Thomas); M. Rett (Melisa); V.R. Lopez-Callada (Vesta Richardson); D. Salmon (Daniel); F.G. Sanchez (Francisco Gimenez); N. Sanz (Nuria); B. Silverman (Bernard); J. Storsaeter (Jann); U. Thirugnanam (Umapathi); N.A.T. van der Maas (Nicoline); K. Yih (Katherine); T. Zhang (Teng Fei); H.S. Izurieta (Hector); B.J. Addis; A. Akhtar (Aysha); J. Cope (Judith); R.L. Davis (Robert); P. Gargiullo (Paul); X. Kurz (Xavier); B. Law (Barbara); I. Sahinovic (Isabelle); J. Tokars (Jerry); P. Serrano (Pedro); A. Cheng (Aixin); N.J. Andrews (Nick); P. Charles (Pat); H. Clothier (Hazel); B. Day (Bruce); T. Day (Timothy); P. Gates (Peter); R. MacDonnell (Richard); L. Roberts (Les); V. Rodriguez-Casero (Vic-toria); T. Wijeratne (Tissa); H.A.L. Kiers (Henk); C. Blyth (Christopher); R. Booy (Robert); E. Elliott (Elizabeth); M.R. Gold (Michael); H. Marshall; P. McIntyre (Peter); P. Richmond (Peter); J. Royle (Jenny); N.W. Wood (Nicholas); Y. Zurynski (Yvonne); G. Calvo (Gonzalo); M. Campins (Magda); N. Corominas (Nuria); F. Torres (Ferran); V. Valls; A. Vilella (Ángels); A. Dutra (Amalia); A. Eick-Cost (Angelia); H.M. Jackson (Henry); K. Garman (Katherine); Z. Hu (Zheng); J. Rigo; J. Badoo (Judith); D Cho (David); L.L. Polakowski (Laura); S.K. Sandhu (Sukhminder); G. Sun (Guoying); H.-S.S. Chan (Hoi-Shan Sophelia); K.-Y. Chan (Kwok-Yin); R. Cheung (Raymond); Y-F. Cheung (Yuk-Fai); S. Cherk (Sharon); S.K Chuang (S.); D. Fok (Dennis); B.-H. Fung (Bun-Hey); K.-F. Ko (Kwai-Fu); K.W. Lau (Ka Wing); K.-K. Lau (Kwok-Kwong); P. Li (Pulin); H.-T. Liu (Hui-Tung); S.-H. Liu (Shao-Haei); K. Mok (Kin); J. So (Joanna); W. Wong (Winnie); S.-P. Wu (Shun-Ping); V. Avagyan (Vardan); R. Ball (Robert); D. Burwen (Dale); R.L. Franks (Riley); J.M. Gibbs (Jonathan); R.E. Kliman (Rebecca); S. Kropp (Silke); T.E. MaCurdy (Thomas); D.B. Martin (David); S.-D.K. Sandhu (Sukhmin-Der); B.B. Worrall (Bradford B.); D.E.F. Fuentes (Dra. Elvira Fuentes); P.C.O. González (Paola Carolina Ojeda); V.F. Reyna (Valerie ); M. Kulldorff (Martin); G. Lee (Grace); T.A. Lieu (Tracy); S. Platt; G.D. Serres (Gaston De); K. Jabin (Kamilah); B.L.S. Soh (Bee Leng Sally); L. Arnheim-Dahlström (Lisen); A. Castot (Anne); H.E. de Melker (Hester); J.P. Dieleman (Jeanne); J. Hallgren (Jonal); B.C. Jacobs (Bart); K. Johansen (Kari); P Kramarz (Piotr); M. Lapeyre (Maryse); T. Leino (Tuija); D. Mølgaard-Nielsen (Ditte); M. Mosseveld (Mees); H.K. Olberg (Henning K); C.-M. Sammon (Cor-Mac); C. Saussier (Christel); M.J. Schuemie (Martijn); A. Sommet (Agnès); P. Sparen (Pär); H. Svanström (Henrik); A.M. Vanrolleghem (Ann M.); D.M. Weibel (Daniel); J.D. Domingo (Javier Diez); J.L. Esparza (José LuísMicó); R.M.O. Lucas (Rafael M. Ortí); J.B.M. Maseres (Juan B. Mollar); J.L.A. Sánchez (José Luís Alfonso); M.G. Sánchez (Mercedes Garcés); V.Z. Viguer (Vicente Zanón); F. Cunningham (Francesca); B. Thakkar (Bharat); R. Zhang (Rongping)

    2013-01-01

    textabstractBackground: The global spread of the 2009 novel pandemic influenza A (H1N1) virus led to the accelerated production and distribution of monovalent 2009 Influenza A (H1N1) vaccines (pH1N1). This pandemic provided the opportunity to evaluate the risk of Guillain-Barré syndrome (GBS), which

  19. Leukocyte adhesion deficiency syndrome: report on the first case in Chile and South America

    Directory of Open Access Journals (Sweden)

    Rodrigo Vásquez-De Kartzow

    Full Text Available CONTEXT: Adhesion molecule deficiency type 1 is a rare disease that should be suspected in any patient whose umbilical cord presents delay in falling off, and who presents recurrent severe infections. Early diagnostic suspicion and early treatment improve the prognosis. CASE REPORT: The case of a four-month-old boy with recurrent hospitalizations because of severe bronchopneumonia and several episodes of acute otitis media with non-purulent drainage of mucus and positive bacterial cultures is presented. His medical history included neonatal sepsis and delayed umbilical cord detachment. Laboratory studies showed marked leukocytosis with predominance of neutrophils and decreased CD11b and CD18. These were all compatible with a diagnosis of leukocyte adhesion deficiency type I [LAD type 1].

  20. Immunology Update: New Vaccines.

    Science.gov (United States)

    Starr, S Paul

    2016-11-01

    A new 9-valent human papillomavirus (HPV) vaccine is effective against more cancer-causing HPV types than previous vaccines. HPV vaccine series started with previous vaccines can be completed with the 9-valent vaccine. Two new influenza vaccines are available for adults 65 years and older: a high-dose vaccine and an enhanced adjuvant vaccine. These elicit stronger antibody responses than standard-dose vaccines. Current guidelines specify no preference for the new versus standard-dose vaccines. Two new group B meningococcal vaccines are intended for use during outbreaks and for patients with asplenia, complement deficiencies, frequent occupational meningococcus exposure, or for patients who desire protection from type B meningococcus. These are not substitutes for the quadrivalent vaccine already in use. For pneumococcus, new recommendations state that 13-valent pneumococcal conjugate vaccine (PCV13) should be administered to patients 65 years and older, followed at least 1 year later by the polyvalent pneumococcal polysaccharide vaccine (PPSV23). For patients ages 19 to 64 years with immunocompromise and not previously vaccinated against pneumococcus, administration of these two vaccines should be separated by at least 8 weeks. Rotavirus vaccine is standard for infants at age 2 months. Also, there is a new cholera vaccine approved for use in the United States. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

  1. DNA mismatch repair deficiency in sporadic colorectal cancer and Lynch Syndrome

    OpenAIRE

    Poulogiannis, George; Frayling, Ian; Arends, Mark

    2009-01-01

    Abstract DNA mismatch repair (MMR) deficiency is one of the best understood forms of genetic instability in colorectal cancer (CRC), and is characterised by the loss of function of the MMR pathway. Failure to repair replication-associated errors due to a defective MMR system allows persistence of mismatch mutations all over the genome, but especially in regions of repetitive DNA known as microsatellites, giving rise to the phenomenon of microsatellite instability (MSI). A high freq...

  2. Androgen deficiency as a predictor of metabolic syndrome in aging men: an opportunity for intervention?

    Science.gov (United States)

    Kapoor, Dheeraj; Jones, T Hugh

    2008-01-01

    The prevalence of metabolic syndrome is increasing globally and is an important risk factor for the development of cardiovascular disease. Longitudinal population studies have found that low testosterone status in men is a risk factor for the later development of metabolic syndrome. Men with metabolic syndrome and type 2 diabetes mellitus have a higher incidence of hypotestosteronaemia. Furthermore, in men, testosterone levels are inversely associated with the degree of carotid and aortic atherosclerosis. Early interventional, short-term studies have shown that testosterone replacement therapy has a beneficial effect on visceral obesity, insulin sensitivity, glycaemic control and lipid profiles in men with diagnosed hypogonadism with and without diabetes. The effect of testosterone therapy on atherogenesis in men is unknown; however, animal studies have shown that testosterone is atheroprotective and can ameliorate the degree of atherosclerosis. Testosterone is an arterial vasodilator and has been shown to improve myocardial ischaemia in men with coronary artery disease. This review discusses the role that testosterone may play in the pathogenesis of metabolic syndrome in men and also examines the potential role of testosterone replacement therapy in this condition.

  3. Improved survival of TNF-deficient mice during the zymosan-induced multiple organ dysfunction syndrome.

    NARCIS (Netherlands)

    Volman, T.J.H.; Hendriks, T.; Verhofstad, A.A.J.; Kullberg, B.J.; Goris, R.J.A.

    2002-01-01

    The purpose of the study was to investigate the course of the zymosan-induced multiple organ dysfunction syndrome (MODS) in the absence of tumor necrosis factor (TNF) in a murine model. Tumor Necrosis Factor-alpha-lymphotoxin-a knockout (TNF/LT-/-) mice (n = 36) and wild-type (TNF/LT+/+) mice (n =

  4. Pulmonary Thromboembolism in Klinefelter%u2019s Syndrome Patient with Deficient of Protein C

    Directory of Open Access Journals (Sweden)

    Mehmet Yigit

    2013-08-01

    Full Text Available Klinefelter syndrome (KS is a common genetic disorder caused by one or more supernumerary X chromosomes. KS poses an increased risk for venous thromboembolic events such as deep venous thrombosis and pulmonary embolism. Klinefelter syndrome is prone to hypercoagulability due to hormonal imbalance and one or more inherited thrombophilic factors. Therefore, patients with KS having a medical history of venous thromboembolism require chest computed tomographic (CT images and oral anticoagulation therapy for a period of at least six months. A 21 year old, male patient diagnosed with Klinefelter syndrome was presented to the emergency department of our hospital with primary complaints of left lower extremity pain lasting for 2 months. Deep venous thromboembosis (DVT was diagnosed via venous doppler ultrasound and pulmonary thromboembolism in his chest CT images. Following anticoagulation treatment, his symptoms recovered. An endocrinologic test should be ordered in patients having klinefelter syndrome with a medical or familial history of venous thromboembolism as well as additional assessment of innate or acquired thrombophilia should be made.

  5. Vaccine adverse events.

    Science.gov (United States)

    Follows, Jill

    2012-01-01

    Millions of adults are vaccinated annually against the seasonal influenza virus. An undetermined number of individuals will develop adverse events to the influenza vaccination. Those who suffer substantiated vaccine injuries, disabilities, and aggravated conditions may file a timely, no-fault and no-cost petition for financial compensation under the National Vaccine Act in the Vaccine Court. The elements of a successful vaccine injury claim are described in the context of a claim showing the seasonal influenza vaccination was the cause of Guillain-Barré syndrome.

  6. Preliminary results: surveillance for Guillain-Barré syndrome after receipt of influenza A (H1N1) 2009 monovalent vaccine - United States, 2009-2010.

    Science.gov (United States)

    2010-06-01

    Guillain-Barré syndrome (GBS) is an uncommon peripheral neuropathy causing paralysis and in severe cases respiratory failure and death. GBS often follows an antecedent gastrointestinal or upper respiratory illness but, in rare cases, can follow vaccination. In 1976, vaccination against a novel swine-origin influenza A (H1N1) virus was associated with a statistically significant increased risk for GBS in the 42 days after vaccination (approximately 10 excess cases per 1 million vaccinations), a consideration in halting the vaccination program in the context of limited influenza virus transmission. To monitor influenza A (H1N1) 2009 monovalent vaccine safety, several federal surveillance systems, including CDC's Emerging Infections Program (EIP), are being used. In October 2009, EIP began active surveillance to assess the risk for GBS after 2009 H1N1 vaccination. Preliminary results from an analysis in EIP comparing GBS patients hospitalized through March 31, 2010, who did and did not receive 2009 H1N1 vaccination showed an estimated age-adjusted rate ratio of 1.77 (GBS incidence of 1.92 per 100,000 person-years among vaccinated persons and 1.21 per 100,000 person-years among unvaccinated persons). If end-of-surveillance analysis confirms this finding, this would correspond to 0.8 excess cases of GBS per 1 million vaccinations, similar to that found in seasonal influenza vaccines. No other federal system to date has detected a statistically significant association between GBS and 2009 H1N1 vaccination. Surveillance and further analyses are ongoing. The 2009 H1N1 vaccine safety profile is similar to that for seasonal influenza vaccines, which have an excellent safety record. Vaccination remains the most effective method to prevent serious illness and death from 2009 H1N1 influenza infection; illness from the 2009 H1N1 influenza virus has been associated with a hospitalization rate of 222 per 1 million and a death rate of 9.7 per 1 million population.

  7. An interferon inducing porcine reproductive and respiratory syndrome virus vaccine candidate elicits protection against challenge with the heterologous virulent type 2 strain VR-2385 in pigs.

    Science.gov (United States)

    Fontanella, Eve; Ma, Zexu; Zhang, Yanjin; de Castro, Alessandra M M G; Shen, Huigang; Halbur, Patrick G; Opriessnig, Tanja

    2017-01-03

    Achieving consistent protection by vaccinating pigs against porcine reproductive and respiratory syndrome virus (PRRSV) remains difficult. Recently, an interferon-inducing PRRSV vaccine candidate strain A2MC2 was demonstrated to be attenuated and induced neutralizing antibodies. The objective of this study was to determine the efficacy of passage 90 of A2MC2 (A2P90) to protect pigs against challenge with moderately virulent PRRSV strain VR-2385 (92.3% nucleic acid identity with A2MC2) and highly virulent atypical PRRSV MN184 (84.5% nucleic acid identity with A2MC2). Forty 3-week old pigs were randomly assigned to five groups including a NEG-CONTROL group (non-vaccinated, non-challenged), VAC-VR2385 (vaccinated, challenged with strain VR-2385), VR2385 (challenged with strain VR-2385), VAC-MN184 (vaccinated, challenged with strain MN184) and a MN184 group (challenged with MN184 virus). Vaccination was done at 3weeks of age followed by challenge at 8weeks of age. No viremia was detectable in any of the vaccinated pigs; however, by the time of challenge, 15/16 vaccinated pigs had seroconverted based on ELISA and had neutralizing antibodies against a homologous strain with titers ranging from 8 to 128. Infection with VR-2385 resulted in mild-to-moderate clinical disease and lesions. For VR-2385 infected pigs, vaccination significantly lowered PRRSV viremia and nasal shedding by 9days post challenge (dpc), significantly reduced macroscopic lung lesions, and significantly increased the average daily weight gain compared to the non-vaccinated pigs. Infection with MN184 resulted in moderate-to-severe clinical disease and lesions regardless of vaccination status; however, vaccinated pigs had significantly less nasal shedding by dpc 5 compared to non-vaccinated pigs. Under the study conditions, the A2P90 vaccine strain was attenuated without detectable shedding, improved weight gain, and offered protection to the pigs challenged with VR-2385 by reduction of virus load and

  8. Field evaluation of the efficacy, compatibility and serologic profiling of a combined vaccine against porcine reproductive and respiratory syndrome and Haemophilus parasuis in nursery pigs.

    Science.gov (United States)

    Palzer, Andreas; Eddicks, Matthias; Zoels, Susanne; Stark, Jasmin; Reese, Sven; Strutzberg-Minder, Katrin; Fiebig, Kerstin; Ritzmann, Mathias

    2015-05-01

    The aim of the study was to compare the efficacy and compatibility of a separate or combined vaccination against the porcine reproductive and respiratory syndrome (PRRS) and Haemophilus (H.) parasuis. The study was conducted in a 1200 head nursery farm. A total of 360 piglets at an age of 26 days were randomized into three groups. Group A was vaccinated separately against H. parasuis (Porcilis(®)Glässer) and PRRS (Porcilis(®)PRRS), group B was vaccinated with a combined vaccine of both vaccines and group C remained unvaccinated as control group. The compatibility was evaluated by measurement of the body temperature and a palpation score of the injection site 0, 4, 24 and 72 h after vaccination. During the nursery and the fattening period the average daily weight gain (ADWG), the number of runts and the mortality was evaluated. Additionally blood samples were taken every 2 weeks during the nursery period to perform an OppA-ELISA and a PCR for PRRS virus. No significant difference could be seen regarding the body temperature between group A and group C. Piglets which were vaccinated with the combined vaccine showed a significantly higher body temperature 4 and 72 h post vaccination than piglets from group A. The palpation score was significantly higher in group A 4 and 24h post vaccination compared to the control group, whereas no significant difference was observed between group A and B. No significant differences between groups were seen in the ADWG during the nursery period. The mortality rate during the nursery period was significantly higher in group C than in group A. The ADWG during fattening was significantly higher in the vaccinated groups than in group C. A PRRS genotype1 field virus was detected at the end of the nursery period. No significant differences were observed in the number of OppA-ELISA positive animals, but vaccinated pigs seemed to react earlier. All pigs of the vaccinated groups that were positive in the OppA-ELISA did not develop Gl

  9. Impact of Diet-Induced Obesity and Testosterone Deficiency on the Cardiovascular System: A Novel Rodent Model Representative of Males with Testosterone-Deficient Metabolic Syndrome (TDMetS)

    OpenAIRE

    Donner, Daniel G.; Elliott, Grace E.; Belinda R. Beck; Bulmer, Andrew C.; Du Toit, Eugene F

    2015-01-01

    Introduction Current models of obesity utilise normogonadic animals and neglect the strong relationships between obesity-associated metabolic syndrome (MetS) and male testosterone deficiency (TD). The joint presentation of these conditions has complex implications for the cardiovascular system that are not well understood. We have characterised and investigated three models in male rats: one of diet-induced obesity with the MetS; a second using orchiectomised rats mimicking TD; and a third co...

  10. Comparison of Host Immune Responses to Homologous and Heterologous Type II Porcine Reproductive and Respiratory Syndrome Virus (PRRSV Challenge in Vaccinated and Unvaccinated Pigs

    Directory of Open Access Journals (Sweden)

    X. Li

    2014-01-01

    Full Text Available Porcine reproductive and respiratory syndrome (PRRS is a high-consequence animal disease with current vaccines providing limited protection from infection due to the high degree of genetic variation of field PRRS virus. Therefore, understanding host immune responses elicited by different PRRSV strains will facilitate the development of more effective vaccines. Using IngelVac modified live PRRSV vaccine (MLV, its parental strain VR-2332, and the heterologous KS-06-72109 strain (a Kansas isolate of PRRSV, we compared immune responses induced by vaccination and/or PRRSV infection. Our results showed that MLV can provide complete protection from homologous virus (VR-2332 and partial protection from heterologous (KS-06 challenge. The protection was associated with the levels of PRRSV neutralizing antibodies at the time of challenge, with vaccinated pigs having higher titers to VR-2332 compared to KS-06 strain. Challenge strain did not alter the cytokine expression profiles in the serum of vaccinated pigs or subpopulations of T cells. However, higher frequencies of IFN-γ-secreting PBMCs were generated from pigs challenged with heterologous PRRSV in a recall response when PBMCs were re-stimulated with PRRSV. Thus, this study indicates that serum neutralizing antibody titers are associated with PRRSV vaccination-induced protection against homologous and heterologous challenge.

  11. Humoral immune responses in rabbits induced by an experimental inactivated severe acute respiratory syndrome coronavirus vaccine prepared from F69 strain

    Institute of Scientific and Technical Information of China (English)

    张传海; 郭中敏; 郑焕英; 陆家海; 王一飞; 鄢心革; 赵勇; 杜雄威; 张欣; 方苓; 凌文华; 戚树源; 余新炳; 钟南山

    2004-01-01

    Background The etiologic agent of severe acute respiratory syndrome (SARS) has been confirmed to be a novel coronavirus (CoV), namely SARS-CoV. Developing safe and effective SARS-CoV vaccines is essential for us to prevent the possible reemergence of its epidemic. Previous experiences indicate that inactivated vaccine is conventional and more hopeful to be successfully developed. Immunogenicity evaluation of an experimental inactivated SARS-CoV vaccine in rabbits was conducted and reported in this paper.Methods The large-scale cultured SARS-CoV F69 strain was inactivated with 0.4% formaldehyde and purified, then used as the immunogen combined with Freund's adjuvant. Eight adult New Zealand rabbits were immunized four times with this experimental inactivated vaccine. Twelve sets of rabbit serum were sampled from the third day to the seventy-fourth day after the first vaccination. The titers of specific anti-SARS-CoV IgG antibody were determined by indirect enzyme-linked immunosorbent assay, and the neutralizing antibody titers were detected with micro-cytopathic effect neutralization test.Conclusions The inactivated SARS-CoV vaccine made from F69 strain owns strong immunogenicity, and the cross neutralization response between the two different SARS-CoV strains gives a hint of the similar neutralizing epitopes, which provide stable bases for the development of inactivated SARS-CoV vaccines.

  12. Posterior Cord Syndrome and Trace Elements Deficiency as an Uncommon Presentation of Common Variable Immunodeficiency

    Directory of Open Access Journals (Sweden)

    Yuri Silva Macedo

    2017-01-01

    Full Text Available Diarrhea is one of the most common symptoms in common variable immunodeficiency, but neurologic manifestations are rare. We presented a 50-year-old woman with recurrent diarrhea and severe weight loss that developed a posterior cord syndrome. Endoscopy found a duodenal villous blunting, intraepithelial lymphocytosis, and lack of plasma cells and magnetic resonance imaging of the spine was normal. Laboratory assays confirmed common variable immunodeficiency syndrome and showed low levels of trace elements (copper and zinc. Treatment was initiated with parenteral replacement of trace elements and intravenous human immunoglobulin and the patient improved clinically. In conclusion, physicians must be aware that gastrointestinal and neurologic disorders may be related to each other and remember to request trace elements laboratory assessment.

  13. Homozygosity for a novel truncating mutation confirms TBX15 deficiency as the cause of Cousin syndrome.

    Science.gov (United States)

    Dikoglu, Esra; Simsek-Kiper, Pelin Ozlem; Utine, Gulen Eda; Campos-Xavier, Belinda; Boduroglu, Koray; Bonafé, Luisa; Superti-Furga, Andrea; Unger, Sheila

    2013-12-01

    Cousin syndrome, also called pelviscapular dysplasia (OMIM 260660), is characterized by short stature, craniofacial dysmorphism, and multiple skeletal anomalies. Following its description in two sibs in 1982, no new cases have been observed until the observation of two unrelated cases in 2008 who were homozygous for frameshift mutations in TBX15. We investigated an adult individual with short stature, a complex craniofacial dysmorphism, malformed and rotated ears, short neck, elbow contractures, hypoacusis, and hypoplasia of scapula and pelvis on radiographs. We identified homozygosity for a novel nonsense mutation (c.841C>T) in TBX15 predicted to cause a premature stop (p.Arg281*) with truncation of the protein. This observation confirms that Cousin syndrome is a consistent and clinically recognizable phenotype caused by loss of function of TBX15.

  14. Gray platelet syndrome and defective thrombo-inflammation in Nbeal2-deficient mice

    OpenAIRE

    Deppermann, Carsten; Cherpokova, Deya; Nurden, Paquita; Schulz, Jan-Niklas; Thielmann, Ina; Kraft, Peter; Vögtle, Timo; Kleinschnitz, Christoph; Dütting, Sebastian; Krohne, Georg; Eming, Sabine A.; Nurden, Alan T; Eckes, Beate; Stoll, Guido; Stegner, David

    2013-01-01

    Platelets are anuclear organelle-rich cell fragments derived from bone marrow megakaryocytes (MKs) that safeguard vascular integrity. The major platelet organelles, α-granules, release proteins that participate in thrombus formation and hemostasis. Proteins stored in α-granules are also thought to play a role in inflammation and wound healing, but their functional significance in vivo is unknown. Mutations in NBEAL2 have been linked to gray platelet syndrome (GPS), a rare bleeding disorder ch...

  15. Abnormal heart rate recovery and deficient chronotropic response after submaximal exercise in young Marfan syndrome patients.

    Science.gov (United States)

    Peres, Paulo; Carvalho, Antônio C; Perez, Ana Beatriz A; Medeiros, Wladimir M

    2016-10-01

    Marfan syndrome patients present important cardiac structural changes, ventricular dysfunction, and electrocardiographic changes. An abnormal heart rate response during or after exercise is an independent predictor of mortality and autonomic dysfunction. The aim of the present study was to compare heart rate recovery and chronotropic response obtained by cardiac reserve in patients with Marfan syndrome subjected to submaximal exercise. A total of 12 patients on β-blocker therapy and 13 off β-blocker therapy were compared with 12 healthy controls. They were subjected to submaximal exercise with lactate measurements. The heart rate recovery was obtained in the first minute of recovery and corrected for cardiac reserve and peak lactate concentration. Peak heart rate (141±16 versus 155±17 versus 174±8 bpm; p=0.001), heart rate reserve (58.7±9.4 versus 67.6±14.3 versus 82.6±4.8 bpm; p=0.001), heart rate recovery (22±6 versus 22±8 versus 34±9 bpm; p=0.001), and heart rate recovery/lactate (3±1 versus 3±1 versus 5±1 bpm/mmol/L; p=0.003) were different between Marfan groups and controls, respectively. All the patients with Marfan syndrome had heart rate recovery values below the mean observed in the control group. The absolute values of heart rate recovery were strongly correlated with the heart rate reserve (r=0.76; p=0.001). Marfan syndrome patients have reduced heart rate recovery and chronotropic deficit after submaximal exercise, and the chronotropic deficit is a strong determinant of heart rate recovery. These changes are suggestive of autonomic dysfunction.

