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- Bolton, W K, et al.
(author)
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Epitope spreading and autoimmune glomerulonephritis in rats induced by a T cell epitope of Goodpasture's antigen
- 2005
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In: Journal of the American Society of Nephrology. - 1046-6673. ; 16:9, s. 2657-2666
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Journal article (peer-reviewed)abstract
- An amino-terminal region of a, chain of type IV collagen noncollagenous domain [alpha(3)(IV)NC1] that induces experimental autoimmune glomerulortephritis (EAG) in rats has been identified. Only recombinant antigens that contain a nine-amino acid (AA) span of alpha(3)(IV)NC1, consistent with a T cell epitope, could induce EAG. It was hypothesized that synthetic peptides of this region should induce EAG. Human and rat peptides of this region were synthesized and rats were immunized to define the nephritogenic epitope. A 13-AA rat peptide induced EAG with proteinuria, decreased renal function, and glomerular basement membrane (GBM)-bound deposits in half of the rats. This peptide induces lymph node cell proliferation and development of antibodies to epitopes of alpha(3)(IV)NC1 external to the peptide immunogen. Carboxy-terminal extension to 21 amino acids results in all rats' demonstrating anti-GBM antibody and severe EAG. Asparagine at position 19 is critical for EAG induction. None of the 50 rats that were immunized with peptide that contained human sequence with isoleucine at position 19 developed EAG, whereas rat sequence with asparagine 19 induced EAG. Truncation of amino terminal AA of the peptide aborts EAG induction. These studies demonstrate that a T cell epitope of alpha(3)(IV)NC1 induces lymph node cell proliferation, EAG, and intramolecular epitope spreading; that the length of this peptide influences the formation of anti-GBM antibody; and that the presence of asparagine at position 19 of the peptide is critical to disease induction.
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- Killander, F, et al.
(author)
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No increased cardiac mortality or morbidity of radiotherapy in breast cancer patients after breast conserving surgery: 20 years follow-up of the randomised x trial.
- 2020
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In: International journal of radiation oncology, biology, physics. - : Elsevier BV. - 1879-355X .- 0360-3016. ; 107:4, s. 701-9
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Journal article (peer-reviewed)abstract
- Radiotherapy (RT) after breast conserving surgery reduces loco-regional recurrences and improves survival, but may cause late side effects. The main purpose of this paper was to investigate long-term side effects after whole breast RT in a randomised clinical trial initiated in 1991 and to report dose-volume data based on individual 3D treatment plans for organs at risk (OR).The trial included 1187 T1-2 N0 breast cancer patients randomised to postoperative tangential whole breast radiotherapy or no further treatment. The prescription dose to the clinical target volume was 48-54 Gy. We present 20 year follow-up on survival, cause of death, morbidity and later malignancies. For a cohort of patients (n=157) with accessible CT-based 3D treatment plans in Dicom-RT format, dose-volume descriptors for OR were derived. In addition, these were compared with dose-volume data for a cohort of patients treated with contemporary RT techniques.The cumulative incidence of cardiac mortality was 12.4 % in the control group and 13.0 % in the RT group (P= 0.8). There was an increase in stroke mortality, 3.4 % in the control group versus 6.7 % in the RT group (P=0.018). Incidences of contra lateral breast cancer and lung cancer were similar between groups. The median Dmean (range) heart dose for left-sided treatments was 3.0 Gy (1.1-8.1) and the corresponding value for patients treated in 2017 was 1.5 Gy (0.4-6.0).In this trial serious late side effects of whole breast radiotherapy were limited and less than previously reported in large meta-analyses. We observed no increased cardiac mortality in irradiated patients with doses to the heart were median Dmean 3.0 Gy for left-sided RT. The observed increase in stroke mortality may partly be secondary to cardiac side effects, complications to anticoagulant treatment, or to chance, rather than a direct side effect of tangential whole breast irradiation.
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| 4. |
- Lebaron, Simon, et al.
(author)
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Rrp5 Binding at Multiple Sites Coordinates Pre-rRNA Processing and Assembly
- 2013
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In: Molecular Cell. - : Elsevier BV. - 1097-2765 .- 1097-4164. ; 52:5, s. 707-719
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Journal article (peer-reviewed)abstract
- In vivo UV crosslinking identified numerous preribosomal RNA (pre-rRNA) binding sites for the large, highly conserved ribosome synthesis factor Rrp5. Intramolecular complementation has shown that the C-terminal domain (CTD) of Rrp5 is required for pre-rRNA cleavage at sites A0-A2 on the pathway of 18S rRNA synthesis, whereas the N-terminal domain (NTD) is required for A3 cleavage on the pathway of 5.8S/25S rRNA synthesis. The CTD was crosslinked to sequences flanking A2 and to the snoRNAs U3, U14, snR30, and snR10, which are required for cleavage at A0-A2. The NTD was crosslinked to sequences flanking A3 and to the RNA component of ribonuclease MRP, which cleaves site A3. Rrp5 could also be directly crosslinked to several large structural proteins and nucleoside triphosphatases. A key role in coordinating preribosomal assembly and processing was confirmed by chromatin spreads. Following depletion of Rrp5, cotranscriptional cleavage was lost and preribosome compaction greatly reduced.
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| 5. |
- Maanja, M, et al.
