Polyoma BK virus (BKV) is frequently identified in the urine of bone marrow transplantation (BMT) patients with hemorrhagic cystitis (HC). However, viruria is common even in asymptomatic patients, making a direct causative role of BKV difficult to establish. This study prospectively quantified BK viruria and viremia in 50 BMT patients to define the quantitative relationship of BKV reactivation with HC. Adenovirus (ADV) was similarly quantified as a control. More than 800 patient samples were quantified for BKV VP1 gene with a real-time quantitative polymerase chain reaction. Twenty patients (40%) developed HC, 6 with gross hematuria (HC grade 2 or higher) and 14 with microscopic hematuria (HC grade 1). When compared with asymptomatic patients, patients with HC had significantly higher peak BK viruria (6 ؋ 10 12 versus 5.7 ؋ 10 7 genome copies/d, P < .001) and larger total amounts of BKV excreted during BMT (4.9 ؋ 10 13 versus 7.7 ؋ 10 8 genome copies, P < .001). There was no detectable increase in BK viremia. Binary logistic regression analysis showed that BK viruria was the only risk factor, with HC not related to age, conditioning regimen, type of BMT, and graft-versus-host disease. Furthermore, the levels of ADV viruria in patients with or without HC were similar and comparable with those of BK viruria in patients without HC, suggesting that the significant increase in BK viruria in HC patients was not due to background viral reactivation or damage to the urothelium. BK viruria was quantitatively related to the occurrence of HC after BMT. (Blood. 2001;98:1971-1978
Arsenic trioxide (As 2 O 3 ) effectively induces remissions in relapsed acute promyelocytic leukaemia (APL), but the safety of its long-term administration is unknown. The anthracycline idarubicin is highly active alone or in combination chemotherapy for the treatment of APL. To minimize arsenic exposure and based on the high sensitivity of APL cells to anthracyclines, we conducted a prospective study to evaluate induction with As 2 O 3 followed by consolidation with idarubicin in the treatment of APL in relapse. Eight patients were treated with As 2 O 3 at a daily dose of 10 mg until remission, followed by three monthly courses of idarubicin, at 6 mg/m 2 /day for 5 days in the first course and 6 mg/ m 2 /day for 2 days in the subsequent two courses. All patients achieved morphological but not molecular remission after As 2 O 3 treatment. During As 2 O 3 therapy, an increase in white cell count peaking at a median of 17 days occurred in all the cases. Serial flow cytometric analysis of apoptosis, with mitochondrial APO2.7 antigen expression and the sub-G1 cell fraction on DNA histogram as markers, showed induction of apoptosis of APL cells in vivo. With both qualitative and real-time quantitative polymerase chain reaction, all patients were shown to attain molecular remission after subsequent idarubicin treatment. With a median follow up of 13 months, seven of eight patients have remained in complete clinical remission, with six patients in molecular remission as well. One patient who was in third remission became PCR-positive after being transiently negative. One patient died from an intracranial extramedullary relapse after achieving marrow molecular remission. We conclude that As 2 O 3 induction followed by idarubicin consolidation is an effective therapy for APL in relapse. This regimen avoids the possible long-term toxicities of As 2 O 3 and mutagenicity of combination chemotherapy, a strategy that might be suitable for this potentially curable leukaemia. Am. J. Hematol. 66:274-279, 2001.
Summary" Using in situ hybridisation to detect the intracellular localisation ofmRNAs we have found that mRNAs expressed fiom intronless cDNAs of normally intronic genes are expressed well but largely retained in nuclei. The degree of nuclear retention is quite variable but in all cases addition of splichlg signals to the expression cassette are required for efficient export of the mRNAs from lmcleus to cytoplasm. In contrast mRNAs expressed from the intronless genes of hamster ]3-adrenergic receptor and human serotolfin receptor type 1A showed veJ3' little nuclear accumulation and strong expression in the cytoplasm independently of splicing signals. The data demonstrate a link between splicing and export and dissemble from the idea that splicing enhances mRNA expression by protecting nascent nuclear mRNAs fiom degradation.
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