Academic literature on the topic 'Genetic/blood disorders'
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Journal articles on the topic "Genetic/blood disorders"
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Kurtzberg, J. "Cord blood transplantation in genetic disorders." Biology of Blood and Marrow Transplantation 10, no. 10 (October 2004): 735–36. http://dx.doi.org/10.1016/j.bbmt.2004.06.021.
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Owayes Muaffaq Hamed, Amjad Abdul-hadi Mohammed, and Raed Salem Alsaffar. "Genetic Metabolism Disorders in Newborn." International Journal for Research in Applied Sciences and Biotechnology 8, no. 1 (January 13, 2021): 77–81. http://dx.doi.org/10.31033/ijrasb.8.1.9.
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Babies with any type of metabolic disorders lack the ability to break down the food well, which may induce too little amino acids, phenylalanine and blood sugar to the body, there are numerous kinds of this disorders, most of babies with a genetic metabolic disease have many mutation in gene that coded an enzyme which results a deficiency in same enzyme are hundreds of these disorders and they were diagnosed by their symptoms and the treatment method. The treatment methods of the metabolic disorder depend on the specific type of disorders, inborn metabolic disease are some-time treated with dietary guidance, and other childcare choices, many hereditary metabolic disease are initially caused by gene mutations and that transferred from parents to offspring.
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Peyvandi, Flora, Tom Kunicki, and David Lillicrap. "Genetic sequence analysis of inherited bleeding diseases." Blood 122, no. 20 (November 14, 2013): 3423–31. http://dx.doi.org/10.1182/blood-2013-05-505511.
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Abstract The genes encoding the coagulation factor proteins were among the first human genes to be characterized over 25 years ago. Since then, significant progress has been made in the translational application of this information for the 2 commonest severe inherited bleeding disorders, hemophilia A and B. For these X-linked disorders, genetic characterization of the disease-causing mutations is now incorporated into the standard of care and genetic information is used for risk stratification of treatment complications. With electronic databases detailing >2100 unique mutations for hemophilia A and >1100 mutations for hemophilia B, these diseases are among the most extensively characterized inherited diseases in humans. Experience with the genetics of the rare bleeding disorders is, as expected, less well advanced. However, here again, electronic mutation databases have been developed and provide excellent guidance for the application of genetic analysis as a confirmatory approach to diagnosis. Most recently, progress has also been made in identifying the mutant loci in a variety of inherited platelet disorders, and these findings are beginning to be applied to the genetic diagnosis of these conditions. Investigation of patients with bleeding phenotypes without a diagnosis, using genome-wide strategies, may identify novel genes not previously recognized as playing a role in hemostasis.
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Elbagoury, Marwan, Abdulelah Ismail Qadi, Ayman Hejazi, Fahad Alabbas, Ghaleb El Yamany, Hussain H. Al Saeed, and Ohoud F. Kashari. "Prevalence of Gaucher Disease in Patients of Unknown Cause of Splenomegaly and/or Thrombocytopenia in Saudi Arabia." Blood 136, Supplement 1 (November 5, 2020): 32–33. http://dx.doi.org/10.1182/blood-2020-140563.
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Rationale: Gaucher disease (GD) is the most common amongst the lysosomal storage disorders. Prevalence of GD in Saudi Arabia is not available in published literature and it is expected to be high and remains undiagnosed. In 2004, a Saudi study reported that GD accounts for 6% of all genetic metabolic disorders. While acid sphingomyelinase deficiency (ASMD) is a rare progressive genetic disorder with no clear data about its incidence in Saudi Arabia. Consequently, this study proposes to determine the prevalence of GD and ASMD in outpatient settings in Saudi Arabia by screening patients with unknown causes of splenomegaly and/or thrombocytopenia. These data will change the local practice and increase the awareness towards GD and ASMD in Saudi Arabia. Objectives: To determine the prevalence of GD in high risk group (defined as patients with splenomegaly and/or thrombocytopenia of unknown cause) and describe their characteristics. We also aim to determine the prevalence of ASMD in high risk group. Methods: A multi-center, observational, study will be conducted in 25 specialty care centres across Saudi Arabia, these centres are mainly focusing on pediatric hematology, adult hematology and hemato-pathology. Female or male patients (aged 2-75 years) will deemed eligible if they have clinical, instrumental or laboratory signs of splenomegaly or thrombocytopenia over a period of 12 months without definitive cause. These patients will be tested for acid β-glucosidase and acid sphingomyelinase enzymes activity on dried blood spot (DBS) samples. Patients with hematological malignancies, hemolytic anemia, and/or thalassemia (except sickle cell disease) will be excluded. A total of 400 patients from Saudi Arabia who fulfill the eligibility criteria will be enrolled in the study. All patient data will be collected in a single visit. Each enrolled patient will visit the investigator for a baseline visit. The investigator will contact them later for sharing the investigation blood test results. During the baseline visit, data and blood sample for enzyme tests and genotyping will be collected by the investigator/designated person at the site. Discussion: Arab world represents one of the leading regions in terms of the incidence of congenital and genetic disorders; a growing body of published literature reported a notable trends towards higher incidence of congenital and genetic diseases, compared to other parts of the world(1). High consanguinity rates which reach up to 60% in some regions, high prevalence of haemoglobinopathies and metabolic disorders, relatively high maternal and parental age, and lack of proper genetic screening were reported as contributing factors for this high prevalence of genetic disorders in the Arab world(1-3). In Saudi Arabia, the situation appears to be no different as previous retrospective studies showed a relatively high incidence of genetic diseases such as inborn error of metabolism. The data of the present study will change the local practice and increase the awareness towards GD and ASMD in Saudi Arabia. References: Al-Gazali L, Hamamy H, Al-Arrayad S. Genetic disorders in the Arab world. BMJ [Internet]. 2006 Oct 21 [cited 2019 Jun 29];333(7573):831-4. Available from: http://www.ncbi.nlm.nih.gov/pubmed/17053236 Al-Gazali LI, Alwash R, Abdulrazzaq YM. United Arab Emirates: Communities and Community Genetics. Public Health Genomics [Internet]. 2005 [cited 2019 Jun 29];8(3):186-96. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16113536 Wahab AA, Bener A, Teebi AS. The incidence patterns of Down syndrome in Qatar. Clin Genet [Internet]. 2006 Mar 30 [cited 2019 Jun 29];69(4):360-2. Available from: http://www.ncbi.nlm.nih.gov/pubmed/16630172 Disclosures No relevant conflicts of interest to declare.
