scholarly journals Prenatal Diagnosis of Thalassemia

2019 ◽  
Vol 33 (7-8) ◽  
pp. 191-9
Author(s):  
Sunarto Sunarto
Keyword(s):  
Prenatal Diagnosis ◽  
Dna Analysis ◽  
Genetic Disorder ◽  
Chorionic Villus ◽  
The Body ◽  
Chorionic Villi ◽  
Globin Chains ◽  
Globin Synthesis ◽  
Fetal Blood Sample

Thalassemia is an individual as well as a community health problem in some countries. It causes a lifelong suffering for the affected individuals. There is no treatment other than supportive, i.e. regular transfusions and removal of iron overload from the body. Only by such continuous and expensive treatment thalassemic patients can-generally achieve nearly normal health, but the health burden of such therapy for a large number of thalassemic patients is unaffordable by the affected communities. Prevention of the births of thalassemic babies is the choice for controlling the thalassemia and has been successful in many countries. For this purpose reliable and time accurate prenatal diagnosis is a conditio sine qua non. Blood fetal sampling is safe and can be done after 16 weeks gestation, amniocentesis after 14 weeks, and even chorionic villi sampling as early as 8 weeks gestation. In vitro globin synthesis analysis applied to the fetal blood sample is very reliable to measure the rate of synthesis of the globin chains that make up the hemoglobin. The-DNA analysis of the fibroblasts obtained by amniocentesis or of the chorionic villus sample is very sensitive and specific for the diagnosis of the genetic disorder in thalassemias. By involving the prenatal diagnosis, the birth of B-homozygous thalassemia has decreased by up to 90%.

scholarly journals Hyaluronate/black phosphorus complexes as a copper chelating agent for Wilson disease treatment

2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Seong-Jong Kim ◽  
Hye Hyeon Han ◽  
Sei Kwang Hahn
Keyword(s):  
Targeted Delivery ◽  
Wilson Disease ◽  
Copper Ions ◽  
Binding Capacity ◽  
Genetic Disorder ◽  
Chelating Agent ◽  
Black Phosphorus ◽  
The Body ◽  
Copper Binding

Abstract Background Wilson disease (WD) is a genetic disorder of copper storage, resulting in pathological accumulation of copper in the body. Because symptoms are generally related to the liver, chelating agents capable of capturing excess copper ions after targeted delivery to the liver are highly required for the treatment of WD. Methods We developed hyaluronate-diaminohexane/black phosphorus (HA-DAH/BP) complexes for capturing copper ions accumulated in the liver for the treatment of WD. Results HA-DAH/BP complexes showed high hepatocyte-specific targeting efficiency, selective copper capturing capacity, excellent biocompatibility, and biodegradability. HA enhanced the stability of BP nanosheets and increased copper binding capacity. In vitro cellular uptake and competitive binding tests verified targeted delivery of HA-DAH/BP complexes to liver cells via HA receptor mediated endocytosis. The cell viability test confirmed the high biocompatibility of HA-DAH/BP complexes. Conclusion HA-DAH/BP complexes would be an efficient copper chelating agent to remove accumulated copper in the liver for the WD treatment.

Effective erythropoiesis and HbF reactivation induced by kit ligand in β-thalassemia

Blood ◽  
2008 ◽  
Vol 111 (1) ◽  
pp. 421-429 ◽  
Author(s):  
Marco Gabbianelli ◽  
Ornella Morsilli ◽  
Adriana Massa ◽  
Luca Pasquini ◽  
Paolo Cianciulli ◽  
...  
Keyword(s):  
Fetal Hemoglobin ◽  
Thalassemia Major ◽  
Globin Genes ◽  
Erythroid Progenitors ◽  
Ineffective Erythropoiesis ◽  
Kit Ligand ◽  
Globin Chains ◽  
In Vitro Response ◽  
Globin Synthesis

