| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
- Vergouwen, Daphne P. C., et al.
(författare)
-
The enigma of sclera-specific autoimmunity in scleritis
- 2024
-
Ingår i: Journal of Autoimmunity. - : Elsevier. - 0896-8411 .- 1095-9157. ; 144
-
Tidskriftsartikel (refereegranskat)abstract
- Scleritis is a severe and painful ophthalmic disorder, in which a pathogenic role for collagen-directed autoimmunity was repeatedly suggested. We evaluated the presence of sclera-specific antibodies in a large cohort of patients with non-infectious scleritis. Therefore, we prospectively collected serum samples from 121 patients with non-infectious scleritis in a multicenter cohort study in the Netherlands. In addition, healthy (n = 39) and uveitis controls (n = 48) were included. Serum samples were tested for anti-native human type II collagen antibodies using a validated enzyme-linked immunosorbent assay (ELISA). Further, sclera-specific antibodies were determined using indirect immunofluorescence (IIF) on primate retinal/scleral cryosections. Lastly, human leukocyte antigen (HLA) typing was performed in 111 patients with scleritis. Anti-type II collagen antibodies were found in 13% of scleritis patients, in 10% of healthy controls and in 11% of uveitis controls (p = 0.91). A specific reaction to scleral nerve tissue on IIF was observed in 33% of patients with scleritis, which was higher than in healthy controls (11%; p = 0.01), but similar to uveitis controls (25%; p = 0.36). Reactivity to the scleral nerve tissue was significantly associated with earlier onset of scleritis (48 versus 56 years; p < 0.001), bilateral involvement (65% versus 42%; p = 0.01), and less frequent development of scleral necrosis (5% versus 22%; p = 0.02). HLA-B27 was found to be twice as prevalent in patients with scleritis (15.3%) compared to a healthy population (7.2%). In conclusion, scleral nerve autoantibody reactivity was more common in scleritis and uveitis patients in contrast to healthy controls. Further research is needed to characterize these scleral-nerve directed antibodies and assess their clinical value.
|
|
| 6. |
- Halama, R., et al.
(författare)
-
Boron isotope record of peak metamorphic ultrahigh-pressure and retrograde fluid-rock interaction in white mica (Lago di Cignana, Western Alps)
- 2020
-
Ingår i: Contributions to Mineralogy and Petrology. - : Springer Science and Business Media LLC. - 0010-7999 .- 1432-0967. ; 175:3
-
Tidskriftsartikel (refereegranskat)abstract
- This study presents boron (B) concentration and isotope data for white mica from (ultra)high-pressure (UHP), subduction-related metamorphic rocks from Lago di Cignana (Western Alps, Italy). These rocks are of specific geological interest, because they comprise the most deeply subducted rocks of oceanic origin worldwide. Boron geochemistry can track fluid-rock interaction during their metamorphic evolution and provide important insights into mass transfer processes in subduction zones. The highest B contents (up to 345 mu g/g B) occur in peak metamorphic phengite from a garnet-phengite quartzite. The B isotopic composition is variable (delta B-11 = - 10.3 to - 3.6%) and correlates positively with B concentrations. Based on similar textures and major element mica composition, neither textural differences, prograde growth zoning, diffusion nor a retrograde overprint can explain this correlation. Modelling shows that B devolatilization during metamorphism can explain the general trend, but fails to account for the wide compositional and isotopic variability in a single, well-equilibrated sample. We, therefore, argue that this trend represents fluid-rock interaction during peak metamorphic conditions. This interpretation is supported by fluid-rock interaction modelling of boron leaching and boron addition that can successfully reproduce the observed spread in delta B-11 and [B]. Taking into account the local availability of serpentinites as potential source rocks of the fluids, the temperatures reached during peak metamorphism that allow for serpentine dehydration, and the high positive delta B-11 values (delta B-11 = 20 +/- 5) modelled for the fluids, an influx of serpentinite-derived fluid appears likely. Paragonite in lawsonite pseudomorphs in an eclogite and phengite from a retrogressed metabasite have B contents between 12 and 68 mu g/g and delta B-11 values that cluster around 0% (delta B-11 = - 5.0 to + 3.5). White mica in both samples is related to distinct stages of retrograde metamorphism during exhumation of the rocks. The variable B geochemistry can be successfully modelled as fluid-rock interaction with low-to-moderate (< 3) fluid/rock ratios, where mica equilibrates with a fluid into which B preferentially partitions, causing leaching of B from the rock. The metamorphic rocks from Lago di Cignana show variable retention of B in white mica during subduction-related metamorphism and exhumation. The variability in the B geochemical signature in white mica is significant and enhances our understanding of metamorphic processes and their role in element transfer in subduction zones.
|
|
| 7. |
- Hellgren, LS, et al.