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Canver, Matthew C., and Stuart H. Orkin. "Customizing the genome as therapy for the β-hemoglobinopathies." Blood 127, no. 21 (May 26, 2016): 2536–45. http://dx.doi.org/10.1182/blood-2016-01-678128.
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Abstract Despite nearly complete understanding of the genetics of the β-hemoglobinopathies for several decades, definitive treatment options have lagged behind. Recent developments in technologies for facile manipulation of the genome (zinc finger nucleases, transcription activator-like effector nucleases, or clustered regularly interspaced short palindromic repeats–based nucleases) raise prospects for their clinical application. The use of genome-editing technologies in autologous CD34+ hematopoietic stem and progenitor cells represents a promising therapeutic avenue for the β-globin disorders. Genetic correction strategies relying on the homology-directed repair pathway may repair genetic defects, whereas genetic disruption strategies relying on the nonhomologous end joining pathway may induce compensatory fetal hemoglobin expression. Harnessing the power of genome editing may usher in a second-generation form of gene therapy for the β-globin disorders.
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Tanaka, Tiffany N., and Rafael Bejar. "MDS overlap disorders and diagnostic boundaries." Blood 133, no. 10 (March 7, 2019): 1086–95. http://dx.doi.org/10.1182/blood-2018-10-844670.
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Abstract Myelodysplastic syndromes (MDS) are clonal diseases defined by clinical, morphologic, and genetic features often shared by related myeloid disorders. The diagnostic boundaries between these diseases can be arbitrary and not necessarily reflective of underlying disease biology or outcomes. In practice, measures that distinguish MDS from related disorders may be difficult to quantify and can vary as disease progression occurs. Patients may harbor findings that are not consistent with a single diagnostic category. Several overlap disorders have been formally described, such as the myelodysplastic/myeloproliferative neoplasms (MDS/MPNs). These disorders are characterized by hematopoietic dysplasia with increased proliferation of monocytes, neutrophils, or platelets. They may have mutational profiles that distinguish them from the disorders they resemble and reflect important differences in pathophysiology. MDS also shares diagnostic borders with other diseases. For example, aplastic anemia and hypoplastic MDS can be difficult to distinguish in patients with pancytopenia and bone marrow hypocellularity. Genetic features may help in this regard, because they can identify differences in prognosis and risk of progression. The boundary between MDS and secondary acute myeloid leukemia (sAML) is arbitrarily defined and has been redefined over the years. Genetic studies have demonstrated that sAML clones can precede clinical progression from MDS by many months, suggesting that MDS with excess blasts could be viewed as an overlap between a dysplastic bone marrow failure syndrome and an oligoblastic leukemia. This review will describe the diagnostic boundaries between MDS, MDS/MPNs, sAML, clonal hematopoiesis of indeterminate potential, clonal cytopenia of undetermined significance, and aplastic anemia and how genetic approaches may help to better define them.
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Marks, I. M. "Genetics of Fear and Anxiety Disorders." British Journal of Psychiatry 149, no. 4 (October 1986): 406–18. http://dx.doi.org/10.1192/bjp.149.4.406.
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From protozoa to mammals, organisms have been selectively bred for genetic differences in defensive behaviour which are accompanied by differences in brain and other biological functions. Studies of twins indicate some genetic control of normal human fear from infancy onwards, of anxiety as a symptom and as a syndrome, and of phobic and obsessive- compulsive phenomena. Anxiety disorders are more common among the relatives of affected probands than of controls, especially among female and first-degree relatives; alcoholism and secondary depression may also be over-represented. Familial influences have been found for panic disorder, agoraphobia, and obsessive-compulsive problems. Panic disorder in depressed probands increases the risk to their relatives of phobia as well as of panic disorder, major depression, and alcoholism. The strongest family history of all anxiety disorders is seen in blood-injury phobia; even though it can be successfully treated by exposure, its roots may lie in a genetically determined specific autonomic susceptibility. Some genetic effects can be modified by environmental means.
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Dahlbäck, Björn. "Advances in understanding pathogenic mechanisms of thrombophilic disorders." Blood 112, no. 1 (July 1, 2008): 19–27. http://dx.doi.org/10.1182/blood-2008-01-077909.
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AbstractVenous thromboembolism is a major medical problem, annually affecting 1 in 1000 individuals. It is a typical multifactorial disease, involving both genetic and circumstantial risk factors that affect a delicate balance between procoagulant and anticoagulant forces. In the last 50 years, the molecular basis of blood coagulation and the anticoagulant systems that control it have been elucidated. This has laid the foundation for discoveries of both common and rare genetic traits that tip the natural balance in favor of coagulation, with a resulting lifelong increased risk of venous thrombosis. Multiple mutations in the genes for anticoagulant proteins such as antithrombin, protein C, and protein S have been identified and constitute important risk factors. Two single mutations in the genes for coagulation factor V (FV Leiden) and prothrombin (20210G>A), resulting from approximately 20 000-year-old mutations with subsequent founder effects, are common in the general population and constitute major genetic risk factors for thrombosis. In celebration of the 50-year anniversary of the American Society of Hematology, this invited review highlights discoveries that have contributed to our present understanding of the systems that control blood coagulation and the genetic factors that are involved in the pathogenesis of venous thrombosis.
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Graham, Nicholas, Joey Ward, Breda Cullen, Keira Johnston, Rona Strawbridge, Amy Ferguson, Daniel Mackay, et al. "SA8INVESTIGATING SHARED GENETIC MECHANISMS BETWEEN MOOD DISORDERS AND BLOOD PRESSURE." European Neuropsychopharmacology 29 (2019): S1192. http://dx.doi.org/10.1016/j.euroneuro.2018.08.230.
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Lutsenko, T. "Fetal microchimerism and prenatal diagnostic of genetic disorders." Cell and Organ Transplantology 4, no. 1 (May 31, 2016): 124–31. http://dx.doi.org/10.22494/cot.v4i1.2.
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It is often require an invasive diagnosis based on karyotyping of cells from amniotic fluid, chorionic villi and cord blood in case of the fetus pathologies during pregnancy. The performance of these procedures has a risk of pregnancy complications or procedure-induced miscarriage. Therefore the investigators have nowadays been developing several approaches which would be capable to replace invasive diagnosis by alternative and safe non-invasive methods for detection of possible pregnancy pathology. Fetal microchimerism phenomenon and reliable strategies of fetal cells enrichment during early embryogenesis are reviewed. Fetal cells circulating in the peripheral blood of pregnant women has been described as a potential source of fetus genetic material in non-invasive prenatal diagnosis for chromosomal aberrations.