In human β-thalassemia, the imbalance between α- and non–α-globin chains causes ineffective erythropoiesis, hemolysis, and anemia: this condition is effectively treated by an enhanced level of fetal hemoglobin (HbF). In spite of extensive studies on pharmacologic induction of HbF synthesis, clinical trials based on HbF reactivation in β-thalassemia produced inconsistent results. Here, we investigated the in vitro response of β-thalassemic erythroid progenitors to kit ligand (KL) in terms of HbF reactivation, stimulation of effective erythropoiesis, and inhibition of apoptosis. In unilineage erythroid cultures of 20 patients with intermedia or major β-thalassemia, addition of KL, alone or combined with dexamethasone (Dex), remarkably stimulated cell proliferation (3-4 logs more than control cultures), while decreasing the percentage of apoptotic and dyserythropoietic cells (<5%). More important, in both thalassemic groups, addition of KL or KL plus Dex induced a marked increase of γ-globin synthesis, thus reaching HbF levels 3-fold higher than in con-trol cultures (eg, from 27% to 75% or 81%, respectively, in β-thalassemia major). These studies indicate that in β-thalassemia, KL, alone or combined with Dex, induces an expansion of effective erythropoiesis and the reactivation of γ-globin genes up to fetal levels and may hence be considered as a potential therapeutic agent for this disease.

scholarly journals Asynchronous globin chain synthesis in rabbit reticulocyte lystates induced by hemin-controlled repressor

Blood ◽  
1978 ◽  
Vol 51 (4) ◽  
pp. 653-658 ◽  
Author(s):  
RS Franco ◽  
JW Hogg ◽  
OJ Martelo
Keyword(s):  
Globin Chain ◽  
Free System ◽  
Globin Chains ◽  
Reticulocyte Lysate ◽  
Chain Imbalance ◽  
Globin Synthesis ◽  
Chain Synthesis ◽  
Globin Chain Synthesis

Abstract To define further the role of hemin-controlled repressor (HCR) in globin synthesis, we studied its effect on the synthesis of individual globin chains in a rabbit reticulocyte lysate cell-free system. In the presence of HCR there was a marked globin chain imbalance, resulting in a lowered alpha/beta ratio. These findings in vitro may have relevance to certain clinical heme deficiency states in which a similar globin chain imbalance has been observed.

Micro- and Nanofluidics for Cell Biology, Cell Therapy, and Cell-Based Drug Testing

2009 ◽  
Author(s):  
Shuichi Takayama ◽  
Dongeun Huh ◽  
Jonathan Song ◽  
Wansik Cha ◽  
Yunseok Heo
Keyword(s):  
Cell Biology ◽  
Mammalian Cells ◽  
Cancer Metastasis ◽  
Dna Analysis ◽  
The Body ◽  
Biological Information ◽  
Screening Methods ◽  
Biological Studies

Many biological studies, drug screening methods, and cellular therapies require culture and manipulation of living cells outside of their natural environment in the body. The gap between the cellular microenvironment in vivo and in vitro, however, poses challenges for obtaining physiologically relevant responses from cells used in basic biological studies or drug screens and for drawing out the maximum functional potential from cells used therapeutically. One of the reasons for this gap is because the fluidic environment of mammalian cells in vivo is microscale and dynamic whereas typical in vitro cultures are macroscopic and static. This presentation will give an overview of efforts in our laboratory to develop microfluidic systems that enable spatio-temporal control of both the chemical and fluid mechanical environment of cells. The technologies and methods close the physiology gap to provide biological information otherwise unobtainable and to enhance cellular performance in therapeutic applications. Specific biomedical topics that will be discussed include, in vitro fertilization on a chip, microfluidic tissue engineering of small airway injuries, breast cancer metastasis on a chip, electrochemical biosensors, and development of tuneable nanofluidic systems towards applications in single molecule DNA analysis.

scholarly journals Potential usefulness of preimplantation genetic diagnosis in the control and prevention of genetic diseases

1999 ◽  
Vol 5 (6) ◽  
pp. 1134-1139
Author(s):  
M. A. El Hazmi
Keyword(s):  
Prenatal Diagnosis ◽  
Preimplantation Genetic Diagnosis ◽  
Genetic Disorder ◽  
Genetic Diseases ◽  
Genetic Diagnosis ◽  
Potential Usefulness ◽  
Vitro Fertilization ◽  
Polar Bodies ◽  
Control And Prevention

