Bailliere's clinical haematology最新文献_第5页

Bailliere's clinical haematology Pub Date : 1998-03-01 DOI: 10.1016/S0950-3536(98)80077-2

MD Griffin P. Rodgers (Chief)

{"title":"9 Pharmacological therapy","authors":"MD Griffin P. Rodgers (Chief)","doi":"10.1016/S0950-3536(98)80077-2","DOIUrl":"10.1016/S0950-3536(98)80077-2","url":null,"abstract":"<div><p>Collectively sickle cell disease and β-thalassaemia are the most commonly inherited single-gene defects world-wide and were the first group of diseases for which DNA-based detection strategies were utilized. Although genotypically distinct, these two groups of diseases exhibit several common clinical features: moderate-to-severe haemolytic anaemia, acute and progressive tissue damage, disease- or treatment-related organ failure and premature death. Within the last two decades, a striking improvement in life expectancy in the two patient populations has been observed, by dint of primary and secondary prevention strategies. However, apart from bone marrow transplantation, a generally applicable, specific and non-toxic form of treatment remains unavailable for these disorders. Nonetheless, a greater appreciation of the developmental control of human globin gene expression coupled with observations of the effects of certain classes of agents to ‘reverse’ erythroid cellular phenotype in in vitro and animal models have led to pharmacological trials to obtain meaningful increases in haemoglobin F production in patients affected by these two severe β-globin disorders. Contemporary understanding of the quantitative relationship between the abnormal molecules in the red cells (aggregates of sickle haemoglobin) in the sickle cell syndromes and aggregated α-globin polypeptides in the β-thalassemia syndromes, and the extent of the red cell and/or organ involvement, has now enabled investigators to predict how much inhibition of these intracellular pathogenic processes might be necessary to achieve partial or total abrogation of disease manifestations. The results of the Multicenter Study of Hydroxyurea and other controlled trials now bear out these predictions.</p></div>","PeriodicalId":77029,"journal":{"name":"Bailliere's clinical haematology","volume":"11 1","pages":"Pages 239-255"},"PeriodicalIF":0.0,"publicationDate":"1998-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0950-3536(98)80077-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21714996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

6 Pathophysiology of sickle cell disease 6镰状细胞病的病理生理学

Bailliere's clinical haematology Pub Date : 1998-03-01 DOI: 10.1016/S0950-3536(98)80074-7

MD Martin H. Steinberg (Associate Chief of Staff for Research and Professor of Medicine)

引用次数: 56

3 β-Thalassaemia Beta-thalassaemia。

Bailliere's clinical haematology Pub Date : 1998-03-01 DOI: 10.1016/S0950-3536(98)80071-1

FRCP, FRCPath Swee Lay Thein (Reader and Honorary Consultant in Haematology)

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引用次数: 42

2 α-Thalassaemia alpha型地中海贫血症。

Bailliere's clinical haematology Pub Date : 1998-03-01 DOI: 10.1016/S0950-3536(98)80070-X

Luigi F. Bernini (Emeritus Professor in Biochemical Genetics, Emeritus Lecturer in Biochemical Genetics at Leiden University), PhD Cornelis L. Harteveld (Researcher in Molecular Genetics)