Dissertations / Theses on the topic "Genetic/blood disorders"
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O'Shaughnessy, D. F. "A study of thalassaemia and other globin gene variants in the Pacific." Thesis, University of Oxford, 1989. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.279894.
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Lotti, Francesco. "Transcriptional targeting of lentiviral vectors to the erythroblastic progeny of hematopoietic stem cells." Thesis, Open University, 2003. http://oro.open.ac.uk/54805/.
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Correction of blood genetic disorders requires permanent gene transfer into self renewing, hematopoietic stem cells (HSC), and regulation of transgene expression in specific cell lineages. HIV-derived lentiviral vectors are very effective in transducing rare, non-dividing stem cell populations without altering their long-term repopulation and differentiation capacity. We developed a strategy for transcriptional targeting' of lentiviral vectors based on replacing the viral LTR control elements with cell lineage specific, genomic control elements. An upstream enhancer (HS2) of the erythroidspecific GATA-l gene was cloned in a second-generation lentiviral vector to replace most of the U3 region of the LTR, immediately upstream of the HIV-l promoter. The modified LTR was used to drive the expression of a reporter gene (GFP), while a second gene (~LNGFR) was placed under the control of an internal, constitutive promoter to monitor cell transduction, or immunoselect transduced cells, independently from the expression of the targeted promoter. The vector was used to transduce cell lines, human CD34+ hematopoietic stem/progenitor cells, and murine bone marrow HSCs. Gene expression was analyzed in the differentiated progeny of transduced stem cells in vitro and in vivo, after transplantation into lethally irradiated co-isogenic (for murine cells) or NOD/SCID (for human cells) mice. The transcriptionally targeted HIV LTR allowed very high level of transgene expression specifically in mature erythroblasts, in a tat-independent fashion and with no alteration in titer, infectivity, and genomic stability of the lentiviral vector. Expression from the targeted LTR was higher, better restricted, and showed significantly less position effect variegation than that obtained by the same combination of enhancer/promoter elements placed in the conventional, internal position. Cloning of the woodchuck hepatitis virus post transcriptional regulatory element (WPRE) at a defined position in the targeted vector, allowed selective accumulation of the genomic with respect to the internal RNA transcript, with no loss of cell-type restriction. A critical advantage of this targeting strategy is the use of the spliced, major viral transcript to express a therapeutic gene, and that of an internal, independently regulated promoter to express an additional gene for either cell marking or in vivo selection purposes.
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Jenkins, Meredith E. "An examination of the human fibrinogen-like protein2 sequence variations and genetic expression by human endothelial cells /." unrestricted, 2005. http://etd.gsu.edu/theses/available/etd-07222005-093438/.
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Thesis (M.S.)--Georgia State University, 2005.Title from title screen. Roberta Attanasio, committee chair; P.C. Tai, W.C. Hooper, committee members. Electronic text (57 p. : col. ill.) : digital, PDF file. Description based on contents viewed Aug. 15, 2007. Includes bibliographical references (p. 55-57).
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Marsh, Victoria Mary Chuck. "Sharing findings on sickle cell disorder in international collaborative biomedical research : an empirical ethics study in coastal Kenya." Thesis, University of Oxford, 2012. http://ora.ox.ac.uk/objects/uuid:b693b762-5ce8-4109-82ea-4cf7ba38675e.
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Against the background of a dilemma experienced by researchers during a genomics study at an established biomedical research centre in Kenya, the broad aims of this thesis are to develop appropriate responses to important ethical questions on sharing information on a common and serious genetic condition, sickle cell disorder, and assess the responsibilities of researchers in this regard. Using an empirical approach to normative reflection across two phases of qualitative research, I explore the nature of important moral concerns related to sharing sickle cell disease information from researchers’ and community members’ points of view; and develop a bottom-up normative analysis around the questions generated. This analysis interweaves community experiences, processes of community reasoning and ex situ normative reflection; placing community views and values centrally while referencing these to wider ethical debates, commentaries and guidelines in the literature. Two main outputs of this thesis are to provide recommendations for information sharing on SCD findings in the genomics study in Kilifi; and to propose a set of key issues to consider for this type of information in other studies and geographic settings. I conclude that researchers have a strong responsibility to share SCD information on affected children with families as a form of ancillary service (validating tests, counselling and care); but less responsibility to actively share carrier information. Concurrent responsibilities are working collaboratively with the Ministry of Health/District General Hospital to plan and implement services for SCD; ensuring counselling services support family stability as far as reasonably possible; and to build forms of community engagement and informed consent that counter risks of diagnostic interpretations of research.
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GUOBADIA, EDWIN AHUNWAN. "The Effects of a Sickle Cell Disease Education Intervention Among College Students." ScholarWorks, 2015. http://scholarworks.waldenu.edu/dissertations/1682.
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Sickle cell disease (SCD) is a genetic disorder that affects millions of people worldwide. According to the Centers for Disease Control and Prevention, over 100,000 Americans have SCD, and more than 2 million Americans have a sickle cell trait (SCT). People with SCD are more likely than others to suffer premature mortality. Genetic screening is an important step in improving quality of life and increasing longevity for those with SCD. Early detection may lead to effective management of the disease and reduction of complicating factors. The purpose of this quasi-experimental study was to determine whether health education about SCD would impact college students' knowledge, attitudes, perceived risk, and intention to seek genetic screening and counseling in relation to the disease. The theoretical foundation for this study was the health belief model (HBM). This study involved 80 college students selected from a North Texas college. These students completed pre and post versions of an SCD questionnaire. Independent samples t tests were used to determine if there were significant differences in pre- and posttest scores of participants in both groups, and a MANOVA was used to determine differences among the scores of participants in the experimental group when grouped by age, gender, race, religiosity, and socioeconomic status. The results of this study showed that SCD health education improved the knowledge of and attitudes towards participants. Future research could explore barriers to seeking SCD screening and genetic counseling. Results of this study may further social change by encouraging the development of college-based health education efforts to increase awareness about SCD.
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Guobadia, Edwin Ahunwan. "The Effects of a Sickle Cell Disease Education Intervention Among College Students." ScholarWorks, 2015. https://scholarworks.waldenu.edu/dissertations/1697.
