PubMed Health⌕ Search

Biomedical subjects

K Paulsson

Publications and source records attributed to K Paulsson.

10 recordsLinked to original sources
PubMed2006

Identification of cryptic aberrations and characterization of translocation breakpoints using array CGH in high hyperdiploid childhood acute lymphoblastic leukemia.

High hyperdiploidy, characterized by non-random trisomies, is the largest cytogenetic subgroup in childhood acute lymphoblastic leukemia (ALL). It is not known whether the gained chromosomes are sufficient for leukemogenesis or if additional genetic aberrations are necessary. However, the suboptimal chromosome morphology of hyperdiploid ALLs makes detection of structural abnormalities difficult if using cytogenetic techniques; alternative methods are, therefore, needed. We performed array comparative genome hybridization (CGH) analyses, with a resolution of 100 kb, of eight cases of high hyperdiploid childhood ALL to characterize structural abnormalities found with G-banding/multicolor fluorescence in situ hybridization (FISH) and to detect novel changes. The non-centromeric breakpoints of four rearrangements, including three translocations and one 1q duplication, were narrowed down to <0.2 Mb. Furthermore, four submicroscopic imbalances involving 0.6-2.7 Mb were detected, comprising two segmental duplications involving 1q22 and 12q24.31 in one case and two hemizygous deletions in 12p13.2-31 - including ETV6 - and in 13q32.3-33.1 in another case. Notably, FISH analysis of the latter revealed an associated reciprocal t(3;13)(q?;32.2-33.1). In conclusion, the array CGH analyses revealed putative leukemia-associated submicroscopic imbalances and rearrangements in 2/8 (25%) hyperdiploid ALLs. The detection and characterization of these additional genetic aberrations will most likely increase our understanding of the pathogenesis of high hyperdiploid childhood ALL.

Adolescent↗
PubMed2006

Trisomy 8 as the sole chromosomal aberration in acute myeloid leukemia and myelodysplastic syndromes.

Trisomy 8 as the sole abnormality is the most common karyotypic finding in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), occurring in approximately 5% and 10% of the cytogenetically abnormal cases, respectively. However, despite the high frequency of +8, much remains to be elucidated as regards its epidemiology, etiology, clinical impact, association with other chromosomal abnormalities, cell of origin, and functional and pathogenetic consequences. Here, we summarize and review these various aspects of trisomy 8, focusing on AMLs and MDS harboring this abnormality as a single change.

Acute Disease↗
PubMed2006

A novel and cytogenetically cryptic t(7;21)(p22;q22) in acute myeloid leukemia results in fusion of RUNX1 with the ubiquitin-specific protease gene USP42.

Although many of the chromosomal abnormalities in hematologic malignancies are identifiable cytogenetically, some are only detectable using molecular methods. We describe a novel cryptic t(7;21)(p22;q22) in acute myeloid leukemia (AML). FISH, 3'RACE, and RT-PCR revealed a fusion involving RUNX1 and the ubiquitin-specific protease (USP) gene USP42. The genomic breakpoint was in intron 7 of RUNX1 and intron 1 of USP42. The reciprocal chimera was not detected - neither on the transcriptional nor on the genomic level - and FISH showed that the 5' part of USP42 was deleted. USP42 maps to a 7p22 region characterized by segmental duplications. Notably, 17 kb duplicons are present 1 Mb proximal to USP42 and 3 Mb proximal to RUNX1; these may be important in the genesis of t(7;21). This is the second cryptic RUNX1 translocation in hematologic malignancies and the first in AML. The USPs have not previously been reported to be rearranged in leukemias. The cellular context in which USP42 is active is unknown, but we here show that it is expressed in normal bone marrow, in primary AMLs, and in cancer cell lines. Its involvement in the t(7;21) suggests that deregulation of ubiquitin-associated pathways may be pathogenetically important in AML.

Acute Disease↗
PubMed2006

High-resolution genome-wide array-based comparative genome hybridization reveals cryptic chromosome changes in AML and MDS cases with trisomy 8 as the sole cytogenetic aberration.

Although trisomy 8 as the sole chromosome aberration is the most common numerical abnormality in acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS), little is known about its pathogenetic effects. Considering that +8 is a frequent secondary change in AML/MDS, cryptic--possibly primary--genetic aberrations may occur in cases with trisomy 8 as the apparently single anomaly. However, no such hidden anomalies have been reported. We performed a high-resolution genome-wide array-based comparative genome hybridization (array CGH) analysis of 10 AML/MDS cases with isolated +8, utilizing a 32K bacterial artificial chromosome array set, providing >98% coverage of the genome with a resolution of 100 kb. Array CGH revealed intrachromosomal imbalances, not corresponding to known genomic copy number polymorphisms, in 4/10 cases, comprising nine duplications and hemizygous deletions ranging in size from 0.5 to 2.2 Mb. A 1.8 Mb deletion at 7p14.1, which had occurred prior to the +8, was identified in MDS transforming to AML. Furthermore, a deletion including ETV6 was present in one case. The remaining seven imbalances involved more than 40 genes. The present results show that cryptic genetic abnormalities are frequent in trisomy 8-positive AML/MDS cases and that +8 as the sole cytogenetic aberration is not always the primary genetic event.

Acute Disease↗
PubMed2001

The incidence of trisomy 8 as a sole chromosomal aberration in myeloid malignancies varies in relation to gender, age, prior iatrogenic genotoxic exposure, and morphology.