  16. Vitamin D Deficiency is Associated with the Metabolic Syndrome in Subjects with Type 2 Diabetes

    Directory of Open Access Journals (Sweden)

    Bahareh Nikooyeh

    2014-09-01

    Conclusions: Our data showed that firstly higher vitamin D status is inversely associated with fasting glycemia, and secondly serum 25(OHD3 predicts MeS risk in the subjects with T2D. Demonstrating the association of hypovitaminosis D with disorders of glucose metabolism and higher risk for development of further complications, notably CVD, may lead to a new target for preventive efforts at the population level. Keywords: Vitamin D, Type 2 diabetes, Metabolic syndrome, Cardiovascular disease

  17. Aldosterone deficiency after unilateral adrenalectomy for Conn’s syndrome: a case report and literature review

    Science.gov (United States)

    Yorke, Ekua; Stafford, Sara; Holmes, Daniel; Sheth, Sachiv; Melck, Adrienne

    2015-01-01

    Introduction Approximately 35% of cases of Conn’s syndrome (primary aldosteronism) result from a solitary functioning adrenal adenoma, and these patients are best managed by adrenalectomy. Postoperative hypoaldosteronism after unilateral adrenalectomy is uncommon. Case presentation We present a case and literature review of hypoaldosteronism after unilateral adrenalectomy for Conn’s syndrome, which demonstrates the insidious and sometimes delayed presentation. Discussion In this clinical case we summarize the previously published cases of post-adrenalectomy hypoaldosteronism based on a PUBMED and EBSCOhost search of all peer-reviewed publications (original articles and reviews) on this topic. A few cases of aldosterone insufficiency post-adrenalectomy for Conn’s syndrome were identified. The etiological factors for prolonged selective suppression of aldosterone secretion after unilateral adrenalectomy remain unclear. Conclusion It is important to be aware of the risk of postoperative hypoaldosteronism in this patient population. Close postoperative follow-up is necessary and strongly recommended, especially in patients with certain risk factors. Patients may need mineralocorticoid supplementation during this period. PMID:25604311

  18. Vaccination with Replication Deficient Adenovectors Encoding YF-17D Antigens Induces Long-Lasting Protection from Severe Yellow Fever Virus Infection in Mice

    DEFF Research Database (Denmark)

    Bassi, Maria R; Larsen, Mads Andreas Bay; Kongsgaard, Michael

    2016-01-01

    The live attenuated yellow fever vaccine (YF-17D) has been successfully used for more than 70 years. It is generally considered a safe vaccine, however, recent reports of serious adverse events following vaccination have raised concerns and led to suggestions that even safer YF vaccines should...

  19. Investigating Reports of Complex Regional Pain Syndrome: An Analysis of HPV-16/18-Adjuvanted Vaccine Post-Licensure Data

    Directory of Open Access Journals (Sweden)

    Frank Huygen

    2015-09-01

    There is not sufficient evidence to suggest an increased risk of developing CRPS following vaccination with HPV-16/18-adjuvanted vaccine. Post-licensure safety surveillance confirms the acceptable benefit-risk of HPV-16/18 vaccination.

  20. Guillain-Barré Syndrome and Adjuvanted Pandemic Influenza A (H1N1) 2009 Vaccines: A Multinational Self-Controlled Case Series in Europe

    Science.gov (United States)

    Dieleman, Jeanne P.; Olberg, Henning K.; de Vries, Corinne S.; Sammon, Cormac; Andrews, Nick; Svanström, Henrik; Mølgaard-Nielsen, Ditte; Hviid, Anders; Lapeyre-Mestre, Maryse; Sommet, Agnès; Saussier, Christel; Castot, Anne; Heijbel, Harald; Arnheim-Dahlström, Lisen; Sparen, Par; Mosseveld, Mees; Schuemie, Martijn; van der Maas, Nicoline; Jacobs, Bart C.; Leino, Tuija; Kilpi, Terhi; Storsaeter, Jann; Johansen, Kari; Kramarz, Piotr; Bonhoeffer, Jan; Sturkenboom, Miriam C. J. M.

    2014-01-01

    Background The risk of Guillain-Barré syndrome (GBS) following the United States' 1976 swine flu vaccination campaign in the USA led to enhanced active surveillance during the pandemic influenza (A(H1N1)pdm09) immunization campaign. This study aimed to estimate the risk of GBS following influenza A(H1N1)pdm09 vaccination. Methods A self-controlled case series (SCCS) analysis was performed in Denmark, Finland, France, Netherlands, Norway, Sweden, and the United Kingdom. Information was collected according to a common protocol and standardised procedures. Cases classified at levels 1–4a of the Brighton Collaboration case definition were included. The risk window was 42 days starting the day after vaccination. Conditional Poisson regression and pooled random effects models estimated adjusted relative incidences (RI). Pseudo likelihood and vaccinated-only methods addressed the potential contraindication for vaccination following GBS. Results Three hundred and three (303) GBS and Miller Fisher syndrome cases were included. Ninety-nine (99) were exposed to A(H1N1)pdm09 vaccination, which was most frequently adjuvanted (Pandemrix and Focetria). The unadjusted pooled RI for A(H1N1)pdm09 vaccination and GBS was 3.5 (95% Confidence Interval (CI): 2.2–5.5), based on all countries. This lowered to 2.0 (95% CI: 1.2–3.1) after adjustment for calendartime and to 1.9 (95% CI: 1.1–3.2) when we accounted for contra-indications. In a subset (Netherlands, Norway, and United Kingdom) we further adjusted for other confounders and there the RI decreased from 1.7 (adjusted for calendar month) to 1.4 (95% CI: 0.7–2.8), which is the main finding. Conclusion This study illustrates the potential of conducting European collaborative vaccine safety studies. The main, fully adjusted analysis, showed that the RI of GBS was not significantly elevated after influenza A(H1N1)pdm09 vaccination (RI = 1.4 (95% CI: 0.7–2.8). Based on the upper limits of the pooled estimate we can rule

  1. Guillain-Barre syndrome and adjuvanted pandemic influenza A (H1N1 2009 vaccines: a multinational self-controlled case series in Europe.

    Directory of Open Access Journals (Sweden)

    Silvana Romio

    Full Text Available BACKGROUND: The risk of Guillain-Barré syndrome (GBS following the United States' 1976 swine flu vaccination campaign in the USA led to enhanced active surveillance during the pandemic influenza (A(H1N1pdm09 immunization campaign. This study aimed to estimate the risk of GBS following influenza A(H1N1pdm09 vaccination. METHODS: A self-controlled case series (SCCS analysis was performed in Denmark, Finland, France, Netherlands, Norway, Sweden, and the United Kingdom. Information was collected according to a common protocol and standardised procedures. Cases classified at levels 1-4a of the Brighton Collaboration case definition were included. The risk window was 42 days starting the day after vaccination. Conditional Poisson regression and pooled random effects models estimated adjusted relative incidences (RI. Pseudo likelihood and vaccinated-only methods addressed the potential contraindication for vaccination following GBS. RESULTS: Three hundred and three (303 GBS and Miller Fisher syndrome cases were included. Ninety-nine (99 were exposed to A(H1N1pdm09 vaccination, which was most frequently adjuvanted (Pandemrix and Focetria. The unadjusted pooled RI for A(H1N1pdm09 vaccination and GBS was 3.5 (95% Confidence Interval (CI: 2.2-5.5, based on all countries. This lowered to 2.0 (95% CI: 1.2-3.1 after adjustment for calendartime and to 1.9 (95% CI: 1.1-3.2 when we accounted for contra-indications. In a subset (Netherlands, Norway, and United Kingdom we further adjusted for other confounders and there the RI decreased from 1.7 (adjusted for calendar month to 1.4 (95% CI: 0.7-2.8, which is the main finding. CONCLUSION: This study illustrates the potential of conducting European collaborative vaccine safety studies. The main, fully adjusted analysis, showed that the RI of GBS was not significantly elevated after influenza A(H1N1pdm09 vaccination (RI = 1.4 (95% CI: 0.7-2.8. Based on the upper limits of the pooled estimate we can rule out with

  2. Difference of all gene expression profiles of rat liver between model of deficient cold syndrome and model of deficient heat syndrome%比较虚寒证与虚热证模型大鼠肝全基因表达谱的差异

    Institute of Scientific and Technical Information of China (English)

    韩冰冰; 王世军

    2011-01-01

    Objective To study the difference of all gene expression profiles of rat liver between model of deficient cold syndrome and model of deficient heat syndrome by using gene chip technology. Methods The rat model of deficient cold syndrome or deficient heat syndrome was established through giving TCM compound formulas. The gene expressions in rats of all groups were detected by using gene chips for screening the genes with differential expressions. The genetic function was commented according their classification. The chip results were tested by using fluorescent quantitation polymerase chain reaction (PCR). Results There were 114 genes with differential expressions in comparison between deficient cold model group and deficient heat model group groups, and they involved mainly the genes related to oxidoreductase activity. Oxidoreductase genes rdlated to fat metabolism and cytochrome P450 genes were down-regulated significantly, which indicated that fiat metabolism and bioconversion decreased in rat model of deficient cold syndrome. Conclusion Deficient cold syndrome and deficient heat syndrome, although being deficient syndrome as well, are different in cold and heat symptoms. The abnormal expressions of the genes related to oxidoreductase activity may be the material base of different symptoms in deficient cold syndrome and deficient heat syndrome.%目的 采用基因芯片技术研究虚寒证与虚热证大鼠肝全基因表达谱的差异.方法 使用中药复方虚寒证、虚热证大鼠模型,基因芯片检测各组大鼠基因表达,筛选差异表达基因,进行基因功能分类注释,荧光定量PCR验证芯片结果.结果 虚寒模型组与虚热模型组比较有114条基因差异表达,主要涉及氧化还原酶相关基因.脂代谢相关氧化还原酶基因显著下调,细胞色素P450家族基因显著下调,提示虚寒证模型大鼠脂代谢与生物转化能力的降低.结论 虚寒证与虚热证虽然同为虚证,但有“寒证”和“

  3. Response to intravenous iron in patients with iron deficiency anemia (IDA) and restless leg syndrome (Willis-Ekbom disease).

    Science.gov (United States)

    Mehmood, Tahir; Auerbach, Michael; Earley, Christopher J; Allen, Richard P

    2014-12-01

    Iron deficiency anemia (IDA) engenders restless legs syndrome (RLS, aka Willis-Ekbom disease). Intravenous (IV) iron can rapidly reverse IDA and would be expected to similarly reverse RLS caused by IDA. This is the first consecutive case series evaluating the effects of IV iron therapy on RLS occurring with IDA (RLS-IDA). RLS-IDA patients were evaluated before and 7-12 months after a 1000-mg IV infusion of low-molecular-weight iron dextran (INFeD(@)) using validated questionnaires and standardized telephone interview. Patients were classified as respondent versus nonrespondent for RLS improvement. Follow-up data were obtained on 42 (70%) of 60 consecutive RLS-IDA patients. The symptoms of RLS were reduced in 76% (32/42) with 47% (20/42) showing an extended response lasting >6 months. The response did not relate to age or gender, but tended to be less among African-Americans than Whites (40% (2/5) vs. 81% (30/37), p = 0.078). White respondents versus nonrespondents had higher hemoglobin levels after treatment (12.1 vs. 11.3 g/dl, p = 0.03). RLS-IDA is reduced after administration of IV iron in most cases, but the 24% failing to respond was higher than expected. The nonrespondents all showed below-normal hemoglobin levels (<12.5 g/dl) suggesting a failure of adequate treatment of the iron deficiency. IV iron treatment of the RLS with IDA likely requires ensuring more than minimally adequate body iron stores to support iron delivery to the brain. For some, this may require a dose higher than the customary 1000-mg IV iron used for the treatment of either IDA or RLS alone. Copyright © 2014 Elsevier B.V. All rights reserved.

  4. Multifactorial origins of heart and gut defects in nipbl-deficient zebrafish, a model of Cornelia de Lange Syndrome.

    Directory of Open Access Journals (Sweden)

    Akihiko Muto

    2011-10-01

    Full Text Available Cornelia de Lange Syndrome (CdLS is the founding member of a class of multi-organ system birth defect syndromes termed cohesinopathies, named for the chromatin-associated protein complex cohesin, which mediates sister chromatid cohesion. Most cases of CdLS are caused by haploinsufficiency for Nipped-B-like (Nipbl, a highly conserved protein that facilitates cohesin loading. Consistent with recent evidence implicating cohesin and Nipbl in transcriptional regulation, both CdLS cell lines and tissues of Nipbl-deficient mice show changes in the expression of hundreds of genes. Nearly all such changes are modest, however--usually less than 1.5-fold--raising the intriguing possibility that, in CdLS, severe developmental defects result from the collective action of many otherwise innocuous perturbations. As a step toward testing this hypothesis, we developed a model of nipbl-deficiency in zebrafish, an organism in which we can quantitatively investigate the combinatorial effects of gene expression changes. After characterizing the structure and embryonic expression of the two zebrafish nipbl genes, we showed that morpholino knockdown of these genes produces a spectrum of specific heart and gut/visceral organ defects with similarities to those in CdLS. Analysis of nipbl morphants further revealed that, as early as gastrulation, expression of genes involved in endodermal differentiation (sox32, sox17, foxa2, and gata5 and left-right patterning (spaw, lefty2, and dnah9 is altered. Experimental manipulation of the levels of several such genes--using RNA injection or morpholino knockdown--implicated both additive and synergistic interactions in causing observed developmental defects. These findings support the view that birth defects in CdLS arise from collective effects of quantitative changes in gene expression. Interestingly, both the phenotypes and gene expression changes in nipbl morphants differed from those in mutants or morphants for genes encoding

  5. A 23 years follow-up study identifies GLUT1 deficiency syndrome initially diagnosed as complicated hereditary spastic paraplegia.

    Science.gov (United States)

    Diomedi, Marina; Gan-Or, Ziv; Placidi, Fabio; Dion, Patrick A; Szuto, Anna; Bengala, Mario; Rouleau, Guy A; Gigli, Gian Luigi

    2016-11-01

    Glucose transporter 1 (GLUT1) deficiency syndrome (GLUT1DS) was initially described in the early 90s as a sporadic clinical condition, characterized by seizures, motor and intellectual impairment with variable clinical presentation, and without a known genetic cause. Although causative mutations in SLC2A1 were later identified and much more is known about the disease, it still remains largely underdiagnosed. In the current study, a previously described Italian family was re-analyzed using whole exome sequencing and clinically re-evaluated. Affected individuals presented with spastic paraplegia as a predominant symptom, with epilepsy and intellectual disability, inherited as an autosomal dominant trait with variable clinical presentation. While a novel variant of hereditary spastic paraplegia (HSP) was initially hypothesized in this family, previous linkage studies of known HSP genes did not identify the genetic cause. Exome-sequencing study identified a p.Arg126Cys mutation in the SLC2A1 gene, encoding GLUT1, which segregated with the affected members of the family. The diagnosis of GLUT1DS was further confirmed by cerebrospinal fluid analysis, and treatment was started with good initial response. The description of this large family provides further clinical information on this rare disease. It also offers an example of how GLUT1DS can be challenging to diagnose, and emphasizes the importance of lumbar puncture in the workflow of similar syndromes. Finally, it suggests that analysis of SLC2A1 should be considered in the diagnostic work up of HSP, especially if it is associated with epilepsy. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  6. Hyponatremia in aneurysmal subarachnoid hemorrhage is due to the syndrome of inappropriate antidiuresis and acute glucocorticoid deficiency

    LENUS (Irish Health Repository)

    Hannon, M J

    2011-06-01

    Hyponatraemia is the most common electrolyte abnormality following subarachnoid haemorrhage (SAH) and contributes to increased morbidity and mortality. Retrospective data suggests that the syndrome of inappropriate diuresis (SIAD) is the most common cause of hyponatraemia in SAH, though cerebral salt wasting has been postulated by some workers to be the predominant abnormality. Data which has shown acute glucocorticoid deficiency following SAH has suggested that some cases of euvolaemic hyponatraemia may also be caused by this mechanism.We prospectively studied the hormonal and haemodynamic influences involved in the development of hyponatraemia in 100 patients (61% female, median age 53 (range 16-82)) with non-traumatic aneurysmal SAH. Each patient had plasma sodium (pNa), urea, osmolality, glucose and 0900h cortisol (PC), and urinary sodium and osmolality measured on days 1, 2, 3, 4, 6, 8, 10 and 12 following SAH. Fluid balance and haemodynamic parameters were recorded daily. Results were compared with 15 patients admitted to ITU following vascular surgery. A PC<300nmol\\/L in a patient in ITU was regarded clinically as inappropriately low.49% of patients developed hyponatraemia (pNa<135 mmol\\/L), including 14% who developed clinically significantly hyponatraemia (pNa<130 mmol\\/L). 36\\/49 (73.4%) developed hyponatraemia between days 1 and 3 post SAH. The median duration of hyponatraemia was 3 days (range 1–10 days).In 35\\/49 (71.4%), hyponatraemia was due to SIAD as defined by standard diagnostic criteria. 14% of SAH patients had at least one PC<300nmol\\/L; 5 of these (35.7%) developed hyponatraemia. In 4 patients hyponatraemia was preceded by acute cortisol deficiency and responded to hydrocortisone treatment. In contrast, all controls had PC>500 nmol\\/L on day 1, and >300 nmol on days 3–12. There were no cases of cerebral salt wasting. There was no relationship between the incidence of hyponatraemia and the defined anatomical territory or severity of

  7. Expression profile of bio-defense genes in Penaeus monodon gills in response to formalin inactivated white spot syndrome virus vaccine.

    Science.gov (United States)

    Sudheer, N S; Poulose, Gigi; Thomas, Ancy; Viswanath, Kiron; Kulkarni, Amod; Narayanan, R B; Philip, Rosamma; Singh, I S Bright

    2015-05-01

    White spot syndrome virus (WSSV) is the most devastating pathogen of penaeid shrimp. While developing technology to vaccinate shrimp against WSSV, it is imperative to look into the immune response of the animal at molecular level. However, very little information has been generated in this direction. The present study is an attempt to understand the expression of bio-defense genes in gill tissues of Penaeus monodon in response to formalin inactivated WSSV. A WSSV vaccine with a viral titer of 1×10(9) DNA copies was prepared and orally administered to P. monodon at a rate of 1.75×10(6) DNA copies of inactivated virus preparation (IVP) day(-1) for 7days. The animals were challenged with WSSV on 1st and 5th day post vaccination, and temporal expression of bio-defense genes in gill tissues was studied. Survival of 100% and 50% were observed respectively on 1st and 5th day post vaccination challenge. The humoral immune genes prophenoloxidase (proPO), alpha 2-macroglobulin (α2M), crustin and PmRACK, and the cell mediated immune genes caspase and Rab7 were up regulated in gill tissue upon vaccination and challenge. The expression of humoral gene crustin and cellular gene Rab7 was related to survival in IVP administered shrimp. Results of the study suggest that these genes have roles in protecting shrimp from WSSV on vaccination.

  8. Review of the results of WT1 peptide vaccination strategies for myelodysplastic syndromes and acute myeloid leukemia from 9 different studies

    Directory of Open Access Journals (Sweden)

    Antonio eDi Stasi

    2015-02-01

    Full Text Available We performed a systematic review of data from seven clinical trials of WT1 peptide vaccination in patients with myelodysplastic syndromes and/or acute myeloid leukemia (MDS/AML, published between 2004 and 2012. A total of fifty-one patients were eligible for analysis. Vaccination with WT1 peptides proved safe and feasible in patients with MDS/AML, in studies from different institutions. Additionally, clinical responses and clinical benefit were observed, with some patients achieving and maintaining remission long term (more than 8 years. A significant correlation between induction of WT1 specific T cells and normalization/reduction of WT1 mRNA levels and progression free survival was noted in a number of studies. However larger studies are warranted to confirm these results. Interestingly, the majority of trials reported the presence of WT1 specific T cells with limited or absent functionality prior to vaccination, which increased in frequency and function after vaccination. In conclusion, WT1 peptide vaccination strategies were safe in this heterogeneous group of patient with MDS/AML. Larger and more homogeneous studies or randomized clinical trials are needed to quantify the contribution of WT1 peptide vaccines to clinical responses and long term survival.

  9. Mice deficient in small leucine-rich proteoglycans: novel in vivo models for osteoporosis, osteoarthritis, Ehlers-Danlos syndrome, muscular dystrophy, and corneal diseases.

    Science.gov (United States)

    Ameye, Laurent; Young, Marian F

    2002-09-01

    Small leucine-rich proteoglycans (SLRPs) are extracellular molecules that bind to TGFbetas and collagens and other matrix molecules. In vitro, SLRPs were shown to regulate collagen fibrillogenesis, a process essential in development, tissue repair, and metastasis. To better understand their functions in vivo, mice deficient in one or two of the four most prominent and widely expressed SLRPs (biglycan, decorin, fibromodulin, and lumican) were recently generated. All four SLRP deficiencies result in the formation of abnormal collagen fibrils. Taken together, the collagen phenotypes demonstrate a cooperative, sequential, timely orchestrated action of the SLRPs that altogether shape the architecture and mechanical properties of the collagen matrix. In addition, SLRP-deficient mice develop a wide array of diseases (osteoporosis, osteoarthritis, muscular dystrophy, Ehlers-Danlos syndrome, and corneal diseases), most of them resulting primarily from an abnormal collagen fibrillogenesis. The development of these diseases by SLRP-deficient mice suggests that mutations in SLRPs may be part of undiagnosed predisposing genetic factors for these diseases. Although the distinct phenotypes developed by the different singly deficient mice point to distinct in vivo function for each SLRP, the analysis of the double-deficient mice also demonstrates the existence of rescuing/compensation mechanisms, indicating some functional overlap within the SLRP family.

  10. International Retrospective Chart Review of Treatment Patterns in Severe Familial Mediterranean Fever, Tumor Necrosis Factor Receptor-Associated Periodic Syndrome, and Mevalonate Kinase Deficiency/Hyperimmunoglobulinemia D Syndrome.

    Science.gov (United States)

    Ozen, Seza; Kuemmerle-Deschner, Jasmin B; Cimaz, Rolando; Livneh, Avi; Quartier, Pierre; Kone-Paut, Isabelle; Zeft, Andrew; Spalding, Steve; Gul, Ahmet; Hentgen, Veronique; Savic, Sinisa; Foeldvari, Ivan; Frenkel, Joost; Cantarini, Luca; Patel, Dony; Weiss, Jeffrey; Marinsek, Nina; Degun, Ravi; Lomax, Kathleen G; Lachmann, Helen J

    2017-04-01

    Periodic fever syndrome (PFS) conditions are characterized by recurrent attacks of fever and localized inflammation. This study examined the diagnostic pathway and treatments at tertiary centers for familial Mediterranean fever (FMF), tumor necrosis factor receptor-associated periodic syndrome (TRAPS), and mevalonate kinase deficiency (MKD)/hyperimmunoglobulinemia D syndrome (HIDS). PFS specialists at medical centers in the US, the European Union, and the eastern Mediterranean participated in a retrospective chart review, providing de-identified data in an electronic case report form. Patients were treated between 2008 and 2012, with at least 1 year of followup; all had clinical and/or genetically proven disease and were on/eligible for biologic treatment. A total of 134 patients were analyzed: FMF (n = 49), TRAPS (n = 47), and MKD/HIDS (n = 38). Fever was commonly reported as severe across all indications. Other frequently reported severe symptoms were serositis for FMF patients and elevated acute-phase reactants and gastrointestinal upset for TRAPS and MKD/HIDS. A long delay from disease onset to diagnosis was seen within TRAPS and MKD/HIDS (5.8 and 7.1 years, respectively) compared to a 1.8-year delay in FMF patients. An equal proportion of TRAPS patients first received anti-interleukin-1 (anti-IL-1) and anti-tumor necrosis factor (anti-TNF) biologic agents, whereas IL-1 blockade was the main choice for FMF patients resistant to colchicine and MKD/HIDS patients. For TRAPS patients, treatment with anakinra versus anti-TNF treatments as first biologic agent resulted in significantly higher clinical and biochemical responses (P = 0.03 and P < 0.01, respectively). No significant differences in responses were observed between biologic agents among other cohorts. Referral patterns and diagnostic delays highlight the need for greater awareness and improved diagnostics for PFS. This real-world treatment assessment supports the need for further

  11. Clinical Associations of Biallelic and Monoallelic TNFRSF13B Variants in Italian Primary Antibody Deficiency Syndromes

    Directory of Open Access Journals (Sweden)

    Federica Pulvirenti

    2016-01-01

    Full Text Available We assessed the prevalence of TNFRSF13B mutations and the clinical correlates in an Italian cohort of 189 CVID, 67 IgAD patients, and 330 healthy controls to substantiate the role of TACI genetic testing in diagnostic workup. We found that 11% of CVID and 13% of IgAD carried at least one mutated TNFRSF13B allele. Seven per cent of CVID had monoallelic-mutations and 4% had biallelic-mutations. The frequency of C104R monoallelic-mutations was not higher than that found in healthy controls. Biallelic-mutations were exclusively found in CVID. CVID patients carrying monoallelic-mutations had an increased prevalence of lymphadenopathy, granulomata, and autoimmune cytopenias. CVID carrying biallelic-mutations had a low prevalence of autoimmunity in comparison with TACI wild-type CVID. Moreover, biallelic-mutated CVID had higher frequency of switched memory B-cells and higher IgM and IgA antibodies to polysaccharide antigens than TACI wild-type and monoallelic-mutated CVID. TACI-mutated IgAD patients had only monoallelic-mutations and did not display clinical difference from IgAD wild-type patients. In conclusion, TNFRSF13B genetic screening of antibody deficiencies may allow the identification of mutational patterns. However, as with counseling for risk assessment, geneticists should be aware that the interpretation of genetic testing for TACI mutations is difficult and the potential impact on clinical management is still limited.

  12. Lesch-Nyhan syndrome: mRNA expression of HPRT in patients with enzyme proven deficiency of HPRT and normal HPRT coding region of the DNA.

