| 1. |
- Planck, Maria, et al.
(författare)
-
Cytogenetic aberrations and heterogeneity of mutations in repeat-containing genes in a colon carcinoma from a patient with hereditary nonpolyposis colorectal cancer.
- 2002
-
Ingår i: Cancer Genetics and Cytogenetics. - 0165-4608. ; 134:1, s. 46-54
-
Tidskriftsartikel (refereegranskat)abstract
- The majority of tumors from patients affected by hereditary nonpolyposis colorectal cancer (HNPCC) exhibit a mutator phenotype characterized by widespread microsatellite instability (MSI) and somatic mutations in repeated sequences in several cancer-associated genes. An inverse relationship between MSI and chromosomal instability (CIN) has been demonstrated and HNPCC-associated tumors are generally characterized by diploid or near-diploid cells with few or no chromosomal rearrangements. We have studied MSI, somatic mutations in repeat-containing genes, DNA-ploidy, and cytogenetic aberrations in a colon carcinoma from a patient with a germline MLH1 mutation. Mutations in coding repeats were assessed in 10 macroscopically separate areas of the primary tumor and in two lymph nodes. Some of the genes studied (E2F4, MSH3, MSH6, TCF4, and TGFBRII) showed a consistent lack of mutations, whereas others (BAX, Caspase-5 and IGFIIR) displayed alterations in some tumor regions but not in others. The tumor had DNA-index 1.1-1.2 and a stable, aberrant karyotype with extra copies of chromosomes 7 and 12 and the structural aberrations i(1q), der(20)t(8;20), and der(22)t(1;22). The finding of CIN, MSI, and somatic mutations in coding repeats in this tumor suggests that these phenomena may act together in HNPCC tumorigenesis. Furthermore, the observed intratumoral heterogeneity of mutations in coding repeats implies these changes occur late in tumorigenesis and, thus, probably play a role in tumor progression rather than initiation.
|
|
| 2. |
|
|
| 3. |
- Estberger, August, et al.
(författare)
-
Are Exercise Therapy Protocols For The Treatment of Hip-Related Pain Adequately Described? A Systematic Review of Intervention Descriptions
- 2023
-
Ingår i: International Journal of Sports Physical Therapy. - : International Journal of Sports Physical Therapy. - 2159-2896. ; 18:1, s. 38-54
-
Forskningsöversikt (refereegranskat)abstract
- Hip-related pain is an umbrella term encompassing pain from non-arthritic hip joint pathologies, such as femoroacetabular impingement syndrome, hip dysplasia, and labral tears. Exercise therapy is commonly recommended for these conditions, but the reporting completeness of these interventions is currently unclear. Purpose The aim of this systematic review was to assess the reporting completeness of exercise therapy protocols for people with hip-related pain. Study design Systematic review according to PRISMA guidelines. Materials and Methods A systematic search was conducted, searching the MEDLINE, CINAHL, and Cochrane databases. The search results were independently screened by two researchers. Inclusion criteria were studies using exercise therapy in people with non-arthritic hip-related pain. Two independent researchers used the Cochrane risk of bias tool version 2 to analyze risk of bias, and the Consensus on Exercise Reporting Template (CERT) checklist and score (1-19) to synthesize reporting completeness. Results Fifty-two studies used exercise therapy for hip-related pain, but only 23 were included in the synthesis as 29 studies had no description of the intervention. CERT scores ranged from 1 to 17 (median 12, IQR 5-15). The most well-described items were tailoring (87%), and the least well-described items were motivation strategies (9%) and starting level (13%). Studies used exercise therapy alone (n=13), or in combination with hip arthroscopy (n=10). Conclusion Only 23 of 52 eligible studies reported sufficient details to be included in the CERT synthesis. The median CERT score was 12 (IQR 5-15), with no study reaching the maximum score of 19. Lack of reporting makes it difficult to replicate interventions in future research, and to draw conclusions on efficacy and dose-response to exercise therapy for hip-related pain.
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
- Estberger, August, et al.
