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71.
The objective of this study was to assess the frequency of factor VIII (FVIII) gene intron 1 and intron 22 inversions and the informativeness of polymorphic markers for the genetic diagnosis of patients with haemophilia A (HA). Fifty unrelated patients with HA were first assessed for the intron 1 and intron 22 inversion mutations. Inversion-negative families were then screened for the bi-allelic intragenic markers--intron 7 G-->A polymorphism, HindIII site in intron 19 and XbaI site in intron 22 and the multiallelic dinucleotide CA repeat alleles in introns 13 and 22. The extragenic, multiallelic VNTR DXS52 (st14) was also analysed. Intron 22 inversion mutation was found in 38% (n = 19) of all patients and 46% of those with severe HA. Intron 1 inversion was found in one (2%) patient. Of the 30 inversion-negative families, XbaI site polymorphism was the single most informative marker (70%, n = 21/30) followed by HindIII (60%, n = 18/30), intron 13 CA repeats (56.66%, n = 17/30), intron 22 CA repeats (50%, n = 15/30), DXS52 VNTR (23.33%, n = 7/30) and intron 7 G-->A polymorphism (6.66%, n = 2/30). The combined use of these markers was informative in 92% (n = 46/50) of HA families. Based on the informativeness of these markers a comprehensive algorithm has been proposed for genetic diagnosis of HA in India. 相似文献
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Structural abnormalities of the X chromosome are rarely found in neoplastic disorders. We describe three patients with a history of idiopathic acquired sideroblastic anemia (IASA); each one had an abnormal clone of cells in the bone marrow, characterized by a structurally abnormal X chromosome. In two of these patients, the predominant karyotype was 47,X,2idic(X)(q13); in the other patient, it was 46,X,t(X;11)(q13;p15). Inasmuch as all three of these cases involved chromosome band Xq13, as did two previously published cases, we suggest that band Xq13 may be more prone to structural rearrangement than other X chromosome bands in hematologic disorders. The common Xq13 chromosome breakpoint and clinical presentation (IASA) among these three patients and the occurrence of an X-linked type of sideroblastic anemia may suggest that an association exists between X chromosome abnormalities and IASA. Perhaps alteration of a gene or chromosome structure in or near band Xq13 predisposes to development of IASA. The fact that two of these patients had preleukemia and the third had overt acute leukemia may imply that patients with IASA and X chromosome abnormalities have a poor prognosis. Cases of IASA without associated X chromosome abnormalities are known; thus, if an association between IASA and an abnormal X chromosome does exist, most likely it involves only some patients with IASA. 相似文献
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Ng AC Khosla S Charatcharoenwitthaya N Kumar SK Achenbach SJ Holets MF McCready LK Melton LJ Kyle RA Rajkumar SV Drake MT 《Blood》2011,118(25):6529-6534
Recent population-based studies demonstrate an increased fracture risk with monoclonal gammopathy of undetermined significance (MGUS). The etiology of this increased risk remains unclear, however, because areal bone mineral density (aBMD) measurements by dual-energy x-ray absorptiometry cannot assess bone microstructural properties critical to determining bone quality and strength. To better define the skeletal effects of MGUS, we performed aBMD and high-resolution peripheral quantitative computed tomography volumetric bone mineral density (vBMD) measurements in 50 MGUS patients (20 females, 30 males; mean ± SEM age, 70.5 ± 1.4 years) and 100 matched control subjects. Relative to controls, MGUS patients had decreased aBMD at the femoral neck (P = .05) and total femur (P < .05) but no differences at other sites. In contrast, high-resolution peripheral quantitative computed tomography showed markedly diminished cortical thickness (P < .05) and increased endocortical area (P < .01). Average vBMD (P < .01), cortical vBMD (P < .001), and trabecular thickness (P < .01) were all significantly decreased in MGUS patients, suggestive of impaired bone formation. Serum levels of the Wnt pathway inhibitor Dickkopf-related protein 1 (P < .001) and osteoclast-activating factor MIP-1α (P < .05) also were significantly elevated in MGUS patients. Our data provide the first evidence of altered bone microstructure in MGUS and suggest that cytokines elevated in osteolytic myeloma also may be associated with bone loss in MGUS. 相似文献
78.
Thandre N Gopinath K P Lakshmi P C Shaji P C Rajalakshmi 《Indian journal of ophthalmology》2013,61(6):298-300
Ocular dirofilariasis is a zoonotic filariasis caused by nematode worm,Dirofilaria. We present a case of dirofilariasis affecting the upper eyelid in a 2-year-old child presenting as an acutely inflammed cyst, from southern Indian state of Kerala. Live adult worm was surgically removed and confirmed to be Dirofilaria repens. Live worm showing continuous movement was seen on the pre-operative high-resolution ultrasound. Ultrasound can be helpful in pre-operative identification of live worm. Imaging findings reported in literature are very few. We describe the clinical, ultrasound, and magnetic resonance imaging (MRI) findings. 相似文献
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Mohammed SI Dhawan D Abraham S Snyder PW Waters DJ Craig BA Lu M Wu L Zheng R Stewart J Knapp DW 《Molecular cancer therapeutics》2006,5(2):329-336
More than 14,000 people die from invasive transitional cell carcinoma (TCC) of the urinary bladder yearly in the United States. Cyclooxygenase (COX)-inhibiting drugs are emerging as potential antitumor agents in TCC. The optimal in vitro or in vivo systems to investigate COX inhibitor antitumor effects have not been defined. The purpose of this study was to determine COX-1 and COX-2 expression and antitumor effects of COX inhibitors in human TCC cell lines (HT1376, RT4, and UMUC3 cells) and xenografts derived from those cell lines. COX-2 expression (Western blot, immunocytochemistry) was high in HT1376, modest in RT4, and absent in UMUC3 cells in vitro. Similarly, COX-2 expression was noted in RT4 but not UMUC3 xenografts. COX-2 expression in HT1376 xenografts was slightly lower than that observed in vitro. None of four COX inhibitors evaluated (celecoxib, piroxicam, valeryl salicylate, and NS398) reduced TCC growth in standard in vitro proliferation assays at concentrations that could be safely achieved in vivo (< or =5 micromol/L). Higher celecoxib concentrations (> or =50 micromol/L) inhibited proliferation and induced apoptosis in all three cell lines. Celecoxib or piroxicam treatment in athymic mice significantly delayed progression of HT1376 xenografts, which express COX-2, but not UMUC3 xenografts that lack COX-2 expression. In conclusion, standard in vitro assays were not useful in predicting COX inhibitor antitumor effects observed in vivo. Athymic mice bearing TCC xenografts provide a useful in vivo system for COX inhibitor studies. Results of this study provide justification for further evaluation of COX inhibitors as antitumor agents against TCC. 相似文献