Mobility and balance problems are common and often debilitating features of Huntington's disease (HD). In this exploratory study we aimed to investigate the influence of disease severity, severity of ...motor deficits, lower limb muscle strength, cognition, executive function, lean muscle mass and reactivity on mobility and balance.
Twenty-two individuals with HD were recruited from the North Metropolitan Area Mental Health Service, Perth, Australia. Pertinent demographic, genetic and disease progression information was recorded prior to testing. Balance was assessed using dynamic and static balance tasks. Mobility was assessed using self-paced and fast-paced mobility measures. Cognitive and executive measures were used to assess verbal learning and memory, information processing speed, attention, response inhibition and cognitive flexibility. Lower limb muscle strength was evaluated by maximal isokinetic and isometric voluntary contractions. Lean tissue mass was quantified using Dual-energy X-ray absorptiometry. Reactivity was measured using Moyart equipment.
Univariate and multivariate linear regression statistical models were used to examine the influence of these measures on mobility and balance. Univariate analyses showed that disease severity as well as measures of information processing speed, attention, cognitive flexibility, response inhibition and lower limb strength, were strongly related with mobility and balance. Additionally multivariate analyses showed that disease severity, cognitive flexibility and knee flexion strength together were better able to explain mobility and balance performance than any single measure (50–85%).
In conclusion, our preliminary results suggest that as well as disease severity, cognitive and executive impairment and reduced lower limb strength contribute significantly to mobility and balance problems.
Background/Aims: Biliary epithelial cells are targets of immune-mediated attack in conditions such as primary biliary cirrhosis and allograft rejection. This has been attributed to the ability of ...biliary epithelial cells to express ligands for T cell receptors. We aimed to investigate the expression of immune recognition elements and the effects of pro-inflammatory and anti-inflammatory cytokines on cell surface phenotypes of normal human biliary epithelial cells and established human liver-derived (PLC/PRF/5, HepG2, Hep3B and CC-SW) lines.
Methods: Cells were cultured in the presence or absence of cytokines for 72 h, and expression of cell surface molecules was assessed by flow cytometry and immunofluorescence.
Results: All cell lines expressed MHC class I, ICAM-1 (CD54), LFA-3 (CD58) and EGF receptor, and all but Hep3B expressed Fas/Apo-1 (CD95). Unlike hepatocyte-derived cell lines, biliary epithelial cells and CC-SW expressed CD40 and CD44. As expected, IFNγ and TNFα upregulated expression of ICAM-1, MHC class I and MHC class II, particularly in biliary epithelial cells. TGFβ downregulated these molecules and downregulated CD95 on biliary epithelial cells, but upregulated LFA-3. The Th2 cytokines had little effect, although IL-4 upregulated CD95 expression on biliary epithelial cells. IFNγ upregulated CD40 expression on biliary epithelial cells, CC-SW and HepG2.
Conclusions: These findings imply that biliary epithelial cells may be capable of interacting with activated T lymphocytes
via CD40 and LFA-3, which are thought to be important T cell accessory ligands for T cell activation in a B7-independent manner. Sensitivity to pro-inflammatory cytokines and expression of CD95 may explain why biliary epithelial cells are primary targets for autoimmune attack.
Background/Aims: Human intrahepatic biliary epithelial cells can express immune recognition elements and are targets for immune attack in several liver pathologies. The aim of this study was to ...investigate the ability of biliary epithelial cells to act as accessory cells for T cell activation in normal and inflammatory conditions.
Methods: Normal biliary epithelial cells were cocultured with allogeneic unstimulated and mitogen- or antigen-stimulated peripheral blood lymphocytes. T cell responses were assessed by flow cytometry.
Results: Biliary epithelial cells did not induce allostimulation in resting T cells and inhibited T cell activation in response to either phytohaemagglutinin, mitogenic anti-CD3 antibody or recall antigen, irrespective of the presence of accessory cells. Biliary epithelial cells did not affect T cell viability, promote or inhibit activation-induced apoptosis nor modulate expression of CD95/Fas. In presence of biliary epithelial cells, stimulated T cells failed to develop an antigen-committed (CD45RO
hi) phenotype and were unresponsive to subsequent CD3 ligation. However, T cells underwent normal activation in the presence of biliary epithelial cells which had been pre-treated with Interferon γ or TGFβ, cytokines implicated in liver disease.