    Science.gov (United States)

    Nguyen, Khue Vu; Naviaux, Robert K; Paik, Kacie K; Nyhan, William L

    2012-08-01

    Inherited mutation of the purine salvage enzyme, hypoxanthine guanine phosphoribosyltransferase (HPRT) gives rise to Lesch-Nyhan syndrome (LNS) or Lesch-Nyhan variants (LNV). We report a case of two LNS affected members of a family with deficiency of activity of HPRT in intact cultured fibroblasts in whom mutation could not be found in the HPRT coding sequence but there was markedly decreased HPRT expression of mRNA. Published by Elsevier Inc.

  13. Sindrom pomanjkanja rastnega hormona pri odraslem - učinki nadomestnega zdravljenja: Syndrome of growth hormone deficiency in adults - effects of growth hormone replacement therapy:

    OpenAIRE

    Pfeifer, Marija

    2001-01-01

    Background. After the cessation of longitudinal growth, growth hormone (GH) continues to subserve an important role in the regulation of body metabolism (stimulation of lipolysis and lipid oxidation, protein synthesis, insulin antagonism, and sodium and water retention) to optimise body composition and function. Most patients with hypopituitarism exhibit the syndrome of GH deficiency with a number of abnormal features which can be reversed with recombinant GH replacement therapy. Conclusions....

  14. Brain microvasculature defects and Glut1 deficiency syndrome averted by early repletion of the glucose transporter-1 protein.

    Science.gov (United States)

    Tang, Maoxue; Gao, Guangping; Rueda, Carlos B; Yu, Hang; Thibodeaux, David N; Awano, Tomoyuki; Engelstad, Kristin M; Sanchez-Quintero, Maria-Jose; Yang, Hong; Li, Fanghua; Li, Huapeng; Su, Qin; Shetler, Kara E; Jones, Lynne; Seo, Ryan; McConathy, Jonathan; Hillman, Elizabeth M; Noebels, Jeffrey L; De Vivo, Darryl C; Monani, Umrao R

    2017-01-20

    Haploinsufficiency of the SLC2A1 gene and paucity of its translated product, the glucose transporter-1 (Glut1) protein, disrupt brain function and cause the neurodevelopmental disorder, Glut1 deficiency syndrome (Glut1 DS). There is little to suggest how reduced Glut1 causes cognitive dysfunction and no optimal treatment for Glut1 DS. We used model mice to demonstrate that low Glut1 protein arrests cerebral angiogenesis, resulting in a profound diminution of the brain microvasculature without compromising the blood-brain barrier. Studies to define the temporal requirements for Glut1 reveal that pre-symptomatic, AAV9-mediated repletion of the protein averts brain microvasculature defects and prevents disease, whereas augmenting the protein late, during adulthood, is devoid of benefit. Still, treatment following symptom onset can be effective; Glut1 repletion in early-symptomatic mutants that have experienced sustained periods of low brain glucose nevertheless restores the cerebral microvasculature and ameliorates disease. Timely Glut1 repletion may thus constitute an effective treatment for Glut1 DS.

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

    Directory of Open Access Journals (Sweden)

    Giri S

    2013-09-01

    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

  16. Dehydroepiandrosterone (DHEA) substitution treatment for severe fatigue in DHEA-deficient patients with primary Sjögren's syndrome.

    Science.gov (United States)

    Virkki, Liisa M; Porola, Pauliina; Forsblad-d'Elia, Helena; Valtysdottir, Sigridur; Solovieva, Svetlana A; Konttinen, Yrjö T

    2010-01-15

    Primary Sjögren's syndrome (SS) is characterized by fatigue and low levels of serum dehydroepiandrosterone/dehydroepiandrosterone sulfate (DHEA/DHEAS). Our aim was to study whether SS patients with severe fatigue and low serum DHEAS values benefit from DHEA substitution (50 mg/day). A multicenter, investigator-based, powered, randomized controlled clinical trial (crossover, washout design) using fatigue as the primary outcome measure was performed on patients with primary SS (n = 107) who had a general fatigue score > or =14 on the 20-item Multiple Fatigue Inventory (MFI-20), combined with age- and sex-adjusted serum DHEAS values below the mean. Fatigue was assessed using MFI-20 subscales, i.e., general fatigue, physical fatigue, mental fatigue, reduced motivation, and activity (scale 4-20), and with a visual analog scale (VAS; scale 0-100). In an intent-to-treat analysis, a 50-mg DHEA substitution dose and placebo similarly improved fatigue. All of the MFI-20 subscales and the fatigue VAS improved from the baseline levels as a result of treatment (P DHEA in DHEA-deficient and severely tired primary SS patients does not help against fatigue better than placebo. This may relate to the prohormone nature of DHEA and its recently described defective intracrine tissue-specific conversion to active sex steroids in SS.

  17. 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

    2011-05-01

    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.

  18. A Protein Kinase C Phosphorylation Motif in GLUT1 Affects Glucose Transport and is Mutated in GLUT1 Deficiency Syndrome.

    Science.gov (United States)

    Lee, Eunice E; Ma, Jing; Sacharidou, Anastasia; Mi, Wentao; Salato, Valerie K; Nguyen, Nam; Jiang, Youxing; Pascual, Juan M; North, Paula E; Shaul, Philip W; Mettlen, Marcel; Wang, Richard C

    2015-06-04

    Protein kinase C has been implicated in the phosphorylation of the erythrocyte/brain glucose transporter, GLUT1, without a clear understanding of the site(s) of phosphorylation and the possible effects on glucose transport. Through in vitro kinase assays, mass spectrometry, and phosphospecific antibodies, we identify serine 226 in GLUT1 as a PKC phosphorylation site. Phosphorylation of S226 is required for the rapid increase in glucose uptake and enhanced cell surface localization of GLUT1 induced by the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA). Endogenous GLUT1 is phosphorylated on S226 in primary endothelial cells in response to TPA or VEGF. Several naturally occurring, pathogenic mutations that cause GLUT1 deficiency syndrome disrupt this PKC phosphomotif, impair the phosphorylation of S226 in vitro, and block TPA-mediated increases in glucose uptake. We demonstrate that the phosphorylation of GLUT1 on S226 regulates glucose transport and propose that this modification is important in the physiological regulation of glucose transport.

  19. Kefir improves fatty liver syndrome by inhibiting the lipogenesis pathway in leptin-deficient ob/ob knockout mice.

    Science.gov (United States)

    Chen, H-L; Tung, Y-T; Tsai, C-L; Lai, C-W; Lai, Z-L; Tsai, H-C; Lin, Y-L; Wang, C-H; Chen, C-M

    2014-09-01

    Fatty liver disease is commonly associated with obesity, insulin resistance and diabetes. Severe fatty liver is sometimes accompanied by steatohepatitis and may lead to the development of hepatocellular carcinoma. At present, there is no effective treatment for non-alcoholic fatty liver disease (NAFLD); thus, recent investigations have focused on developing effective therapeutics to treat this condition. This study aimed to evaluate the effects of kefir on the hepatic lipid metabolism of ob/ob mice, which are commonly used to model fatty liver disease. In this study, we used leptin receptor-deficient ob/ob mice as an animal disease model of NAFLD. Six-week-old ob/ob mice were orally administered the dairy product kefir (140 mg kg(-1) of body weight (BW) per day) for 4 weeks. The data demonstrated that kefir improved fatty liver syndrome on BW, energy expenditure and basal metabolic rate by inhibiting serum glutamate oxaloacetate transaminase (GOT) and glutamate pyruvate transaminase (GPT) activities (Pkefir administration also significantly reduced the macrovesicular fat quantity in liver tissue. In addition, kefir markedly decreased the expression of the genes sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC) (Pkefir improves NAFLD on BW, energy expenditure and basal metabolic rate by inhibiting the lipogenesis pathway and that kefir may have the potential for clinical application to the prevention or treatment of NAFLD.

  20. [Changes of acquired immune deficiency syndrome related knowledge, attitudes, behaviors and their influencing factors among college students in Beijing].

    Science.gov (United States)

    2017-06-18

    To compare acquired immune deficiency syndrome (AIDS) related knowledge, attitudes, behaviors and their influencing factors among college students in different years in Beijing, and to provide evidence for targeted health education among college students in future. College students were selected by the stratified cluster sampling method, and a questionnaire survey was conducted among college students in year 2006 and 2016 in Beijing. The sample sizes were 1 800 and 3 001 college students, respectively. The contents of the questionnaire included: socio-demographic characteristics, AIDS related knowledge, AIDS related attitude, sex intercourse and its related risk behaviors, condom use intension, and AIDS related health education. Compared with the year 2006, the average AIDS knowledge scores of college students in year 2016 dropped from 12.78±1.95 to 11.90±2.56 (t=12.91, Pinfluencing factors of intention on condom use were male (OR=0.713), self-efficacy of condom purchase (OR=0.876), never received sex education before college (OR=0.752), self-efficacy of condom use (OR=1.135), belief of condom use (OR=1.775), and attitude towards AIDS patients (OR=1.136). AIDS related knowledge, attitudes and behaviors among college students have been changed, AIDS related health education should be designed and improved based on new characteristics of college students. AIDS health education in colleges should pay more attention to sex attitude and sex responsibility and self-protection awareness among college students as well.

  1. Studies on 'zinc deficiency syndrome' in black bengal goats (Capra hircus) fed with fodder (Andropogon gayanus) grown on soil treated with an excess of calcium and phosphorus fertilizer.

    Science.gov (United States)

    Ray, S K; Roychoudhury, R; Bandopadhyay, S K; Basu, S

    1997-11-01

    Overliming and excessive application of superphosphate caused a zinc deficiency in the soil and so reduced the uptake of zinc by fodder plants. Bucks reared on such fodder had significantly (p zinc in their hair compared with controls and suffered from 'conditioned zinc deficiency syndrome' with a significant (p zinc sulphate very rapidly improved these conditions to near normality. Histological examination of samples of skin and testis from the zinc-deficient bucks revealed formation of excessive keratin, retention of nuclei in the stratum corneum and reduction in the width of the stratum granulosum in the skin, while samples of testis indicated degenerative changes, including atrophy of the seminiferous tubules, hyperplasia of the germinal epithelium and thickening of the walls of blood vessels.

  2. Strain-dependence of the Angelman Syndrome phenotypes in Ube3a maternal deficiency mice.

    Science.gov (United States)

    Born, Heather A; Dao, An T; Levine, Amber T; Lee, Wai Ling; Mehta, Natasha M; Mehra, Shubhangi; Weeber, Edwin J; Anderson, Anne E

    2017-08-16

    Angelman syndrome (AS) is a genetic neurodevelopmental disorder, most commonly caused by deletion or mutation of the maternal allele of the UBE3A gene, with behavioral phenotypes and seizures as key features. Currently no treatment is available, and therapeutics are often ineffective in controlling AS-associated seizures. Previous publications using the Ube3a maternal deletion model have shown behavioral and seizure susceptibility phenotypes, however findings have been variable and merit characterization of electroencephalographic (EEG) activity. In this study, we extend previous studies comparing the effect of genetic background on the AS phenotype by investigating the behavioral profile, EEG activity, and seizure threshold. AS C57BL/6J mice displayed robust behavioral impairments, spontaneous EEG polyspikes, and increased cortical and hippocampal power primarily driven by delta and theta frequencies. AS 129 mice performed poorly on wire hang and contextual fear conditioning and exhibited a lower seizure threshold and altered spectral power. AS F1 hybrid mice (C57BL/6J × 129) showed milder behavioral impairments, infrequent EEG polyspikes, and fewer spectral power alterations. These findings indicate the effect of common genetic backgrounds on the Ube3a maternal deletion behavioral, EEG, and seizure threshold phenotypes. Our results will inform future studies on the optimal strain for evaluating therapeutics with different AS-like phenotypes.

  3. Acquired immune deficiency syndrome in Thailand. A report of two cases.

    Science.gov (United States)

    Limsuwan, A; Kanapa, S; Siristonapun, Y

    1986-03-01

    As a major tourist attraction for heterosexuals and homosexuals, Thailand stands to experience major increases in the rate of acquired immunodeficiency syndrome (AIDS). This article describes 2 AIDS cases in Thailand, including the 1st documented case. The 1st case involved a 28-year-old unmarried Thai male who travelled to the US in 1981 for postgraduate work and had contact with both female prostitutes and homosexual men. In 1982-83, the patient demonstrated fever, fatigue, meningitis, and finally Pneumocystis carinii. He was hospitalized in 1984 for fever, bilateral deafness, and diarrhea. Serologic analysis revealed antibodies to human T-cell lymphotropic virus type III (HTLV- III). Death occurred in January 1985. The 2nd patient was a 52-year- old single man who had moved from West Germany to Thailand 10 years previously to admission in 1985 for upper gastrointestinal bleeding. The patient, a homosexual, make frequent visits to Germany and was an alcoholic. The initial clinical diagnosis was ruptured esophageal varices with cirrhosis. The patient further had a history of herpes simplex genitalis. The subsequent course of the disease process included massive blood loss and interstitial pneumonitis. Serology revealed antibodies to HTLV-III. Death occurred in August 1985. Both of these patients belonged to groups at high risk of AIDS and had clinical, serologic, and immunologic indicators that enabled confirmation of the AIDS diagnosis.

  4. Progeroid syndrome patients with ZMPSTE24 deficiency could benefit when treated with rapamycin and dimethylsulfoxide

    Science.gov (United States)

    Akinci, Baris; Sankella, Shireesha; Gilpin, Christopher; Ozono, Keiichi; Garg, Abhimanyu; Agarwal, Anil K.

    2017-01-01

    Patients with progeroid syndromes such as mandibuloacral dysplasia, type B (MADB) and restrictive dermopathy (RD) harbor mutations in zinc metalloproteinase (ZMPSTE24), an enzyme essential for posttranslational proteolysis of prelamin A to form mature lamin A. Dermal fibroblasts from these patients show increased nuclear dysmorphology and reduced proliferation; however, the efficacy of various pharmacological agents in reversing these cellular phenotypes remains unknown. In this study, fibroblasts from MADB patients exhibited marked nuclear abnormalities and reduced proliferation that improved upon treatment with rapamycin and dimethylsulfoxide but not with other agents, including farnesyl transferase inhibitors. Surprisingly, fibroblasts from an RD patient with a homozygous null mutation in ZMPSTE24, resulting in exclusive accumulation of prelamin A with no lamin A on immunoblotting of cellular lysate, exhibited few nuclear abnormalities and near-normal cellular proliferation. An unbiased proteomic analysis of the cellular lysate from RD fibroblasts revealed a lack of processing of vimentin, a cytoskeletal protein. Interestingly, the assembly of the vimentin microfibrils in MADB fibroblasts improved with rapamycin and dimethylsulfoxide. We conclude that rapamycin and dimethylsulfoxide are beneficial for improving nuclear morphology and cell proliferation of MADB fibroblasts. Data from a single RD patient's fibroblasts also suggest that prelamin A accumulation by itself might not be detrimental and requires additional alterations at the cellular level to manifest the phenotype. PMID:28050601

  5. Alzheimer's Disease and Vascular Deficiency: Lessons from Imaging Studies and Down Syndrome

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    Arlene Reed-Cossairt

    2012-01-01

    Full Text Available Down syndrome (DS individuals are at high risk for developing Alzheimer's disease (AD and consequently provide a unique opportunity to examine the factors leading to the onset of AD. This paper focuses on the neglected vascular parallels between AD and DS that can readily be examined in DS. Several recent AD studies provide evidence that internal jugular vein (IJV reflux may result in white matter lesions and a 30% decrease in cerebrospinal fluid (CSF clearance of amyloid-β. At the same time, studies analyzing the synthesis of amyloid-β in DS showed greater than expected amounts of Aβ than would be predicted by the increase in gene dosage, perhaps due to slower clearance. These studies are discussed along with the possibility that the venous and CSF dysfunction found in AD patients may be present early in life in persons with DS, leaving them particularly vulnerable to early onset AD. Studying IJV function in DS provides an opportunity to understand the role of vascular function in the initiation of AD.

  6. Deficient Purposeful Use of Forepaws in Female Mice Modelling Rett Syndrome

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    Bianca De Filippis

    2015-01-01

    Full Text Available Rett syndrome (RTT is a rare neurodevelopmental disorder, characterized by severe behavioural and physiological symptoms. Mutations in the methyl CpG binding protein 2 gene (MECP2 cause more than 95% of classic cases. Motor abnormalities represent a significant part of the spectrum of RTT symptoms. In the present study we investigated motor coordination and fine motor skill domains in MeCP2-308 female mice, a validated RTT model. This was complemented by the in vivo magnetic resonance spectroscopy (MRS analysis of metabolic profile in behaviourally relevant brain areas. MeCP2-308 heterozygous female mice (Het, 10-12 months of age were impaired in tasks validated for the assessment of purposeful and coordinated forepaw use (Morag test and Capellini handling task. A fine-grain analysis of spontaneous behaviour in the home-cage also revealed an abnormal handling pattern when interacting with the nesting material, reduced motivation to explore the environment, and increased time devoted to feeding in Het mice. The brain MRS evaluation highlighted decreased levels of bioenergetic metabolites in the striatal area in Het mice compared to controls. Present results confirm behavioural and brain alterations previously reported in MeCP2-308 males and identify novel endpoints on which the efficacy of innovative therapeutic strategies for RTT may be tested.

  7. 试论肾虚痹证(类风湿性关节炎)发育生物学基础%Background of Developmental Biology on Bi Syndrome of the Deficiency of Kidney (Rheumatoid Arthritis)

    Institute of Scientific and Technical Information of China (English)

    张浩; 吕爱平

    2003-01-01

    According to traditional Chinese medicine, the kidney promotes the growth and develepment of the body, the deficiency of kidney is a important pathogenesis of Bi syndome (Rheumatoid Arthritis, RA). Modem medicial research shows that RA has abnormality in developmental biology. The paper detects the background of developmental biology on Bi syndrome of the deficiency of kidney.

  8. Endurance training ameliorates complex 3 deficiency in a mouse model of Barth syndrome.

    Science.gov (United States)

    Soustek, Meghan S; Baligand, Celine; Falk, Darin J; Walter, Glenn A; Lewin, Alfred S; Byrne, Barry J

    2015-09-01

    Barth syndrome (BTHS) is an X-linked metabolic disorder that causes cardiomyopathy in infancy and is linked to mutations within the Tafazzin (TAZ) gene. The first mouse model, a TAZ knockdown model (TAZKD), has been generated to further understand the bioenergetics leading to cardiomyopathy. However, the TAZKD model does not show early signs of cardiomyopathy, and cardiac pathophysiology has not been documented until 7-8 months of age. Here we sought to determine the impact of endurance training on the cardiac and skeletal muscle phenotype in young TAZKD mice. TAZKD exercise trained (TAZKD-ET) and control exercise trained (CON-ET) mice underwent a 35-day swimming protocol. Non-trained aged matched TAZKD and CON mice were used as controls. At the end of the protocol, cardiac MRI was used to assess cardiac parameters. Cardiac MRI showed that training resulted in cardiac hypertrophy within both groups and did not result in a decline of ejection fraction. TAZKD mice exhibited a decrease in respiratory complex I, III, and IV enzymatic activity in cardiac tissue compared to control mice; however, training led to an increase in complex III activity in TAZKD-ET mice resulting in similar levels to those of CON-ET mice. (31)P magnetic resonance spectroscopy of the gastrocnemius showed a significantly lowered pH in TAZKD-ET mice post electrical-stimulation compared to CON-ET mice. Endurance training does not accelerate cardiac dysfunction in young TAZKD mice, but results in beneficial physiological effects. Furthermore, our results suggest that a significant drop in intracellular pH levels may contribute to oxidative phosphorylation defects during exercise.

  9. Muscle force and endurance in untreated and human growth hormone or insulin-like growth factor-I-treated patients with growth hormone deficiency or Laron syndrome.

    Science.gov (United States)

    Brat, O; Ziv, I; Klinger, B; Avraham, M; Laron, Z

    1997-01-01

    Muscle force and endurance of four muscle groups (biceps, triceps, hamstrings and quadriceps) were measured by a computerized device in three groups: (A) 4 boys with isolated growth hormone deficiencies (IGHD) examined before at 10 and 24 months of hGH treatment; (B) 5 children (2 F, 3 M) with Laron syndrome were examined 3.5-4 years after initiation of insulin-like growth factor-I (IGF-I) treatment, and (C) comprised 8 untreated adults (5 F, 3 M) with Laron syndrome. For each patient, 2 matched controls, by age, sex, physical activity and height below the 50th percentile, were examined. GH- or IGF-I-deficient patients before treatment revealed reduced muscle force and endurance. GH treatment (0.6 U/kg/week) restored muscle force and endurance, progressively, mainly in the boys with puberty. Three to 4 years of IGF-I treatment (150 micrograms/kg/day) in patients with Laron syndrome proved to have a weaker effect than GH in restoring muscle force. The difference in effectiveness between hGH and IGF-I in restoring muscle force may be due to either the more marked muscle underdevelopment in Laron syndrome patients than in patients with IGHD or a difference in action potential between the two hormones.

  10. Postural Orthostatic Tachycardia With Chronic Fatigue After HPV Vaccination as Part of the “Autoimmune/Auto-inflammatory Syndrome Induced by Adjuvants”

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    Lucija Tomljenovic PhD

    2014-03-01

    Full Text Available We report the case of a 14-year-old girl who developed postural orthostatic tachycardia syndrome (POTS with chronic fatigue 2 months following Gardasil vaccination. The patient suffered from persistent headaches, dizziness, recurrent syncope, poor motor coordination, weakness, fatigue, myalgias, numbness, tachycardia, dyspnea, visual disturbances, phonophobia, cognitive impairment, insomnia, gastrointestinal disturbances, and a weight loss of 20 pounds. The psychiatric evaluation ruled out the possibility that her symptoms were psychogenic or related to anxiety disorders. Furthermore, the patient tested positive for ANA (1:1280, lupus anticoagulant, and antiphospholipid. On clinical examination she presented livedo reticularis and was diagnosed with Raynaud’s syndrome. This case fulfills the criteria for the autoimmune/auto-inflammatory syndrome induced by adjuvants (ASIA. Because human papillomavirus vaccination is universally recommended to teenagers and because POTS frequently results in long-term disabilities (as was the case in our patient, a thorough follow-up of patients who present with relevant complaints after vaccination is strongly recommended.

  11. Generational Association Studies of Dopaminergic Genes in Reward Deficiency Syndrome (RDS Subjects: Selecting Appropriate Phenotypes for Reward Dependence Behaviors

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    Frank Fornari

    2011-11-01

    Full Text Available Abnormal behaviors involving dopaminergic gene polymorphisms often reflect an insufficiency of usual feelings of satisfaction, or Reward Deficiency Syndrome (RDS. RDS results from a dysfunction in the “brain reward cascade,” a complex interaction among neurotransmitters (primarily dopaminergic and opioidergic. Individuals with a family history of alcoholism or other addictions may be born with a deficiency in the ability to produce or use these neurotransmitters. Exposure to prolonged periods of stress and alcohol or other substances also can lead to a corruption of the brain reward cascade function. We evaluated the potential association of four variants of dopaminergic candidate genes in RDS (dopamine D1 receptor gene [DRD1]; dopamine D2 receptor gene [DRD2]; dopamine transporter gene [DAT1]; dopamine beta-hydroxylase gene [DBH]. Methodology: We genotyped an experimental group of 55 subjects derived from up to five generations of two independent multiple-affected families compared to rigorously screened control subjects (e.g., N = 30 super controls for DRD2 gene polymorphisms. Data related to RDS behaviors were collected on these subjects plus 13 deceased family members. Results: Among the genotyped family members, the DRD2 Taq1 and the DAT1 10/10 alleles were significantly (at least p < 0.015 more often found in the RDS families vs. controls. The TaqA1 allele occurred in 100% of Family A individuals (N = 32 and 47.8% of Family B subjects (11 of 23. No significant differences were found between the experimental and control positive rates for the other variants. Conclusions: Although our sample size was limited, and linkage analysis is necessary, the results support the putative role of dopaminergic polymorphisms in RDS behaviors. This study shows the importance of a nonspecific RDS phenotype and informs an understanding of how evaluating single subset behaviors of RDS may lead to spurious results. Utilization of a nonspecific

  12. Screening non-classical 21-hydroxylase gene deficiency from patients diagnosed as polycystic ovary syndrome by gene assay

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    Jie HU

    2016-04-01

    Full Text Available Objective  To screen non-classical 21-hydroxylase deficiency (NC-21OHD from patients diagnosed as polycystic ovary syndrome (PCOS by gene assay. Methods  Ninety-eight patients with PCOS were enrolled according to 2003 Rotterdam criteria from Department of Endocrinology, Tangdu Hospital of Fourth Military Medical University, and they were divided into three groups according to the modified Ferriman-Gallway (mF-G score as follows: group A with score 0-2; group B with score 3-5, and group C with score ≥6. Meanwhile, 30 healthy subjects from the Medical Center of the Hospital were recruited as control group. Peripheral blood of all subjects were collected for extracting DNA, the CYP21A2 gene were amplified by 5 pairs of specific primers, and then the PCR products were sequenced by Shanghai Sangon Co. The subjects would accept test for serum cortisol and adrenocorticotropic hormone (ACTH at 8:00am if their CYP21A2 was proved to be abnormal. Results  Thirty subjects of control group had no any defects in CYP21A2, but 5 of 98 patients with PCOS were proved to be deficient in CYP21A2, and the genotypes were V281L/920-921insT (P1, V281L/I230M (P2, V281L/Normal (P3, P4, P5, respectively, and all of them were heterozygous mutations. The incidences of NC-21OHD in group C and B were 28.6% and 3.3%, respectively. Genotype P1 had been identified to belong to NC-21OHD, which was consistent with its clinical phenotype. All genotypes P3, P4 and P5 belonged to carriers. But for P2, since I230M hadn't been reported in literature, the patient with V281L/I230M couldn't be classified now. Serum biochemical results showed that only in P1 the cortisol was close to the normal lower level, and ACTH was close to the normal upper limit of the reported level in the literature, and the remainders were all normal. Conclusions  Although PCOS and NC-21OHD are very similar in clinical manifestations, they are different completely in the pathogenesis and treatment. So it

  13. [Adverse ocular effects of vaccinations].