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Sickle cell disease (SCD) is a genetic disorder that affects millions of people worldwide. According to the Centers for Disease Control and Prevention, over 100,000 Americans have SCD, and more than 2 million Americans have a sickle cell trait (SCT). People with SCD are more likely than others to suffer premature mortality. Genetic screening is an important step in improving quality of life and increasing longevity for those with SCD. Early detection may lead to effective management of the disease and reduction of complicating factors. The purpose of this quasi-experimental study was to determine whether health education about SCD would impact college students' knowledge, attitudes, perceived risk, and intention to seek genetic screening and counseling in relation to the disease. The theoretical foundation for this study was the health belief model (HBM). This study involved 80 college students selected from a North Texas college. These students completed pre and post versions of an SCD questionnaire. Independent samples t tests were used to determine if there were significant differences in pre- and posttest scores of participants in both groups, and a MANOVA was used to determine differences among the scores of participants in the experimental group when grouped by age, gender, race, religiosity, and socioeconomic status. The results of this study showed that SCD health education improved the knowledge of and attitudes towards participants. Future research could explore barriers to seeking SCD screening and genetic counseling. Results of this study may further social change by encouraging the development of college-based health education efforts to increase awareness about SCD.
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Lido, Ândria Carla Vito. "Estudo do gene do hormônio de crescimento hipofisário (GH1) em indivíduos com baixa estatura idiopática." Universidade de São Paulo, 2014. http://www.teses.usp.br/teses/disponiveis/5/5135/tde-20102014-145337/.
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O sistema hormônio de crescimento (GH) / fator de crescimento insulina- símile tipo 1 (IGF-1) é o principal determinante e regulador do crescimento linear pósnatal. O GH é codificado pelo gene Growth Hormone 1 (GH1). Mutações no GH1 com efeito dominante negativo e herança autossômica dominante são as principais causas monogênicas de deficiência isolada de hormônio de crescimento (DIGH), enquanto deleções ou mutações de ponto no GH1 causam formas raras autossômicas recessivas de DIGH. No grupo de pacientes com DIGH do ambulatório de Endocrinologia do Desenvolvimento do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, foram identificadas apenas deleções em homozigose no GH1 mesmo após estudo criterioso deste gene. Esta diferença em relação aos dados descritos na literatura poderia ser justificada pelo critério diagnóstico para a DIGH adotado pelo nosso grupo, sendo utilizado pico de GH em teste de estímulo inferior a 3,3 ug/L, em contraste com os valores de corte descritos na literatura que variam de 7 a 10 ug/L. Devido a esse fator, pacientes com mutações no GH1 com herança autossômica dominante poderiam estar sendo erroneamente diagnosticados como portadores de baixa estatura familiar ou idiopática (BEI) em nosso serviço. Adicionalmente, mutações que originam moléculas de GH biologicamente inativas também poderiam estar presentes nestes pacientes. Pelos fatores acima apresentados, expandimos o estudo do GH1 para um grupo de crianças classificadas como BEI. Foram selecionadas 98 de 487 crianças avaliadas em nosso serviço com baixa estatura utilizando os seguintes critérios: peso e comprimento normais para idade gestacional ao nascimento, escore-Z da altura < -2, escore-Z do IGF-1 < -1 e pico de resposta de GH >= 3,3 ug/L no teste de estímulo. DNA foi extraído de leucócitos periféricos desses pacientes para rastreamento de mutações no gene GH1. Realizamos estudo molecular por reação em cadeia da polimerase e sequenciamento automático de toda a região codificadora do GH1. Segregação familiar foi realizada para as variantes alélicas identificadas. Em nossa casuística, foram identificadas 10 variantes alélicas nos éxons 4 e 5 e no íntron 4 do GH1, sendo três variantes ainda não descritas na literatura (c.407G > A/p.Val122Ile, c.507C > T/p.Tyr169Tyr e c.456+19G > T). A análise in silico de todas as variantes identificadas indicou ausência de predição de efeito deletério sobre a proteína do GH. Estudo complementar realizado pelo nosso grupo identificou em crianças diagnosticadas com DIGH grave apenas uma paciente com mutação no GH1 responsável pela forma dominante desta doença. Em conclusão, mutações no GH1 causadoras da forma autossômica dominante de DIGH ou Tipo II não foram encontradas em nossa casuística, o que sugere que estas mutações sejam infrequentes em nossa populaçãoThe growth hormone (GH) / insulin-like growth factor-1 (IGF-1) axis is the most important hormonal regulator of post-natal linear growth. GH is encoded by the Growth Hormone 1 gene (GH1). Mutations in GH1 with dominant inheritance, which exerts a dominant negative effect on the bioactive GH isoforms, are the main causes of monogenic isolated deficiency of growth hormone (IGHD), while deletions or point mutations in GH1 are responsible for a rare autosomal recessive form of IGHD. However, only homozygous deletions were identified in patients with IGHD from Unidade de Endocrinologia do Desenvolvimento do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, even after detailed investigation of GH1. This difference regarding to literature can be caused by different criteria used to diagnose IGHD in our group, which adopted the cutoff value of peak GH < 3.3ug/L in response to stimulation test, in contrast to literature that describes other groups that use the cutoff peak value of the 7 - 10ug/L. Consequently, patients with autosomal dominant inheritance mutations in GH1 could be being erroneously diagnosed, as having idiopathic short stature (ISS) in our group. Additionally, mutations that cause biologically inactive GH can also be responsible for short stature in these patients. Due to the factors described above, we decided to screen mutations in GH1 in a group of children classified as ISS. We selected 98 of 487 children followed in our department with short stature according to the following criteria: normal birth weight and length for gestational age, height SDS <= -2, IGF-1 SDS < -1 and peak GH in stimulation test >= 3.3 ug/L. Genomic DNA was extracted from peripheral blood leucocytes of the patients to screen for mutations in GH1. We performed molecular analysis by polymerase chain reaction and automated sequencing of the entire coding region of the GH1. Segregation analysis was performed in the presence of allelic variations. In our casuistic, we identified 10 allelic variants in exon 4, exon 5 and intron 4 of GH1, three of which have not been described (c.407G > A/p.Val122Ile, c.507C > T/p.Tyr169Tyr and c.456+19G >T). In silico analysis predicted that none of the mutant alleles would result in deleterious effect on the GH protein. An additional study in children diagnosed with severe IGHD, identified just one patient with the pathogenic GH1 mutation responsible for the dominant form of this disease. In summary, defects in GH1 responsible for the autosomal dominant form of IGHD or Type II were not found in our cohort of Brazilian patients, suggesting that these mutations are infrequent in our population
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Chami, Nathalie. "Genetic determinants of rare disorders and complex traits : insights into the genetics of dilated cardiomyopathy and blood cell traits." Thèse, 2017. http://hdl.handle.net/1866/19324.
