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A Villegas JA Mu?oz CF Risue?o JM Castro J Sánchez P Ropero FA González 《Canadian Metallurgical Quarterly》1997,108(20):781-783
We describe the haematological data and molecular results of a native family from Cádiz in that one is produced the a within heterozygous beta 0 thalassaemia (IVS-1, nt 1-G-->A), heterozygous alpha+ thalassaemia (-alpha 3.7) and alpha gene triplication (alpha alpha alpha 3.7). PATIENTS AND METHODS) We are studied 7 members to a family composed by father (I1), mother (I2) and five children (II1, II2, II3, II4, II5). The molecular biology study of the alpha gene was realized by Southern blot method using the restriction enzymes Bam HI, Bgl II and Eco RI and hybridized with alpha probe of the plasmid PRB 1 (fragment of 1.5 Kb digested with the enzyme Pst I). The genes were studied by the technique of the polymerase chain reaction (PCR), modified according to designated method "Amplification Refractory Mutation System" (ARMS). RESULTS: The father (I1) presents an interaction of therozygous beta 0 thalassaemia with heterozygous alpha + thalassaemia (beta 0/beta 1;alpha alpha/-alpha 3). The mother (I2) shows an alpha gene triplication (beta A/beta A: alpha alpha alpha 3.7/alpha alpha). Finally the children are expressed 5 possibilities: II4 he is normal (beta A/beta A; alpha alpha/alpha alpha), II2 he has alpha gene triplication (beta A/beta A; alpha alpha/alpha alpha alpha 3.7), II3 he has heterozygous beta 0 thalassaemia (beta 0/beta A; alpha alpha/alpha alpha), II5 he has interaction between heterozygous beta 0 thalassaemia and heterozygous alpha gene triplication (beta 0/beta A; alpha alpha alpha 3.7/alpha alpha) and II1 presents an interaction between a heterozygous beta 0 thalassaemia and together with the lost of one alpha gene in one chromosome he also presents a alpha gene triplication in other one (beta o/beta A; alpha alpha/alpha alpha). The hematological data of II5 corresponds to a intermediate thalassemia with not transfusion dependent feature an opposite to II1 that presents a heterozygous thalassemic trait features with 4 alpha genes. DISCUSSION: The phenotypical expression of the different interactions of these mutations in this family, points out, the relevant role that the unbalance globins chains plays in the pathogenesis and development of the clinical manifestations of the patients with the thalassaemia syndromes. 相似文献
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PC Giordano CL Harteveld HL Haak D Batelaan P van Delft RJ Plug M Emonts R Zanardini LF Bernini 《Canadian Metallurgical Quarterly》1998,103(2):370-376
We describe a family with beta thalassaemia, apparently not linked to the beta-globin gene cluster, in combination with alpha thalassaemia. The propositus, an adult Dutch Caucasian male, and his son presented with microcytic hypochromic parameters. Their lysates displayed the normal adult pattern on electrophoresis. The HbA2 concentration, which is usually increased in beta thalassaemia, was normal. The in vitro biosynthetic rate of the globin chains was strongly unbalanced even in the presence of a coexisting alpha-thalassaemia defect. Routine analysis of the beta genes, including the promoter region, was performed repeatedly by polymerase chain reaction (PCR), denaturing gradient gel electrophoresis (DGCE) and direct sequencing. No molecular abnormalities were detected. Large beta deletions were excluded by haplotype determination, using seven polymorphic markers distributed over an area of 50 kb, from 1 kb 5' of the epsilon gene to 4 kb 3' of the beta gene. The haplotype analysis of the beta-gene cluster revealed that the unaffected daughter had received the same beta haplotype as her beta-thalassaemic brother from their beta-thalassaemic father. These data suggest that the beta-gene cluster shared by father and son was not directly associated with a reduced beta-globin chain expression. In order to exclude the remote possibility of a beta-locus-control region (LCR) rearrangement in the paternal haplotype of the daughter, the sequence of the HS2 element was examined in the nuclear family. We compared the haematological and clinical data of this family with the data reported in the limited number of similar cases. We discuss the possibility that the mutation of a trans-acting erythroid factor(s), not linked to the beta-genes cluster, may impair the beta-gene expression of both alleles. 相似文献