    Science.gov (United States)

    Ness, T; Hengel, H

    2016-07-01

    Vaccinations are very effective measures for prevention of infections but are also associated with a long list of possible side effects. Adverse ocular effects following vaccination have been rarely reported or considered to be related to vaccinations. Conjunctivitis is a frequent sequel of various vaccinations. Oculorespiratory syndrome and serum sickness syndrome are considered to be related to influenza vaccinations. The risk of reactivation or initiation of autoimmune diseases (e. g. uveitis) cannot be excluded but has not yet been proven. Overall the benefit of vaccination outweighs the possible but very low risk of ocular side effects.

  14. 接种乙型肝炎疫苗偶合婴幼儿猝死综合征1例%A case of sudden infant death syndrome coupled to vaccination of hepatitis B vaccine

    Institute of Scientific and Technical Information of China (English)

    马敬仓; 杨传欣; 刘景顺

    2015-01-01

    目的:调查某病例在接种乙型肝炎疫苗后发生死亡是否由注射乙型肝炎疫苗所引起。方法对病例开展个案调查,收集病例出生病历资料、就诊资料、尸检资料,汇总分析后提出诊断意见。结果该病例于2013年12月20日上午接种第二剂次乙肝疫苗后,当天16:00开始发热, T 38.6℃,当地村级卫生室医学处置效果不佳,于2013年12月27日3时死亡;山东法医司法鉴定中心根据尸检结果,鉴定意见为符合婴幼儿猝死综合征。经市级预防接种异常反应调查诊断专家组诊断,不属于预防接种异常反应。结论该病例接种疫苗偶合了婴幼儿猝死综合征,与预防接种无关。%Objective To investigate whether the occurrence of a death case was caused by the vaccination of hepatitis B vaccine.Methods An investigation was carried out for the case, and the birth data, medical records, medical data, and autopsy data were summarized and analyzed for diagnosis opinion.Results The case received the second dose vaccination of hepatitis B vaccine in the morning of December 20, 2013, and had fever of T38.6℃ at 16:00 in the afternoon. There was no obvious treatment effect at the local village medical clinic, and the patient t died at 3 am on December 27, 2013. According to the results of the autopsy conducted by Shandong center for forensic identification, the expert opinion was given as the sudden infant death syndrome. Diagnosis views from the municipal vaccination investigation diagnosis experts showed that it was not belong to the adverse events following immunization.Conclusion The case, after vaccination, is coupled to sudden infant death syndrome, and has no relation with the vaccination.

  15. A hantavirus pulmonary syndrome (HPS) DNA vaccine delivered using a spring-powered jet injector elicits a potent neutralizing antibody response in rabbits and nonhuman primates.

    Science.gov (United States)

    Kwilas, Steve; Kishimori, Jennifer M; Josleyn, Matthew; Jerke, Kurt; Ballantyne, John; Royals, Michael; Hooper, Jay W

    2014-01-01

    Sin Nombre virus (SNV) and Andes virus (ANDV) cause most of the hantavirus pulmonary syndrome (HPS) cases in North and South America, respectively. The chances of a patient surviving HPS are only two in three. Previously, we demonstrated that SNV and ANDV DNA vaccines encoding the virus envelope glycoproteins elicit high-titer neutralizing antibodies in laboratory animals, and (for ANDV) in nonhuman primates (NHPs). In those studies, the vaccines were delivered by gene gun or muscle electroporation. Here, we tested whether a combined SNV/ANDV DNA vaccine (HPS DNA vaccine) could be delivered effectively using a disposable syringe jet injection (DSJI) system (PharmaJet, Inc). PharmaJet intramuscular (IM) and intradermal (ID) needle-free devices are FDA 510(k)-cleared, simple to use, and do not require electricity or pressurized gas. First, we tested the SNV DNA vaccine delivered by PharmaJet IM or ID devices in rabbits and NHPs. Both IM and ID devices produced high-titer anti-SNV neutralizing antibody responses in rabbits and NHPs. However, the ID device required at least two vaccinations in NHP to detect neutralizing antibodies in most animals, whereas all animals vaccinated once with the IM device seroconverted. Because the IM device was more effective in NHP, the Stratis(®) (PharmaJet IM device) was selected for follow-up studies. We evaluated the HPS DNA vaccine delivered using Stratis(®) and found that it produced high-titer anti-SNV and anti-ANDV neutralizing antibodies in rabbits (n=8/group) as measured by a classic plaque reduction neutralization test and a new pseudovirion neutralization assay. We were interested in determining if the differences between DSJI delivery (e.g., high-velocity liquid penetration through tissue) and other methods of vaccine injection, such as needle/syringe, might result in a more immunogenic DNA vaccine. To accomplish this, we compared the HPS DNA vaccine delivered by DSJI versus needle/syringe in NHPs (n=8/group). We found

  16. A Hantavirus Pulmonary Syndrome (HPS) DNA Vaccine Delivered Using a Spring-powered Jet Injector Elicits a Potent Neutralizing Antibody
Response in Rabbits and Nonhuman Primates

    Science.gov (United States)

    Kwilas, Steve; Kishimori, Jennifer M.; Josleyn, Matthew; Jerke, Kurt; Ballantyne, John; Royals, Michael; Hooper, Jay W.

    2014-01-01

    Sin Nombre virus (SNV) and Andes virus (ANDV) cause most of the hantavirus pulmonary syndrome (HPS) cases in North and South America, respectively. The chances of a patient surviving HPS are only two in three. Previously, we demonstrated that SNV and ANDV DNA vaccines encoding the virus envelope glycoproteins elicit high-titer neutralizing antibodies in laboratory animals, and (for ANDV) in nonhuman primates (NHPs). In those studies, the vaccines were delivered by gene gun or muscle electroporation. Here, we tested whether a combined SNV/ANDV DNA vaccine (HPS DNA vaccine) could be delivered effectively using a disposable syringe jet injection (DSJI) system (PharmaJet, Inc). PharmaJet intramuscular (IM) and intradermal (ID) needle-free devices are FDA 510(k)-cleared, simple to use, and do not require electricity or pressurized gas. First, we tested the SNV DNA vaccine delivered by PharmaJet IM or ID devices in rabbits and NHPs. Both IM and ID devices produced high-titer anti-SNV neutralizing antibody responses in rabbits and NHPs. However, the ID device required at least two vaccinations in NHP to detect neutralizing antibodies in most animals, whereas all animals vaccinated once with the IM device seroconverted. Because the IM device was more effective in NHP, the Stratis® (PharmaJet IM device) was selected for follow-up studies. We evaluated the HPS DNA vaccine delivered using Stratis® and found that it produced high-titer anti-SNV and anti-ANDV neutralizing antibodies in rabbits (n=8/group) as measured by a classic plaque reduction neutralization test and a new pseudovirion neutralization assay. We were interested in determining if the differences between DSJI delivery (e.g., high-velocity liquid penetration through tissue) and other methods of vaccine injection, such as needle/syringe, might result in a more immunogenic DNA vaccine. To accomplish this, we compared the HPS DNA vaccine delivered by DSJI versus needle/syringe in NHPs (n=8/group). We found that

  17. Understanding the syndrome of techno-centrism through the epidemiology of vaccines as preventive tools

    Directory of Open Access Journals (Sweden)

    Vikas Bajpai

    2012-01-01

    Full Text Available Conquering disease and ill health has been an age old pursuit of man. The scientific and technological revolution of the last century ushered in major and important advances in preventive and curative medical technology which fired a new hope in the fight against communicable diseases. However, the experience over centuries shows that major decline in communicable diseases began much before the advent of modern technology due to advances in the socio-economic and environmental conditions of the people. There has been an attempt by the multilateral and unilateral agencies to supplant the expedient of technological interventions like vaccination campaigns as a substitute to socio-economic advancement in the third world countries. The dividends of this approach have been equivocal and have had an effect of distorting public health priorities in the third world. There seems to be an obsession with technology among the policy planners - a phenomenon that we call as techno-centrism; the latest example of which is the pulse polio campaign. This paper draws upon an epidemiological approach to vaccination programs as a tool to unravel this phenomenon.

  18. Dopaminergic deficiency syndrome in the picture of severe brain injury in the presence of protracted depression of consciousness

    Directory of Open Access Journals (Sweden)

    M. V. Chelyapina

    2014-01-01

    Full Text Available Objective: to determine the clinical and electroencephalographic (EEG signs of dopaminergic deficiency (DD when recovering consciousness in patients with severe brain injury (SBI.Patients and methods. Thirty-five patients (23 men and 12 women; mean age 29±13 years, who had experienced SBI accompanied by coma (mean duration 17±6 days and treated at the Acad. N.N. Burdenko Research Institute of Neurosurgery, were examined. The comprehensive examination included neurological and mental status evaluation and EEG with dynamic assessment of the pattern.Results and discussion. The authors defined a constellation of neurological symptoms as increased extrapyramidal muscle tone, resting tremor, and specific autonomic dysfunction, which was characteristic of autonomic status and some forms of mutism, and, in accordance with the data available in the literature, was defined as DD syndrome. The latter accompanied by characteristic EEG changes: its pattern’s higher synchronized β-activity (13–14 Hz enhanced in the frontal and anterior temporal regions. The administration of amantadine sulfate was followed by an increase (even as compared with the normal value in the dynamics of the power of mainly of β3 (at frequencies of 17–23 Hz and θ2 (5.9–7.4 Hz bands along the anterior regions more frequently on the right; by the amplification of intrahemispheric connections (in the occipitotemporal regions in the β3 band (more often on the right and θ one (5.9–7.4 Hz in the right occipitotemporal region. The agent had no significant effect on the SBI outcome assessed 12 months after injury, but it affected the clinical symptoms of DD.

  19. Project youth inform--a school-based sexually transmitted disease/acquired immune deficiency syndrome education programme.

    Science.gov (United States)

    Soon, T; Chan, R K; Goh, C L

    1995-07-01

    A pilot project, ¿Youth Inform¿ endorsed by the Ministry of Health and Ministry of Education, Singapore, was undertaken in 1992 for 2 years. It aims to enhance sexually transmitted disease (STDs)/human immunodeficiency virus (HIV) control in Singapore by providing structured information for young people between the ages of 16 to 20 years in Polytechnics, Junior Colleges, Centralised Institutes and Pre-University Centres. Project Youth Inform comprises 8 components. They include a focus group discussion, a training seminar for teachers, a lecture/slide presentation cum question-and-answer session, an educational booklet/bookmark, exhibitions, a video, provisions for anonymous questions, and an evaluation. The programme is conducted during school hours at the premises of the institutions and the attendance per session is between 150 to 350 students. A total of 152 sessions have been completed for all the schools. It is ongoing and is currently administered by the School Health Service and Training and Health Education Department. Feedback from principals, teachers and students was gathered formally through surveys and informally through interviews and observations. One thousand students were randomly selected for the survey to assess their responses towards the programme. Eighty-six percent reported that they found it educational and informative. Indicators found to have an influence on the effectiveness of the programme were timing, vocabulary used (medical terms) and integration of the programme into the school's curriculum. In conclusion, Project Youth Inform was on the whole positively received. However, it is essential to constantly accommodate and adapt to new facts and methods of teaching and maintain close coordination with the Ministries and the schools. An effective STD/acquired immune deficiency syndrome programme is an important step towards the prevention, management and control of the epidemic.

  20. Adjuvanted poly(lactic-co-glycolic acid nanoparticle-entrapped inactivated porcine reproductive and respiratory syndrome virus vaccine elicits cross-protective immune response in pigs

    Directory of Open Access Journals (Sweden)

    Binjawadagi B

    2014-01-01

    Full Text Available Basavaraj Binjawadagi,1,2 Varun Dwivedi,1 Cordelia Manickam,1,2 Kang Ouyang,1 Yun Wu,3 Ly James Lee,3 Jordi B Torrelles,4 Gourapura J Renukaradhya1,21Food Animal Health Research Program, Ohio Agricultural Research and Development Center, 2Department of Veterinary Preventive Medicine, Ohio State University, Wooster, OH, USA; 3NanoScale Science and Engineering Center for Affordable Nanoengineering of Polymeric Biomedical Devices, 4Department of Microbial Infection and Immunity, Ohio State University, Columbus, OH, USAAbstract: Porcine reproductive and respiratory syndrome (PRRS, caused by the PRRS virus (PRRSV, is an economically devastating disease, causing daily losses of approximately $3 million to the US pork industry. Current vaccines have failed to completely prevent PRRS outbreaks. Recently, we have shown that poly(lactic-co-glycolic acid (PLGA nanoparticle-entrapped inactivated PRRSV vaccine (NP-KAg induces a cross-protective immune response in pigs. To further improve its cross-protective efficacy, the NP-KAg vaccine formulation was slightly modified, and pigs were coadministered the vaccine twice intranasally with a potent adjuvant: Mycobacterium tuberculosis whole-cell lysate. In vaccinated virulent heterologous PRRSV-challenged pigs, the immune correlates in the blood were as follows: 1 enhanced PRRSV-specific antibody response with enhanced avidity of both immunoglobulin (Ig-G and IgA isotypes, associated with augmented virus-neutralizing antibody titers; 2 comparable and increased levels of virus-specific IgG1 and IgG2 antibody subtypes and production of high levels of both T-helper (Th-1 and Th2 cytokines, indicative of a balanced Th1–Th2 response; 3 suppressed immunosuppressive cytokine response; 4 increased frequency of interferon-γ+ lymphocyte subsets and expanded population of antigen-presenting cells; and most importantly 5 complete clearance of detectable replicating challenged heterologous PRRSV and close to threefold

  1. Mitochondrial respiratory chain enzyme assay and DNA analysis in peripheral blood leukocytes for the etiological study of Chinese children with Leigh syndrome due to complex I deficiency.

    Science.gov (United States)

    Ma, Yan Yan; Wu, Tong Fei; Liu, Yu Peng; Wang, Qiao; Li, Xi Yuan; Zhang, Yao; Song, Jin Qing; Wang, Yu Jie; Yang, Yan Ling

    2013-02-01

    Mitochondrial respiratory chain complex I enzyme deficiency is the most commonly seen mitochondrial respiratory chain disorder. Although screening and diagnostic methods are available overseas, clinically feasible diagnostic methods have not yet been established in China. In this study, four Chinese boys with Leigh syndrome due to complex I deficiency were diagnosed by mitochondrial respiratory chain enzyme assay and DNA analysis using peripheral blood leukocytes. Four patients were admitted at the age of 5-14 years because of unexplained progressive neuromuscular symptoms, including motor developmental delay or regression, weakness, and seizures. Their cranial magnetic resonance imaging revealed typical finding as Leigh syndrome. Peripheral leukocyte mitochondrial respiratory chain complex I activities were found decreased to 9.6-33.1 nmol/min/mg mitochondrial protein(control 44.0 ± 5.4 nmol/min/mg). The ratios of complex I to citrate synthase activity were also decreased (8.9-19.8% in patients vs. control 48 ± 11%). Three mtDNA mutations were identified from three out of four patients, supporting the diagnosis of complex I deficiency. Point mutations m.10191T>C in mitochondrial ND3 gene, m.13513G>A in ND5 gene and m.14,453G>A in ND6 gene were detected in three patients.

  2. An AP4B1 frameshift mutation in siblings with intellectual disability and spastic tetraplegia further delineates the AP-4 deficiency syndrome.

    Science.gov (United States)

    Abdollahpour, Hengameh; Alawi, Malik; Kortüm, Fanny; Beckstette, Michael; Seemanova, Eva; Komárek, Vladimír; Rosenberger, Georg; Kutsche, Kerstin

    2015-02-01

    The recently proposed adaptor protein 4 (AP-4) deficiency syndrome comprises a group of congenital neurological disorders characterized by severe intellectual disability (ID), delayed or absent speech, hereditary spastic paraplegia, and growth retardation. AP-4 is a heterotetrameric protein complex with important functions in vesicle trafficking. Mutations in genes affecting different subunits of AP-4, including AP4B1, AP4E1, AP4S1, and AP4M1, have been reported in patients with the AP-4 deficiency phenotype. We describe two siblings from a non-consanguineous couple who presented with severe ID, absent speech, microcephaly, growth retardation, and progressive spastic tetraplegia. Whole-exome sequencing in the two patients identified the novel homozygous 2-bp deletion c.1160_1161delCA (p.(Thr387Argfs*30)) in AP4B1. Sanger sequencing confirmed the mutation in the siblings and revealed it in the heterozygous state in both parents. The AP4B1-associated phenotype has previously been assigned to spastic paraplegia-47. Identification of a novel AP4B1 alteration in two patients with clinical manifestations highly similar to other individuals with mutations affecting one of the four AP-4 subunits further supports the observation that loss of AP-4 assembly or functionality underlies the common clinical features in these patients and underscores the existence of the clinically recognizable AP-4 deficiency syndrome.

  3. Mice Exposed to Chronic Intermittent Hypoxia Simulate Clinical Features of Deficiency of both Qi and Yin Syndrome in Traditional Chinese Medicine.

    Science.gov (United States)

    Chai, Chengzhi; Kou, Junping; Zhu, Danni; Yan, Yongqing; Yu, Boyang

    2011-01-01

    Deficiency of both Qi and Yin Syndrome (DQYS) is one of the common syndromes in traditional Chinese medicine (TCM), mainly characterized by tiredness, emaciation, anorexia, fidget, palpitation and rapid pulse, and so forth. Currently, there is no available animal model which can reflect the clinical features of this syndrome. In the present paper, we observed the time-course changes of whole behavior, body weight, food intake, locomotive activity and electrocardiogram in mice exposed to chronic intermittent hypoxia for 6 weeks, and measured bleeding time at last according to the clinical features of DQYS and one key pathological factor. The results showed that the mice exposed to intermittent hypoxia for certain time presented lackluster hair, dull looking hair, resistance, attacking, body weight loss, food intake decline, locomotive activity decrease, heart rate quickening and T wave elevating, which were similar to the major clinical features of DQYS. Meanwhile, bleeding time shortening was also found, which was consistent with the clinical fact that DQYS often accompanied with blood stasis. The possible explanation was also outlined according to the available literature. Such findings suggested chronic intermittent hypoxia could induce similar symptoms and signs in mice accorded with the clinical features of DQYS, which provided a suitable animal model for evaluation of drugs for the treatment of this syndrome and further exploration of pathological process or correlation of the syndrome and related diseases.

  4. Mice Exposed to Chronic Intermittent Hypoxia Simulate Clinical Features of Deficiency of both Qi and Yin Syndrome in Traditional Chinese Medicine

    Directory of Open Access Journals (Sweden)

    Chengzhi Chai

    2011-01-01

    Full Text Available Deficiency of both Qi and Yin Syndrome (DQYS is one of the common syndromes in traditional Chinese medicine (TCM, mainly characterized by tiredness, emaciation, anorexia, fidget, palpitation and rapid pulse, and so forth. Currently, there is no available animal model which can reflect the clinical features of this syndrome. In the present paper, we observed the time-course changes of whole behavior, body weight, food intake, locomotive activity and electrocardiogram in mice exposed to chronic intermittent hypoxia for 6 weeks, and measured bleeding time at last according to the clinical features of DQYS and one key pathological factor. The results showed that the mice exposed to intermittent hypoxia for certain time presented lackluster hair, dull looking hair, resistance, attacking, body weight loss, food intake decline, locomotive activity decrease, heart rate quickening and T wave elevating, which were similar to the major clinical features of DQYS. Meanwhile, bleeding time shortening was also found, which was consistent with the clinical fact that DQYS often accompanied with blood stasis. The possible explanation was also outlined according to the available literature. Such findings suggested chronic intermittent hypoxia could induce similar symptoms and signs in mice accorded with the clinical features of DQYS, which provided a suitable animal model for evaluation of drugs for the treatment of this syndrome and further exploration of pathological process or correlation of the syndrome and related diseases.

  5. Progress on DNA Vaccine of Porcine Reproductive and Respiratory Syndrome%猪繁殖与呼吸综合征核酸疫苗研究进展

    Institute of Scientific and Technical Information of China (English)

    李亮亮; 张雪梅; 汤小龙; 周恩民; 穆杨

    2014-01-01

    Porcine reproductive and respiratory syndrome (PRRS)is a viral infectious disease for the swine industry.Porcine reproductive and respiratory syndrome virus (PRRSV)is the causative disease agent of the disease.It has caused great economic losses every year in the pig industry worldwide.Currently the most effective measures to prevent the disease is vaccination.Due to some disadvantages,traditional vac-cines can not eradicate the disease compeletely.As a new type of vaccine,DNA vaccine can induce the body to produce the humoral immune response and cellular immune response simultaneously,it has many advan-tages.Thesis focused on the action mechanism of porcine reproductive and respiratory syndrome nucleic acid vaccine,the advantages and disadvantages.This review may provide the beneficial reference to research PRRS nucleic acid vaccine and control the disease.%猪繁殖与呼吸综合征(PRRS)是由猪繁殖与呼吸综合征病毒(PRRSV)引起的一种严重危害养猪业的病毒性传染病,该病每年给全球养猪业造成巨大的经济损失。目前用于防控该病最有效的方法是疫苗接种,由于传统疫苗存在一些不足之处,对于根除该病仍然存在较大难度。核酸疫苗作为一种新型疫苗,不仅能诱导机体产生体液免疫应答和细胞免疫应答,而且具有较多优点。论文主要就猪繁殖与呼吸综合征核酸疫苗的作用机制、优缺点,以及研究现状进行简要综述,以期为 PRRS核酸疫苗研究和该病的防控提供参考。

  6. Sexually Transmitted Infections Among Hospitalized Patients With Human Immunodeficiency Virus Infection and Acquired Immune Deficiency Syndrome (HIV/AIDS) in Zahedan, Southeastern Iran.

    Science.gov (United States)

    Hashemi-Shahri, Seyed Mohammad; Sharifi-Mood, Batool; Kouhpayeh, Hamid-Reza; Moazen, Javad; Farrokhian, Mohsen; Salehi, Masoud

    2016-09-01

    Studies show that nearly 40 million people are living with human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) around the world and since the beginning of the epidemic, about 35 million have died from AIDS. Heterosexual intercourse is the most common route for transmission of HIV infection (85%). People with a sexually transmitted infection (STI), such as syphilis, genital herpes, chancroid, or bacterial vaginosis, are more likely to obtain HIV infection during sex. On the other hand, a patient with HIV can acquire other infections such as hepatitis C virus (HCV) and hepatitis B virus (HBV) and also STIs. Co-infections and co-morbidities can affect the treatment route of patients with HIV/AIDs. Sometimes, physicians should treat these infections before treating the HIV infection. Therefore, it is important to identify co-infection or comorbidity in patients with HIV/AIDS. This study was conducted in order to understand the prevalence of HIV/AIDS/STI co-infection. In this cross-sectional study, we evaluated all HIV/AIDS patients who were admitted to the infectious wards of Boo-Ali hospital (Southeastern Iran) between March 2000 and January 2015. All HIV/AIDS patients were studied for sexually transmitted infections (STI) such as syphilis, gonorrhea, hepatitis B virus (HBV) and genital herpes. A questionnaire including data on age, sex, job, history of vaccination against HBV, hepatitis B surface antigen (HBsAg), hepatitis B core antibody (anti-HBc), hepatitis B surface antigen (anti-HBs), HCV-Ab, venereal disease research laboratory (VDRL) test, fluorescent treponemal antibody absorption (FTA-Abs) test, and urine culture was designed. Data was analyzed by the Chi square test and P values of VDRL. The FTA-Abs was positive for all patients who were positive for VDRL. Gonorrhea was found in seven patients (17%) and three cases had genital herpes in clinical examinations. All patients who had positive test results for these STIs

  7. NY-ESO-1 Vaccination in Combination with Decitabine Induces Antigen-Specific T-Lymphocyte Responses in Patients with Myelodysplastic Syndrome.

    Science.gov (United States)

    Griffiths, Elizabeth A; Srivastava, Pragya; Matsuzaki, Junko; Brumberger, Zachary; Wang, Eunice S; Kocent, Justin; Miller, Austin; Roloff, Gregory W; Wong, Hong Yuen; Paluch, Benjamin E; Lutgen-Dunckley, Linda G; Martens, Brandon L; Odunsi, Kunle; Karpf, Adam R; Hourigan, Christopher S; Nemeth, Michael J

    2017-09-25

    Treatment options are limited for patients with high-risk myelodysplastic syndrome (MDS). The azanucleosides, azacitidine and decitabine, are front-line therapy for MDS that induce promoter demethylation and gene expression of the highly immunogenic tumor antigen NY-ESO-1. We demonstrated that AML patients receiving decitabine exhibit induction of NY-ESO-1 expression in circulating blasts. We hypothesized that vaccinating against NY-ESO-1 in MDS patients receiving decitabine would capitalize upon induced NY-ESO-1 expression in malignant myeloid cells to provoke an NY-ESO-1-specific-MDS directed cytotoxic T-cell immune response. In a phase I study, 9 MDS patients received an HLA unrestricted NY-ESO-1 vaccine (CDX-1401 + poly-ICLC) in a non-overlapping schedule every four weeks with standard dose decitabine. Analysis of samples serially obtained from the 7 patients who reached the end-of-study demonstrated induction of NY-ESO-1 expression in 7/7 patients and NY-ESO-1 specific CD4+ and CD8+ T-lymphocyte responses in 6/7 and 4/7 of the vaccinated patients respectively. Myeloid cells expressing NY-ESO-1, isolated from a patient at different time-points during decitabine therapy, were capable of activating a cytotoxic response from autologous NY-ESO-1-specific T-lymphocytes. Vaccine responses were associated with a detectable population of CD141Hi conventional dendritic cells, which are critical for the uptake of NY-ESO-1 vaccine and have a recognized role in anti-tumor immune responses. These data indicate that vaccination against induced NY-ESO-1 expression can produce an antigen-specific immune response in a relatively non-immunogenic myeloid cancer and highlight the potential for induced-antigen directed immunotherapy in a group of patients with limited options. Copyright ©2017, American Association for Cancer Research.