Prenatal diagnosis of molecular mutations can be of immense value, since diagnosis followed by genetic counselling provides the most appropriate approach to genetic diseases control and prevention. However, ethical, psychosocial and religious considerations hamper adoption of prenatal diagnosis in communities where termination of a pregnancy may not be acceptable. Recently, preimplantation genetic diagnosis has attracted considerable interest. This involves in vitro fertilization, followed by genetic disorder diagnosis using polar bodies or cells extracted from a blastomere stage. The normal blastomere is implanted in the womb and pregnancy proceeds naturally. If an abnormality is diagnosed, the blastomere is not implanted, thus preventing pregnancy with the affected fetus. This paper outlines the potential usefulness of preimplantation genetic diagnosis in the control and prevention of genetic disease in our part of the world

Prenatal Diagnosis for Pediatricians

PEDIATRICS ◽  
1989 ◽  
Vol 84 (4) ◽  
pp. 741-744
Author(s):  
Keyword(s):  
Prenatal Diagnosis ◽  
Genetic Disorder ◽  
Chorionic Villus ◽  
Fetal Tissue ◽  
Maternal Serum ◽  
Family Counseling ◽  
Current Status ◽  
Chorionic Villus Sampling ◽  
Tissue Sampling ◽  
Umbilical Blood

This statement is for the pediatrician who may be called upon to care for the child with a birth defect or genetic disorder. The involved family may wish to know and may benefit from methods that convert probability statements about recurrence risks into facts about the fetus. Many families will find knowledge and choice better than chance. Rapid advances in technology have prompted the Committee on Genetics to retire the June 1980 statement and to prepare a new one. The purpose of this revised statement is to inform the pediatrician about the current status of antenatal diagnosis as it relates to genetic and family counseling in clinical practice. The pediatrician may be called upon to help address questions about the natural history of the disorder under consideration and the possibility of intrauterine treatment. Prenatal diagnosis can give information that may improve the outcome of pregnancy and can be helpful to the obstetrician in the management of labor and delivery. The availability of prenatal diagnosis gives couples options they might not otherwise have, including termination of an affected pregnancy or preparation for the birth of an abnormal child. This enables many couples to have children, when without this information they would have chosen to be childless. The techniques currently in use or under investigation for prenatal diagnosis include (1) fetal tissue sampling: amniocentesis, chorionic villus sampling, percutaneous umbilical blood sampling, precutaneous skin biopsy, and other organ biopsies; (2) fetal visualization: ultrasound, fetoscopy, magnetic resonance imaging, and radiography; and (3) maternal serum α-fetoprotein screening. INDICATIONS FOR FETAL TISSUE SAMPLING

Improvement of erythropoiesis in β-thalassemic mice by continuous erythropoietin delivery from muscle

Blood ◽  
2000 ◽  
Vol 95 (9) ◽  
pp. 2793-2798 ◽  
Author(s):  
Delphine Bohl ◽  
Assumpció Bosch ◽  
Ana Cardona ◽  
Anna Salvetti ◽  
Jean Michel Heard
Keyword(s):  
Erythrocyte Membranes ◽  
Erythroid Cell ◽  
Suitable Model ◽  
Mouse Muscle ◽  
Membrane Function ◽  
Globin Chains ◽  
Long Term Treatment ◽  
Globin Synthesis

β-Thalassemias are highly prevalent genetic disorders that can cause severe hemolytic anemia. The main pathophysiologic feature of β-thalassemia is the accumulation of unpaired -globin chains in erythrocyte precursors and red blood cells (RBCs). This accumulation alters cell membrane function and results in early cell destruction and ineffective erythropoiesis. Correction of globin chain imbalance through the induction of fetal hemoglobin (HbF) synthesis is a tentative therapeutic approach for this class of diseases. In short-term in vitro or in vivo assays, recombinant human erythropoietin increases the frequency of erythroid precursors programmed to HbF in humans and to β-minor globin in mice. In contrast, long-term treatment of β-thalassemic patients did not induce HbF significantly. We took advantage of highly efficient adeno-associated virus–mediated (AAV-mediated) gene transfer into mouse muscle to induce a robust and sustained secretion of mouse erythropoietin in β-thalassemic mice, which represent a suitable model for human β-thalassemia intermedia. A 1-year follow-up of 12 treated animals showed a stable correction of anemia associated with improved RBC morphology, increased β-minor globin synthesis, and decreased amounts of -globin chains bound to erythrocyte membranes. More effective erythropoiesis probably accounted for a reduction of erythroid cell proliferation, as shown by decreased proportions of circulating reticulocytes and by reduced iron 59 (59Fe) incorporation into erythroid tissues. This study indicates that the continuous delivery of high amounts of autologous erythropoietin induced a sustained stimulation of β-minor globin synthesis and a stable improvement of erythropoiesis in the β-thalassemic mouse model.

