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11.
S. L. Thein J. S. Wainscoat M. Sampietro J. M. Old D. Cappellini G. Fiorelli B. Modell D. J. Weatherall 《British journal of haematology》1987,65(3):367-373
We have identified 14 Asian patients with homozygous beta zero thalassaemia who had a mild clinical disorder related to an augmented production of haemoglobin F. None of their parents had an elevated level of Hb F. Restriction fragment length polymorphism analysis of the beta-globin cluster of these patients and a control group of Asian thalassaemia major patients showed that 6/14 of the thalassaemia intermedia patients were homozygous for a particular 5' beta-globin haplotype (-+-++), in contrast to 1/42 of the thalassaemia major patients. Furthermore, the -+-++ beta haplotype is also associated with amelioration of disease severity in beta thalassaemia in an Italian population. This beta haplotype is linked to a DNA sequence variation 5' (at position -158) to the G gamma globin gene which can be detected by the presence (+) of an Xmn I restriction enzyme site. The possible role of the Xmn I-gamma polymorphism in relation to this variant HPFH is discussed. We conclude that much of the observed clinical variability of beta thalassaemia can now be explained by the inheritance of beta thalassaemia chromosomes with different propensities for fetal haemoglobin production. 相似文献
12.
Lwin T Mra R Aye KT Oo K Thein S Moe K 《The Southeast Asian journal of tropical medicine and public health》1999,30(2):251-256
A study was conducted in the Infectious Diseases Hospital, Yangon, for one year from August 1996 to 1997, to assess the extent and the factors related to HIV transmission among sexual partners of HIV/AIDS cases. It was a cross-sectional comparative study on 67 (61 males, 6 females) HIV positive individuals with or without AIDS, and their sexual partners. Separate interviews of index cases and partners were done, and clinical examination and laboratory tests for HIV and sexually transmitted diseases (STDs) were performed. HIV transmission was found in 41.8% of the partners. Male-to-female transmission was 39.3% (n=61) and female to male transmission was 66.7% (n=6), Seven and one half percent of the partners were suffering from AIDS. There were 4 (6.6%) pregnant mothers and 1 (25%) was HIV positive. Though 75% of the partners did not use condoms during their married life, HIV transmission was significantly reduced in the condom users (odds ratio (OR) = 0.18, 95% confidence interval (CI) 0.02-0.98 p = < 0.05). The seropositive men who were less than 30 years of age had greater HIV transmission (OR = 5.67, 95% CI 1.13-36.46). However, socio-demographic factors, number of marital partners and age of first sex partners, duration of marriage, number of sexual relationships between these couples, duration of HIV positivity and AIDS infection, immunological status of the index group and STD positivity among partners had no significant association with the transmission of HIV. This study demonstrated that the transmission of HIV was high among the sexual partners of persons with HIV infection. It also highlighted the requirement of effective counseling and preventive measures against HIV infection among the couples. 相似文献
13.
The molecular basis of thalassaemia major and thalassaemia intermedia in Asian Indians: application to prenatal diagnosis 总被引:3,自引:0,他引:3
S. L. Thein C. Hesketh R. B. Wallace D. J. Weatherall 《British journal of haematology》1988,70(2):225-231
A study of the molecular pathology of beta thalassaemia in the Asian Indian immigrant population in the U.K. included 37 patients with thalassaemia major and 14 with thalassaemia intermedia. Using a combination of oligonucleotide probe hybridization and restriction endonuclease analysis the mutations in 100/102 (98%) of the beta thalassaemia genes were characterized. Nine different types were found, of which six are associated with beta zero, one with severe beta+ and two with mild beta+ thalassaemia. Comparison of the beta-globin gene cluster haplotypes, alpha globin genotypes and beta gene mutations of the thalassaemia major group with the thalassaemia intermedia group suggests that the co-inheritance of a high Hb F determinant associated with the - + - + + 5' beta haplotype and the inheritance of a mild beta-thalassaemia mutation are the major ameliorating factors of disease severity in Asian Indians. In comparison with other population groups. beta thalassaemia in Asian Indians is not associated with one or two predominant mutations. Despite this, prenatal diagnosis by direct detection is possible in the majority of families by restriction analysis and a limited number of oligonucleotide probes since the majority of severely affected individuals are homozygous for a single mutation. The characterization of these mutations should be useful for the planning of prenatal diagnosis programmes for beta thalassaemia in other Asian Indian communities. 相似文献
14.