  8. Emergence of mosaic recombinant strains potentially associated with vaccine JXA1-R and predominant circulating strains of porcine reproductive and respiratory syndrome virus in different provinces of China.

    Science.gov (United States)

    Zhao, Huajian; Han, Qinggong; Zhang, Lei; Zhang, Zhiyong; Wu, Yufeng; Shen, Hong; Jiang, Ping

    2017-04-04

    Porcine reproductive and respiratory syndrome virus (PRRSV) has caused several outbreaks in China since 2006. However, the genetic diversity of PRRSV in China has greatly increased by rapid evolution or recombination events. Modified live-attenuated vaccines are widely used to control this disease worldwide. Although the risk and inefficacy of the vaccine has been reported, the genetic diversity between epidemic field strains and vaccine strains in China has not been completely elucidated. A total of 293 clinical samples were collected from 72 pig farms in 16 provinces of China in 2015 for PRRSV detection. A total of 28 infected samples collected from 24 pig farms in nine provinces were further selected for immunohistochemical analysis and whole genome sequencing of PRRSV. Phylogenetic analysis and recombination screening were performed with the full genome sequences of the 28 strains and other 623 reference sequences of PRRSV. Of 293 clinical samples, 117 (39.93%) were positive for PRRSV by RT-PCR. Phylogenetic results showed that the 28 strains were nested into sublineage 10.5 (classic highly pathogenic [HP]-PRRSV), sublineage 10.6 (HP-PRRSV-like strains and related recombinants), sublineage 10.7 (potential vaccine JXA1-R-like strains), and lineage 9 (NADC30-like strains and recombinants of NADC30-like strains), respectively, suggesting that multiple subgenotypes of PRRSV currently circulate in China. Recombination analyses showed that nine of 28 isolates and one isolate from other laboratory were potential complicated recombinants between the vaccine JXA1-R-like strains and predominant circulating strains. These results indicated an increase in recombination rates of PRRSV under current vaccination pressure and a more pressing situation for PRRSV eradication and control in China.

  9. Gut microbial diversity analysis using Illumina sequencing for functional dyspepsia with liver depression-spleen deficiency syndrome and the interventional Xiaoyaosan in a rat model

    Science.gov (United States)

    Qiu, Juan-Juan; Liu, Zhe; Zhao, Peng; Wang, Xue-Jun; Li, Yu-Chun; Sui, Hua; Owusu, Lawrence; Guo, Hui-Shu; Cai, Zheng-Xu

    2017-01-01

    AIM To investigate gut microbial diversity and the interventional effect of Xiaoyaosan (XYS) in a rat model of functional dyspepsia (FD) with liver depression-spleen deficiency syndrome. METHODS The FD with liver depression-spleen deficiency syndrome rat model was established through classic chronic mild unpredictable stimulation every day. XYS group rats received XYS 1 h before the stimulation. The models were assessed by parameters including state of the rat, weight, sucrose test result and open-field test result. After 3 wk, the stools of rats were collected and genomic DNA was extracted. PCR products of the V4 region of 16S rDNA were sequenced using a barcoded Illumina paired-end sequencing technique. The primary composition of the microbiome in the stool samples was determined and analyzed by cluster analysis. RESULTS Rat models were successfully established, per data from rat state, weight and open-field test. The microbiomes contained 20 phyla from all samples. Firmicutes, Bacteroidetes, Proteobacteria, Cyanobacteria and Tenericutes were the most abundant taxonomic groups. The relative abundance of Firmicutes, Proteobacteria and Cyanobacteria in the model group was higher than that in the normal group. On the contrary, the relative abundance of Bacteroidetes in the model group was lower than that in the normal group. Upon XYS treatment, the relative abundance of all dysregulated phyla was restored to levels similar to those observed in the normal group. Abundance clustering heat map of phyla corroborated the taxonomic distribution. CONCLUSION The microbiome relative abundance of FD rats with liver depression-spleen deficiency syndrome was significantly different from the normal cohort. XYS intervention may effectively adjust the gut dysbacteriosis in FD. PMID:28223725

  10. 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 ...

  11. 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 ...

  12. 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.

    Science.gov (United States)

    Vangroenweghe, D

    2001-06-29

    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.

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

    Institute of Scientific and Technical Information of China (English)

    杨蓉蓉

    2014-01-01

    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

  14. West Syndrome in an Infant with Vitamin B[subscript 12] Deficiency in the Absence of Macrocytic Anaemia

    Science.gov (United States)

    Erol, Ilknur; Alehan, Fusun; Gumus, Ayten

    2007-01-01

    Vitamin B[subscript 12] deficiency in infants often produces haematological and neurological deficits, including macrocytic anaemia, neurodevelopmental delay or regression, irritability, weakness, hypotonia, ataxia, apathy, tremor, and seizures. The diagnosis of vitamin B[subscript 12] deficiency can be difficult when the typical macrocytic…

  15. West Syndrome in an Infant with Vitamin B[subscript 12] Deficiency in the Absence of Macrocytic Anaemia

    Science.gov (United States)

    Erol, Ilknur; Alehan, Fusun; Gumus, Ayten

    2007-01-01

    Vitamin B[subscript 12] deficiency in infants often produces haematological and neurological deficits, including macrocytic anaemia, neurodevelopmental delay or regression, irritability, weakness, hypotonia, ataxia, apathy, tremor, and seizures. The diagnosis of vitamin B[subscript 12] deficiency can be difficult when the typical macrocytic…

  16. Porcine respiratory disease complex: Interaction of vaccination and porcine circovirus type 2, porcine reproductive and respiratory syndrome virus, and Mycoplasma hyopneumoniae.

    Science.gov (United States)

    Chae, Chanhee

    2016-06-01

    Porcine respiratory disease is a multifactorial and complex disease caused by a combination of infectious pathogens, environmental stressors, differences in production systems, and various management practices; hence the name porcine respiratory disease complex (PRDC) is used. Porcine circovirus type 2 (PCV2), porcine reproductive and respiratory syndrome virus (PRRSV), and Mycoplasma hyopneumoniae are considered to be the most important pathogens that cause PRDC. Although interactions among the three major respiratory pathogens are well documented, it is also necessary to understand the interaction between vaccines and the three major respiratory pathogens. PRRSV and M. hyopneumoniae are well known to potentiate PCV2-associated lesions; however, PRRSV and mycoplasmal vaccines can both enhance PCV2 viraemia regardless of the effects of the actual PRRSV or M. hyopneumoniae infection. On the other hand, M. hyopneumoniae potentiates the severity of pneumonia induced by PRRSV, and vaccination against M. hyopneumoniae alone is also able to decrease PRRSV viraemia and PRRSV-induced lung lesions in dually infected pigs. This review focuses on (1) interactions between PCV2, PRRSV, and M. hyopneumoniae; and (2) interactions between vaccines and the three major respiratory pathogens.

  17. Recent topics related to testosterone deficiency syndrome in Japan%日本近期关于睾酮缺乏综合征的话题

    Institute of Scientific and Technical Information of China (English)

    Akira Tsujimura; Norio Nonomura

    2011-01-01

    Androgens, the levels of which decrease with ageing, play many physiological roles in various organs. Testosterone deficiency syndrome (TDS) has received widespread attention in the last several years. First-line treatment for TDS should be testosterone replacement therapy (TRT), which is reported to improve several TDS symptoms. Recently, a clinical practice manual for TDS was written and published by a collaborative team from the Japanese Urological Association and the Japanese Society for the Study of the Aging Male to recommend standard procedures for the diagnosis, treatment, prevention and monitoring of adverse reactions to TRT and for post-treatment assessment. In this manual, intramuscular injection of testosterone enanthate or human chorionic gonadotropin and the testosterone gel 'Glowmin' were recommended as TRT. Currently, two topics related to TDS are being focused on in Japan: the relationship between TDS and metabolic syndrome and treatment options for eugonadai patients with TDS symptoms. In this review,the possibility of TRT for metabolic syndrome as well as the relationship between testosterone and adiponectin, which is a key molecule in metabolic syndrome, is discussed. Finally, the possibility of herbal medicines as a treatment option for patients with TDS is addressed, especially for eugonadal patients, because eugonadal men with TDS symptoms account for approximately 30% of the general population. The increase in the levels of several cytokines, such as iL-8, IL-13, interferon-γ and tumor necrosis factor-a, after herbal medicine treatment may be the reason for this efficacy.

  18. Atypical Manifestation of LPS-Responsive beige- like anchor (LRBA Deficiency Syndrome as an Autoimmune Endocrine Disorder without Enteropathy and Immunodeficiency.

    Directory of Open Access Journals (Sweden)

    Shahrzad Bakhtiar

    2016-09-01

    Full Text Available Monogenic primary immunodeficiency syndromes can affect one or more endocrine organs by autoimmunity during childhood. Clinical manifestations include type1 diabetes mellitus, hypothyroidism, adrenal insufficiency and vitiligo. LPS-responsive beige-like anchor protein (LRBA deficiency was described in 2012 as a novel primary immunodeficiency, predominantly causing immune dysregulation and early onset enteropathy. We describe the heterogeneous clinical course of LRBA deficiency in two siblings, mimicking an autoimmune polyendocrine disorder in one of them in presence of the same underlying genetic mutation. The third child of consanguineous Egyptian parents (Patient 1 presented at six months of age with intractable enteropathy and failure to thrive. Later on he developed symptoms of adrenal insufficiency, autoimmune haemolytic anaemia, thrombocytopenia, and infectious complications due to immunosuppressive treatment. The severe enteropathy was non-responsive to the standard treatment and led to death at the age of 22 years. His younger sister (Patient 2 presented at the age of 12 to the endocrinology department with decompensated hypothyroidism, perioral vitiligo, delayed pubertal development, and growth failure without enteropathy and immunodeficiency.Using whole-exome sequencing (WES we identified a homozygous frameshift mutation (c.6862delT, p.Y2288MfsX29 in the LRBA gene in both siblings. To our knowledge our patient (patient 2 is the first case of LRBA deficiency described with predominant endocrine phenotype without immunodeficiency and enteropathy. LRBA deficiency should be considered as underlying disease in pediatric patients presenting with autoimmune endocrine symptoms. The same genetic mutation can manifest with a broad phenotypic spectrum without genotype-phenotype correlation. The awareness for disease symptoms among non-immunologists might be a key to early diagnosis. Further functional studies in LRBA deficiency are necessary to

  19. Anti-radiation vaccine: Immunologically-based Prophylaxis of Acute Toxic Radiation Syndromes Associated with Long-term Space Flight

    Science.gov (United States)

    Popov, Dmitri; Maliev, Vecheslav; Jones, Jeffrey; Casey, Rachael C.

    2007-01-01

    Protecting crew from ionizing radiation is a key life sciences problem for long-duration space missions. The three major sources/types of radiation are found in space: galactic cosmic rays, trapped Van Allen belt radiation, and solar particle events. All present varying degrees of hazard to crews; however, exposure to high doses of any of these types of radiation ultimately induce both acute and long-term biological effects. High doses of space radiation can lead to the development of toxicity associated with the acute radiation syndrome (ARS) which could have significant mission impact, and even render the crew incapable of performing flight duties. The creation of efficient radiation protection technologies is considered an important target in space radiobiology, immunology, biochemistry and pharmacology. Two major mechanisms of cellular, organelle, and molecular destruction as a result of radiation exposure have been identified: 1) damage induced directly by incident radiation on the macromolecules they encounter and 2) radiolysis of water and generation of secondary free radicals and reactive oxygen species (ROS), which induce chemical bond breakage, molecular substitutions, and damage to biological molecules and membranes. Free-radical scavengers and antioxidants, which neutralize the damaging activities of ROS, are effective in reducing the impact of small to moderate doses of radiation. In the case of high doses of radiation, antioxidants alone may be inadequate as a radioprotective therapy. However, it remains a valuable component of a more holistic strategy of prophylaxis and therapy. High doses of radiation directly damage biological molecules and modify chemical bond, resulting in the main pathological processes that drive the development of acute radiation syndromes (ARS). Which of two types of radiation-induced cellular lethality that ultimately develops, apoptosis or necrosis, depends on the spectrum of incident radiation, dose, dose rate, and

  20. Concurrent vaccination of pigs with type 1 and type 2 porcine reproductive and respiratory syndrome virus (PRRSV) protects against type 1 PRRSV but not against type 2 PRRSV on dually challenged pigs.

    Science.gov (United States)

    Park, Changhoon; Choi, Kyuhyung; Jeong, Jiwoon; Kang, Ikjae-; Park, Su-Jin; Chae, Chanhee

    2015-12-01

    The objective of the present study was to evaluate the effect of concurrent vaccination of pigs with both type 1 and type 2 porcine reproductive and respiratory syndrome virus (PRRSV) vaccine against heterologous dual challenge of both genotypes and compare with single vaccination of pigs against heterologous single challenge of both genotypes. Pigs were administered both type 1 and type 2 PRRSV vaccine concurrently into separate anatomical sites at 28 days of age and inoculated intranasally with both genotypes at 63 days of age. Neutralizing antibodies (NA) were not detected in any pigs in any group (NA titer vaccination of pigs with two PRRSV genotypes had significantly lower numbers of type 1 and type 2 PRRSV-specific interferon-γ secreting cells (IFN-γ-SC) compared to vaccination of pigs with type 1 or type 2 PRRSV only. Despite the decreased induction of type 1 PRRSV-specific IFN-γ-SC, concurrent vaccination is still able to reduce type 1 PRRSV viremia whereas the decreased induction of type 2 PRRSV-specific IFN-γ-SC by concurrent vaccination correlates with lack of reduction of type 2 PRRSV viremia after dual challenge. The results of this study demonstrated that concurrent vaccination of pigs with two PRRSV genotypes is able to reduce the levels of type 1 PRRSV viremia and lung lesions but not able to reduce the levels of type 2 PRRSV viremia and lung lesions.

  1. The assessment of efficacy of porcine reproductive respiratory syndrome virus inactivated vaccine based on the viral quantity and inactivation methods

    National Research Council Canada - National Science Library

    Kim, Hyunil; Kim, Hye Kwon; Jung, Jung Ho; Choi, Yoo Jung; Kim, Jiho; Um, Chang Gyu; Hyun, Su Bin; Shin, Sungho; Lee, Byeongchun; Jang, Goo; Kang, Bo Kyu; Moon, Hyoung Joon; Song, Dae Sub

    2011-01-01

    ...). Although inactivated PRRSV vaccines are preferred for their safety, they are weak at inducing humoral immune responses and controlling field PRRSV infection, especially when heterologous viruses are involved...

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

    Science.gov (United States)

    Goaster, Jacqueline Le; Bourée, Patrice; Ifergan, Charles; Tangy, Frederic; Olivier, René; Haenni, Anne-Lise

    2015-01-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Jacqueline Le Goaster

    2015-05-01

    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.

  4. Influences of dietary biotin and avidin on growth, survival, deficiency syndrome and hepatic gene expression of juvenile Nile tilapia Oreochromis niloticus.

    Science.gov (United States)

    Sarker, Pallab Kumer; Yossa, Rodrigue; Karanth, Santhosh; Ekker, Marc; Vandenberg, Grant W

    2012-08-01

    This study was undertaken to assess the interactive effects of dietary biotin and avidin on growth, feed conversion, survival and deficiency syndrome of tilapia and to determine the influence of dietary biotin deficiency on the expression of key genes related to biotin metabolism in tilapia. Six iso-nitrogenous and iso-energetic diets based on a common purified basal diet (vitamin-free casein as the protein source) were prepared for this study. The six dietary groups were 0 g avidin with 0 mg biotin (A0B0), 0 g avidin with 0.06 mg biotin/kg diet (A0B1), four avidin-supplemented diets incorporating at a incremental concentrations 0.25, 0.5, 1.0 and 2.0 g/kg diet with 0.06 mg biotin/kg diet (A15B1, A30B1, A60B1 and A120B1). Fish were hand-fed three times a day to apparent satiation for 12 weeks. Each diet was fed to three replicate groups of fish. Fish were kept in glass aquaria in a recirculating aquaculture system under standardized environmental conditions. Growth was significantly higher in fish that received the biotin-supplemented diet (A0B1), compared to diets lacking biotin or supplemented with avidin. Tilapia fed higher concentration of avidin-supplemented diets (A60B1 and A120B1) showed significant growth depression and displayed severe deficiency syndromes such as lethargy, anorexia, circular swimming and convulsions, which ultimately lead to death. There was a strong proportional linear relationship between the avidin content of the diet and feed conversion ratio, FCR (y = 0.43x + 0.135; r = 0.960; P protein efficiency ratio, PER (y = -0.309x + 2.195; r = 0.961; P levels of biotinidase, pyruvate carboxylase, propionyl-CoA carboxylase-A and propionyl-CoA carboxylase-B transcripts were noted in fish fed all graded level of avidin-supplemented diets. A broken-line analysis indicated that feeding tilapia a diet with 44.5 times more avidin than the dietary biotin requirement can induce deficiency syndromes including retarded growth, when

  5. Fiber knob domain lacking the shaft sequence but fused to a coiled coil is a candidate subunit vaccine against egg-drop syndrome.

    Science.gov (United States)

    Harakuni, Tetsuya; Andoh, Kiyohiko; Sakamoto, Ryu-Ichi; Tamaki, Yukihiro; Miyata, Takeshi; Uefuji, Hirotaka; Yamazaki, Ken-Ichi; Arakawa, Takeshi

    2016-06-08

    Egg-drop syndrome (EDS) virus is an avian adenovirus that causes a sudden drop in egg production and in the quality of the eggs when it infects chickens, leading to substantial economic losses in the poultry industry. Inactivated EDS vaccines produced in embryonated duck eggs or cell culture systems are available for the prophylaxis of EDS. However, recombinant subunit vaccines that are efficacious and inexpensive are a desirable alternative. In this study, we engineered chimeric fusion proteins in which the trimeric fiber knob domain lacking the triple β-spiral motif in the fiber shaft region was genetically fused to trimeric coiled coils, such as those of the engineered form of the GCN4 leucine zipper peptide or chicken cartilage matrix protein (CMP). The fusion proteins were expressed predominantly as soluble trimeric proteins in Escherichia coli at levels of 15-80mg/L of bacterial culture. The single immunization of chickens with the purified fusion proteins, at a dose equivalent to 10μg of the knob moiety, elicited serum antibodies with high hemagglutination inhibition (HI) activities, similar to those induced by an inactivated EDS vaccine. A dose-response analysis indicated that a single immunization with as little as 1μg of the knob moiety of the CMP-knob fusion protein was as effective as the inactivated vaccine in inducing antibodies with HI activity. The immunization of laying hens had no apparent adverse effects on egg production and effectively prevented clinical symptoms of EDS when the chickens were challenged with pathogenic EDS virus. This study demonstrates that the knob domain lacking the shaft sequence but fused to a trimeric coiled coil is a promising candidate subunit vaccine for the prophylaxis of EDS in chickens. Copyright © 2016 Elsevier Ltd. All rights reserved.

  6. Insulin resistance in Saudi postmenopausal women with and without metabolic syndrome and its association with vitamin D deficiency

    Directory of Open Access Journals (Sweden)

    Eman M. Alissa, PhD

    2015-03-01

    Conclusions: These observations suggest that hypovitaminosis D may be associated with the risk of developing metabolic syndrome. Interrelationships between IR, metabolic syndrome, and hypovitaminosis D are of particular interest in Saudi population, given the high prevalence of these conditions in this region.

  7. Research on conceptual framework of PRO scale in spleen Qi deficiency syndrome%脾气虚证PRO量表概念框架的探讨

    Institute of Scientific and Technical Information of China (English)

    林建东; 胡镜清; 刘保延

    2013-01-01

    [Objective] To develop a conceptual framework of patient-reported outcomes (PRO) scale in spleen Qi deficiency syndrome for the further development of scale items, the establishment of the item pool and lay a theoretical foundation. [Methods] The work was performed under the guidance of traditional Chinese medicine (TCM) theory and the direction of psychometrics. The formation of the conceptual framework of PRO scale in spleen Qi deficiency syndrome is set up according to the clinical features of spleen Qi deficiency syndrome, the production principles and processes of PRO scale in United States Food and Drug Administration (FDA) and combined with the WHO concept of health, TCM holistic concept and physiological functions of the spleen. [Results] The scale is composed of four domains: physiology domain, psychology domain, independence domain and social domain. The physiology domain is composed of three facets, which are symptoms of spleen deficiency, symptoms of Qi deficiency and symptoms of the five viscera. The psychology domain is composed of negative feelings and positive feelings. The independence domain is composed of three faces of the activities of daily living and work learning ability. The social domain is composed of social support and social relations. [Conclusion] The four domains and nine fields that formed by preliminary study of defmeing and explaining the conception of Spleen Qi Deficiency Syndrome generalize about the connotation and extension of it allsidely.%[目的]构建脾气虚证患者报告结局(PRO)量表的概念框架为进一步发展量表条目、建立条目池和量表的研制奠定理论基础.[方法]在中医传统理论的指导下,参照美国食品药品监督管理局(FDA)所规定的PRO量表的制作原则及流程,根据脾气虚证的临床特点,结合世界卫生组织(WHO)的健康概念、中医整体观念及脾脏的生理功能构建量表的概念框架.[结果]量表分为生理、心理、独立性和社会4

  8. Lower extremity compartment syndrome in the setting of iliofemoral deep vein thrombosis, phlegmasia cerulea dolens and factor VII deficiency.

    Science.gov (United States)

    Abdul, Wahid; Hickey, Ben; Wilson, Chris

    2016-04-25

    Acute compartment syndrome requires urgent fasciotomies to prevent irreversible muscle damage. We present a case of massive iliofemoral deep vein thrombosis (DVT) presenting as acute compartment syndrome. A healthy 21-year-old man presented with a 2-day history of worsening left leg pain with swelling and bluish discolouration. Clinical diagnosis of compartment syndrome secondary to phlegmasia cerulea dolens (PCD) was made and he underwent emergency fasciotomies. Postoperative venous duplex confirmed a massive iliofemoral DVT and intravenous heparin was started. Following skin grafting, the patient made a good recovery. Massive iliofemoral DVT is an uncommon cause of compartment syndrome and has been reported in lower limbs, secondary to PCD. Failure to treat early carries a high degree of morbidity, with amputation rates up to 50% and mortality rates between 25% and 40%. It is important to recognise compartment syndrome as an acute presentation of PCD. Urgent fasciotomies can prevent limb amputation and mortality. 2016 BMJ Publishing Group Ltd.

  9. [Iron deficiency and digestive disorders].

    Science.gov (United States)

    Cozon, G J N

    2014-11-01

    Iron deficiency anemia still remains problematic worldwide. Iron deficiency without anemia is often undiagnosed. We reviewed, in this study, symptoms and syndromes associated with iron deficiency with or without anemia: fatigue, cognitive functions, restless legs syndrome, hair loss, and chronic heart failure. Iron is absorbed through the digestive tract. Hepcidin and ferroportin are the main proteins of iron regulation. Pathogenic micro-organisms or intestinal dysbiosis are suspected to influence iron absorption. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  10. Hair and skin sterols in normal mice and those with deficient dehydrosterol reductase (DHCR7), the enzyme associated with Smith-Lemli-Opitz syndrome

    Science.gov (United States)

    Serra, Montserrat; Matabosch, Xavier; Ying, Lee; Watson, Gordon; Shackleton, Cedric

    2010-01-01

    Our recent studies have focused on cholesterol synthesis in mouse models for 7-dehydrosterolreductase (DHCR7) deficiency, also known as Smith-Lemli-Opitz syndrome. Investigations of such mutants have relied on tissue and blood levels of the cholesterol precursor 7-dehydrocholesterol (7DHC) and its 8-dehydro isomer. In this investigation by gas chromatography/mass spectrometry (GC/MS) we have identified and quantified cholesterol and its precursors (7DHC, desmosterol, lathosterol, lanosterol and cholest-7,24-dien-3β-ol) in mouse hair. The components were characterized and their concentrations were compared to those found in mouse skin and serum. Hair appeared unique in that desmosterol was a major sterol component, almost matching in concentration cholesterol itself. In DHCR7 deficient mice, dehydrodesmosterol (DHD) was the dominant hair Δ7 sterol. Mutant mouse hair had much higher concentrations of 7-dehydrosterols relative to cholesterol than did serum or tissue at all ages studied. The 7DHC/C ratio in hair was typically about sevenfold the value in serum or skin and the DHD/D ratio was 100X that of the serum 7DHC/C ratio. Mutant mice compensate for their DHCR7 deficiency with maturity, and the tissue and blood 7DHC/C become close to normal. That hair retains high relative concentrations of the dehydro precursors suggests that the apparent up-regulation of Dhcr7 seen in liver is slower to develop at the site of hair cholesterol synthesis. PMID:20804844

  11. Histopathological comparison of Kearns-Sayre syndrome and PGC-1α-deficient mice suggests a novel concept for vacuole formation in mitochondrial encephalopathy.

    Science.gov (United States)

    Szalardy, L; Molnar, M; Torok, R; Zadori, D; Vecsei, L; Klivenyi, P; Liberski, P; Kovacs, G G

    2016-01-01

    Despite the current hypotheses about myelinic and astrocytic ion-dyshomeostasis underlying white (WM) and grey matter (GM) vacuolation in mitochondrial encephalopathies, there is a paucity of data on the exact mechanism of vacuole formation. To revisit the concepts of vacuole formation associated with mitochondrial dysfunction, we performed a comparative neuropathological analysis in Kearns-Sayre syndrome (KSS) and full-length peroxisome proliferator-activated receptor-g coactivator-1a (FL-PGC-1a)-deficient mice, a recently proposed morphological model of mitochondrial encephalopathies. Brain tissues from an individual with genetically proven KSS (22-year-old man) and aged FL-PGC-1a-deficient and wild-type (male, 70-75-week-old) mice were analysed using ultrastructural and immunohistochemical methods, with a specific focus on myelin-related, oligodendroglial, axonal and astrocytic pathologies. Besides demonstrating remarkable similarities in the lesion profile of KSS and FL-PGC-1a-deficient mice, this study first provides morphological evidence for the identical origin of WM and GM vacuolation as well as for the presence of intracytoplasmic oligodendroglial vacuoles in mitochondriopathies. Based on these observations, the paper proposes a theoretical model for the development of focal myelin vacuolation as opposed to the original concepts of intramyelin oedema. Placing oligodendrocytes in the centre of tissue lesioning in conditions related to defects in mitochondria, our observations support the rationale for cytoprotective targeting of oligodendrocytes in mitochondrial encephalopathies, and may also have implications in brain aging and multiple sclerosis, as discussed.