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Les facteurs génétiques peuvent apporter des réponses à plusieurs questions que nous nous posons sur les traits humains, les maladies et la réaction aux médicaments, entre autres. Avec le temps, le développement continu d'outils d'analyse génétique nous a permis d'examiner ces facteurs et de trouver des explications pertinentes. Cette thèse explore plusieurs méthodes et outils génétiques, tels que le séquençage pan-exomique et le génotypage sur puce, dans un contexte d'analyse familial et populationnel pour étudier ces facteurs génétiques qui jouent un rôle dans une maladie rare, la cardiomyopathie dilatée (DCM), et dans deux traits complexes soient les globules rouges et les plaquettes.
DCM est une maladie rare qui est définie par un ventricule gauche dilaté et une dysfonction systolique. Environ 30% des cas de DCM sont héréditaires, et plus de 50 gènes ont été associés à un rôle dans la pathogénicité de DCM. Le dépistage génétique est un outil de référence dans la gestion clinique de DCM familiale. Par contre, pour la majorité des patients, les tests génétiques ne parviennent pas à identifier une mutation causale dans un gène candidat.
Les cellules sanguines remplissent une variété de fonctions biologiques, incluant le transport de l'oxygène, les fonctions immunologiques, ainsi que la guérison de plaies. Les niveaux de ces cellules et leurs paramètres auxiliaires sont mesurés par un test sanguin, et une différence avec les valeurs optimales peut signifier certains troubles. De plus, ces traits sont étudiés méticuleusement dans le contexte des maladies cardiovasculaires (CVD) où différents niveaux sont associés avec un risque variable de CVD ou sont des prédicteurs de complications de CVD.
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J'ai examiné la DCM et les traits sanguins avec comme objectif de découvrir des nouvelles associations de mutations génétiques. Pour la DCM, j'ai évalué la pertinence d'un séquençage pan-exomique dans un environnement clinique. Je rapporte plusieurs nouvelles mutations dans des gènes candidats (DSP, LMNA, MYH7, MYPN, RBM20, TNNT2) et des mutations nonsenses dans deux gènes nouvellement associés (TTN et BAG3), et je démontre que les mutations nonsenses influencent la maladie d'une manière différente des autres mutations causales. Je rapporte aussi une mutation dans un nouveau gène, FLNC, qui cause une forme rare et distincte de cardiomyopathie. Pour l'étude des traits complexes, dans le grand consortium Blood Cell Consortium (BCX), j'ai utilisé l’exomechip pour disséquer le rôle des variantes rares et communes dans les globules rouges et les plaquettes. J'ai identifié 16 nouvelles régions génomiques associées avec les globules rouges et 15 avec les plaquettes, parmi lesquelles se retrouvent plusieurs variantes de basses fréquences (MAP1A, HNF4A, ITGA2B, APOH), et j'ai démontré un chevauchement significatif de régions associées avec d'autres traits, incluant les lipides.
Mes résultats sur la DCM ont mis en évidence le rôle de plusieurs gènes candidats, et suggèrent un traitement différent au niveau de la gestion clinique des patients qui portent des mutations dans BAG3 et FLNC. En ce qui concerne les traits sanguins, mes résultats contribuent à enrichir le répertoire de régions associées avec ces traits, soulignant l'importance de l'utilisation de grands ensembles de données pour détecter les variantes rares ou de basses fréquences. La découverte de gènes dans les maladies rares et les traits complexes contribue à la compréhension des mécanismes sous-jacents qui ultimement favorisera de meilleurs diagnostics, gestions et traitements de maladies.Genetic factors hold within them the answers to many questions we have on human traits, disease, and drug response among others. With time, the continuously advancing genetic tools have enabled us to examine those factors and provided and continue to provide astonishing answers. This thesis utilizes various methods of genetic tools such as exome sequencing and chip-based genotyping data in the context of both family and population-based analyses to interrogate the genetic factors that play a role in a rare disease, dilated cardiomyopathy (DCM), and in two complex traits, red blood cells and platelets. DCM is a rare disease that is defined by a dilated left ventricle and systolic dysfunction. It is estimated that 30% of DCM cases are hereditary and more than 50 genes have been linked to play a role in the pathogenesis of DCM. Genetic screening of known genes is a gold standard tool in the clinical management of familial DCM. However, in the majority of probands, genetic testing fails to identify the causal mutation. Blood cells play a variety of biological functions including oxygen transport, immunological functions, and wound healing. Levels of these cells and their associated indices are measured by a blood test, and deviation from optimal values may indicate certain disorders. Additionally, these traits are heavily studied in the context of cardiovascular disease (CVD) where different levels associate with a variable risk of CVD or are predictors of CVD complications or outcomes (for example, a higher level of white blood cells or lower level of hemoglobin). I examined both DCM and blood cell traits and aimed to discover new mutations and variants that are associated with each. For DCM, I evaluated the value of whole exome vi sequencing in a clinical setting, and I report a number of novel mutations in candidate genes (DSP, LMNA, MYH7, MYPN, RBM20, TNNT2) and truncating mutations in two newly established genes, TTN and BAG3, and I demonstrate that truncating mutations in the latter influence disease differently than other causal mutations. I also report a mutation in a novel gene, FLNC that causes a rare and distinct form of cardiomyopathy. In examining complex traits, I dissected the role of common and rare variants in red blood cells and platelets within a large consortium, the Blood Cell Consortium (BCX) using the ExomeChip, and identified 16 novel loci associated with red blood cell traits and 15 with platelet traits, some of which harbored low-frequency variants (MAP1A, HNF4A, ITGA2B, APOH), and demonstrated a substantial overlap with other phenotypes predominantly lipids. My results on DCM establish the role of a number of candidate genes in this disorder and suggest a different course of clinical management for patients that carry mutations in BAG3 and FLNC. As for blood cell traits, my results contributed to expanding the repertoire of loci associated with red blood cell and platelet traits and illustrate the importance of using large datasets to discover low-frequency or rare variants. Gene discovery in rare disease and complex traits gives insight into the underlying mechanisms which ultimately contributes to a better diagnosis, management, and treatment of disease.
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KOSOBUDOVÁ, Hana. "Kongenitální choroby skotu." Master's thesis, 2012. http://www.nusl.cz/ntk/nusl-137031.