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Both beta thalassaemia and HbE disease are microcytic red cell disorders. Pregnancy however induces macrocytosis which makes screening with the mean cell volume (MCV) difficult in antenatal patients. In addition, population screening for HbE has not been widely reported in the literature and the screening criteria for beta thalassaemia may not necessarily apply. A study of the value of the MCV for routine screening for both beta thalassaemia and HbE traits in 3696 antenatal patients of different gestational ages was carried out. All patients with an MCV < or = 80 fL received confirmatory tests for haemoglobinopathies. The MCV rose by only 2.0% in pregnancy. A total of 494 patients (13.4% of the general population) had an MCV < or = 80 fL. Of these microcytic patients, 11.3% (56) and 4.7% (23) were eventually confirmed to have beta thalassaemia and HbE traits respectively. The mean MCV for the 3696 antenatal patients was 87.8 fL (SD 7.5) compared to patients with beta thalassaemia and HbE traits, which were 67.5 fL (SD 4.5) and 75.7 fL (SD 4.1). HbE traits were less microcytic than beta thalassaemia traits and overlapped significantly with the general population. Beta thalassaemia trait and HbE trait detected by this screening method constituted 1.52% and 0.62% respectively of the total antenatal population screened. The MCV remains a valid screening parameter in pregnancy for beta thalassaemia trait. As for HbE trait, applying a discriminant value of 80 fL to the MCV in the population screening would miss a significant proportion of the HbE traits.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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Hemoglobin (Hb) F-Mauritius, a new A gamma chain variant, was identified from a dried blood spot collected from a heelprick during neonatal screening for the main hemoglobinopathies. This hemoglobin is the first gamma chain variant having a one residue deletion: it concerns alanine at position gamma 23. Hb F-Mauritius is therefore the counterpart of Hb Freiburg, an unstable variant of the beta chain in which the valine residue that occupies position beta 23 is deleted. The structural modification of Hb F-Mauritius was characterized by miniaturized protein chemistry methods, including sequence determination by mass spectrometry measurements. Hb Freiburg was used as a control in several experimental procedures. The hypothesis that a similar mechanism for deletion has occurred in Hb F-Mauritius and in Hb Freiburg is supported by the high percentage of homology observed between the beta and gamma globin genes. In addition, the first exon of the beta-globin has been recognized as a hotspot for deletion: several beta-thalassemic mutations, or abnormal Hbs, with deletions of short nucleotide sequences map in this region. 相似文献
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Functional human globin messenger RNA was isolated from reticulocytes of two patients with homozygous beta 0-thalassemia, three patients with sickle cell beta 0-thalassemia, and one patient doubly heterozygous for beta 0-thalassemia and hemoglobin Lepore. When incubated in the Krebs type II mouse ascites tumor-cell-free system, messenger RNA from these patients actively directed the synthesis of human beta s and/or alpha- and gamma-globin chains but failed to stimulate the synthesis of any beta A-chains, even though nonthalassemic human globin mRNA preparations consistently stimulated two to four times as much beta A- or beta S-globin chain synthesis as alpha-chain synthesis when incubated in the same system under the same conditions. These results strongly suggest that functional beta A-chain-specific globin mRNA is absent in beta 0-thalassemia. 相似文献
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PB Nakajima JP Menetski DB Roth M Gellert MJ Bosma 《Canadian Metallurgical Quarterly》1995,3(5):609-621
The T cell receptor (TCR) delta locus lies within the TCR alpha locus and is excised from the chromosome by V alpha-J alpha rearrangement. We show here that delta sequences persist in a large fraction of the DNA from mature CD4+CD8- alpha beta+ mouse thymocytes. Virtually all delta loci in these cells are rearranged and present in extrachromosomal DNA. In immature alpha beta lineage thymocytes (CD3-/loCD4+CD8+) and in CD4+CD8- alpha beta+ thymocytes expressing a transgene-encoded alpha beta receptor, rearranged delta genes are present both in chromosomal and extrachromosomal DNA. Thus, contrary to earlier proposals, commitment to the alpha beta lineage does not require recombinational silencing of the delta locus or its deletion by a site-specific mechanism prior to V alpha-J alpha rearrangement. 相似文献