(författare)
-
Nuclear-specific accumulation of telomerase reverse transcriptase (TERT) mRNA in TERT promoter mutated follicular thyroid tumours visualised by in situ hybridisation: a possible clinical screening tool?
- 2022
-
Ingår i: Journal of clinical pathology. - : BMJ. - 1472-4146 .- 0021-9746. ; 75:10, s. 658-662
-
Tidskriftsartikel (refereegranskat)abstract
- Upregulation of the telomerase reverse transcriptase (TERT) gene is a frequent finding in follicular thyroid carcinomas (FTCs) with metastatic features. The augmented expression is usually caused by TERT promoter mutations. As TERT protein immunohistochemistry might not correlate to TERT mRNA levels in follicular thyroid tumours, we therefore sought to determine if visualisation of TERT mRNA through in situ hybridisation could highlight high-risk cases.MethodsWe collected formalin-fixated paraffin-embedded tissues from 26 follicular thyroid tumours; 7 FTCs, 2 follicular thyroid tumours of uncertain malignant potential (FT-UMPs) and a single Hürthle cell carcinoma with established TERT promoter mutations and gene expression, as well as 16 FTCs with no TERT gene aberrancy or gene expression, and assessed them using RNA Scope in situ hybridisation (ISH) and TERT probes targeting the two main TERT transcripts (TERT1 and TERT2).ResultsTERT 1 and/or 2 mRNA was found by ISH in 8/10 cases with established promoter mutations and mRNA expression, whereas all 16 cases without TERT gene aberrancies or gene expression were negative (Fisher’s exact p<0.001). Strikingly, TERT mRNA was visualised in the nuclear compartment only, thereby corroborating earlier studies suggesting a non-conventional role for TERT in tumour biology. Moreover, TERT mRNA expression was scattered across the tissue sections and only found in a few percentages of tumour nuclei.ConclusionsTERT mRNA seems to be focally expressed and localised exclusively to the nucleus in TERT promoter mutated follicular thyroid tumours, possibly reflecting a true biological and unorthodox phenomenon worthy of further investigations.
|
|
| 8. |
- Hellgren, LS, et al.
(författare)
-
Prognostic Utility of the Ki-67 Labeling Index in Follicular Thyroid Tumors: a 20-Year Experience from a Tertiary Thyroid Center
- 2022
-
Ingår i: Endocrine pathology. - : Springer Science and Business Media LLC. - 1559-0097 .- 1046-3976. ; 33:2, s. 231-242
-
Tidskriftsartikel (refereegranskat)abstract
- Follicular thyroid tumors pose a diagnostic challenge on the preoperative level, as the discrimination between follicular thyroid carcinoma (FTC) and adenoma (FTA) demands careful histopathological investigation. Moreover, prognostication of FTCs is mostly based on tumor size and extent of invasive properties, while immunohistochemical markers pinpointing high-risk cases are lacking. We have routinely established a Ki-67 labeling index for follicular thyroid tumors since 1999. To assess the potential value of Ki-67 as an adjunct tool to (1) correctly separate FTCs from FTAs and (2) help identify poor-prognosis FTCs, we collected histopathological and clinical data from 818 follicular thyroid tumors with a histological Ki-67 labeling index established in clinical routine practice (516 FTAs, 252 FTCs, and 50 follicular thyroid tumors of uncertain malignant potential (FT-UMPs)). The Ki-67 labeling index was higher in FTCs (mean 5.8%) than in FTAs (mean 2.6%) (P < 0.001), and a receiver operating characteristic curve analysis revealed a cut-off value of 4% to separate FTC from FTA with a sensitivity and specificity of 65% and 83%, respectively. Similarly, a Ki-67 labeling index above 4% was found to identify FTCs that later metastasized from clinically indolent FTCs with a sensitivity and specificity of 80% and 48%, respectively. Ki-67 constituted an independent predictor of future FTC metastases/recurrence and death of disease, and a value > 4% was a reliable prognostic marker within individual pT staging groups. We conclude that Ki-67 is a potentially valuable marker for the prognostication of FTCs, and future implementation in the histopathological assessments of follicular thyroid tumors could be beneficial if reproduced in international series.
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