{"title":"2 α-Thalassaemia","authors":"Luigi F. Bernini (Emeritus Professor in Biochemical Genetics, Emeritus Lecturer in Biochemical Genetics at Leiden University), PhD Cornelis L. Harteveld (Researcher in Molecular Genetics)","doi":"10.1016/S0950-3536(98)80070-X","DOIUrl":"10.1016/S0950-3536(98)80070-X","url":null,"abstract":"<div><p>α-Thalassaemias are genetic defects extremely frequent in some populations and are characterized by the decrease or complete suppression of α-globin polypeptide chains. The gene cluster, which codes for and controls the production of these polypeptides, maps near the telomere of the short arm of chromosome 16, within a G + C rich and early-replicating DNA region. The genes expressed during the embryonic (ζ) or fetal and adult stage (α<sub>2</sub> and α<sub>1</sub>) can be modified by point mutations which affect either the processing-translation of mRNA or make the polypeptide chains extremely unstable. Much more frequent are the deletions of variable size (from ≈ 3 to more than 100 kb) which remove one or both α genes in <em>cis</em> or even the whole gene cluster. Deletions of a single gene are the result of unequal pairing during meiosis, followed by reciprocal recombination. These unequal cross-overs, which produce also α gene triplications and quadruplications, are made possible by the high degree of homology of the two α genes and of their flanking sequences. Other deletions involving one or more genes are due to recombinations which have taken place within non-homologous regions (illegitimate recombinations) or in DNA segments whose homology is limited to very short sequences. Particularly interesting are the deletions which eliminate large DNA areas 5′ of ζ or of both α genes. These deletions do not include the structural genes but, nevertheless, suppress completely their expression. Larger deletions involving the tip of the short arm of chromosome 16 by truncation, interstitial deletions or translocations result in the contiguous gene syndrome ATR-16. In this complex syndrome α-thalassaemia is accompanied by mental retardation and variable dismorphic features. The study of mutations of the 5′ upstream flanking region has led to the discovery of a DNA sequence, localized 40 kb upstream of the ζ-globin gene, which controls the expression of the α genes (α major regulatory element or HS-40). In the acquired variant of haemoglobin H (HbH) disease found in rare individuals with myelodysplastic disorders and in the X-linked mental retardation associated with α-thalassaemia, a profound reduction or absence of α gene expression has been observed, which is not accompanied by structural alterations of the coding or controlling regions of the α gene complex. Most probably the acquired α-thalassaemia is due to the lack of soluble activators (or presence of repressors) which act in <em>trans</em> and affect the expression of the homologous clusters and are coded by genes not (closely) linked to the α genes. The ATR-X syndrome results from mutations of the XH2 gene, located on the X chromosome (Xq13.3) and coding for a transacting factor which regulates gene expression. The interaction of the different α-thalassaemia determinants results in three phenotypes: the α-thalassaemic trait, clinically silent and presenting only limited alterations of","PeriodicalId":77029,"journal":{"name":"Bailliere's clinical haematology","volume":"11 1","pages":"Pages 53-90"},"PeriodicalIF":0.0,"publicationDate":"1998-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0950-3536(98)80070-X","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21714470","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 37

5 Thalassaemia: clinical management 地中海贫血:临床管理

Bailliere's clinical haematology Pub Date : 1998-03-01 DOI: 10.1016/S0950-3536(98)80073-5

MD, FRCP(C) Nancy Olivieri (Director, Hemoglobinopathy Program)

引用次数: 29

7 Sickle cell disease: clinical management 镰状细胞病的临床管理

Bailliere's clinical haematology Pub Date : 1998-03-01 DOI: 10.1016/S0950-3536(98)80075-9

MD Samir K. Ballas

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引用次数: 56

10 Current status of stem cell therapy and prospects for gene therapy for the disorders of globin synthesis 干细胞治疗现状及基因治疗球蛋白合成障碍的前景

Bailliere's clinical haematology Pub Date : 1998-03-01 DOI: 10.1016/S0950-3536(98)80078-4

MD C. Anthony Blau (Assitant Professor of Medicine)