(author)
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An electrocardiography score predicts heart failure hospitalization or death beyond that of cardiovascular magnetic resonance imaging
- 2022
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 12:1, s. 18364-
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Journal article (peer-reviewed)abstract
- The electrocardiogram (ECG) and cardiovascular magnetic resonance imaging (CMR) provide powerful prognostic information. The aim was to determine their relative prognostic value. Patients (n = 783) undergoing CMR and 12-lead ECG with a QRS duration < 120 ms were included. Prognosis scores for one-year event-free survival from hospitalization for heart failure or death were derived using continuous ECG or CMR measures, and multivariable logistic regression, and compared. Patients (median [interquartile range] age 55 [43–64] years, 44% female) had 155 events during 5.7 [4.4–6.6] years. The ECG prognosis score included (1) frontal plane QRS-T angle, and (2) heart rate corrected QT duration (QTc) (log-rank 55). The CMR prognosis score included (1) global longitudinal strain, and (2) extracellular volume fraction (log-rank 85). The combination of positive scores for both ECG and CMR yielded the highest prognostic value (log-rank 105). Multivariable analysis showed an association with outcomes for both the ECG prognosis score (log-rank 8.4, hazard ratio [95% confidence interval] 1.29 [1.09–1.54]) and the CMR prognosis score (log-rank 47, hazard ratio 1.90 [1.58–2.28]). An ECG prognosis score predicted outcomes independently of CMR. Combining the results of ECG and CMR using both prognosis scores improved the overall prognostic performance.
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| 8. |
- Arvestad, Lars, et al.
(author)
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Expressed sequence tags from the midgut and an epithelial cell line of Chironomus tentans : annotation, bioinformatic classification of unknown transcripts and analysis of expression levels
- 2005
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In: Insect molecular biology (Print). - : Wiley. - 0962-1075 .- 1365-2583. ; 14:6, s. 689-695
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Journal article (peer-reviewed)abstract
- Expressed sequence tags (ESTs) were generated from two Chironomus tentans cDNA libraries, constructed from an embryo epithelial cell line and from larva midgut tissue. 8584 5'-end ESTs were generated and assembled into 3110 tentative unique transcripts, providing the largest contribution of C. tentans sequences to public databases to date. Annotation using BLAST gave 1975 (63.5%) transcripts with a significant match in the major gene/protein databases, 1170 with a best match to Anopheles gambiae and 480 to Drosophila melanogaster. 1091 transcripts (35.1%) had no match to any database. Studies of open reading frames suggest that at least 323 of these contain a coding sequence, indicating that a large proportion of the genes in C. tentans belong to previously unknown gene families.
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| 9. |
- Bauren, G, et al.
(author)
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Demonstration of a dynamic, transcription-dependent organization of pre-mRNA splicing factors in polytene nuclei
- 1996
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In: The Journal of cell biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 133:5, s. 929-941
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Journal article (peer-reviewed)abstract
- We describe the dynamic organization of pre-mRNA splicing factors in the intact polytene nuclei of the dipteran Chironomus tentans. The snRNPs and an SR non-snRNP splicing factor are present in excess, mainly distributed throughout the interchromatin. Approximately 10% of the U2 snRNP and an SR non-snRNP splicing factor are associated with the chromosomes, highly enriched in active gene loci where they are bound to RNA. We demonstrate that the splicing factors are specifically recruited to a defined gene upon induction of transcription during physiological conditions. Concomitantly, the splicing factors leave gene loci in which transcription is turned off. We also demonstrated that upon general transcription inhibition, the splicing factors redistribute from active gene loci to the interchromatin. Our findings demonstrate the dynamic intranuclear organization of splicing factors and a tight linkage between transcription and the intranuclear organization of the splicing machinery.
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| 10. |
- Bauren, G, et al.
(author)
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Transcriptional termination in the Balbiani ring 1 gene is closely coupled to 3'-end formation and excision of the 3'-terminal intron
- 1998
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In: Genes & development. - : Cold Spring Harbor Laboratory. - 0890-9369 .- 1549-5477. ; 12:17, s. 2759-2769
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Journal article (peer-reviewed)abstract
- We have analyzed transcription termination, 3′-end formation, and excision of the 3′-terminal intron in vivo in the Balbiani ring 1 (BR1) gene and its pre-mRNA. We show that full-length RNA transcripts are evenly spaced on the gene from a position 300 bp upstream to a region 500–700 bp downstream of the polyadenylation sequence. Very few full-length transcripts and no short, cleaved, nascent transcripts could be observed downstream of this region. Pre-mRNA with 10–20 adenylate residues accumulates at the active gene and then rapidly leaves from the gene locus. Only polyadenylated pre-mRNAs could be detected in the nucleoplasm. Our results are consistent with the hypothesis that transcription termination occurs in a narrow region for the majority of transcripts, simultaneous with 3′-end formation. Excision of the 3′-terminal intron occurs before 3′-end formation in about 5% of the nascent transcripts. When transcription terminates, 3′ cleavage takes place and 10–20 adenylate residues are added, the 3′-terminal intron is excised from additionally about 75% of the pre-mRNA at the gene locus. Our data support a close temporal and spatial coupling of transcription termination and the cleavage and initial polyadenylation of 3′-end formation. Excision of the 3′-terminal intron is highly stimulated as the cleavage/polyadenylation complex assembles and 3′-end formation is initiated.
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