  12. Clinical observation on acupuncture for diarrhea-predominant irritable bowel syndrome patients in syndrome of liver-stagnation and spleen-deficiency and its impact on Th1 /Th2

    Institute of Scientific and Technical Information of China (English)

    吴晓亮

    2014-01-01

    Objective To observe clinical therapeutic effects of acupuncture for pattern of liver-stagnation and spleen-deficiency in diarrhea-predominant irritable bowel syndrome(D-IBS)and its impact on cell factors.Methods Forty cases were selected and divided into an acupuncture group(21 cases)in which acupuncture was applied and a medicine group(19 cases)in which oral administration of dicetel and bifidobacterium lactobacillus triple viable capsulas were applied.The symptom scores,level of Th1-type

  13. Do dopaminergic gene polymorphisms affect mesolimbic reward activation of music listening response? Therapeutic impact on Reward Deficiency Syndrome (RDS).

    Science.gov (United States)

    Blum, Kenneth; Chen, Thomas J H; Chen, Amanda L H; Madigan, Margaret; Downs, B William; Waite, Roger L; Braverman, Eric R; Kerner, Mallory; Bowirrat, Abdalla; Giordano, John; Henshaw, Harry; Gold, Mark S

    2010-03-01

    affected by an individual's D2 density in the VTA mediated interaction of the NAc. It is therefore hypothesized that carriers of DRD2 A1 allele may respond significantly differently to carriers of the DRD2 A2 genotype. In this regard, carriers of the D2 A1 allele have a blunted response to glucose and monetary rewards. In contrast powerful D2 agonists like bromocryptine show a heightened activation of the reward circuitry only in DRD2 A1 allele carriers. If music causes a powerful activation in spite of the DRD2 A1 allele due to a strong DA neuronal release which subsequently impinges on existing D2 receptors, then it is reasonable to assume that music is a strong indirect D2 agonist (by virtue of DA neuronal release in the NAc) and may have important therapeutic applicability in Reward Deficiency Syndrome (RDS) related behaviors including Substance Use Disorder (SUD). Ross et al. [18] found that music therapy appears to be a novel motivational tool in a severely impaired inpatient sample of patients with co-occurring mental illness and addiction.

  14. Pathogenesis of peroxisomal deficiency disorders (Zellweger syndrome may be mediated by misregulation of the GABAergic system via the diazepam binding inhibitor

    Directory of Open Access Journals (Sweden)

    Breitling Rainer

    2004-03-01

    Full Text Available Abstract Background Zellweger syndrome (ZS is a fatal inherited disease caused by peroxisome biogenesis deficiency. Patients are characterized by multiple disturbances of lipid metabolism, profound hypotonia and neonatal seizures, and distinct craniofacial malformations. Median live expectancy of ZS patients is less than one year. While the molecular basis of peroxisome biogenesis and metabolism is known in considerable detail, it is unclear how peroxisome deficiency leads to the most severe neurological symptoms. Recent analysis of ZS mouse models has all but invalidated previous hypotheses. Hypothesis We suggest that a regulatory rather than a metabolic defect is responsible for the drastic impairment of brain function in ZS patients. Testing the hypothesis Using microarray analysis we identify diazepam binding inhibitor/acyl-CoA binding protein (DBI as a candidate protein that might be involved in the pathogenic mechanism of ZS. DBI has a dual role as a neuropeptide antagonist of GABA(A receptor signaling in the brain and as a regulator of lipid metabolism. Repression of DBI in ZS patients could result in an overactivation of GABAergic signaling, thus eventually leading to the characteristic hypotonia and seizures. The most important argument for a misregulation of GABA(A in ZS is, however, provided by the striking similarity between ZS and "benzodiazepine embryofetopathy", a malformation syndrome observed after the abuse of GABA(A agonists during pregnancy. Implications of the hypothesis We present a tentative mechanistic model of the effect of DBI misregulation on neuronal function that could explain some of the aspects of the pathology of Zellweger syndrome.

  15. 46,XY DSD with Female or Ambiguous External Genitalia at Birth due to Androgen Insensitivity Syndrome, 5-Reductase-2 Deficiency, or 17-Hydroxysteroid Dehydrogenase Deficiency: A Review of Quality of Life Outcomes

    Directory of Open Access Journals (Sweden)

    Mazur Tom

    2009-08-01

    Full Text Available Disorders of sex development refer to a collection of congenital conditions in which atypical development of chromosomal, gonadal, or anatomic sex occurs. Studies of 46,XY DSD have focused largely on gender identity, gender role, and sexual orientation. Few studies have focused on other domains, such as physical and mental health, that may contribute to a person's quality of life. The current review focuses on information published since 1955 pertaining to psychological well-being, cognition, general health, fertility, and sexual function in people affected by androgen insensitivity syndromes, 5- reductase-2 deficiency, or 17-hydroxysteroid dehydrogenase-3 deficiency—reared male or female. The complete form of androgen insensitivity syndrome has been the focus of the largest number of investigations in domains other than gender. Despite this, all of the conditions included in the current review are under-studied. Realms identified for further study include psychological well-being, cognitive abilities, general health, fertility, and sexual function. Such investigations would not only improve the quality of life for those affected by DSD but may also provide information for improving physical and mental health in the general population.

  16. STUDY OF CLINICO- EPIDEMIOLOGICAL PROFILE OF PATIENTS ADMITTED WITH INFANTILE TREMOR SYNDROME (ITS AND STATUS OF TRACE ELEMENTS (ZINC, COPPER DEFICIENCY IN THEM

    Directory of Open Access Journals (Sweden)

    Mohan Makwana

    2017-03-01

    Full Text Available BACKGROUND Under nutrition is one of the major problems in the field of Paediatrics. The greatest risk of malnutrition is in the first two years of life. The effects of this early damage on health, brain development, intelligence, educability and productivity are potentially reversible. The current study was an attempt to find out the clinico epidemiological profile, evaluate them for trace elements deficiency and most appropriate management options in those who are admitted with infantile tremor syndrome. MATERIALS AND METHODS The current study was a hospital based cross sectional study that was conducted in the Department of Paediatrics, Dr. S. N. Medical College Jodhpur. Duration of study was One Year. Any child up to the age of three years of age admitted in the paediatric wards with typical features of infantile tremor syndrome. RESULTS Maximum numbers of patients were found between 6 months to 12 months of age, there was slight male predominance. The majority of infants in our study (85% were exclusively breast fed, 66% of cases were having low serum Copper level. 9% of cases were having low serum zinc level. 8% of cases were having low serum copper level with tremors. CONCLUSION In our study the fact that NTS is mainly seen in children who are exclusively breast feed for a longer period with delayed introduction of weaning foods. The main presenting features remain developmental delay, hyper pigmentation and anemia. Among nutritional factors, deficiency of copper and zinc in children plays a big role in development of disease. Thus to prevent the development of nutritional tremor syndrome stress should be on early timely introduction of weaning foods, especially rich in copper and zinc. What is already known about this Study- low levels of trace elements like copper and zinc may be responsible for typical clinical manifestations in patients of infantile tremor syndrome. Pronged and Exclusive breast feeding further aggravate these features

  17. ALDH1A1 Deficiency in Gorlin Syndrome Suggests a Central Role for Retinoic Acid and ATM Deficits in Radiation Carcinogenesis.

    Science.gov (United States)

    Weber, Thomas J; Magnaldo, Thierry; Xiong, Yijia

    2014-09-11

    We hypothesize that aldehyde dehydrogenase 1A1 (ALDH1A1) deficiency will result in impaired ataxia-telangiectasia mutated (ATM) activation in a retinoic acid-sensitive fashion. Data supporting this hypothesis include (1) reduced ATM activation in irradiated primary dermal fibroblasts from ALDH1A1-deficient Gorlin syndrome patients (GDFs), relative to ALDH1A1-positive normal human dermal fibroblasts (NHDFs) and (2) increased ATM activation by X-radiation in GDFs pretreated with retinoic acid, however, the impact of donor variability on ATM activation in fibroblasts was not assessed and is a prudent consideration in future studies. Clonogenic survival of irradiated cells showed differential responses to retinoic acid as a function of treatment time. Long-term (5 Day) retinoic acid treatment functioned as a radiosensitizer and was associated with downregulation of ATM protein levels. Short-term (7 h) retinoic acid treatment showed a trend toward increased survival of irradiated cells and did not downregulate ATM protein levels. Using a newly developed IncubATR technology, which defines changes in bulk chemical bond patterns in live cells, we can discriminate between the NHDF and GDF phenotypes, but treatment of GDFs with retinoic acid does not induce reversion of bulk chemical bond patterns associated with GDFs toward the NHDF phenotype. Collectively, our preliminary investigation of the Gorlin phenotype has identified deficient ALDH1A1 expression associated with deficient ATM activation as a possible susceptibility factor that is consistent with the high incidence of spontaneous and radiation-induced carcinogenesis in these patients. The IncubATR technology exhibits sufficient sensitivity to detect phenotypic differences in live cells that may be relevant to radiation health effects.

  18. Vitamin D Deficiency in Adult Patients with Schizophreniform and Autism Spectrum Syndromes: A One-Year Cohort Study at a German Tertiary Care Hospital

    Directory of Open Access Journals (Sweden)

    Dominique Endres

    2016-10-01

    Full Text Available Introduction: Vitamin D has many immunomodulatory, anti-inflammatory, and neuroprotective functions, and previous studies have demonstrated an association between vitamin D deficiency and neuropsychiatric disease. The aim of our study was to analyze the prevalence of vitamin D deficiency in a one-year cohort of adult inpatients with schizophreniform and autism-spectrum syndromes in a naturalistic in-patient setting in Germany. Participants and methods: Our study was comprised of 60 adult schizophreniform and 23 adult high-functioning autism spectrum patients who were hospitalized Page: 2between January and December of 2015. We compared our findings with a historical German reference cohort of 3,917 adults using Pearson’s two-sided chi-squared test. The laboratory measurements of 25-hydroxyvitamin D2/3 (25(OHvitamin D were obtained using a chemiluminescence immunoassay. Results: In the schizophreniform group, we found decreased ( 30 ng/ml were observed in only 5% of the schizophreniform patients, 8.7% of the autism spectrum patients, and 21.9% of the healthy controls. Discussion: We found very high rates of 25(OHvitamin D deficiency in both patient groups, and have discussed whether our findings might be related to alterations in the immunological mechanisms. Irrespective of the possible pathophysiological links between vitamin D deficiency and schizophrenia or autism spectrum disorders, a more frequent measurement of vitamin D levels seems to be justified in these patient groups. Further prospective, controlled, blinded, and randomized research should be conducted to analyze the effectiveness of vitamin D supplementation on the improvement of psychiatric symptoms.

  19. Defects in neural stem cell proliferation and olfaction in Chd7 deficient mice indicate a mechanism for hyposmia in human CHARGE syndrome.

    Science.gov (United States)

    Layman, W S; McEwen, D P; Beyer, L A; Lalani, S R; Fernbach, S D; Oh, E; Swaroop, A; Hegg, C C; Raphael, Y; Martens, J R; Martin, D M

    2009-06-01

    Mutations in CHD7, a chromodomain gene, are present in a majority of individuals with CHARGE syndrome, a multiple anomaly disorder characterized by ocular Coloboma, Heart defects, Atresia of the choanae, Retarded growth and development, Genital hypoplasia and Ear anomalies. The clinical features of CHARGE syndrome are highly variable and incompletely penetrant. Olfactory dysfunction is a common feature in CHARGE syndrome and has been potentially linked to primary olfactory bulb defects, but no data confirming this mechanistic link have been reported. On the basis of these observations, we hypothesized that loss of Chd7 disrupts mammalian olfactory tissue development and function. We found severe defects in olfaction in individuals with CHD7 mutations and CHARGE, and loss of odor evoked electro-olfactogram responses in Chd7 deficient mice, suggesting reduced olfaction is due to a dysfunctional olfactory epithelium. Chd7 expression was high in basal olfactory epithelial neural stem cells and down-regulated in mature olfactory sensory neurons. We observed smaller olfactory bulbs, reduced olfactory sensory neurons, and disorganized epithelial ultrastructure in Chd7 mutant mice, despite apparently normal functional cilia and sustentacular cells. Significant reductions in the proliferation of neural stem cells and regeneration of olfactory sensory neurons in the mature Chd7(Gt/+) olfactory epithelium indicate critical roles for Chd7 in regulating neurogenesis. These studies provide evidence that mammalian olfactory dysfunction due to Chd7 haploinsufficiency is linked to primary defects in olfactory neural stem cell proliferation and may influence olfactory bulb development.

  20. Idiopathic combined, autoantibody-mediated ADAMTS-13/factor H deficiency in thrombotic thrombocytopenic purpura-hemolytic uremic syndrome in a 17-year-old woman: a case report

    Directory of Open Access Journals (Sweden)

    Patschan Daniel

    2011-12-01

    Full Text Available Abstract Introduction Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome is a life-threatening condition with various etiopathogeneses. Without therapy approximately 90% of all patients die from the disease. Case presentation We report the case of a 17-year-old Caucasian woman with widespread hematomas and headache. Due to hemolytic anemia, thrombocytopenia, and schistocytosis, thrombotic thrombocytopenic purpura-hemolytic uremic syndrome was suspected and plasma exchange therapy was initiated immediately. Since her thrombocyte level did not increase during the first week of therapy, plasma treatment had to be intensified to a twice-daily schedule. Further diagnostics showed markedly reduced activities of both ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 - also known as von Willebrand factor-cleaving protease and factor H. Test results for antibodies against both proteins were positive. While plasma exchange therapy was continued, rituximab was given once weekly for four consecutive weeks. After the last dose, thrombocytes and activities of ADAMTS-13 and factor H increased into the normal range. Our patient improved and was discharged from the hospital. Conclusions Since no clinical symptoms/laboratory findings indicated a malignant or specific autoimmune-mediated disorder, the diagnosis made was thrombotic thrombocytopenic purpura-hemolytic uremic syndrome due to idiopathic combined, autoantibody-mediated ADAMTS-13/factor H deficiency.

  1. 脾阳虚证用药规律浅析%Analysis of the Drug Use Law for Spleen Deficiency Syndrome

    Institute of Scientific and Technical Information of China (English)

    张杰; 李莉; 唐林; 孟静岩

    2016-01-01

    Objective:To discuss the drug use law for spleen yang deficiency syndrome by statistical analysis of the formulas used for spleen yang deficiency syndrome in modem clinical application.Methods:The statistical software SPSS17.0 was applied to analyze the use frequency of the Chinese herbs in formulas for spleen yang deficiency.The properties,flavors and efficacies of the Chinese herbs are analyzed.Results:Totally 83 formulas containing 86 herbs.According to the use frequency of the herbs,Gancao (Radix et Rhizoma Glycyrrhizae),Ganjiang (Rhizoma Zingiberis),Renshen (Radix et Rhizoma Ginseng),Baizhu (Rhizoma Atractylodis Macrocephalae),Chenpi (Pericarpium Citri Reticulatae),Fuzi (Radix Aconiti Lateralis Praeparata),Muxiang (Radix Aucklandiae),Rougui (Cortex Cinnamomi),Fuling (Poria) and Dingxiang (Flos Caryophylli) are the commonly-used herbs,most of which are qi-tonifying,interior-warming and qi-regulating herbs.According to the distribution of the properties and flavors,it shows that warm,hot and neutral properties and pungent,sweet and bitter flavors are the most and most of them are pungent-heat,pungent-warm,sweet-neutral and pungent,bitter-warm herbs.Conclusion:For the drug use law of spleen yang deficiency syndrome,herbs with warm and hot in nature,pungent,sweet in flavor (Gancao,Renshen,Baizhu),qi-tonifying and interior-regulating in function (Renshen,Fuzi) are most commonly used,which provides theoretical basis for the clinical treatment of spleen yang deficiency syndrome.%目的:通过对近现代临床应用于脾阳虚证的方剂进行统计分析,探讨脾阳虚证用药规律.方法:运用SPSS 19.0统计软件,对脾阳虚证方剂中的中药进行频次分析,并对所用中药的性味、功效进行统计分析结果:共收集方剂83首,涉及药物86味.药物使用频次显示甘草、干姜、人参、白术、陈皮、附子、禾香、肉桂、茯苓、丁香等为常用药物,以补气药、温里药、理气药为主.性味分布情况显示

  2. Fifteen years of epidemiologic, virologic and syndromic influenza surveillance: A focus on type B virus and the effects of vaccine mismatch in Liguria region, Italy

    Science.gov (United States)

    Grammatico, Federico; Canepa, Paola

    2017-01-01

    ABSTRACT In order to estimate the burden of influenza and to describe the genetic evolutionary pattern and antigenic variability of type B viral strains, data deriving from 3 surveillance systems active in Liguria region, Northern Italy, were described. Since the re-emergence of the Victoria lineage in 2001, the clinical-epidemiological and syndromic surveillances demonstrated the heavy burden of influenza like illness (ILI) syndrome. Focusing on type B influenza virus, it predominated or played a relevant epidemic role in the 50% of the evaluated influenza seasons. Furthermore, the virologic surveillance demonstrated the frequent co-circulation of both lineages an heterogeneous circulation of different influenza B strains, determining a partial or complete mismatch in at least 6 influenza seasons. The undemonstrated cross-reactivity between lineages and the unpredictability of predominant lineage arose the scientific debate about the opportunity to include the quadrivalent influenza vaccine among the preventive tools to improve the protection against type B viruses. The integration of different surveillance systems highly contribute to estimate the poorly evaluated burden of type B influenza virus and help to find variants to include in the vaccine formulation. PMID:27924684

  3. HPV vaccine

    Science.gov (United States)

    ... cervix - HPV vaccine; Abnormal Pap smear - HPV vaccine; Vaccination - HPV vaccine ... and Gynecologists. Committee opinion No. 641: human papillomavirus vaccination. Obstet Gynecol . 2015;126(3):e38-e43. PMID: ...

  4. Immunogenicity, safety and tolerability of monovalent 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine in children and adolescents with Williams or Cornelia De Lange syndrome.

    Science.gov (United States)

    Esposito, Susanna; Selicorni, Angelo; Daleno, Cristina; Valzano, Antonia; Cerutti, Marta; Galeone, Carlotta; Consolo, Silvia; Menni, Francesca; Principi, Nicola

    2011-06-01

    In some subjects with severe neurological diseases, a reduced immune response to seasonal influenza vaccine has been demonstrated. Patients with Williams or Cornelia de Lange syndrome frequently have abnormalities in neurodevelopment. This study has evaluated the immunogenicity, safety and tolerability of a monovalent 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine in these subjects. Eighteen patients with Williams syndrome (ten males; mean age ± standard deviation [SD] 12.74 ± 4.49 years), 11 with Cornelia de Lange syndrome (six males; mean age 12.90 ± 4.85 years) and 30 age- and gender-matched healthy controls (16 males; mean age 12.49 ± 4.55 years), never vaccinated against influenza, received a dose of the vaccine between 1 and 30 November 2009. Four weeks later, the seroconversion rates in the three groups were between 72% and 80% and the seroprotection rates were 100%, with a similar increase in antibody levels. Two months later, most of the subjects remained seroconverted with no statistically significant difference between the groups, and about 94% of the patients with Williams syndrome, all of those with Cornelia de Lange syndrome and all of the healthy controls were still seroprotected. Safety and tolerability were very good, with no difference between the groups. None of the patients developed documented influenza during the study period. These results show that the immunogenicity, safety, and tolerability of a single dose of the monovalent 2009 pandemic influenza A/H1N1 MF59-adjuvanted vaccine in children and adolescents with Williams or Cornelia de Lange syndrome and moderate to severe mental disabilities is very good, and similar to that of healthy subjects.

  5. Assessing the functionality of viral entry-associated domains of porcine reproductive and respiratory syndrome virus during inactivation procedures, a potential tool to optimize inactivated vaccines.

    Science.gov (United States)

    Delrue, Iris; Delputte, Peter L; Nauwynck, Hans J

    2009-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) causes severe economic losses in the pig industry worldwide. Currently, vaccines based on inactivated PRRSV provide limited protection of pigs against infection, most likely because viral epitopes associated with the induction of neutralizing antibodies are not or poorly conserved during inactivation. To analyze the effect of inactivation procedures on the interaction of PRRSV with receptors involved in virus entry, a new assay was set up in this study. Viral entry-associated domains are most likely important for the induction of neutralizing antibodies, since neutralizing antibodies block interaction of PRRSV with cellular receptors. To investigate the interaction of PRRSV with the cellular receptors upon different inactivation procedures, attachment to and internalization of inactivated PRRSV into macrophages were monitored. AT-2 could not inactivate PRRSV completely and is therefore not useful for vaccine development. PRRSV inactivated with ultraviolet light, binary ethyleneimine and gamma irradiation, which all mainly have an effect at the genomic level, showed no difference compared to control live virus at all levels of virus entry, whereas PRRSV treated with formaldehyde, glutaraldehyde and pH changes, which all have a modifying effect on proteins, was not able to internalize into macrophages anymore. These results suggest that inactivation with methods with a main effect on the viral genome preserve PRRSV entry-associated domains and are useful for future development of an effective inactivated vaccine against PRRSV. Although PRRSV incubation at 37 degrees C can completely inactivate PRRSV with preservation of entry-associated domains, this method is not recommended for vaccine development, since the mechanism is yet unknown.

  6. Refeeding syndrome.

    Science.gov (United States)

    Fernández López, M T; López Otero, M J; Alvarez Vázquez, P; Arias Delgado, J; Varela Correa, J J

    2009-01-01

    Refeeding syndrome is a complex syndrome that occurs as a result of reintroducing nutrition (oral, enteral or parenteral) to patients who are starved or malnourished. Patients can develop fluid-balance abnormalities, electrolyte disorders (hypophosphataemia, hypokalaemia and hypomagnesaemia), abnormal glucose metabolism and certain vitamin deficiencies. Refeeding syndrome encompasses abnormalities affecting multiple organ systems, including neurological, pulmonary, cardiac, neuromuscular and haematological functions. Pathogenic mechanisms involved in the refeeding syndrome and clinical manifestations have been reviewed. We provide suggestions for the prevention and treatment of refeeding syndrome. The most important steps are to identify patients at risk, reintroduce nutrition cautiously and correct electrolyte and vitamin deficiencies properly.

  7. Vitamin B2 deficiency enhances the pro-inflammatory activity of adipocyte, consequences for insulin resistance and metabolic syndrome development.

    Science.gov (United States)

    Mazur-Bialy, Agnieszka Irena; Pocheć, Ewa

    2017-06-01

    Adipose tissue is an endocrine organ important for regulation of such physiological processes as energy metabolism or lipids homeostasis. In an obesity state, it participates in the induction of chronic systemic inflammation accompanied by pro-inflammatory cytokines and fatty acid elevation. For this reasons, adipose tissue is involved in, e.g., insulin resistance, type 2 diabetes or hyperlipidemia development. In our previous study, we have shown that riboflavin deficiency induces a pathological pro-inflammatory response of macrophages, the main component of adipose tissue. Therefore, in the current study, we investigated the alteration of the pro-inflammatory activity of adipocytes. The study was conducted on mouse 3T3 L1 preadipocytes differentiated to adipocyte and culture in the state of riboflavin deficiency (3.1nM) or control condition (10.4nM). The cell viability, adiposity and glucose uptake was assessed. Moreover, mRNA expression, as well as crucial pro-inflammatory cytokines (TNFα, IL-6) and adipokines (adiponectin, leptin, resistin) release and NFκB activation, were evaluated. Results showed that riboflavin deprivation induced a significant elevation in adipocyte lipolysis and enhance obesity-related apoptosis of adipocytes. The generation of reactive oxygen species was enhanced in riboflavin-deficient adipocytes by 43%. Moreover, NFκB phosphorylation and the expression and release of both TNFα, IL-6 as well as leptin were elevated in a deficient group what was accompanied by a reduction of adiponectin level. Our study shows that riboflavin deficiency can promote the intensification of pro-inflammatory activity of adipocyte cells, leading consequently to the severity of chronic inflammation that accompanies obesity state. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. On-demand anakinra treatment is effective in mevalonate kinase deficiency

    NARCIS (Netherlands)

    Bodar, E.J.; Kuijk, L.M.; Drenth, J.P.H.; Meer, J.W. van der; Simon, A.; Frenkel, J.

