| 1. |
- Benson, Merrill D., et al.
(author)
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Tissue biopsy for the diagnosis of amyloidosis : experience from some centres
- 2022
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In: Amyloid. - : Informa UK Limited. - 1350-6129 .- 1744-2818. ; 29:1, s. 8-13
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Journal article (peer-reviewed)abstract
- A reliable diagnosis of amyloidosis is usually based on a tissue biopsy. With increasing options for specific treatments of the different amyloid diseases, an exact and valid diagnosis including determination of the biochemical fibril nature is imperative. Biopsy sites as well as amyloid typing principles vary and this paper describes methods employed at some laboratories specialised in amyloidosis in Europe, Japan and USA.
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| 2. |
- Kozian, Alf, 1969-, et al.
(author)
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Increased Alveolar Damage after Mechanical Ventilation in a Porcine Model of Thoracic Surgery
- 2010
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In: Journal of Cardiothoracic and Vascular Anesthesia. - : Elsevier BV. - 1053-0770 .- 1532-8422. ; 24:4, s. 617-623
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Journal article (peer-reviewed)abstract
- Objective: Mechanical stress during one-lung ventilation (OLV) results in lung injury. This experiment compares effects of mechanical ventilation, OLV and surgical manipulation on diffuse alveolar damage (DAD) after application of different anesthetic regimes. Design: Prospective, randomized, controlled, blinded animal experiment. Setting: University hospital. Objects: Twenty-one piglets. Interventions: Animals (27.5kg) were randomized into four groups: spontaneous breathing (SB, n=3); two-lung ventilation (TLV, n=6); OLV during desflurane (n=6) and propofol anesthesia (n=6). SB pigs were killed after induction of anesthesia. Lung tissue samples were analyzed to obtain reference values for alveolar damage. TLV pigs underwent standard TLV (VT=10ml/kg, FIO2=0.40, PEEP=5cmH2O). In OLV pigs, after lung separation by a bronchial blocker, OLV (VT=10ml/kg) and thoracic surgery were performed. After the procedure the pigs were killed. Lung tissue samples were harvested for histological examination. Lung injury was quantified by DAD score; sequestration of leukocytes was assessed by recruitment of CD45+-cells into the lungs. Main Results: TLV resulted in increased DAD scores in both lungs (TLV vs. SB: 6.9 vs. 2.7; p<0.05); the number of CD45+-cells was not increased (TLV vs. SB: 8.7 vs. 5.0 cells/view). OLV and surgical manipulation increased DAD and leukocyte sequestration without differences between the ventilated and manipulated lungs. Leukocyte recruitment was not differently affected by the anesthetic regimen (propofol vs. desflurane: CD45+-cells/view: 13.5 vs. 11.3). Conclusions: TLV resulted in increased DAD scores in the lungs as compared with SB. OLV and thoracic surgery further increased lung injury and leukocyte recruitment independently of the administration of propofol or desflurane anesthesia.
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| 3. |
- Kozian, Alf, 1969-, et al.
(author)
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One-lung ventilation induces hyperperfusion and alveolar damage in the ventilated lung : an experimental study
- 2008
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In: British Journal of Anaesthesia. - : Elsevier BV. - 0007-0912 .- 1471-6771. ; 100:4, s. 549-559
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Journal article (peer-reviewed)abstract
- BACKGROUND: One-lung ventilation (OLV) increases mechanical stress in the lung and affects ventilation and perfusion (V, Q). There are no data on the effects of OLV on postoperative V/Q matching. Thus, this controlled study evaluates the influence of OLV on V/Q distribution in a pig model using a gamma camera technique [single-photon emission computed tomography (SPECT)] and relates these findings to lung histopathology after OLV. METHODS: Eleven anaesthetized and ventilated pigs (V(T)=10 ml kg(-1), Fio2=0.40, PEEP=5 cm H2O) were studied. After lung separation, OLV and thoracotomy were performed in seven pigs (OLV group). During OLV and in a two-lung ventilation (TLV), control group (n=4) ventilation settings remained unchanged. SPECT with (81m)Kr (ventilation) and (99m)Tc-labelled macro-aggregated albumin (perfusion) was performed before, during, and 90 min after OLV/TLV. Finally, lung tissue samples were harvested and examined for alveolar damage. RESULTS: OLV affected ventilation and haemodynamic variables, but there were no differences between the OLV group and the control group before and after OLV/TLV. SPECT revealed an increase of perfusion in the dependent lung compared with baseline (49-56%), and a corresponding reduction of perfusion (51-44%) in non-dependent lungs after OLV. No perfusion changes were observed in the control group. This resulted in increased low V/Q regions and a shift of V/Q areas to 0.3-0.5 (10(-0.5)-10(-0.3)) in dependent lungs of OLV pigs and was associated with an increased diffuse alveolar damage score. CONCLUSIONS: OLV in pigs results in a substantial V/Q mismatch, hyperperfusion, and alveolar damage in the dependent lung and may thus contribute to gas exchange impairment after thoracic surgery.
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| 4. |
- Nilsson, Peter, et al.
(author)
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Structural typing of systemic amyloidoses by luminescent-conjugated polymer spectroscopy.