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K Mizukami DR Grayson MD Ikonomovic R Sheffield DM Armstrong 《Canadian Metallurgical Quarterly》1998,56(1-2):268-272
Our work on the role of glutamate in Alzheimer's disease (AD)-related neuronal vulnerability and death provided significant insight into the potential contribution of the gamma-aminobutyric acid (GABA) neurotransmitter system as it participates in countering the neurotoxic effects of excessive glutamate receptor stimulation. Our previous studies demonstrate that beta2/3 GABAA receptor subunit immunoreactivity is relatively well preserved in hippocampi with AD pathology. To further elucidate the molecular basis for this observation, we employed in situ hybridization histochemistry to examine the levels of beta2 and beta3 receptor subunit mRNAs in the hippocampus of 19 elderly subjects presenting with a broad range of pathologic severity (i.e., Braak stage I-VI). Semi-quantitative analysis with film autoradiograms revealed that beta2 mRNA signal was highest in the granule cell layer, CA2 and CA1 subfields, while beta3 mRNA hybridization was highest in the granule cell layer, followed by CA2>/=CA3>/=CA1 regions. No significant difference in beta2 mRNA expression was detected among the pathologically mild, moderate or severe groups. In contrast, levels of beta3 mRNA in the pathologically severe group was significantly decreased compared to the mild group within all subregions examined except CA4. Our data suggest that alterations in the expression of GABAA receptor subunits in the AD hippocampus differ between specific receptor subunits with the amount of beta2 mRNA being relatively well-preserved, while beta3 mRNA levels were decreased. 相似文献
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Regulation of human globin gene expression in mouse erythroleukemia x human fibroblast hybrid cells 总被引:1,自引:0,他引:1
D Vembu NS Young M Willing E Church L Sanders-Haigh WF Anderson 《Canadian Metallurgical Quarterly》1982,8(2):163-178
A somatic cell hybrid, XX-8, was obtained from a fusion of tetraploid mouse erythroleukemia cells with human Lesch-Nyhan skin fibroblasts. This hybrid cell was previously shown (1) to produce human beta- but no human gamma-globin mRNA sequences after induction with dimethylsulfoxide. In this study we show that: (a) human beta- and gamma-globin genes are present in XX-8 cells in approximately equal numbers; (b) no human gamma-globin mRNA sequences can be detected in either the cytoplasmic or nuclear RNA fractions even with several different inducers; (c) after induction the human beta-globin gene is converted from a DNase I insensitive or closed structure to a DNase I open configuration, while the human gamma-globin gene remains closed; and (d) no human beta-globin polypeptide can be detected in the intact induced cells, indicating that fibroblast globin genes, even when induced to make mRNA in an erythroid environment, do not synthesize an RNA that is translated efficiently. 相似文献
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3' non-coding region sequences in eukaryotic messenger RNA 总被引:46,自引:0,他引:46
The sequence A-A-U-A-A-A is present in six different purified messenger RNA molecules (specifically the alpha-and beta-globulin mRNAs of rabbit and human, the immunoglobulin light chain mRNA of mouse (MOPC 21) and the ovalbumin mRNA of chicken) about 20 residues away from the 3'-terminal poly (A) sequence. In addition, a large selection of the 3' non-coding regions of rabbit and human globulin mRNAs (both the alpha and beta globin mRNAs) are 85% homologous, demonstrating that this region is significantly conserved in evolution. 相似文献
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Agonist-mediated regulation of beta2-adrenoceptors in mononuclear leukocytes has been examined at the protein but not at the mRNA level. In the present study, incubation of mononuclear leukocytes with the beta-agonist (-)-isoproterenol (10(-6) M) for up to 42 hr led to a maximum decrease in both beta2-adrenoceptor mRNA concentration and total receptor number of ca. 56 and 70%, respectively. The decrease in the mRNA level, however, was slower than for the protein level. After 4 hr of incubation with the beta-agonist, the protein level decreased to a minimum of 65% of the initial amount, while an incubation of 8 hr was necessary to reach a similar decrease in the level of mRNA (69% of the initial level). Measurements of mRNA stability revealed a reduction in the half-life of beta2-adrenoceptor mRNA from 2.7 to 1.1 hr following 4 hr of incubation with (-)-isoproterenol. Our data clearly demonstrate that treatment of human mononuclear leukocytes with (-)-isoproterenol induces a beta2-adrenoceptor down-regulation together with a slower time course of mRNA down-regulation which is partly due to a reduction of mRNA stability. 相似文献