    2011-01-01

    BACKGROUND: Mevalonate kinase deficiency (MKD) is a hereditary autoinflammatory syndrome marked by recurrent attacks of fever and inflammation. Severe enzyme deficiency results in mevalonic aciduria (MA) and milder deficiency in hyperimmunoglobulin D syndrome (HIDS). Treatment remains a challenge. O

  9. Factor V Leiden mutation, prothrombin gene mutation, and deficiencies in coagulation inhibitors associated with Budd-Chiari syndrome and portal vein thrombosis: results of a case-control study

    NARCIS (Netherlands)

    H.L.A. Janssen (Harry); J.P. Vandenbroucke; F.R. Rosendaal (Frits); B. van Hoek (Bart); J.R. Meinardi; F.P. Vleggaar (Frank); S.H. van Uum; E.B. Haagsma (Els); F.J.M. van der Meer; J. van Hattum (Jan); R.A. Chamuleau; R.P.R. Adang (Rob)

    2000-01-01

    textabstractIn a collaborative multicenter case-control study, we investigated the effect of factor V Leiden mutation, prothrombin gene mutation, and inherited deficiencies of protein C, protein S, and antithrombin on the risk of Budd-Chiari syndrome (BCS) and portal vein thrombosi

  10. Study on comprehensive monitoring of mouse and effect of hemorrhagic fever with renal syndrome vaccine in high prevalence areas of natural focus infectious disease of Zhejiang province in 1994-2010

    Institute of Scientific and Technical Information of China (English)

    龚震宇

    2012-01-01

    Objective To study the comprehensive monitoring mechanism of mouse and the effect of hemorrhagic fever with renal syndrome(HFRS) vaccine in the high prevalence areas of natural focus infectious disease of Zhejiang province in 1994-2010. Methods The night trapping method was used to monitor the population proportion, density

  11. Development of a swine specific 9-plex Luminex cytokine assay and assessment of immunity after porcine reproductive and respiratory syndrome virus (PRRSV) vaccination: Elevated serum IL-12 levels are not predictive of protect

    Science.gov (United States)

    A Luminex multiplex swine cytokine assay was developed to measure 9 cytokines simultaneously in pig serum and tested in a porcine reproductive and respiratory syndrome virus (PRRSV) vaccine/challenge study. This assay detects innate (IL-1ß, IL-6, IL-8, IFNa, TNFa); regulatory (IL-10), Th1 (IL-12, I...

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

    Science.gov (United States)

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

    2015-04-01

    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.

  13. [Gougerot-Sjögren syndrome, periarteritis nodosa, non-Hodgkin's lymphoplasmocytic lymphoma and acquired C4 deficiency].

    Science.gov (United States)

    Herreman, G; Ferme, I; Diebold, J; Baviera, E; Audouin, J; Bazin, C; Godeau, P

    1983-01-01

    A Sjögren syndrome was confirmed histologically in a 19 year old woman. Four years later, periarteritis nodosa (PAN) with characteristic vascular lesions on muscle biopsy occurred simultaneously with lymphatic hyperplasia comprising splenomegaly and polyadenopathy. The PAN was cured with corticosteroids and cyclophosphamide and the lymphadenopathy regressed. Several months after treatment was stopped the lymphadenopathy recurred which histologically resembled a malignant non-hodgkin lymphoplasmocytoma secreting an IgM kappa monoclonal immunonoglobulin. During the PAN and the establishment of the lymphoproliferative syndrome a severe C4 deficit was detected which disappeared after chemotherapy.

  14. Impact of Diet-Induced Obesity and Testosterone Deficiency on the Cardiovascular System: A Novel Rodent Model Representative of Males with Testosterone-Deficient Metabolic Syndrome (TDMetS.

    Directory of Open Access Journals (Sweden)

    Daniel G Donner

    Full Text Available Current models of obesity utilise normogonadic animals and neglect the strong relationships between obesity-associated metabolic syndrome (MetS and male testosterone deficiency (TD. The joint presentation of these conditions has complex implications for the cardiovascular system that are not well understood. We have characterised and investigated three models in male rats: one of diet-induced obesity with the MetS; a second using orchiectomised rats mimicking TD; and a third combining MetS with TD which we propose is representative of males with testosterone deficiency and the metabolic syndrome (TDMetS.Male Wistar rats (n = 24 were randomly assigned to two groups and provided ad libitum access to normal rat chow (CTRL or a high fat/high sugar/low protein "obesogenic" diet (OGD for 28 weeks (n = 12/group. These groups were further sub-divided into sham-operated or orchiectomised (ORX animals to mimic hypogonadism, with and without diet-induced obesity (n = 6/group. Serum lipids, glucose, insulin and sex hormone concentrations were determined. Body composition, cardiovascular structure and function; and myocardial tolerance to ischemia-reperfusion were assessed.OGD-fed animals had 72% greater fat mass; 2.4-fold greater serum cholesterol; 2.3-fold greater serum triglycerides and 3-fold greater fasting glucose (indicative of diabetes mellitus compared to CTRLs (all p<0.05. The ORX animals had reduced serum testosterone and left ventricle mass (p<0.05. In addition to the combined differences observed in each of the isolated models, the OGD, ORX and OGD+ORX models each had greater CK-MB levels following in vivo cardiac ischemia-reperfusion insult compared to CTRLs (p<0.05.Our findings provide evidence to support that the MetS and TD independently impair myocardial tolerance to ischemia-reperfusion. The combined OGD+ORX phenotype described in this study is a novel animal model with associated cardiovascular risk factors and complex myocardial

  15. Impact of Diet-Induced Obesity and Testosterone Deficiency on the Cardiovascular System: A Novel Rodent Model Representative of Males with Testosterone-Deficient Metabolic Syndrome (TDMetS).

    Science.gov (United States)

    Donner, Daniel G; Elliott, Grace E; Beck, Belinda R; Bulmer, Andrew C; Du Toit, Eugene F

    2015-01-01

    Current models of obesity utilise normogonadic animals and neglect the strong relationships between obesity-associated metabolic syndrome (MetS) and male testosterone deficiency (TD). The joint presentation of these conditions has complex implications for the cardiovascular system that are not well understood. We have characterised and investigated three models in male rats: one of diet-induced obesity with the MetS; a second using orchiectomised rats mimicking TD; and a third combining MetS with TD which we propose is representative of males with testosterone deficiency and the metabolic syndrome (TDMetS). Male Wistar rats (n = 24) were randomly assigned to two groups and provided ad libitum access to normal rat chow (CTRL) or a high fat/high sugar/low protein "obesogenic" diet (OGD) for 28 weeks (n = 12/group). These groups were further sub-divided into sham-operated or orchiectomised (ORX) animals to mimic hypogonadism, with and without diet-induced obesity (n = 6/group). Serum lipids, glucose, insulin and sex hormone concentrations were determined. Body composition, cardiovascular structure and function; and myocardial tolerance to ischemia-reperfusion were assessed. OGD-fed animals had 72% greater fat mass; 2.4-fold greater serum cholesterol; 2.3-fold greater serum triglycerides and 3-fold greater fasting glucose (indicative of diabetes mellitus) compared to CTRLs (all p<0.05). The ORX animals had reduced serum testosterone and left ventricle mass (p<0.05). In addition to the combined differences observed in each of the isolated models, the OGD, ORX and OGD+ORX models each had greater CK-MB levels following in vivo cardiac ischemia-reperfusion insult compared to CTRLs (p<0.05). Our findings provide evidence to support that the MetS and TD independently impair myocardial tolerance to ischemia-reperfusion. The combined OGD+ORX phenotype described in this study is a novel animal model with associated cardiovascular risk factors and complex myocardial pathology

  16. Nitric oxide mediates aortic disease in mice deficient in the metalloprotease Adamts1 and in a mouse model of Marfan syndrome.

    Science.gov (United States)

    Oller, Jorge; Méndez-Barbero, Nerea; Ruiz, E Josue; Villahoz, Silvia; Renard, Marjolijn; Canelas, Lizet I; Briones, Ana M; Alberca, Rut; Lozano-Vidal, Noelia; Hurlé, María A; Milewicz, Dianna; Evangelista, Arturo; Salaices, Mercedes; Nistal, J Francisco; Jiménez-Borreguero, Luis Jesús; De Backer, Julie; Campanero, Miguel R; Redondo, Juan Miguel

    2017-02-01

    Heritable thoracic aortic aneurysms and dissections (TAAD), including Marfan syndrome (MFS), currently lack a cure, and causative mutations have been identified for only a fraction of affected families. Here we identify the metalloproteinase ADAMTS1 and inducible nitric oxide synthase (NOS2) as therapeutic targets in individuals with TAAD. We show that Adamts1 is a major mediator of vascular homeostasis, given that genetic haploinsufficiency of Adamts1 in mice causes TAAD similar to MFS. Aortic nitric oxide and Nos2 levels were higher in Adamts1-deficient mice and in a mouse model of MFS (hereafter referred to as MFS mice), and Nos2 inactivation protected both types of mice from aortic pathology. Pharmacological inhibition of Nos2 rapidly reversed aortic dilation and medial degeneration in young Adamts1-deficient mice and in young or old MFS mice. Patients with MFS showed elevated NOS2 and decreased ADAMTS1 protein levels in the aorta. These findings uncover a possible causative role for the ADAMTS1-NOS2 axis in human TAAD and warrant evaluation of NOS2 inhibitors for therapy.

  17. Vitamin B1-deficient mice show impairment of hippocampus-dependent memory formation and loss of hippocampal neurons and dendritic spines: potential microendophenotypes of Wernicke–Korsakoff syndrome

    Science.gov (United States)

    Inaba, Hiroyoshi; Kishimoto, Takuya; Oishi, Satoru; Nagata, Kan; Hasegawa, Shunsuke; Watanabe, Tamae; Kida, Satoshi

    2016-01-01

    Patients with severe Wernicke–Korsakoff syndrome (WKS) associated with vitamin B1 (thiamine) deficiency (TD) show enduring impairment of memory formation. The mechanisms of memory impairment induced by TD remain unknown. Here, we show that hippocampal degeneration is a potential microendophenotype (an endophenotype of brain disease at the cellular and synaptic levels) of WKS in pyrithiamine-induced thiamine deficiency (PTD) mice, a rodent model of WKS. PTD mice show deficits in the hippocampus-dependent memory formation, although they show normal hippocampus-independent memory. Similarly with WKS, impairments in memory formation did not recover even at 6 months after treatment with PTD. Importantly, PTD mice exhibit a decrease in neurons in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and reduced density of wide dendritic spines in the DG. Our findings suggest that TD induces hippocampal degeneration, including the loss of neurons and spines, thereby leading to enduring impairment of hippocampus-dependent memory formation. PMID:27576603

  18. Vitamin B1-deficient mice show impairment of hippocampus-dependent memory formation and loss of hippocampal neurons and dendritic spines: potential microendophenotypes of Wernicke-Korsakoff syndrome.

    Science.gov (United States)

    Inaba, Hiroyoshi; Kishimoto, Takuya; Oishi, Satoru; Nagata, Kan; Hasegawa, Shunsuke; Watanabe, Tamae; Kida, Satoshi

    2016-12-01

    Patients with severe Wernicke-Korsakoff syndrome (WKS) associated with vitamin B1 (thiamine) deficiency (TD) show enduring impairment of memory formation. The mechanisms of memory impairment induced by TD remain unknown. Here, we show that hippocampal degeneration is a potential microendophenotype (an endophenotype of brain disease at the cellular and synaptic levels) of WKS in pyrithiamine-induced thiamine deficiency (PTD) mice, a rodent model of WKS. PTD mice show deficits in the hippocampus-dependent memory formation, although they show normal hippocampus-independent memory. Similarly with WKS, impairments in memory formation did not recover even at 6 months after treatment with PTD. Importantly, PTD mice exhibit a decrease in neurons in the CA1, CA3, and dentate gyrus (DG) regions of the hippocampus and reduced density of wide dendritic spines in the DG. Our findings suggest that TD induces hippocampal degeneration, including the loss of neurons and spines, thereby leading to enduring impairment of hippocampus-dependent memory formation.

  19. Histopathological comparison of Kearns-Sayre syndrome and PGC-1α-deficient mice suggests a novel concept for vacuole formation in mitochondrial encephalopathy

    Directory of Open Access Journals (Sweden)

    Levente Szalardy

    2016-03-01

    Full Text Available Despite the current hypotheses about myelinic and astrocytic ion-dyshomeostasis underlying white (WM and grey matter (GM vacuolation in mitochondrial encephalopathies, there is a paucity of data on the exact mechanism of vacuole formation. To revisit the concepts of vacuole formation associated with mitochondrial dysfunction, we performed a comparative neuropathological analysis in Kearns-Sayre syndrome (KSS and full-length peroxisome proliferator-activated receptor-g coactivator-1a (FL-PGC-1a-deficient mice, a recently proposed morphological model of mitochondrial encephalopathies. Brain tissues from an individual with genetically proven KSS (22-year-old man and aged FL-PGC-1a-deficient and wild-type (male, 70-75-week-old mice were analysed using ultrastructural and immunohistochemical methods, with a specific focus on myelin-related, oligodendroglial, axonal and astrocytic pathologies. Besides demonstrating remarkable similarities in the lesion profile of KSS and FL-PGC-1a-deficient mice, this study first provides morphological evidence for the identical origin of WM and GM vacuolation as well as for the presence of intracytoplasmic oligodendroglial vacuoles in mitochondriopathies. Based on these observations, the paper proposes a theoretical model for the development of focal myelin vacuolation as opposed to the original concepts of intramyelin oedema. Placing oligodendrocytes in the centre of tissue lesioning in conditions related to defects in mitochondria, our observations support the rationale for cytoprotective targeting of oligodendrocytes in mitochondrial encephalopathies, and may also have implications in brain aging and multiple sclerosis, as discussed.

  20. Deficient IgA and IgG2 anti-pneumococcal antibody levels and response to vaccination in otitis prone children

    NARCIS (Netherlands)

    Dhooge, IJ; van Kempen, MJP; Sanders, LAM; Rijkers, GT

    2002-01-01

    Objective: To evaluate the isotype and IgG subclass distribution of anti-pneumococcal antibodies and response to polysaccharide vaccination in otitis prone children. Methods: IgG1, IgG2 and IgA antibodies to pneumococcal serotypes 3, 4, 6B, 9V, 14, 19F and 23F were determined in otitis prone

  1. B7 costimulation molecules encoded by replication-defective, vhs-deficient HSV-1 improve vaccine-induced protection against corneal disease.

    Directory of Open Access Journals (Sweden)

    Jane E Schrimpf

    Full Text Available Herpes simplex virus 1 (HSV-1 causes herpes stromal keratitis (HSK, a sight-threatening disease of the cornea for which no vaccine exists. A replication-defective, HSV-1 prototype vaccine bearing deletions in the genes encoding ICP8 and the virion host shutoff (vhs protein reduces HSV-1 replication and disease in a mouse model of HSK. Here we demonstrate that combining deletion of ICP8 and vhs with virus-based expression of B7 costimulation molecules created a vaccine strain that enhanced T cell responses to HSV-1 compared with the ICP8⁻vhs⁻ parental strain, and reduced the incidence of keratitis and acute infection of the nervous system after corneal challenge. Post-challenge T cell infiltration of the trigeminal ganglia and antigen-specific recall responses in local lymph nodes correlated with protection. Thus, B7 costimulation molecules expressed from the genome of a replication-defective, ICP8⁻vhs⁻ virus enhance vaccine efficacy by further reducing HSK.

  2. Vaccination of sows against type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) before artificial insemination protects against type 2 PRRSV challenge but does not protect against type 1 PRRSV challenge in late gestation

    Science.gov (United States)

    2014-01-01

    The objective of the present study was to determine the effects of the commercially available type 2 Porcine Reproductive and Respiratory Syndrome Virus (PRRSV)-based modified live vaccine against type 1 and type 2 PRRSV challenge in pregnant sows. Half of the sows in the study were vaccinated with a type 2 PRRSV-based vaccine 4 weeks prior to artificial insemination while the other half remained non-vaccinated. Sows were then challenged intranasally with type 1 or type 2 PRRSV at 93 days of gestation. The sows which received the type 2 PRRSV-based vaccine followed by type 2 PRRSV challenge had significantly higher neutralizing antibody titers against type 2 PRRSV than they did against type 1 PRRSV. These same sows had higher frequencies of IFN-γ-secreting cells when stimulated with type 2 PRRSV compared to those stimulated with type 1 PRRSV. Subsequent virological evaluation demonstrated that the type 2 PRRSV-based vaccine reduced the type 2 PRRSV load but not the type 1 PRRSV load present in the blood of the sows. Additionally, vaccination of pregnant sows with the type 2 PRRSV-based vaccine effectively reduced the level of type 2 PRRSV nucleic acids observed in fetal tissues from type 2 PRRSV-challenged sows but did not reduce the level of type 1 PRRSV nucleic acid observed in fetal tissues from type 1 PRRSV-challenged sows. This study demonstrates that the vaccination of pregnant sows with the type 2 PRRSV-based vaccine protects against type 2 PRRSV challenge but does not protect against type 1 PRRSV challenge. PMID:24484238

  3. Individuals with Smith-Magenis syndrome display profound neurodevelopmental behavioral deficiencies and exhibit food-related behaviors equivalent to Prader-Willi syndrome.

    Science.gov (United States)

    Alaimo, Joseph T; Barton, Laura V; Mullegama, Sureni V; Wills, Rachel D; Foster, Rebecca H; Elsea, Sarah H

    2015-12-01

    Smith-Magenis syndrome (SMS) is a neurodevelopmental disorder associated with intellectual disability, sleep disturbances, early onset obesity and vast behavioral deficits. We used the Behavior Problems Inventory-01 to categorize the frequency and severity of behavioral abnormalities in a SMS cohort relative to individuals with intellectual disability of heterogeneous etiology. Self-injurious, stereotyped, and aggressive/destructive behavioral scores indicated that both frequency and severity were significantly higher among individuals with SMS relative to those with intellectual disability. Next, we categorized food behaviors in our SMS cohort across age using the Food Related Problems Questionnaire (FRPQ) and found that problems began to occur in SMS children as early as 5-11 years old, but children 12-18 years old and adults manifested the most severe problems. Furthermore, we evaluated the similarities of SMS adult food-related behaviors to those with intellectual disability and found that SMS adults had more severe behavioral problems. Many neurodevelopmental disorders exhibit syndromic obesity including SMS. Prader-Willi syndrome (PWS) is the most frequent neurodevelopmental disorder with syndromic obesity and has a well-established management and treatment plan. Using the FRPQ we found that SMS adults had similar scores relative to PWS adults. Both syndromes manifest weight gain early in development, and the FRPQ scores highlight specific areas in which behavioral similarities exist, including preoccupation with food, impaired satiety, and negative behavioral responses. SMS food-related behavior treatment paradigms are not as refined as PWS, suggesting that current PWS treatments for prevention of obesity may be beneficial for individuals with SMS.

  4. Auditory and visual cortical activity during selective attention in fragile X syndrome: A cascade of processing deficiencies

    NARCIS (Netherlands)

    M.J.W. van der Molen; M.W. van der Molen; K.R. Ridderinkhof; B.C.J. Hamel; L.M.G. Curfs; G.J.A. Ramakers

    2012-01-01

    OBJECTIVE: This study examined whether attention deficits in fragile X syndrome (FXS) can be traced back to abnormalities in basic information processing. METHOD: Sixteen males with FXS and 22 age-matched control participants (mean age 29 years) performed a standard oddball task to examine selective

  5. Deficiency in origin licensing proteins impairs cilia formation: implications for the aetiology of meier-gorlin syndrome

    NARCIS (Netherlands)

    Stiff, T.; Alagoz, M.; Alcantara, D.; Outwin, E.; Brunner, H.G.; Bongers, M.H.F.; O'Driscoll, M.; Jeggo, P.A.

    2013-01-01

    Mutations in ORC1, ORC4, ORC6, CDT1, and CDC6, which encode proteins required for DNA replication origin licensing, cause Meier-Gorlin syndrome (MGS), a disorder conferring microcephaly, primordial dwarfism, underdeveloped ears, and skeletal abnormalities. Mutations in ATR, which also functions duri

  6. Mechanisms of vitamin deficiency in chronic alcohol misusers and the development of the Wernicke-Korsakoff syndrome.

    Science.gov (United States)

    Thomson, A D

    2000-01-01

    The classic signs of vitamin deficiency only occur in states of extreme depletion and are unreliable indicators for early treatment or prophylaxis of alcoholic patients at risk. Post-mortem findings demonstrate that thiamine (vitamin B1) deficiency sufficient to cause irreversible brain damage is not diagnosed ante mortem in 80-90% of these patients. The causes of vitamin deficiency are reviewed with special attention to the inhibition of oral thiamine hydrochloride absorption in man caused by malnutrition present in alcoholic patients or by the direct effects of ethanol on intestinal transport. As the condition of the patient misusing alcohol progresses, damage to brain, liver, gastrointestinal tract, and pancreas continue (with other factors discussed) to further compromise the patient. Decreased intake, malabsorption, reduced storage, and impaired utilization further reduce the chances of unaided recovery. Failure of large oral doses of thiamine hydrochloride to provide an effective treatment for Wernicke's encephalopathy emphasizes the need for adequate and rapid replacement of depleted brain thiamine levels by repeated parenteral therapy in adequate doses.

  7. Metabolic Signatures of Kidney Yang Deficiency Syndrome and Protective Effects of Two Herbal Extracts in Rats Using GC/TOF MS

    Directory of Open Access Journals (Sweden)

    Linjing Zhao

    2013-01-01

    Full Text Available Kidney Yang Deficiency Syndrome (KDS-Yang, a typical condition in Chinese medicine, shares similar clinical signs of the glucocorticoid withdrawal syndrome. To date, the underlying mechanism of KDS-Yang has been remained unclear, especially at the metabolic level. In this study, we report a metabolomic profiling study on a classical model of KDS-Yang in rats induced by hydrocortisone injection to characterize the metabolic transformation using gas chromatography/time-of-flight mass spectrometry. WKY1, a polysaccharide extract from Astragalus membranaceus and Lycium barbarum, and WKY2, an aqueous extract from a similar formula containing Astragalus membranaceus, Lycium barbarum, Morinda officinalis, Taraxacum mongolicum, and Cinnamomum cassia presl, were used separately for protective treatments of KDS-Yang. The changes of serum metabolic profiles indicated that significant alterations of key metabolic pathways in response to abrupt hydrocortisone perturbation, including decreased energy metabolism (lactic acid, acetylcarnitine, lipid metabolism (free fatty acids, 1-monolinoleoylglycerol, and cholesterol, gut microbiota metabolism (indole-3-propionic acid, biosynthesis of catecholamine (norepinephrine, and elevated alanine metabolism, were attenuated or normalized with different degrees by the pretreatment of WKY1 or WKY2, which is consistent with the observations in which the two herbal agents could ameliorate biochemical markers of serum cortisone, adrenocorticotropic (ACTH, and urine 17-hydroxycorticosteroids (17-OHCS.

  8. Vaccine Safety

    Science.gov (United States)

    ... Vaccine Safety Shingles (Herpes Zoster) Vaccine Safety Smallpox Vaccine Safety Common Concerns Adjuvants Autism CDC Statement: 2004 Pediatrics Paper on MMR and Autism Fainting (Syncope) Febrile ...

  9. Early life vaccination

    DEFF Research Database (Denmark)

    Nazerai, Loulieta; Bassi, Maria Rosaria; Uddbäck, Ida Elin Maria

    2016-01-01

    the first period of life and provide a pertinent alternative in infant vaccinology. To address this, infant mice were vaccinated with three different adenoviral vectors and the CD8+ T-cell response after early life vaccination was explored. We assessed the frequency, polyfunctionality and in vivo...... cytotoxicity of the elicited memory CD8+ T cells, as well as the potential of these cells to respond to secondary infections and confer protection. We further tested the impact of maternal immunity against our replication-deficient adenoviral vector during early life vaccination. Overall, our results indicate...

  10. The Combined Deficiency of Immunoproteasome Subunits Affects Both the Magnitude and Quality of Pathogen- and Genetic Vaccination-Induced CD8+ T Cell Responses to the Human Protozoan Parasite Trypanosoma cruzi

    Science.gov (United States)

    Ersching, Jonatan; Vasconcelos, José R.; Ferreira, Camila P.; Caetano, Braulia C.; Machado, Alexandre V.; Bruna–Romero, Oscar; Baron, Monique A.; Ferreira, Ludmila R. P.; Cunha-Neto, Edécio; Rock, Kenneth L.

    2016-01-01

    The β1i, β2i and β5i immunoproteasome subunits have an important role in defining the repertoire of MHC class I-restricted epitopes. However, the impact of combined deficiency of the three immunoproteasome subunits in the development of protective immunity to intracellular pathogens has not been investigated. Here, we demonstrate that immunoproteasomes play a key role in host resistance and genetic vaccination-induced protection against the human pathogen Trypanosoma cruzi (the causative agent of Chagas disease), immunity to which is dependent on CD8+ T cells and IFN-γ (the classical immunoproteasome inducer). We observed that infection with T. cruzi triggers the transcription of immunoproteasome genes, both in mice and humans. Importantly, genetically vaccinated or T. cruzi-infected β1i, β2i and β5i triple knockout (TKO) mice presented significantly lower frequencies and numbers of splenic CD8+ effector T cells (CD8+CD44highCD62Llow) specific for the previously characterized immunodominant (VNHRFTLV) H-2Kb-restricted T. cruzi epitope. Not only the quantity, but also the quality of parasite-specific CD8+ T cell responses was altered in TKO mice. Hence, the frequency of double-positive (IFN-γ+/TNF+) or single-positive (IFN-γ+) cells specific for the H-2Kb-restricted immunodominant as well as subdominant T. cruzi epitopes were higher in WT mice, whereas TNF single-positive cells prevailed among CD8+ T cells from TKO mice. Contrasting with their WT counterparts, TKO animals were also lethally susceptible to T. cruzi challenge, even after an otherwise protective vaccination with DNA and adenoviral vectors. We conclude that the immunoproteasome subunits are key determinants in host resistance to T. cruzi infection by influencing both the magnitude and quality of CD8+ T cell responses. PMID:27128676

  11. Deficiency of the purine metabolic gene HPRT dysregulates microRNA-17 family cluster and guanine-based cellular functions: a role for EPAC in Lesch-Nyhan syndrome.