(författare)
-
Less hip range of motion is associated with a greater alpha angle in people with longstanding hip and groin pain
- 2021
-
Ingår i: Knee Surgery, Sports Traumatology, Arthroscopy. - : Springer Science and Business Media LLC. - 0942-2056 .- 1433-7347. ; 29:12, s. 4091-4099
-
Tidskriftsartikel (refereegranskat)abstract
- Purpose: A higher alpha angle has been proposed to correlate with lower hip range of motion, but the association in people with longstanding hip and groin pain is currently unclear. The aims were to: (1) assess the association between range of motion and alpha angle in patients with longstanding hip and groin pain; (2) examine if a cut-off value in range of motion variables could identify patients with an alpha angle above or below 60°. Methods: Seventy-two participants were consecutively recruited from an orthopaedic department after referral for hip- and groin-related pain. Passive hip range of motion was measured in flexion, internal rotation with 90° hip flexion, internal rotation in neutral hip position, external rotation with 90° hip flexion, and abduction. The alpha angle was calculated from a frog-leg lateral radiograph. Linear regression examined the association between range of motion and alpha angle, and an ROC-curve analysis was performed to identify the sensitivity and specificity of range of motion cut-offs. Results: Lower range of motion in internal rotation in flexion, external rotation, and abduction were associated with higher alpha angle. Internal rotation of 27° or less displayed good sensitivity (81%) and specificity (85%) to detect an alpha angle above 60°, while a cut-off of 41° in external rotation and 27° in abduction showed a sensitivity of 72% and specificity of 50% and 60%, respectively. Conclusion: Less internal rotation in flexion, external rotation, and abduction are associated with a greater alpha angle in a cohort of people with longstanding hip and groin pain. A cut-off of 27° in internal rotation has good sensitivity and specificity to identify people with an alpha angle above or below 60° and have the potential to be used in the clinical setting to identify patients that require further imaging, or that are unlikely to have cam morphology. Level of evidence: II.
|
|
| 7. |
- Ezzat, Kariem, et al.
(författare)
-
The viral protein corona directs viral pathogenesis and amyloid aggregation
- 2019
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
-
Tidskriftsartikel (refereegranskat)abstract
- Artificial nanoparticles accumulate a protein corona layer in biological fluids, which significantly influences their bioactivity. As nanosized obligate intracellular parasites, viruses share many biophysical properties with artificial nanoparticles in extracellular environments and here we show that respiratory syncytial virus (RSV) and herpes simplex virus type 1 (HSV-1) accumulate a rich and distinctive protein corona in different biological fluids. Moreover, we show that corona pre-coating differentially affects viral infectivity and immune cell activation. In addition, we demonstrate that viruses bind amyloidogenic peptides in their corona and catalyze amyloid formation via surface-assisted heterogeneous nucleation. Importantly, we show that HSV-1 catalyzes the aggregation of the amyloid beta-peptide (A beta(42)), a major constituent of amyloid plaques in Alzheimer's disease, in vitro and in animal models. Our results highlight the viral protein corona as an acquired structural layer that is critical for viral-host interactions and illustrate a mechanistic convergence between viral and amyloid pathologies.
|
|
| 8. |
- Gisselsson Nord, David, et al.
(författare)
-
Differentially amplified chromosome 12 sequences in low- and high-grade osteosarcoma.
- 2002
-
Ingår i: Genes, Chromosomes and Cancer. - : Wiley. - 1045-2257. ; 33:2, s. 133-140
-
Tidskriftsartikel (refereegranskat)abstract
- Most osteosarcomas are highly aggressive malignancies characterized by a complex pattern of chromosome abnormalities. However, a subgroup of low-grade, parosteal tumors exhibits a relatively simple aberration pattern dominated by ring chromosomes carrying amplified material from chromosome 12. To assess whether sequences from this chromosome were differentially amplified in low- and high-grade osteosarcomas, copy numbers of the CCND2, ETV6, KRAS2, and D12S85 regions in 12p and the MDM2 region in 12q were evaluated by interphase or metaphase fluorescence in situ hybridization (FISH) in 24 osteosarcomas. Amplification of MDM2 was detected in all five low-grade and four high-grade osteosarcomas, all of which showed ring chromosomes. An overrepresentation of 12p sequences was found in 1/5 low-grade and in 9/19 high-grade tumors. Multicolor single-copy FISH analysis of metaphase cells from six high-grade tumors showed that extra 12p material either occurred together with MDM2 in ring chromosomes or was scattered over the genome as a result of complex structural rearrangements. Most tumors (8/10) not containing amplification of the assessed chromosome 12 loci exhibited a nondiploid pattern at evaluation with probes for centromeric alpha satellite sequences. These findings indicate that gain of sequences from the short arm of chromosome 12 could be a possible genetic pathway in the development of aggressive osteosarcoma.