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In the framework of this thesis was performed genotyping of 46 specimens of the breed Czech red cattle from the University farm in Czech Budejovice, which monitored the incidence of autosomal recessive genetic disorders, specifically bovine citrullinemia (BC) in exon 5 and deficiency of blood coagulation factor XI (FXI) in exon 9 and 12. Genotyping for BC was done using PCR/RFLP methods and for the disorder FXI in both exons genotypes were determined on the basis of different length of fragments using PCR technology and horizontal agarose electrophoresis. The presence of mutant allele was detected only in the locus for BC and that is in 7 heterozygous carriers, who produced three bands with a length of 185 bp fragments, 103 bp and 82 bp. The frequency of mutant allele and the frequency of heterozygous carriers to 7.6% and 15.2%. Results of the study show that the presence of mutant allele for BC in our tested panel of animals is relatively high. In the future it will be necessary to adopt measures that will lead to the elimination of this allele. Otherwise, its further dissemination would have a negative impact on the health of the population and there might occur complications in the regeneration of Czech red cattle, which is one of our farm animal genetic resources. The literature review deals with the problems of congenital disorders and discusses the importance of health heredity and understanding of the genomic information of cattle.
Books on the topic "Genetic/blood disorders"
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Bahou, Wadie Farid. Genetics for haematologists: The molecular genetic basis of haematological disorders. London: ReMEDICA, 2000.
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Dr, Cooper David N., ed. The molecular genetics of haemostasis and its inherited disorders. Oxford: Oxford University Press, 1994.
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Blood matters: A journey along the genetic frontier. London: Granta, 2009.
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Molecular genetics and immunoanalysis in blood coagulation. Weinheim, F.R.G: VCH, 1988.
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International, Symposium on Blood Transfusion (19th 1994 Groningen Netherlands). Hereditary diseases and blood transfusion: Proceedings of the Nineteenth International Symposium on Blood Transfusion, Groningen, 1994. Dordrecht: Kluwer Academic, 1995.
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James, Andra H. 100 questions & answers about Von Willebrand disease. Sudbury, Mass: Jones and Bartlett, 2009.
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Davie, E. W. (Earl W.), Sueishi Katsuo, Ikeda Yasuo, Iwanaga Sadaaki, Saitō Hidehiko 1939-, and SpringerLink (Online service), eds. Recent Advances in Thrombosis and Hemostasis 2008. Tokyo: Springer Japan, 2008.
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Parker, James N., and Philip M. Parker. X-linked sideroblastic anemia: A bibliography and dictionary for physicians, patients, and genome researchers [to internet references]. San Diego, CA: ICON Health Publications, 2007.
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Parker, James N., and Philip M. Parker. Abetalipoproteinemia: A bibliography and dictionary for physicians, patients, and genome researchers [to internet references]. San Diego, CA: ICON Health Publications, 2007.
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Parker, James N., and Philip M. Parker. Smith-Lemli-Opitz syndrome: A bibliography and dictionary for physicians, patients, and genome researchers [to internet references]. San Diego, CA: ICON Health Publications, 2007.
Find full textBook chapters on the topic "Genetic/blood disorders"
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Clarke, Angus. "Disorders of blood and immune function." In Harper's Practical Genetic Counselling, 387–94. Eighth edition | Boca Raton : CRC Press, [2020] | Preceded by Practical genetic counselling / Peter S. Harper. 7th ed. 2010.: CRC Press, 2019. http://dx.doi.org/10.1201/9780367371944-27.
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Elias, Sherman. "Amniocentesis and Fetal Blood Sampling." In Genetic Disorders and the Fetus, 63–93. Oxford, UK: Wiley-Blackwell, 2010. http://dx.doi.org/10.1002/9781444314342.ch2.
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Romero, Roberto, John C. Hobbins, and Maurice J. Mahoney. "Fetal Blood Sampling and Fetoscopy." In Genetic Disorders and the Fetus, 571–98. Boston, MA: Springer US, 1986. http://dx.doi.org/10.1007/978-1-4684-5155-9_18.
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Odibo, Anthony O. "Amniocentesis, Chorionic Villus Sampling, and Fetal Blood Sampling." In Genetic Disorders and the Fetus, 68–97. Hoboken, NJ, USA: John Wiley & Sons, Inc., 2015. http://dx.doi.org/10.1002/9781118981559.ch2.
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Zwiebel, J. A. "Is there a Role for Transfusion Medicine in the Genetic Correction of Genetic Disorders and other Diseases?" In Hereditary Diseases and Blood Transfusion, 189–207. Boston, MA: Springer US, 1995. http://dx.doi.org/10.1007/978-1-4615-2017-7_16.
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"Disorders of Blood and Immune Function." In Practical Genetic Counselling, 333–41. CRC Press, 2010. http://dx.doi.org/10.1201/b13471-30.
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Pollak, Eleanor S., and Katherine A. High. "Genetic disorders of coagulation." In Oxford Textbook of Medicine, 4518–31. Oxford University Press, 2010. http://dx.doi.org/10.1093/med/9780199204854.003.220604_update_001.
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Much of what is understood about specific coagulation proteins has emerged from the careful study of hereditary disorders of blood coagulation. Haemophilia is a familial X-linked disorder due to deficiency of either factor VIII (haemophilia A) or factor IX (haemophilia B), components of the intrinsic enzymatic complex that activates factor X. The severity of the disease correlates with predicted concentrations of activated factor protein, and those with activity levels below 1% are defined as having severe disease....
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Rai, Parul, Ewelina K. Mamcarz, and Jane S. Hankins. "Newborn Genetic Screening for Blood Disorders." In Neonatal Hematology, 93–112. 3rd ed. Cambridge University Press, 2021. http://dx.doi.org/10.1017/9781108773584.008.
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"Disorders of the Human Circulatory System." In Examining the Causal Relationship Between Genes, Epigenetics, and Human Health, 288–324. IGI Global, 2019. http://dx.doi.org/10.4018/978-1-5225-8066-9.ch013.
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This chapter focuses on genetic disorders affecting the human circulatory system. Genetic disorders can occur due to a defect in a single gene or in a set of genes. The body's circulatory system is made up of the heart and blood vessels (arteries, arterioles, veins, venules, and capillaries). The system carries both blood and lymphatic fluid in two circuits: pulmonary circulation (blood through the lungs for oxygenation) and systemic circuits (from the heart to all body parts). Fourteen disorders are presented in this chapter including sickle cell disease, Gaucher Disease, chronic myeloid leukaemia, Niemann-Pick Disease, haemophilia, atherosclerosis, ataxia telangiectasia, haemoglobinuria, thalassemia, William's syndrome, porphyria, long QT syndrome, and alpha-I-antitrypsin deficiency.
