| 1. |
- Andersson, Anna, et al.
(författare)
-
Paired multiplex reverse-transcriptase polymerase chain reaction (PMRT-PCR) analysis as a rapid and accurate diagnostic tool for the detection of MLL fusion genes in hematologic malignancies
- 2001
-
Ingår i: Leukemia. - 1476-5551. ; 15:8, s. 1293-1293
-
Tidskriftsartikel (refereegranskat)abstract
- The MLL gene in chromosome band 11q23 is frequently rearranged in acute lymphoblastic and acute myeloid leukemias. To date, more than 50 different chromosomal regions are known to participate in translocations involving 11q23, many of which affect MLL. The pathogenetically important outcome of these rearrangements is most likely the creation of a fusion gene consisting of the 5' part of the MLL gene and the 3' end of the partner gene. Although abnormalities of the MLL gene as such are generally associated with poor survival, recent data suggest that the prognostic impact varies among the different fusion genes generated. Hence, detection of the specific chimeric gene produced is important for proper prognostication and clinical decision making. We have developed a paired multiplex reverse-transcriptase polymerase chain reaction analysis to facilitate a rapid and accurate detection of the most frequent MLL fusion genes in adult and childhood acute leukemias. To increase the specificity, two sets of primers were designed for each fusion gene, and these paired primer sets were run in parallel in two separate multiplex one-step PCR reactions. Using the described protocol, we were able to amplify successfully, in one single assay, the six clinically relevant fusion genes generated by the t(4;11)(q21;q23) [MLL/AF4], t(6;11)(q27;q23) [MLL/AF6], t(9;11)(p21-22;q23) [MLL/AF9], t(10;11)(p11-13;q23) [MLL/AF10], t(11;19)(q23;p13.1) [MLL/ELL], and t(11;19)(q23; p13.3) [MLL/ENL] in cell lines, as well as in patient material.
|
|
| 2. |
- Bergman, ASF, et al.
(författare)
-
Diltiazem infusion for renal protection in cardiac surgical patients with preexisting renal dysfunction
- 2002
-
Ingår i: Journal of Cardiothoracic and Vascular Anesthesia. - : Elsevier BV. - 1532-8422 .- 1053-0770. ; 16:3, s. 294-299
-
Tidskriftsartikel (refereegranskat)abstract
- Objective: To evaluate if the calcium channel blocker diltiazem protects postoperatively renal function in cardiac surgical patients with preexisting mild-to-moderate renal dysfunction. Design: Prospective, randomized, placebo-controlled, double-blind, clinical study. Setting: Cardiothoracic anesthesia department at a university hospital. Participants: Adult patients undergoing elective cardiac surgery using cardiopulmonary bypass, with a preoperatively elevated serum creatinine level (n = 24). Interventions: Randomized infusions of diltiazem (bolus 0.25 mg/kg followed by a continuous infusion of 1.7 pg/kg/min) (DTZ, n = 12) or placebo (C, n = 12) were started 30 minutes before induction of anesthesia and continued for 24 hours. Measurements and Main Results: Median plasma concentrations of diltiazem (DTZ group) were 79 mug/L before cardiopulmonary bypass, 67 mug/L at the end of cardiopulmonary bypass, and 164 mug/L at 24 hours postoperatively. Serum creatinine levels; on postoperative days 1, 3, and 5; and 3 weeks postoperatively were similar between groups. lohexol clearance did not differ between the groups on day 5 but was higher in the DTZ group than in the placebo group 3 weeks after surgery (median, 51 v 40 mL/min/1.73 m(2); p < 0.05). Urinary N-acetyl-β-glucosamidase concentrations were similar between the groups during the study but were increased from baseline on days 2 and 4 and 3 weeks postoperatively. Conclusion: Diltiazem can be safely used in patients who have mild-to-moderate renal dysfunction and undergo cardiac surgery using cardiopulmonary bypass. Within the limits of this study, the data suggest that addition of prophylactic diltiazem may prevent further glomerular damage resulting from cardiopulmonary bypass and may improve glomerular function 3 weeks after cardiac surgery.
|
|
| 3. |
- Gisselsson, D, et al.
(författare)
-
Abnormal nuclear shape in solid tumors reflects mitotic instability
- 2001
-
Ingår i: American Journal of Pathology. - 1525-2191. ; 158:1, s. 199-206
-
Tidskriftsartikel (refereegranskat)abstract
- Abnormalities in nuclear morphology are frequently observed in malignant tissues but the mechanisms behind these phenomena are still poorly understood. In this study, the relation between abnormal nuclear shape and chromosomal instability was explored in short-term tumor cell cultures. Mitotically unstable ring and dicentric chromosomes were identified by fluorescence in situ hybridization at metaphase and subsequently localized in interphase nuclei from five malignant soft tissue tumors. The vast majority (71 to 86%) of nuclear blebs, chromatin strings, and micronuclei contained material from the unstable chromosomes, whereas few (<11%) were positive for stable chromosomes. Nuclear morphology was also evaluated in fibroblasts and an osteosarcoma cell line exposed to irradiation. A linear correlation was found between the frequency of abnormalities in nuclear shape, on one hand, and cells with unstable chromosomes (r = 0.87) and anaphase bridge configurations (r = 0.98), on the other hand. The relation between nuclear shape and karyotypic pattern was investigated further in cultures from 58 tumors of bone, soft tissue, and epithelium. Blebs, strings, and micronuclei were significantly more frequent in tumors that contained rings, dicentrics, or telomeric associations than in those exhibiting only stable aberrations (P: < 0.001) and a positive correlation (r = 0.78) was found between the frequency of such nuclear abnormalities and the intratumor heterogeneity of structural chromosome aberrations. These results indicate that the formation of nuclear blebs, chromatin strings, and micronuclei in malignant tissues is closely related to the breakage-fusion-bridge type of mitotic disturbances. Abnormalities in nuclear shape may thus primarily be regarded as an indicator of genetic instability and intratumor heterogeneity, independent of cytogenetic complexity and the grade of malignancy.
|
|
| 4. |
- Gisselsson Nord, David, et al.
(författare)
-
Chromosomal breakage-fusion-bridge events cause genetic intratumor heterogeneity
- 2000
-
Ingår i: Proceedings of the National Academy of Sciences. - : Proceedings of the National Academy of Sciences. - 1091-6490 .- 0027-8424. ; 97:10, s. 5357-5362
-
Tidskriftsartikel (refereegranskat)abstract
- It has long been known that rearrangements of chromosomes through breakage-fusion-bridge (BFB) cycles may cause variability of phenotypic and genetic traits within a cell population. Because intercellular heterogeneity is often found in neoplastic tissues, we investigated the occurrence of BFB events in human solid tumors. Evidence of frequent BFB events was found in malignancies that showed unspecific chromosome aberrations, including ring chromosomes, dicentric chromosomes, and telomeric associations, as well as extensive intratumor heterogeneity in the pattern of structural changes but not in tumors with tumor-specific aberrations and low variability. Fluorescence in situ hybridization analysis demonstrated that chromosomes participating in anaphase bridge formation were involved in a significantly higher number of structural aberrations than other chromosomes. Tumors with BFB events showed a decreased elimination rate of unstable chromosome aberrations after irradiation compared with normal cells and other tumor cells. This result suggests that a combination of mitotically unstable chromosomes and an elevated tolerance to chromosomal damage leads to constant genomic reorganization in many malignancies, thereby providing a flexible genetic system for clonal evolution and progression.
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