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To determine whether the Th1 response in tuberculosis correlated with IL-12R expression, we measured expression of the IL-12R beta 1 and IL-12R beta 2 subunits, as well as IL-12R beta 2 mRNA expression in tuberculosis patients and healthy tuberculin reactors. In tuberculosis patients, IFN-gamma production by Mycobacterium tuberculosis-stimulated PBMC was reduced, the percentages of T cells expressing IL-12R beta 1 and IL-12R beta 2 were significantly decreased, and IL-12R beta 2 mRNA expression was also markedly reduced. In contrast, in pleural fluid and lymph nodes at the site of disease in tuberculosis patients, in which IFN-gamma production is enhanced, IL-12R beta 2 mRNA expression was also increased. In M. tuberculosis-stimulated peripheral blood T cells from tuberculosis patients, anti-IL-10 and anti-TGF-beta enhanced IL-12R beta 1 and IL-12R beta 2 expression, and IFN-gamma production. In M. tuberculosis-stimulated peripheral blood T cells from healthy tuberculin reactors, recombinant IL-10 and TGF-beta reduced IL-12R beta 1 and IL-12R beta 2 expression, as well as IFN-gamma production. In combination with prior studies showing increased production of TGF-beta by blood monocytes from tuberculosis patients, this suggests that increased TGF-beta production is the underlying abnormality that reduces IL-12R beta 1 and IL-12R beta 2 expression in tuberculosis. Our findings provide evidence that IL-12R expression correlates well with IFN-gamma production in human tuberculosis, and that expression of IL-12R beta 1 and IL-12R beta 2 may play a central role in mediating a protective Th1 response. 相似文献
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A 70 year old Black woman had chronic hemolytic anemia without recurrent painful crises. Hemoglobin pattern by electrophoresis was hemoglobin S (69 to 71 per cent), hemoglobin A2 (4.6 per cent) and hemoglobin F (24 to 27 per cent). No hemoglobin A was detected, and the hemoglobin F was distributed heterogeneously in the red cells. Reticulocyte alpha/nonalpha globin chain synthetic ratios were 1.44 to 1.62. Thus, the patient had a high hemoglobin F variant of S-beta zero (betao) thalassemia which has not been described previously. Her clinical course has been mild in comparison with S-betao thalassemia patients who do not have extremely elevated hemoglobin F levels. 相似文献
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H Hassoun JN Vassiliadis J Murray SJ Yi M Hanspal RE Ware SS Winter SS Chiou J Palek 《Canadian Metallurgical Quarterly》1995,96(6):2623-2629
We describe a spectrin variant characterized by a truncated beta chain and associated with hereditary spherocytosis. The clinical phenotype consists of a moderate hemolytic anemia with striking spherocytosis and mild spiculation of the red cells. We describe the biochemical characteristics of this truncated protein which constitutes only 10% of the total beta spectrin present on the membrane, resulting in spectrin deficiency. Analysis of reticulocyte cDNA revealed the deletion of exons 22 and 23. We show, using Southern blot analysis, that this truncation results from a 4.6-kb genomic deletion. To elucidate the basis for the decreased amount of the truncated protein on the membrane and the overall spectrin deficiency, we show that (a) the mutated gene is efficiently transcribed and its mRNA abundant in reticulocytes, (b) the mutant protein is normally synthesized in erythroid progenitor cells, (c) the stability of the mutant protein in the cytoplasm of erythroblasts parallels that of the normal beta spectrin, and (d) the abnormal protein is inefficiently incorporated into the membrane of erythroblasts. We conclude that the truncation within the beta spectrin leads to inefficient incorporation of the mutant protein into the skeleton despite its normal synthesis and stability. We postulate that this misincorporation results from conformational changes of the beta spectrin subunit affecting the binding of the abnormal heterodimer to ankyrin, and we provide evidence based on binding assays of recombinant synthetic peptides to inside-out-vesicles to support this model. 相似文献