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Healy, Eugene. "Disorders of pigmentation." In Oxford Textbook of Medicine, edited by Graham S. Ogg, 4656–64. Oxford University Press, 2010. http://dx.doi.org/10.1093/med/9780199204854.003.2308_update_001.
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Normal human skin colour results from the reflection of light from haemoglobin in blood, and carotenoids and melanin pigmentation in skin. The melanin pigmentation is the major component determining differences in skin colour between races. Increases and decreases in skin pigmentation (hyperpigmentation and hypopigmentation, respectively) may be localized or generalized, can result from a wide variety of physiological or pathological processes, including both genetic and acquired factors, and may reflect underlying systemic disease....
Conference papers on the topic "Genetic/blood disorders"
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Zaninetti, C., J. Rivera, E. Leinoe, M. Wolff, C. Freyer, and A. Greinacher. "Diagnosis of inherited platelet disorders: comparison between immunofluorescence analysis on the blood smear and genetic testing." In 65th Annual Meeting of the Society of Thrombosis and Haemostasis Research. Georg Thieme Verlag KG, 2021. http://dx.doi.org/10.1055/s-0041-1728106.
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Свиридова, Алина Викторовна, Мария Владимировна Абрамян, and Владимир Вячеславович Алексеев. "PATHOGENESIS OF HEADACHE AND ARTERIAL HYPERTENSION AS THE FIRST SYMPTOMS OF ACUTE DISORDERS OF CEREBRAL CIRCULATION, AND THEIR INFLUENCE ON THE DEVELOPMENT AND EXODUS OF THE DISEASE." In Поколение будущего: сборник избранных статей Международной студенческой научной конференции (Санкт-Петербург, Ноябрь 2020). Crossref, 2020. http://dx.doi.org/10.37539/pb188.2020.37.55.005.
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Представлен патогенез наиболее ранних симптомов острых нарушений мозгового кровообращения, к которым относятся артериальная гипертензия и головная боль. Предположен адаптивный характер повышения артериального давления при ишемическом инсульте, что в острую фазу заболевания благоприятно влияет на его развитие и исход. Рассмотрен генез головной боли разных видов острых нарушений мозгового кровообращения. The pathogenesis of the earliest symptoms of acute disorders of cerebral circulation, which include arterial hypertension and headache, is presented. Assume adaptive nature increase blood pressure in an ischemic stroke, in the acute phase of the disease favorably affects its development and exodus. The genesis of headaches of different types of acute disorders of cerebral circulation is considered.
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Rachev, Alexander, W. Robert Taylor, and Raymond P. Vito. "Calculation of the Outcomes of Adaptive and Maladaptive Remodeling of Arteries Subjected to Sustained Hypertension Using a 3D Two-Layered Model." In ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80092.
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Arteries respond to long-term alterations in arterial pressure and blood flow by changing geometry, structure, and composition. This response is termed as remodeling and plays an important role in normal arterial physiology and in the genesis and progression of certain vascular disorders. In healthy mature arteries, remodeling represents an adaptive process that tends to restore the local mechanical environment of vascular cells to baseline levels and thereby to preserve the optimal performance of the arterial function. The objective of this study is twofold — to develop a general method for calculation the remodeling outputs of an artery considered as a two-layered tube; and to provide results for adaptive and maladaptive remodeling of a coronary artery.
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Shida, Shuya, Hiroyuki Kosukegawa, and Makoto Ohta. "Development of a Methodology for Adaptation of Refractive Index Under Controlling Kinematic Viscosity for PIV." In ASME 2011 International Mechanical Engineering Congress and Exposition. ASMEDC, 2011. http://dx.doi.org/10.1115/imece2011-64388.
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Blood vessel diseases such as ischemic cardiac disease or cerebral aneurysm are life-threatening disorders and as large a cause of death as cancer in many countries. The rupture of a cerebral aneurysm usually causes subarachnoidal hemorrhage the mortality of which is very high. Previous studies have proved that the genesis and growth of aneurysm are related to hemodynamics. Especially, in endovascular therapy for cerebral aneurysms using medical devices such as coils or stents, hemodynamics in an aneurysm are related to thrombosis formation in the aneurysm and to its repair. In vascular research using a biomodel (blood vessel phantom with mechanical properties similar to a human artery) for treating cerebral aneurysm, the working fluid, termed Blood-Mimicking Fluid (BMF), should mimic human blood with respect to viscosity so as to obtain realistic blood flow modeling in in vitro measurements. Moreover, refractive indices of BMF must be adjusted to fit biomodel materials because the materials used for Particle Image Velocimetry, one of the best tools for measurement of flow, have various refractive indices. For simultaneous adjustment of the two parameters, i.e. kinematic viscosity and refractive index, an aqueous mixture of glycerol and sodium iodide has been used in previous research. In this paper, we develop a systematic way to precisely find the two targeted parameters of BMF by showing the measurement values of the refractive index and the viscosity of the two aqueous solutions. The refractive index to light of fluorescent was measured with a critical angle refractometer while temperature of sample was also measured. And a vibration-type viscometer was used to obtain the dynamic viscosity under the same condition as refractive index measurement. These measurements were carried out at room temperature and pressure, respectively. As a result of detailed measurements at various proportions, refractive indices of the aqueous solution of glycerol (Gly. aq.) increase monotonically. On the one hand, the kinematic viscosity of Gly. aq. increases very slightly with its proportion and that of the aqueous solution of sodium iodide (NaI aq.) exhibits unique behavior. The results of combining Gly. aq. and NaI aq. indicate that the mixture has a wide range of kinematic viscosity, including the value of blood (around 3.8 mm2/s), at the targeted refractive index. In conclusion, this mixing method is useful for BMF preparation with the adjustment of refractive index and kinematic viscosity.
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Liu, Chung Y., Dominic Chung, Earl Davie, and Leonard Chess. "FORMER STUDIES OF FIBRINOGEN NEW YORK I : ANALYSIS OF HE GENUINIC C DISORDER for the deletion OF MINO ACID SEQUENCE 9-72 OF THE Bβ CHAIN." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644697.