    Science.gov (United States)

    Guibinga, Ghiabe-Henri; Murray, Fiona; Barron, Nikki; Pandori, William; Hrustanovic, Gorjan

    2013-11-15

    Lesch-Nyhan syndrome (LNS) is a neurodevelopmental disorder caused by mutations in the gene encoding the purine metabolic enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). A series of motor, cognitive and neurobehavioral anomalies characterize this disease phenotype, which is still poorly understood. The clinical manifestations of this syndrome are believed to be the consequences of deficiencies in neurodevelopmental pathways that lead to disordered brain function. We have used microRNA array and gene ontology analysis to evaluate the gene expression of differentiating HPRT-deficient human neuron-like cell lines. We set out to identify dysregulated genes implicated in purine-based cellular functions. Our approach was based on the premise that HPRT deficiency affects preeminently the expression and the function of purine-based molecular complexes, such as guanine nucleotide exchange factors (GEFs) and small GTPases. We found that several microRNAs from the miR-17 family cluster and genes encoding GEF are dysregulated in HPRT deficiency. Most notably, our data show that the expression of the exchange protein activated by cAMP (EPAC) is blunted in HPRT-deficient human neuron-like cell lines and fibroblast cells from LNS patients, and is altered in the cortex, striatum and midbrain of HPRT knockout mouse. We also show a marked impairment in the activation of small GTPase RAP1 in the HPRT-deficient cells, as well as differences in cytoskeleton dynamics that lead to increased motility for HPRT-deficient neuron-like cell lines relative to control. We propose that the alterations in EPAC/RAP1 signaling and cell migration in HPRT deficiency are crucial for neuro-developmental events that may contribute to the neurological dysfunctions in LNS.

  12. CHD7 deficiency in "Looper", a new mouse model of CHARGE syndrome, results in ossicle malformation, otosclerosis and hearing impairment.

    Directory of Open Access Journals (Sweden)

    Jacqueline M Ogier

    Full Text Available CHARGE syndrome is a rare human disorder caused by mutations in the gene encoding chromodomain helicase DNA binding protein 7 (CHD7. Characteristics of CHARGE are varied and include developmental ear and hearing anomalies. Here we report a novel mouse model of CHD7 dysfunction, termed Looper. The Looper strain harbours a nonsense mutation (c.5690C>A, p.S1897X within the Chd7 gene. Looper mice exhibit many of the clinical features of the human syndrome, consistent with previously reported CHARGE models, including growth retardation, facial asymmetry, vestibular defects, eye anomalies, hyperactivity, ossicle malformation, hearing loss and vestibular dysfunction. Looper mice display an otosclerosis-like fusion of the stapes footplate to the cochlear oval window and blepharoconjunctivitis but not coloboma. Looper mice are hyperactive and have vestibular dysfunction but do not display motor impairment.

  13. Reversible acute axonal polyneuropathy associated with Wernicke-Korsakoff syndrome: impaired physiological nerve conduction due to thiamine deficiency?

    Science.gov (United States)

    Ishibashi, S; Yokota, T; Shiojiri, T; Matunaga, T; Tanaka, H; Nishina, K; Hirota, H; Inaba, A; Yamada, M; Kanda, T; Mizusawa, H

    2003-05-01

    Acute axonal polyneuropathy and Wernicke-Korsakoff encephalopathy developed simultaneously in three patients. Nerve conduction studies (NCS) detected markedly decreased compound muscle action potentials (CMAPs) and sensory nerve action potentials (SNAPs) with minimal conduction slowing; sympathetic skin responses (SSRs) were also notably decreased. Sural nerve biopsies showed only mild axonal degeneration with scattered myelin ovoid formation. The symptoms of neuropathy lessened within two weeks after an intravenous thiamine infusion. CMAPs, SNAPs, and SSRs also increased considerably. We suggest that this is a new type of peripheral nerve impairment: physiological conduction failure with minimal conduction delay due to thiamine deficiency.

  14. The contribution of the vaccine adverse event text mining system to the classification of possible Guillain-Barré syndrome reports.

    Science.gov (United States)

    Botsis, T; Woo, E J; Ball, R

    2013-01-01

    We previously demonstrated that a general purpose text mining system, the Vaccine adverse event Text Mining (VaeTM) system, could be used to automatically classify reports of an-aphylaxis for post-marketing safety surveillance of vaccines. To evaluate the ability of VaeTM to classify reports to the Vaccine Adverse Event Reporting System (VAERS) of possible Guillain-Barré Syndrome (GBS). We used VaeTM to extract the key diagnostic features from the text of reports in VAERS. Then, we applied the Brighton Collaboration (BC) case definition for GBS, and an information retrieval strategy (i.e. the vector space model) to quantify the specific information that is included in the key features extracted by VaeTM and compared it with the encoded information that is already stored in VAERS as Medical Dictionary for Regulatory Activities (MedDRA) Preferred Terms (PTs). We also evaluated the contribution of the primary (diagnosis and cause of death) and secondary (second level diagnosis and symptoms) diagnostic VaeTM-based features to the total VaeTM-based information. MedDRA captured more information and better supported the classification of reports for GBS than VaeTM (AUC: 0.904 vs. 0.777); the lower performance of VaeTM is likely due to the lack of extraction by VaeTM of specific laboratory results that are included in the BC criteria for GBS. On the other hand, the VaeTM-based classification exhibited greater specificity than the MedDRA-based approach (94.96% vs. 87.65%). Most of the VaeTM-based information was contained in the secondary diagnostic features. For GBS, clinical signs and symptoms alone are not sufficient to match MedDRA coding for purposes of case classification, but are preferred if specificity is the priority.

  15. Striatal neurodevelopment is dysregulated in purine metabolism deficiency and impacts DARPP-32, BDNF/TrkB expression and signaling: new insights on the molecular and cellular basis of Lesch-Nyhan Syndrome.

    Directory of Open Access Journals (Sweden)

    Ghiabe-Henri Guibinga

    Full Text Available Lesch-Nyhan Syndrome (LNS is a neurodevelopmental disorder caused by mutations in the gene encoding the purine metabolic enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT. This syndrome is characterized by an array of severe neurological impairments that in part originate from striatal dysfunctions. However, the molecular and cellular mechanisms underlying these dysfunctions remain largely unidentified. In this report, we demonstrate that HPRT-deficiency causes dysregulated expression of key genes essential for striatal patterning, most notably the striatally-enriched transcription factor B-cell leukemia 11b (Bcl11b. The data also reveal that the down-regulated expression of Bcl11b in HPRT-deficient immortalized mouse striatal (STHdh neural stem cells is accompanied by aberrant expression of some of its transcriptional partners and other striatally-enriched genes, including the gene encoding dopamine- and cAMP-regulated phosphoprotein 32, (DARPP-32. Furthermore, we demonstrate that components of the BDNF/TrkB signaling, a known activator of DARPP-32 striatal expression and effector of Bcl11b transcriptional activation are markedly increased in HPRT-deficient cells and in the striatum of HPRT knockout mouse. Consequently, the HPRT-deficient cells display superior protection against reactive oxygen species (ROS-mediated cell death upon exposure to hydrogen peroxide. These findings suggest that the purine metabolic defect caused by HPRT-deficiency, while it may provide neuroprotection to striatal neurons, affects key genes and signaling pathways that may underlie the neuropathogenesis of LNS.

  16. Striatal neurodevelopment is dysregulated in purine metabolism deficiency and impacts DARPP-32, BDNF/TrkB expression and signaling: new insights on the molecular and cellular basis of Lesch-Nyhan Syndrome.

    Science.gov (United States)

    Guibinga, Ghiabe-Henri; Barron, Nikki; Pandori, William

    2014-01-01

    Lesch-Nyhan Syndrome (LNS) is a neurodevelopmental disorder caused by mutations in the gene encoding the purine metabolic enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). This syndrome is characterized by an array of severe neurological impairments that in part originate from striatal dysfunctions. However, the molecular and cellular mechanisms underlying these dysfunctions remain largely unidentified. In this report, we demonstrate that HPRT-deficiency causes dysregulated expression of key genes essential for striatal patterning, most notably the striatally-enriched transcription factor B-cell leukemia 11b (Bcl11b). The data also reveal that the down-regulated expression of Bcl11b in HPRT-deficient immortalized mouse striatal (STHdh) neural stem cells is accompanied by aberrant expression of some of its transcriptional partners and other striatally-enriched genes, including the gene encoding dopamine- and cAMP-regulated phosphoprotein 32, (DARPP-32). Furthermore, we demonstrate that components of the BDNF/TrkB signaling, a known activator of DARPP-32 striatal expression and effector of Bcl11b transcriptional activation are markedly increased in HPRT-deficient cells and in the striatum of HPRT knockout mouse. Consequently, the HPRT-deficient cells display superior protection against reactive oxygen species (ROS)-mediated cell death upon exposure to hydrogen peroxide. These findings suggest that the purine metabolic defect caused by HPRT-deficiency, while it may provide neuroprotection to striatal neurons, affects key genes and signaling pathways that may underlie the neuropathogenesis of LNS.

  17. Dengue virus vaccine development.

    Science.gov (United States)

    Yauch, Lauren E; Shresta, Sujan

    2014-01-01

    Dengue virus (DENV) is a significant cause of morbidity and mortality in tropical and subtropical regions, causing hundreds of millions of infections each year. Infections range from asymptomatic to a self-limited febrile illness, dengue fever (DF), to the life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). The expanding of the habitat of DENV-transmitting mosquitoes has resulted in dramatic increases in the number of cases over the past 50 years, and recent outbreaks have occurred in the United States. Developing a dengue vaccine is a global health priority. DENV vaccine development is challenging due to the existence of four serotypes of the virus (DENV1-4), which a vaccine must protect against. Additionally, the adaptive immune response to DENV may be both protective and pathogenic upon subsequent infection, and the precise features of protective versus pathogenic immune responses to DENV are unknown, complicating vaccine development. Numerous vaccine candidates, including live attenuated, inactivated, recombinant subunit, DNA, and viral vectored vaccines, are in various stages of clinical development, from preclinical to phase 3. This review will discuss the adaptive immune response to DENV, dengue vaccine challenges, animal models used to test dengue vaccine candidates, and historical and current dengue vaccine approaches.

  18. Prof WANG Xiao-yun's Experience in Treating Climacteric Syndrome from the Pathogenesis of Kidney Deficiency and Liver Stagnancy

    Institute of Scientific and Technical Information of China (English)

    XU Ying; LIU Jian; WANG Xiao-yun

    2010-01-01

    @@ Prof. WANG Xiao-yun, a chief physician in the Second Affiliated Hospital of Guangzhou TCM University (Guangdong Provincial Hospital of TCM), is a leading physician, professor, and the supervisor of doctoral students in the national key subject of TCM gynecology. Having been engaged in TCM gynecological clinical practice and scientific researches for about 30 years, Prof. WANG has obtained rich experience in the treatment of obstinate and miscellaneous diseases of gynecology, especially in the analysis of pathogenesis and differential treatment of climacteric syndrome.

  19. Novel Homozygous Missense Mutation in SPG20 Gene Results in Troyer Syndrome Associated with Mitochondrial Cytochrome c Oxidase Deficiency.

    Science.gov (United States)

    Spiegel, Ronen; Soiferman, Devorah; Shaag, Avraham; Shalev, Stavit; Elpeleg, Orly; Saada, Ann

    2016-08-19

    Troyer syndrome is an autosomal recessive form of hereditary spastic paraplegia (HSP) caused by deleterious mutations in the SPG20 gene. Although the disease is associated with a loss of function mechanism of spartin, the protein encoded by SPG20, the precise pathogenesis is yet to be elucidated. Recent data indicated an important role for spartin in both mitochondrial maintenance and function. Here we report a child presenting with progressive spastic paraparesis, generalized muscle weakness, dysarthria, impaired growth, and severe isolated decrease in muscle cytochrome c oxidase (COX) activity. Whole exome sequencing identified the homozygous c.988A>G variant in SPG20 gene (p.Met330Val) resulting in almost complete loss of spartin in skeletal muscle. Further analyses demonstrated significant tissue specific reduction of COX 4, a nuclear encoded subunit of COX, in muscle suggesting a role for spartin in proper mitochondrial respiratory chain function mediated by COX activity. Our findings need to be verified in other Troyer syndrome patients in order to classify it as a form of HSP caused by mitochondrial dysfunction.

  20. Loss of H3K9me3 Correlates with ATM Activation and Histone H2AX Phosphorylation Deficiencies in Hutchinson-Gilford Progeria Syndrome

    Science.gov (United States)

    Zhang, Haoyue; Sun, Linlin; Wang, Kun; Wu, Di; Trappio, Mason; Witting, Celeste; Cao, Kan

    2016-01-01

    Compelling evidence suggests that defective DNA damage response (DDR) plays a key role in the premature aging phenotypes in Hutchinson-Gilford progeria syndrome (HGPS). Studies document widespread alterations in histone modifications in HGPS cells, especially, the global loss of histone H3 trimethylated on lysine 9 (H3K9me3). In this study, we explore the potential connection(s) between H3K9me3 loss and the impaired DDR in HGPS. When cells are exposed to a DNA-damaging agent Doxorubicin (Dox), double strand breaks (DSBs) are generated that result in the phosphorylation of histone H2A variant H2AX (gammaH2AX) within an hour. We find that the intensities of gammaH2AX foci appear significantly weaker in the G0/G1 phase HGPS cells compared to control cells. This reduction is associated with a delay in the recruitment of essential DDR factors. We further demonstrate that ataxia-telangiectasia mutated (ATM) is responsible for the amplification of gammaH2AX signals at DSBs during G0/G1 phase, and its activation is inhibited in the HGPS cells that display significant loss of H3K9me3. Moreover, methylene (MB) blue treatment, which is known to save heterochromatin loss in HGPS, restores H3K9me3, stimulates ATM activity, increases gammaH2AX signals and rescues deficient DDR. In summary, this study demonstrates an early DDR defect of attenuated gammaH2AX signals in G0/G1 phase HGPS cells and provides a plausible connection between H3K9me3 loss and DDR deficiency. PMID:27907109

  1. Development of an attenuated live vaccine against highly pathogenic porcine reproductive and respiratory syndrome%高致病性猪繁殖与呼吸综合征活疫苗的研制

    Institute of Scientific and Technical Information of China (English)

    冷雪; 李真光; 夏铭崎; 和彦良; 武华

    2011-01-01

    将高致病性猪繁殖与呼吸综合征病毒致弱株TJM株与耐热冻干保护剂混合制备弱毒活疫苗,并对该活疫苗进行安全性、免疫保护效果和保存期试验。结果显示,4~5周龄仔猪接种该疫苗后体温正常,无任何临床可见异常。该疫苗接种猪对强毒攻击的保护率达4/5以上;将其置于2~8℃保存24个月,病毒效价降低不超过100.5 TCID50/mL。表明该疫苗对猪安全,免疫保护效果良好,且便于保存。%An attenuated highly pathogenic porcine reproductive and respiratory syndrome virus(HP-PRRSV) vaccine was developed by blending the attenuated HP-PRRSV TJM strain with heat endurable protective agent.The safety and efficacy(immunogenicity) in host animals and the period of validity at 2 to 8℃ of the vaccine were tested. In order to test the safety of the vaccine,4 to 5 weeks-old pigs were inoculated with 2mL(106.7TCID50/mL) of the vaccine.In the efficacy study,4 to 5 weeks-old pigs were vaccinated with 1mL of 105.0TCID50 of the vaccine. The animals were challenged with virulent virus on day 28 post-vaccination. To determine the period of validity,the vaccine was sampled on month 3,6,9,12,18,21,and 24 post-vaccination at 2 to 8℃ to test the virus titer. Results revealed that the pigs did not show any clinical diseases post-vaccination.Immunogenicity study demonstrated that the vaccine provided at least four fifths protection to pigs against the HP-PRRSV infection and clinical diseases caused by the challenge.The virus titer decreased no more than 100.5TCID50/mL after 24 month at 2 to 8℃. The results indicated that the vaccine is safe,efficacy to host animals,and easy to be reserved.

  2. Species-specific difference in expression and splice-site choice in Inpp5b, an inositol polyphosphate 5-phosphatase paralogous to the enzyme deficient in Lowe Syndrome.

    Science.gov (United States)

    Bothwell, Susan P; Farber, Leslie W; Hoagland, Adam; Nussbaum, Robert L

    2010-10-01

    The oculocerebrorenal syndrome of Lowe (OCRL; MIM #309000) is an X-linked human disorder characterized by congenital cataracts, mental retardation, and renal proximal tubular dysfunction caused by loss-of-function mutations in the OCRL gene that encodes Ocrl, a type II phosphatidylinositol bisphosphate (PtdIns4,5P(2)) 5-phosphatase. In contrast, mice with complete loss-of-function of the highly homologous ortholog Ocrl have no detectable renal, ophthalmological, or central nervous system abnormalities. We inferred that the disparate phenotype between Ocrl-deficient humans and mice was likely due to differences in how the two species compensate for loss of the Ocrl enzyme. We therefore turned our attention to Inpp5b, another type II PtdIns4,5P(2) 5-phosphatase encoded by Inpp5b in mice and INPP5B in humans, as potential compensating genes in the two species, because Inpp5b/INPP5B are the most highly conserved paralogs to Ocrl/OCRL in the respective genomes of both species and Inpp5b demonstrates functional overlap with Ocrl in mice in vivo. We used in silico sequence analysis, reverse-transcription PCR, quantitative PCR, and transient transfection assays of promoter function to define splice-site usage and the function of an internal promoter in mouse Inpp5b versus human INPP5B. We found mouse Inpp5b and human INPP5B differ in their transcription, splicing, and primary amino acid sequence. These observations form the foundation for analyzing the functional basis for the difference in how Inpp5b and INPP5B compensate for loss of Ocrl function and, by providing insight into the cellular roles of Ocrl and Inpp5b, aid in the development of a model system in which to study Lowe syndrome.

  3. Deficient plakophilin-1 expression due to a mutation in PKP1 causes ectodermal dysplasia-skin fragility syndrome in Chesapeake Bay retriever dogs.

    Directory of Open Access Journals (Sweden)

    Thierry Olivry

    Full Text Available In humans, congenital and hereditary skin diseases associated with epidermal cell-cell separation (acantholysis are very rare, and spontaneous animal models of these diseases are exceptional. Our objectives are to report a novel congenital acantholytic dermatosis that developed in Chesapeake Bay retriever dogs. Nine affected puppies in four different litters were born to eight closely related clinically normal dogs. The disease transmission was consistent with an autosomal recessive mode of inheritance. Clinical signs occurred immediately after birth with superficial epidermal layers sloughing upon pressure. At three month of age, dogs exhibited recurrent superficial skin sloughing and erosions at areas of friction and mucocutaneous junctions; their coat was also finer than normal and there were patches of partial hair loss. At birth, histopathology revealed severe suprabasal acantholysis, which became less severe with ageing. Electron microscopy demonstrated a reduced number of partially formed desmosomes with detached and aggregated keratin intermediate filaments. Immunostaining for desmosomal adhesion molecules revealed a complete lack of staining for plakophilin-1 and anomalies in the distribution of desmoplakin and keratins 10 and 14. Sequencing revealed a homozygous splice donor site mutation within the first intron of PKP1 resulting in a premature stop codon, thereby explaining the inability to detect plakophilin-1 in the skin. Altogether, the clinical and pathological findings, along with the PKP1 mutation, were consistent with the diagnosis of ectodermal dysplasia-skin fragility syndrome with plakophilin-1 deficiency. This is the first occurrence of ectodermal dysplasia-skin fragility syndrome in an animal species. Controlled mating of carrier dogs would yield puppies that could, in theory, be tested for gene therapy of this rare but severe skin disease of children.

  4. Prenatal diagnosis of the carbohydrate-deficient glycoprotein syndrome type 1A (CDG1A) by a combination of enzymology and genetic linkage analysis after amniocentesis or chorionic villus sampling.

    Science.gov (United States)

    Charlwood, J; Clayton, P; Keir, G; Mian, N; Young, E; Winchester, B

    1998-07-01

    Two pregnancies at risk for the carbohydrate-deficient glycoprotein syndrome Type 1A (CDG1A, phosphomannomutase deficient) were monitored by enzyme and genetic linkage analyses. The index case in both families had a proven deficiency of phosphomannomutase (PMM). An unaffected fetus was predicted in family 1 following amniocentesis. Normal PMM activity was found in cultured amniotic fluid cells and there was no elevation of lysosomal enzymes in the amniotic fluid. Genetic linkage analysis using microsatellite markers closely linked to the CDG1A gene confirmed this prediction. A healthy child was born. In the second family direct assay of chorionic villi showed a profound deficiency of PMM and genetic linkage analysis showed the fetus to have the same haplotype as the proband. The pregnancy was terminated and a deficiency of PMM was confirmed in cultured fibroblasts from the fetus. Reliable prenatal diagnosis of CDG Type 1A (PMM-deficient) can be achieved by a combination of biochemical and molecular genetic tests.

  5. 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

    2009-01-01

    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.

  6. Congenital β-lipoprotein deficiency

    NARCIS (Netherlands)

    Buchem, F.S.P. van; Pol, G.; Gier, J. de; Böttcher, C.J.F.; Pries, C.

    1966-01-01

    There are several degrees of β-lipoprotein deficiency. If there is no β-lipoprotein present, or if there are only traces of it, the Bassen-Kornzweig syndrome develops. A constant feature of this syndrome is disturbed fat absorption with accumulation of fat in the epithelium of intestinal mucosa and

  7. Neuro-Genetics of Reward Deficiency Syndrome (RDS) as the Root Cause of "Addiction Transfer": A New Phenomenon Common after Bariatric Surgery.

    Science.gov (United States)

    Blum, Kenneth; Bailey, John; Gonzalez, Anthony M; Oscar-Berman, Marlene; Liu, Yijun; Giordano, John; Braverman, Eric; Gold, Mark

    2011-12-23

    Now after many years of successful bariatric (weight-loss) surgeries directed at the obesity epidemic clinicians are reporting that some patients are replacing compulsive overeating with newly acquired compulsive disorders such as alcoholism, gambling, drugs, and other addictions like compulsive shopping and exercise. This review article explores evidence from psychiatric genetic animal and human studies that link compulsive overeating and other compulsive disorders to explain the phenomenon of addiction transfer. Possibly due to neurochemical similarities, overeating and obesity may act as protective factors reducing drug reward and addictive behaviors. In animal models of addiction withdrawal from sugar induces imbalances in the neurotransmitters, acetylcholine and dopamine, similar to opiate withdrawal. Many human neuroimaging studies have supported the concept of linking food craving to drug craving behavior. Previously our laboratory coined the term Reward Deficiency Syndrome (RDS) for common genetic determinants in predicting addictive disorders and reported that the predictive value for future RDS behaviors in subjects carrying the DRD2 Taq A1 allele was 74%. While poly genes play a role in RDS, we have also inferred that disruptions in dopamine function may predispose certain individuals to addictive behaviors and obesity. It is now known that family history of alcoholism is a significant obesity risk factor. Therefore, we hypothesize here that RDS is the root cause of substituting food addiction for other dependencies and potentially explains this recently described Phenomenon (addiction transfer) common after bariatric surgery.

  8. Short-term impact of a classical ketogenic diet on gut microbiota in GLUT1 Deficiency Syndrome: A 3-month prospective observational study.

    Science.gov (United States)

    Tagliabue, Anna; Ferraris, Cinzia; Uggeri, Francesca; Trentani, Claudia; Bertoli, Simona; de Giorgis, Valentina; Veggiotti, Pierangelo; Elli, Marina

    2017-02-01

    The classical ketogenic diet (KD) is a high-fat, very low-carbohydrate normocaloric diet used for drug-resistant epilepsy and Glucose Transporter 1 Deficiency Syndrome (GLUT1 DS). In animal models, high fat diet induces large alterations in microbiota producing deleterious effects on gut health. We carried out a pilot study on patients treated with KD comparing their microbiota composition before and after three months on the diet. Six patients affected by GLUT1 DS were asked to collect fecal samples before and after three months on the diet. RT - PCR analysis was performed in order to quantify Firmicutes, Bacteroidetes, Bifidobacterium spp., Lactobacillus spp., Clostridium perfringens, Enterobacteriaceae, Clostridium cluster XIV, Desulfovibrio spp. and Faecalibacterium prausnitzii. Compared with baseline, there were no statistically significant differences at 3 months in Firmicutes and Bacteroidetes. However fecal microbial profiles revealed a statistically significant increase in Desulfovibrio spp. (p = 0.025), a bacterial group supposed to be involved in the exacerbation of the inflammatory condition of the gut mucosa associated to the consumption of fats of animal origin. A future prospective study on the changes in gut microbiota of all children with epilepsy started on a KD is warranted. In patients with dysbiosis demonstrated by fecal samples, it my be reasonable to consider an empiric trial of pre or probiotics to potentially restore the «ecological balance» of intestinal microbiota. Copyright © 2016 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.

  9. Pharmacogenomics of insulin-like growth factor-I generation during GH treatment in children with GH deficiency or Turner syndrome

    Science.gov (United States)

    Stevens, A; Clayton, P; Tatò, L; Yoo, H W; Rodriguez-Arnao, M D; Skorodok, J; Ambler, G R; Zignani, M; Zieschang, J; Della Corte, G; Destenaves, B; Champigneulle, A; Raelson, J; Chatelain, P

    2014-01-01

    Individual responses to growth hormone (GH) treatment are variable. Short-term generation of insulin-like growth factor-I (IGF-I) is recognized as a potential marker of sensitivity to GH treatment. This prospective, phase IV study used an integrated genomic analysis to identify markers associated with 1-month change in IGF-I (ΔIGF-I) following initiation of recombinant human (r-h)GH therapy in treatment-naïve children with GH deficiency (GHD) (n=166) or Turner syndrome (TS) (n=147). In both GHD and TS, polymorphisms in the cell-cycle regulator CDK4 were associated with 1-month ΔIGF-I (P<0.05). Baseline gene expression was also correlated with 1-month ΔIGF-I in both GHD and TS (r=0.3; P<0.01). In patients with low IGF-I responses, carriage of specific CDK4 alleles was associated with MAPK and glucocorticoid receptor signaling in GHD, and with p53 and Wnt signaling pathways in TS. Understanding the relationship between genomic markers and early changes in IGF-I may allow development of strategies to rapidly individualize r-hGH dose. PMID:23567489

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

    Science.gov (United States)

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

    1993-01-01

    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.

  11. Seven weeks of Western diet in apolipoprotein-E-deficient mice induce metabolic