Prenatal diagnosis of homozygous α°-thalassaemia by direct DNA analysis of chorionic villi in Singapore

1989 ◽  
Vol 25 (3) ◽  
pp. 161-163
Author(s):  
J. A. M. A. TAN ◽  
H. B. WONG ◽  
A. KITZIS ◽  
E. H. YAP ◽  
C. ANANDAKUMAR ◽  
...  
Keyword(s):  
Prenatal Diagnosis ◽  
Dna Analysis ◽  
Chorionic Villi

scholarly journals Hyaluronate – Black Phosphorus Conjugates as a Copper Chelating Agent for Wilson Disease Treatment

2021 ◽  
Author(s):  
Seong-Jong Kim ◽  
Hye Hyeon Han ◽  
Sei Kwang Hahn
Keyword(s):  
Targeted Delivery ◽  
Wilson Disease ◽  
Copper Ions ◽  
Binding Capacity ◽  
Genetic Disorder ◽  
Chelating Agent ◽  
Black Phosphorus ◽  
The Body ◽  
Copper Binding

Abstract Background: Wilson disease (WD) is a genetic disorder of copper storage, resulting in pathological accumulation of copper in the body. Because symptoms are generally related to the liver, chelating agents capable of capturing excess copper ions after targeted delivery to the liver are highly required for the treatment of WD. Methods: We developed hyaluronate - black phosphorus (HA-BP) conjugates for capturing copper ions accumulated in the liver for the treatment of WD.Results: HA-BP conjugates showed high hepatocyte-specific targeting efficiency, selective copper capturing capacity, excellent biocompatibility, and biodegradability. HA enhanced the stability of BP nanosheets and increased copper binding capacity. In vitro cellular uptake and competitive binding tests verified targeted delivery of HA-BP conjugates to liver cells via HA receptor mediated endocytosis. The cell viability test confirmed the high biocompatibility of HA-BP conjugates.Conclusion: HA-BP conjugates would be an efficient copper chelating agent to remove accumulated copper in the liver for the WD treatment.

Combined Use of DNA Probes in First-Trimester Prenatal Diagnosis of Hemophilia A

1987 ◽  
Vol 58 (04) ◽  
pp. 988-992 ◽  
Author(s):  
M Sampietro ◽  
G Camerino ◽  
M Romano ◽  
M D Cappellini ◽  
G Fiorelli ◽  
...  
Keyword(s):  
At Risk ◽  
Prenatal Diagnosis ◽  
Factor Viii ◽  
Dna Analysis ◽  
Hemophilia A ◽  
Chorionic Villus ◽  
Great Majority ◽  
First Trimester ◽  
Fetal Plasma ◽  
Combined Use

SummaryFirst-trimester prenatal diagnoses of hemophilia A were heretofore obtained by using either intragenic factor VIII markers or linked cxtragcnic polymorphic markers. Postulating that the combined use of all the available intragenic and extragenic markers can render such diagnoses more frequently feasible and more reliable, we carried out ten first-trimester prenatal diagnoses in male fetuses at risk for hemophilia A by DNA analysis of chorionic villus employing in combination the intragenic Bcl I polymorphism and the St 14 (DXS 52) or DX 13 (DXS 15) extragenic probes. A diagnosis of hemophilia was obtained in three fetuses, with a diagnosis of normal fetus obtained in the remaining seven. Seven diagnoses are confirmed by factor VIII assays carried out at the time of abortion, in the mid-Trimester or at birth. A factor VIII probe recognizing Bcl I polymorphism was useful in 4 of 6 diagnoses; St 14, in 5 of 6; and DX 13 in 3 of 5. In two cases, St 14 was the only useful probe for diagnosis. Even though no recombination between extragenic probes and factor VIII gene was detected in this study, when only extragenic markers were informative we advised diagnostic confirmation on fetal plasma obtained by fetoscopy. Hence, first-trimester prenatal diagnosis of hemophilia A is feasible for the great majority of fetuses at risk through combined use of all the available intragenic and extragenic probes, providing key family members are available.

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