- 2010
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In: The American journal of pathology. - : Elsevier BV. - 1525-2191 .- 0002-9440. ; 176:2, s. 563-574
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Journal article (peer-reviewed)abstract
- Most systemic amyloidoses are progressive and lethal, and their therapy depends on the identification of the offending proteins. Here we report that luminescent-conjugated thiophene polymers (LCP) sensitively detect amyloid deposits. The heterodisperse polythiophene acetic acid derivatives, polythiophene acetic acid (PTAA) and trimeric PTAA, emitted yellow-red fluorescence on binding to amyloid deposits, whereas chemically homogeneous pentameric formic thiophene acetic acid emitted green-yellow fluorescence. The geometry of LCPs modulates the spectral composition of the emitted light, thereby reporting ligand-induced steric changes. Accordingly, a screen of PTAA-stained amyloid deposits in histological tissue arrays revealed striking spectral differences between specimens. Blinded cluster assignments of spectral profiles of tissue samples from 108 tissue samples derived from 96 patients identified three nonoverlapping classes, which were found to match AA, AL, and ATTR immunotyping. We conclude that LCP spectroscopy is a sensitive and powerful tool for identifying and characterizing amyloid deposits.
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| 5. |
- Nyström, Sofia N., 1974-
(author)
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Deposition and Resolution of AA Amyloid
- 2009
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Doctoral thesis (other academic/artistic)abstract
- Amyloidosis is a group of protein misfolding diseases characterized by extracellulardeposition of fibrillar protein aggregates. Today more than 25 different human amyloidogenicproteins have been identified, causing a variety of pathological conditions that includeAlzheimer’s disease, type 2 diabetes and prion diseases. Amyloid A (AA) amyloidosis is acomplication to long standing inflammatory disorders and amyloid is formed from N-terminalfragments of the acute phase protein serum amyloid A. AA amyloidosis developsspontaneously in many mice strains in response to inflammatory stimulation. Amyloidformation is nucleation dependent and develops after a lag phase of months. If an extract fromamyloid loaded tissue is administered to the animal, the lag phase is shortened to days. Thetissue extract is referred to as amyloid enhancing factor, AEF.In paper I we demonstrate that the active component of AEF is the amyloid fibril itself. We doalso show that AEF retains its activity over a long period of time and is active in very low(femtomolar) doses. AEF activity can be transmitted in a serial manner, also by oraladministration. Thus, AEF shares several characteristics with the infectious prion protein. Wetherefore suggest that AEF induces protein conformational changes in a prion like manner andthat experimental AA amyloidosis is a transmissible disease.In paper II we showed that peripheral blood monocytes recovered from mice with AAamyloidosis carry AEF activity but plasma does not. AA amyloid was detected in occasionalmonocytes. It is possible that these fibrils serve as seeds or nuclei for conformational changesand subsequent amyloid deposition in the recipient animal.In paper III mechanisms of amyloid clearance in experimental AA amyloidosis were studied.During amyloid clearance antibodies directed against AA were detected. Immunoglobulinsdid also co-localize with AA deposits. Amyloid fibrils were detected intracellular inmacrophages. These findings suggest that immune mechanisms contribute to AA amyloidclearance in mice and that macrophages are key players in the process. Immunoglobulins mayserve as opsonins facilitating phagocytosis of amyloid.It is believed that the early stages of amyloidogenesis are common in all forms of amyloiddiseases and that the amyloid formation process is cytotoxic. There are few studies onbiological effects of AA deposition in post mitotic tissue such as the heart. In paper IV weinvestigate the effects of cardiac AA amyloid deposition. Our results indicate that cardiac AAdeposition is associated with increased autophagic activity.In conclusion this thesis provides new insights to the dynamics of the turnover of AA amyloidand the mechanisms involved. Our results clearly show that the innate capacity of amyloidclearance is efficient.
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| 6. |
- Sjölander, Daniel, et al.
(author)
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Evaluation of the fluorescent amyloid ligand h-FTAA in human tissues with systemic and localized amyloid
- 2014
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Other publication (other academic/artistic)abstract
- Rapid and accurate detection of amyloid deposits in routine surgical pathology settings are of great importance. The use of fluorescence microscopy in combination with appropriate amyloid specific dyes is very promising in this regard. Most systemic amyloidosis are progressive and lethal. Disease specific therapy depends on the identification of the offending proteins. Here we report that a luminescent conjugated oligothiophene, h-FTAA, rapidly and with high sensitivity and selectivity detects amyloid deposits in verified clinical samples from systemic amyloidosis patients with AA, AL, and ATTR types; as well as in tissues laden with localized amyloidosis of AANF, AIAPP and ASem1 type. The probe h-FTAA emitted yellow red fluorescence on binding to amyloid deposits, whereas no apparent staining was observed in surrounding tissue. Screening of 114 amyloid containing tissues derived from §07 verified (Congo red birefringence and immunohistochemistry) amyloidosis patients revealed complete correlation between h-FTAA and Congo red fluorescence. We conclude that h-FTAA is a fluorescent hypersensitive, rapid and powerful tool for identifying amyloid deposits in tissue sections. H-FTAA staining can be utilized as a rapid complementary technique for accurate detection of amyloid in routine surgical pathology settings. It was also revealed that within 5 of 15 age matched Congo red negative control samples h-FTAA detects microdeposits of amyloid-like protein aggregates in liver and kidney. The results emphasize the potential of the dye for detection of prodromal amyloidosis as well as for discovery of novel amyloid-like protein aggregates in humans.
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