|
|
| 9. |
- Gisselsson Nord, David, et al.
(författare)
-
Interphase chromosomal abnormalities and mitotic missegregation of hypomethylated sequences in ICF syndrome cells
- 2005
-
Ingår i: Chromosoma. - : Springer Science and Business Media LLC. - 0009-5915 .- 1432-0886. ; 114:2, s. 118-126
-
Tidskriftsartikel (refereegranskat)abstract
- The immunodeficiency, centromeric region instability, facial anomalies (ICF) syndrome is a rare autosomal recessive disease. Usually, it is caused by mutations in the DNA methyltransferase 3B gene, which result in decreased methylation of satellite DNA in the juxtacentromeric heterochromatin at 1qh, 16qh, and 9qh. Satellite II-rich 1qh and 16qh display high frequencies of abnormalities in mitogen-stimulated ICF lymphocytes without these cells being prone to aneuploidy. Here we show that in lymphoblastoid cell lines from four ICF patients, there was increased colocalization of the hypomethylated 1qh and 16qh sequences in interphase, abnormal looping of pericentromeric DNA sequences at metaphase, formation of bridges at anaphase, chromosome 1 and 16 fragmentation at the telophase-interphase transition, and, in apoptotic cells, micronuclei with overrepresentation of chromosome 1 and 16 material. Another source of anaphase bridging in the ICF cells was random telomeric associations between chromosomes. Our results elucidate the mechanism of formation of ICF chromosome anomalies and suggest that 1qh-16qh associations in interphase can lead to disturbances of mitotic segregation, resulting in micronucleus formation and sometimes apoptosis. This can help explain why specific types of 1qh and 16qh rearrangements are not present at high frequencies in ICF lymphoid cells despite diverse 1qh and 16qh aberrations continuously being generated.
|
|
| 10. |
- Gisselsson Nord, David, et al.
(författare)
-
Locus-specific multifluor FISH analysis allows physical characterization of complex chromosome abnormalities in neoplasia
- 2000
-
Ingår i: Genes, Chromosomes and Cancer. - 1045-2257. ; 28:3, s. 347-352
-
Tidskriftsartikel (refereegranskat)abstract
- Novel techniques in molecular cytogenetics have radically improved the ability to characterize genetic changes in neoplastic cells. In parallel, a rapid development in high-throughput genomics has resulted in detailed physical maps of the human genome. Combining these two fields, we have developed a method for the simultaneous visualization of several physically defined segments along a chromosome. Seven YAC clones and one subtelomeric cosmid clone from chromosome 12 were labeled with unique combinations of four fluors and hybridized to metaphase chromosomes from neoplastic cells. In a uterine leiomyoma and a myxoid liposarcoma with translocations 12;14 and 12;16, the breakpoints in chromosome 12 could be localized to the HMGIC and CHOP regions, respectively. In the other tumors, more complex aberrations were visualized, including two inversions in 12q with a common breakpoint between MDM2 and D12S332 in a pleomorphic adenoma, amplification of MDM2 and CDK4 in ring chromosomes from a malignant fibrous histiocytoma, and amplification of KRAS2 together with other unbalanced rearrangements in two pancreatic adenocarcinomas. Combinatorially labeled single-copy probes may thus simultaneously provide physical localization of breakpoints and an overview of complex structural rearrangements.
|
|