Conclusions: In normal liver, biliary epithelial cells inhibit rather than promote T cell activation, but their anergising effects may be overcome in response to trauma.
Many organizations seek to ensure that machine learning (ML) and artificial intelligence (AI) systems work as intended in production but currently do not have a cohesive methodology in place to do ...so. To fill this gap, we propose MLTE (Machine Learning Test and Evaluation, colloquially referred to as "melt"), a framework and implementation to evaluate ML models and systems. The framework compiles state-of-the-art evaluation techniques into an organizational process for interdisciplinary teams, including model developers, software engineers, system owners, and other stakeholders. MLTE tooling supports this process by providing a domain-specific language that teams can use to express model requirements, an infrastructure to define, generate, and collect ML evaluation metrics, and the means to communicate results.
Studies investigating changes in gene expression in urothelial carcinoma have generally compared tumors of different stages and grades but comparisons between low-grade, noninvasive tumors and normal ...urothelium are needed to identify genes involved in early tumor development. We isolated the urothelium from a low-grade tumor and corresponding normal mucosa by laser capture microdissection on frozen sections. The RNA extracted was amplified to generate suppressive subtractive cDNA libraries. Random sequencing of cDNA clones identified approximately 100 unique species. Of these 83% were known genes, 15% had homology to genes with an unknown function in humans, and 2% did not show homology to any published gene sequence. Two of the known genes, the 67-kd laminin receptor (67LR) and tumor-associated trypsin inhibitor (TATI), had previously been associated with metastatic progression in many tumor types, although 67LR has not been investigated in urothelial tumors. Immunolabeling of the original tissue with antibodies against these two genes confirmed overexpression, validating our strategy: 67LR was not expressed in the normal urothelium but was present in the tumor, whereas TATI expression was confined to umbrella cells in the normal urothelium, but extended to all cell layers in the tumor. We investigated both markers further in a separate series of tumors of different stages and grades. TATI was more consistently overexpressed than 67LR in all tumor grades and stages. Levels of secreted TATI were significantly higher in urine samples from patients with tumors compared to controls. Our strategy, combining laser capture microdissection and cDNA library construction, has identified genes that may be involved in the early phases of urothelial tumor development rather than with disease progression, highlighting the importance of comparing tumor with normal rather than just tumors of different stages and grades.
NORMAL HUMAN LIVER ORGAN CULTURE CRUICKSHANK, SHEENA M; SOUTHGATE, JENNIFER; TREJDOSIEWICZ, LUDWIK K
In vitro cellular & developmental biology. Animal,
04/2001, Letnik:
37, Številka:
4
Journal Article
Studies investigating changes in gene expression in urothelial carcinoma have generally compared tumors of different stages and grades but comparisons between low-grade, noninvasive tumors and normal ...urothelium are needed to identify genes involved in early tumor development. We isolated the urothelium from a low-grade tumor and corresponding normal mucosa by laser capture microdissection on frozen sections. The RNA extracted was amplified to generate suppressive subtractive cDNA libraries. Random sequencing of cDNA clones identified ∼100 unique species. Of these 83% were known genes, 15% had homology to genes with an unknown function in humans, and 2% did not show homology to any published gene sequence. Two of the known genes, the 67-kd laminin receptor (67LR) and tumor-associated trypsin inhibitor (TATI), had previously been associated with metastatic progression in many tumor types, although 67LR has not been investigated in urothelial tumors. Immunolabeling of the original tissue with antibodies against these two genes confirmed overexpression, validating our strategy: 67LR was not expressed in the normal urothelium but was present in the tumor, whereas TATI expression was confined to umbrella cells in the normal urothelium, but extended to all cell layers in the tumor. We investigated both markers further in a separate series of tumors of different stages and grades. TATI was more consistently overexpressed than 67LR in all tumor grades and stages. Levels of secreted TATI were significantly higher in urine samples from patients with tumors compared to controls. Our strategy, combining laser capture microdissection and cDNA library construction, has identified genes that may be involved in the early phases of urothelial tumor development rather than with disease progression, highlighting the importance of comparing tumor with normal rather than just tumors of different stages and grades.
Normal human liver organ culture Cruickshank, Sheena M.; Southgate, Jennifer; Trejdosiewicz, Ludwik K.
In vitro cellular & developmental biology. Animal,
4/2001, Letnik:
37, Številka:
4
Journal Article
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