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Fibrinogens New York I and la (NY-I and NY-la) have been purified from blood plasma samples of a^ sister and a brother in a white family with thrombotic tendency. Both are heterozygous and contain both thrombin-clottable fibrinogen with two normal Bβ-chains and thrombin-nonclottable fibrinogen with two abnormal Bβ chains. The abnormal β-chains result- fran deletions of ammo acid residues 9-72, which are encoded exactly by exon II of the gene. To study the genomic disorder for this deletion, gencmic DNAs were isolated respectively from leukocytes of NY-la, NY-Ib (a nonaffected brother), and four normal individuals outside the NY-I family, and analysed in Southern blotting experiments with a human gencmic DNA probe containing exons I-V. Digestion of various DNAs were performed with two different restriction enzymes, and these digestions were analyzed respectively by agrose electroptoresis.Digestion with Hind III reveals 3 cleavage sites (one site in intron A near exon II)witn formation of two fragments of equal size (2 bands : 3.1kb and 3.1 kb) in normal, NY-la and NY-Id, but an extra fragment (one band = 6.0 kb) in NY-Ia.Digestion with Pvu II reveals 3 cleavage sites (one site in exonII) with formation of two fragments (2 bands : 7.5 kb and 2.9kb)m normal, NY-Ia and NY-Ib, but an extra fragment (one band - 5.7 kb) in NY-Ia. These results show that one Hind III and one Pvu II cleavage sites which are present in the normal allele are absent in the abnormal allele of NY-Ia. Thus, these studies indicate that generic disorder is associated with the patient (NY-Ia) with a thrombotic tendency, and further suggest that the genomic defect in the aonormal allele is near the junction of intron A and exon II. A possible mechanism for this genomic disorder is due to that an inverse double crossover have taken place in a region covering this junction, resulting in m abnormal RNA-splicing site in this junction. Thus, exon II is eliminated with intron A during RNA processing and absent in the abnormal rnRNA. Accordingly, the β(9-72) amino acid sequence disappears from one abnromal β-chains.
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Wachtfogel, Yanina T., Yizhar Floman, Meir Liebergall, Robert W. Colman, and Amiram Eldor. "PLATELET ALPHA2-ADRENERGIC RECEPTOR ABNORMALITIES IN PATIENTS WITH IDIOPATHK: SCOLIOSIS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644567.
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Idiopathic scoliosis is a genetic multisystem disease involving skeletal, biochemical, central nervous svstem, muscle and blood platelet abnormalities. Platelets of patients with idiopathic scoliosis have been shown to have decreased adenosine diphosphate and epinephrine-induced aggregation. Similarities between the contractile protein system of platelets and muscle have made the platelet a popular model for certain aspects of muscle physiology. This study confirmed that 64% of the patient platelets tested exhibited a significantly decreased sensitivity to aggregation bv epinephrine. In seven of the eleven patients studied, epinephrine induced aggregation was markedly decreased, i.e., the threshold of agonist was markedly elevated ≥11 uM). The geometric mean concentration of epinephrine required to produce complete second-wave aggregation in idiopathic scoliosis patients was 8μM. as compared to a control concentration of luM. We therefore examined the platelet alpha2-adrenergic receptors of 17 patients with idiopathic scoliosis bv measuring ligand binding using the selective antagonist, methyl yohimbine. Platelets from healthv individuals had 185 ± 16 sites per platelet with a Kd of 1.90 ± 0.32 nM, while patients with idiopathic scoliosis had 54 ± 22 sites per platelet with a of 1.02 ± 0.03 nM. The number of binding sites per platelet in idiopathic scoliosis patients were significantly decreased (p < 0.05) as compared to controls , while the was not significantly different (p > 0.05) between the two groups. Seven of these patients exhibited a significant decrease (p < 0.05) in the number of alpha2-adrenergic receptors on their platelets while the binding in 7 additional patients was undetectable.Three patients exhibited normal receptor number and affinity as compared to normal individuals. This study indicates a profound alteration in the number and function of the alpha2-adrenergic receptors in platelets of patients with idiopathic scoliosis and indicates the functional heterogeneity of the receptor disorder. Further investigation of platelet abnormalities may give insight into the putative muscle defects.
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Antonarakis, E. "The Molecular Genetics of Hemophilia A Stylianos." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643980.
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Hemophilia A is a common X linked hereditary disorder of blood coagulation due to deficiency of factor 8. The gene for factor 8 has been cloned and characterized (Nature 312:326-342, 1984). It is divided into 26 exons and 25 introns and spans 186 kb of DNA. The CGNA is 9 kb and codes for 2351 amino acids. The first 19 amino acids comprise the secretory leader peptide and the mature excreted polypeptide consists of 2332 amino acids. The nucleotide sequence of the exons and the exon-intron junctions is known and the complete amino acid sequence has been deducedSeveral laboratories have used cloned factor 8 DNA sequences as probes to characterized mutations that are responsible for hemophilia A in certain pedigrees. These mutations have been characterized by restriction analysis, oligonucleotide hybridization, cloning and sequencing of DNA from appropriate patientsIn about 500 patients with hemophilia A examined, the molecular defect has been recognized in 39. Both gross alterations (mainly deletions) and point mutations of the factor 8 gene have been found.A total of 19 different deletions have been observed. No two unrelated pedigrees share the same exact deletion.The size of the deleted DNA varies from 1.5 kb to more than 210 kb. All but one of these deletions are associated with severe hemophilia A. A deletion of 6 kb that contains exon 22 only is associated with moderate hemophilia. Some deletions are present in patients with inhibitors to factor 8. No correlation of the size or the position of the deletions can be found with the presence of inhibitors to factor 8.A total of 20 point mutations have been characterized. All are recognized by restriction analysis and involve Taq I sites. All are mutations of CpG dinucleotides and generate nonsense or missence codons. Unrelated pedigrees have the same single nucleotide change because of independent origin of the same mutation. In many instances de novo occurrence of a point mutation has been observed. CpG dinucleotides are hot spots for mutation to TG or CA presumably because of spontaneous deamination of methylcytosine. Some point mutations are present in patients with inhibitors but no correlation of the site of mutation and inhibitor formation has been found. The nonsense mutations are present in patients with severe hemophilia A. A missense mutation (Arg Gin) in exon 26 was found in a patient with mild hemophilia while another Arg Gin mutation in exon 24 has been observed in a patient with severe disease. The creation of a donor splice site in IVS 4 of factor 8 gene has been observed in a patient with mild hemophilia.Few DNA polymorphisms within the factor 8 gene and two other closely linked polymorphisms have been used for carrier detection and prenatal diagnosis of hemophilia A. These DNA markers are useful in more than 90% of families at risk for hemophilia A.The author thanks Drs. Gitschier, Din, Olek, Pirastou, Lawn for communication of their data prior to publication.The hemophilia project at Johns Hopkins was supported by an Institutional grant and NIH grant to S.S.A. and Haig H. Kazazian, Jr.