Although trisomy 8 as a sole change is one of the most common chromosomal abnormalities in myeloid malignancies, it is largely unknown if the incidence of this aberration is influenced by other factors of clinical importance. In the present study, the frequencies of isolated +8 in relation to gender, age, previous treatment with chemo- or radiotherapy, and morphologic subtype were ascertained in published, as well as in our own unpublished, cases of acute myeloid leukemia (AML; n=4,246), myelodysplastic syndromes (MDS; n=1,817), and chronic myeloproliferative disorders (MPD; n=530). The frequencies of +8 were higher in MDS and MPD than in AML (7.5% vs. 5.6%; P<0.01) and varied among the morphologic subtypes of AML and MDS (P<0.001 and P<0.05, respectively). Trisomy 8 was more common in women than in men with MPD (11% vs. 5.1%; P<0.05). Furthermore, the frequencies of +8 were higher in de novo AML and MDS than in treatment-related cases (6.0% vs. 2.8%; P<0.01 and 8.6% vs. 1.5%; P<0.001, respectively). The incidence also varied significantly with age in AML (P<0.001), being more common in elderly patients. Although the causes for this frequency heterogeneity remain to be elucidated, possible explanations may include different environmental exposures affecting the origin of +8 in AML, MDS, and MPD and the presence of different underlying cryptic primary aberrations.

Age Factors↗
PubMed1997

Experimental exposure of male volunteers to N-methyl-2-pyrrolidone (NMP): acute effects and pharmacokinetics of NMP in plasma and urine.

OBJECTIVES: To study the acute effects of exposure to the increasingly used solvent, N-methyl-2-pyrrolidone (NMP) in male volunteers. Further, to determine the NMP concentration in plasma and urine during and after the exposure. METHODS: Six male volunteers were exposed for eight hours on four different days to 0, 10, 25, and 50 mg/m3 NMP. Plasma was collected and urine was sampled during and after the exposure. Changes in nasal volume were measured by acoustic rhinometry and in airway resistance by spirometry. RESULTS: The eight-hour experimental exposure to 10, 25, and 50 mg/m3 did not induce discomfort to eyes or upper airways. Acute changes in nasal volume were not found, and no changes in the spirometric data could be registered. The elimination curves suggested a non-linear pattern and at the end of exposure showed mean (range) half lifes of NMP in plasma of about 4.0 (2.9-5.8) hours and in urine 4.5 (3.5-6.6) hours. The unmetabolised NMP found in urine samples collected during exposure and at the subsequent 44 hours corresponded to about 2% of the calculated absorbed dose. At the end of the exposure there was a close correlation between exposures and the plasma concentration and urinary excretion of NMP. CONCLUSIONS: NMP was absorbed through the respiratory tract and readily eliminated from the body, mainly by biotransformation to other compounds. Exposure to 10, 25, or 50 mg/m3 NMP did not cause nose, eye, or airway irritation. Thus, NMP is a mild irritant.

Acute Disease↗
PubMed1994

Urinary excretion of methylamines in men with varying intake of fish from the Baltic Sea.

Fish contain methylamines, especially trimethylamine N-oxide (TMAO), trimethylamine (TMA), and dimethylamine (DMA). Further, DMA may be formed TMA and TMAO. DMA is a precursor of nitrosodimethylamine (NDMA), which is a potent carcinogen. Levels of DMA, TMA, and TMAO in urine were used as indicators of the dietary exposure and in vivo formation of these amines in 44 men, representing 3 groups with different fish consumption habits. The levels of TMA (median 0.24 mmol/mol creatinine; range 0-2.7) and TMAO (median 38 mmol/mol creatinine; range 8-290) were significantly associated with the weekly intake of fish (r = .47, p = .001, and r = .53, p = .0002, respectively), while no such relation was found for DMA (median 24 mmol/mol creatinine; range 5-46). Further, urinary levels of TMA and TMAO were dependent on recent intake of fish.

Adult↗
PubMed1989

The selenium method for treatment of lakes for elevated levels of mercury in fish.

Selenium in the form of sodium selenite (Na2SeO3) incorporated in a rubber matrix was introduced into a Swedish lake which is black-listed for fishing because of high mercury levels in fish tissues. The lake is not acidified. The level of selenium in the lake was raised from 0.4 to approximately 3-5 micrograms Se l-1, and sustained at this level for a period of greater than 3 years. The mercury content of pike (Esox lucius) was found to have fallen markedly after the lake had been treated for only 1 year. The mercury content was halved over the whole weight range and stayed below the black-list limit during the treatment period. After the first year the mercury content of perch (Perca fluviatilis) muscle had also decreased. The reduction for those between 8 and 11 cm long (3-6 years old) was found to be 77%; for those between 12 and 16 cm long (7-9 years old), 65%; and for those between 17 and 25 cm long (greater than 9 years), 77%. After 2 years, the total reduction was 85% for perch 12-16 cm long and 75% for those 17-25 cm long. By the end of the third year, the mercury content had decreased by 84% in those that measured between 17 and 25 cm. The selenium treatment also resulted in a very marked decrease in the mercury content of the muscle of roach (Leuciscus rutilus). The decrease, from 0.5-1.0 to 0.06-0.08 mg Hg/kg muscle, was independent of size. The treatment of lakes with selenium has been found to be one of the few known methods of lowering the mercury content of fish quickly and easily.

Animals↗