{"title":"10 Current status of stem cell therapy and prospects for gene therapy for the disorders of globin synthesis","authors":"MD C. Anthony Blau (Assitant Professor of Medicine)","doi":"10.1016/S0950-3536(98)80078-4","DOIUrl":"10.1016/S0950-3536(98)80078-4","url":null,"abstract":"<div><p>Sickle cell anaemia and β-thalassaemia are today curable through the use of stem cell transplantation. Nevertheless, the disadvantages inherent in stem cell transplantation underscore the need for better therapies. A recent finding of potentially major importance is that complete eradication of host haematopoiesis is not an absolute requirement for achieving therapeutic effects in thalassaemia and sickle cell anaemia. Future stem cell transplantation protocols will use less toxic conditioning regimens in an effort to achieve a state of stable mixed chimerism between donor and host haematopoietic elements. An improved understanding of globin gene regulation and stem cell biology will allow for the first gene therapy trials for sickle cell anaemia and β-thalassaemia in the relatively near future. Initial gene therapy protocols will emphasize safety, are likely to target progenitor cells, and will involve repeated cycles of mobilization, transduction and reinfusion, with little or no conditioning. These first generation gene therapy trials are unlikely to confer major therapeutic benefits, but will provide the foundation upon which subsequent, more effective protocols will be based.</p></div>","PeriodicalId":77029,"journal":{"name":"Bailliere's clinical haematology","volume":"11 1","pages":"Pages 257-275"},"PeriodicalIF":0.0,"publicationDate":"1998-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0950-3536(98)80078-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21714997","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 8

Index 指数

Bailliere's clinical haematology Pub Date : 1998-03-01 DOI: 10.1016/S0950-3536(98)80079-6

引用次数: 0

4 Pathophysiology of thalassaemia 4地中海贫血的病理生理

Bailliere's clinical haematology Pub Date : 1998-03-01 DOI: 10.1016/S0950-3536(98)80072-3

MD, FRCP, FRS D.J. Weatherall (Regius Professor of Medicine and Honorary Director)

引用次数: 127

8 Prenatal diagnosis and screening of the haemoglobinopathies 8血红蛋白病的产前诊断和筛查

Bailliere's clinical haematology Pub Date : 1998-03-01 DOI: 10.1016/S0950-3536(98)80076-0

MD Antonio Cao (Professor of Paediatrics, Director), MD Renzo Galanello (Associate Professor of Paediatric Haematology), PhD M. Cristina Rosatelli (Assistant Professor of Molecular Biology)

{"title":"8 Prenatal diagnosis and screening of the haemoglobinopathies","authors":"MD Antonio Cao (Professor of Paediatrics, Director), MD Renzo Galanello (Associate Professor of Paediatric Haematology), PhD M. Cristina Rosatelli (Assistant Professor of Molecular Biology)","doi":"10.1016/S0950-3536(98)80076-0","DOIUrl":"10.1016/S0950-3536(98)80076-0","url":null,"abstract":"<div><p>This paper reviews the most important aspects of carrier detection procedures, genetic counselling, population screening and prenatal diagnosis of the thalassaemias and sickle cell anaemia. Carrier detection can be made retrospectively, following the birth of an affected child, or prospectively. Carrier detection and genetic counselling in at-risk populations for α-thalassaemia and sickle cell anaemia is carried out mostly retro-spectively. However prospective carrier screening is ongoing in Cuba and Guadeloupe for sickle cell anaemia and, in a very limited way, in some South East Asian populations, for α-thalassaemia. For β-thalassaemia, several programmes, based on carrier screening and counselling of couples at marriage, preconception or early pregnancy, are operating in several Mediterranean at-risk populations. These programmes have been very effective, as indicated by increasing knowledge on thalassaemia and its prevention by the target population and by the marked decline of the incidence of thalassaemia major. Carrier detection is carried out by haematological methods followed by mutation detection by DNA analysis. Prenatal diagnosis is accomplished by mutation analysis on PCR-amplified DNA from chorionic villi. Future prospects include automation of the process of mutation-detection, simplification of preconception and preimplantation diagnosis and fetal diagnosis by analysis of fetal cells in maternal circulation.</p></div>","PeriodicalId":77029,"journal":{"name":"Bailliere's clinical haematology","volume":"11 1","pages":"Pages 215-238"},"PeriodicalIF":0.0,"publicationDate":"1998-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0950-3536(98)80076-0","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"21714476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 68