Background:
Chondral lesions of the knee are commonly found during arthroscopic partial meniscectomy. The literature advises against arthroscopic medial meniscectomy in the presence of advanced chondral derangement because of unfavorable outcome. Recent studies have shown an association between obesity and chondropathy in patients with meniscal tears. The aim of this study was to assess whether body mass index (BMI) correlates with the severity of chondral lesions in patients with isolated medial meniscus tears (i.e. without ligamentous or lateral meniscal injury).Materials and Methods:
837 knee arthroscopies were performed in a regional referral center of arthroscopic surgery between January 2011 and December 2012. Of these 168 (109 males, 59 females) patients with no axial knee deformity and no radiological signs of osteoarthritis who have had arthroscopic debridement for isolated torn medial meniscus were included in the study. The correlation between different demographic factors and the level of chondral damage reported at surgery was evaluated. The mean age of patient was 50 years (range 13-82 years) and an average BMI was 28.2 kg/m2 (range17.5-42.5 kg/m2).Results:
Overall, regression analysis showed both age and BMI to be linearly correlated to chondral score (r = 0.53, P < 0.04); however, there were no advanced chondral lesions found in patients younger than 40 years of age and all severe lesions were at age 50 years or more. Therefore, further analysis was performed for age subgroups: patients were grouped as younger than 40, between the age of 40 and 50 (middle age) and older than 50 years. The BMI was linearly correlated to the severity of chondral score exclusively in the middle aged group (i.e. 40-50 years old). There was no correlation between activity level and chondral damage. Women had worse chondral lesions than men in all age groups.Conclusion:
Higher BMI in middle aged patients with isolated medial meniscus tears and unremarkable radiographs may predict more advanced chondral lesions at arthroscopy. 相似文献15.
Analysis of the human alpha-globin gene cluster reveals a highly informative genetic locus. 总被引:31,自引:1,他引:31
D R Higgs J S Wainscoat J Flint A V Hill S L Thein R D Nicholls H Teal H Ayyub T E Peto A G Falusi et al. 《Proceedings of the National Academy of Sciences of the United States of America》1986,83(14):5165-5169
Extensive molecular studies have characterized 15 dimorphic and 2 multiallelic genetic markers within the human alpha-globin gene cluster. Analysis of these markers in 9 populations has shown that the alpha-globin locus is remarkably polymorphic and is therefore an ideal marker on chromosome 16 for the construction of a human genetic linkage map. The combined analysis of 9 polymorphic markers has established alpha-globin haplotypes that provide the means to study the molecular genetics and common mutants of this cluster. The novel association of a conventional restriction fragment length polymorphism haplotype and linked, hypervariable regions of DNA should allow a comparison of the rate of change of such markers. 相似文献
16.
Pullarkat VA Bueso-Ramos C Lai R Kroft S Wilson CS Pullarkat ST Bu X Thein M Lee M Brynes RK 《American journal of hematology》2003,73(1):12-17
The majority of patients with systemic mastocytosis with associated clonal, hematological non-mast cell lineage disease (SM-AHNMD) have a myeloid stem cell malignancy including myelodysplastic syndromes (MDS), myelodysplastic/myeloproliferative disorders, acute myeloid leukemia (AML), or chronic myeloproliferative disease. The clinicopathologic features of SM-AHNMD have not been fully characterized. We describe seven cases of this entity: 3 with MDS, 3 with AML, and 1 with chronic myelomonocytic leukemia. In the majority of cases, SM was diagnosed concurrently with the myeloid malignancy and aberrant mast cell morphology was observed. The commonly described c-kit enzymatic site mutation Asp816Val was detected only in 2 cases, while 3 patients carried the Asp816His mutation. Among the 3 cases with AML, 2 patients carried the translocation t(8;21). On the basis of our results and other reported cases, there appears to be a specific association between SM and AML with t(8;21). Concurrent occurrence of SM may define a subset of patients with de novo AML and other myeloid malignancies who have an adverse prognosis. As clinically effective tyrosine kinase inhibitors that inhibit enzymatic-type c-kit mutations are being developed, detection of mast cell proliferation associated with myeloid malignancy may have important therapeutic implications. 相似文献
17.
J. Rochette R. Barnetson L. Kiger J. Kister T. J. Littlewood R. Webster C. Poyart S. L. Thein 《British journal of haematology》1994,86(1):118-124
We report an uncommon association of δβ thalassaemia and a haemoglobin (Hb) variant with high oxygen affinity in an Asian Indian family. Minimal polycythaemia was seen in a heterozygote for this novel Hb variant, Hb Headington (β72 (E16) Ser→Arg), while compound heterozygosity for Hb Headington and the Indian G γ (A γδβ) thalassaemia produces a marked increase in erythrocytosis with a concomitant increase in the level of the variant Hb. The HbF in such compound heterozygotes remains at a level consistent with that usually observed in individuals heterozygous for the G γ (A γδβ)° thalassaemia alone. The purified Hb variant showed an increased oxygen affinity, moderately decreased co-operativity and a normal Bohr effect. Results of functional studies suggest that the high oxygen affinity of Hb Headington is due to the Ser→Arg substitution which disrupts the normal and tight interaction between A. B and E helices leading to a destabilization of the T deoxy-structure of the abnormal haemoglobin. 相似文献
18.
Stephan Menzel Helen Rooks Diana Zelenika Siana N. Mtatiro Akshala Gnanakulasekaran Emma Drasar Sharon Cox Li Liu Mariam Masood Nicholas Silver Chad Garner Nisha Vasavda Jo Howard Julie Makani Adekunle Adekile Betty Pace Tim Spector Martin Farrall Mark Lathrop Swee Lay Thein 《Annals of human genetics》2014,78(6):434-451
19.
Rooks H Clark B Best S Rushton P Oakley M Thein OS Cuthbert AC Britland A Ruf A Thein SL 《Blood cells, molecules & diseases》2012,49(3-4):121-127
We describe a novel deletion causing εγδβ thalassemia in a Pakistani family. The Pakistani deletion is 506kb in length, and the second largest εγδβ thalassemia deletion reported to date. It removes the entire β globin gene (HBB) cluster, extending from 431kb upstream to 75kb downstream of the ε globin gene (HBE). The breakpoint junction occurred within a 160bp palindrome embedded in LINE/LTR repeats, and contained a short (9bp) region of direct homology which may have contributed to the recombination event. Characterization of the deletion breakpoints has been particularly challenging due to the complexity of DNA deletion, insertion and inversion, involving a multitude of methodologies, mirroring the changing DNA analysis technologies. 相似文献
20.
Arne J. Venjakob Stephan Vogt Klaus Stöckl Thomas Tischer Philipp J. Jost Eckart Thein Andreas B. Imhoff Hermann Anetzberger 《Journal of orthopaedic research》2013,31(11):1820-1827
Local cooling is very common after bone and joint surgery. Therefore the knowledge of bone blood flow during local cooling is of substantial interest. Previous studies revealed that hypothermia leads to vasoconstriction followed by decreased blood flow levels. The aim of this study was to characterize if local cooling is capable of inducing reduced blood flow in bone tissue using a stepwise‐reduced temperature protocol in experimental rabbits. To examine bone blood flow we utilized the fluorescent microsphere (FM) method. In New Zealand white rabbits one randomly chosen hind limb was cooled stepwise from 32 to 2°C, whereas the contra lateral hind limb served as control. Injection of microspheres was performed after stabilization of bone and muscle temperature at each temperature level. Bones were removed, dissected and fluorescence intensity was determined to calculate blood flow values. We found that blood flow of all cooled regions decreased relative to the applied external temperature. At maximum cooling blood flow was almost completely disrupted, indicating local cooling as powerful regulatory mechanism for regional bone blood flow (RBBF). Postoperative cooling therefore may lead to strongly decreased bone blood flow values. As a result external cooling has capacity to both diminish bone healing and reduce bleeding complications. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 31:1820–1827, 2013 相似文献