6 research outputs found
Study on the Phagocytosis of Asbestos Fibers and the Mechanisms for its Frustrated Phagocytosis in Macrophages
No full textAsbestos is a group of mineral silicates with fibrous morphology, which cause various respiratory diseases, including mesothelioma. Fiber toxicology has evolved a paradigm to explain the toxicity of asbestos fibers. It states that fibers >15 um cannot be completely engulfed by alveolar macrophages, thereby aborting phagocytosis in a process called frustrated phagocytosis. To study the mechanisms that cause this phenomenon, we investigated the phagocytosis of asbestos by confocal microscopy in cultured murine and human macrophages. Our findings showed unexpected differences in asbestos phagocytosis between murine and human cells. While murine macrophages completely engulfed fibers >15 um, albeit through a process that deviated from the canonical phagocytic pathway, phagocytosis arrested at the phagocytic cup stage in human macrophages. Strikingly, we restored phagocytosis in human macrophages by indirectly opsonizing fibers, which directed their uptake via Fcy-receptors. Altogether our results indicate that phagocytic receptors for asbestos determine its frustrated phagocytosis.M.Sc.2019-11-16 00:00:0
Study on the Phagocytosis of Asbestos Fibers and the Mechanisms for its Frustrated Phagocytosis in Macrophages
No full textAsbestos is a group of mineral silicates with fibrous morphology, which cause various respiratory diseases, including mesothelioma. Fiber toxicology has evolved a paradigm to explain the toxicity of asbestos fibers. It states that fibers >15 um cannot be completely engulfed by alveolar macrophages, thereby aborting phagocytosis in a process called frustrated phagocytosis. To study the mechanisms that cause this phenomenon, we investigated the phagocytosis of asbestos by confocal microscopy in cultured murine and human macrophages. Our findings showed unexpected differences in asbestos phagocytosis between murine and human cells. While murine macrophages completely engulfed fibers >15 um, albeit through a process that deviated from the canonical phagocytic pathway, phagocytosis arrested at the phagocytic cup stage in human macrophages. Strikingly, we restored phagocytosis in human macrophages by indirectly opsonizing fibers, which directed their uptake via Fcy-receptors. Altogether our results indicate that phagocytic receptors for asbestos determine its frustrated phagocytosis.M.Sc.2019-11-16 00:00:0
Upper limb nerve conduction parameters of healthy young adults
No full textAcross sectional study was done among to measure the upper limb nerve conduction parameters in median and ulnar nerves. Age, height, weight and BMI of healthy volunteers were recorded. Nerve conduction study was performed to measure Distal Latency (DL) (ms), Proximal Latency (PL) (ms) and Conduction Velocity (CV) (m/s) in both motor and sensory of Median and Ulnar nerves in 99 individuals at University of Jaffna. The mean ages were 21.4 ± 1.2, 21.7 ± 1 in males and females respectively. There were significant differences between males and females in PL and DL of motor and sensory nerves, but not CV except for left motor ulnar and right sensory ulnar nerves (p<0.05). NCS parameters between left and right limbs were not statistically significant. Mean of median motor DL, PL, and CV were 3(±0.4), 7.4(±0.6), 62.7(±4) in males and 2.8(±0.3), 6.8(±0.6), 61.7(±5.4) in females respectively while the respective parameters in Ulnar motor nerves were 2.2(±0.2), 7.4(±0.6), 64.8(±5.5) in males and 2.1(±0.1), 6.9(±0.6), 66.6(±6.3) in females. Mean DL, PL and CV of sensory median were 2.8(±0.2), 6.6(±0.4), 69.7(±4.6) and 2.6(±0.3), 6.9(±0.6), 70.9(±7.9) in males and females respectively while the respective values in Ulnar sensory were 2.4(±0.3), 7.5(±0.6), 67.4(±5) in males and 2.2(±0.3), 6.9(±0.6), 71.9(±6) in females. Height had significant (p<0.05) correlation with latencies but not CV. CV was faster in sensory than motor nerves (p <0.001).Our results establish normal NCS values for Median and Ulnar nerves in young healthy adults enabling better interpretations of NCS
The iron and testosterone levels in amoebic liver abscess patients - a preliminary study from northern Sri Lanka
No full textAmoebic liver abscesses (ALA) are observed among adult males who consume locally brewed alcohol in the tropics. The contributory role of alcohol-induced hepatic iron stores and the male hormone testosterone were said to be playing a pivotal role in the pathogenesis of ALA. This descriptive preliminary study was intended to see a possible relationship of serum iron profile and testosterone level among toddy (a local palm wine) drinkers who presented with ALA to the Teaching Hospital Jaffna. Results have shown very high serum ferritin levels (902.58ng/ml) in these patients with ALA. However, the serum iron levels (43.05µg/dl) and the transferrin saturation levels (22.01%) were observed to be normal or below normal and Total Iron Binding Capacity (TIBC) level was unexpectedly low (193.3µg/dl) for the corresponding low serum iron levels. Furthermore, the serum testosterone level (2.44ng/ml) was also low or low normal when compared with the reference range in the study population. As this preliminary study contrasts with previously postulated theories, further study is recommended to arrive at a concrete conclusion.</p
Disposable Immunochips for the Detection of <i>Legionella pneumophila</i> Using Electrochemical Impedance Spectroscopy
No full textThe rapid diagnosis of Legionellosis is crucial for the
effective treatment of this disease. Currently, most clinical laboratories utilize rapid immunoassays that are sufficient for the detection of Legionella serogroup 1, but not other clinically relevant serogroups. In this report,
the development of a disposable immunochip system is described in
connection with electrochemical impedance spectroscopy and fluorescence
microscopy. The immunochips were prepared by covalently immobilizing
fluorophore-conjugated L. pneumophila antibodies
on Au chips. The analytical performance of the immunochips was optimized
as a prescreening tool for L. pneumophila. The versatile
immunochips described here can be easily adapted for the monitoring
of all Legionella serogroups in clinical and environmental
samples
Cross-ancestry, cell-type-informed atlas of gene, isoform, and splicing regulation in the developing human brain [preprint]
No full textThis article is a preprint. Preprints are preliminary reports of work that have not been certified by peer review.Genomic regulatory elements active in the developing human brain are notably enriched in genetic risk for neuropsychiatric disorders, including autism spectrum disorder (ASD), schizophrenia, and bipolar disorder. However, prioritizing the specific risk genes and candidate molecular mechanisms underlying these genetic enrichments has been hindered by the lack of a single unified large-scale gene regulatory atlas of human brain development. Here, we uniformly process and systematically characterize gene, isoform, and splicing quantitative trait loci (xQTLs) in 672 fetal brain samples from unique subjects across multiple ancestral populations. We identify 15,752 genes harboring a significant xQTL and map 3,739 eQTLs to a specific cellular context. We observe a striking drop in gene expression and splicing heritability as the human brain develops. Isoform-level regulation, particularly in the second trimester, mediates the greatest proportion of heritability across multiple psychiatric GWAS, compared with eQTLs. Via colocalization and TWAS, we prioritize biological mechanisms for ~60% of GWAS loci across five neuropsychiatric disorders, nearly two-fold that observed in the adult brain. Finally, we build a comprehensive set of developmentally regulated gene and isoform co-expression networks capturing unique genetic enrichments across disorders. Together, this work provides a comprehensive view of genetic regulation across human brain development as well as the stage- and cell type-informed mechanistic underpinnings of neuropsychiatric disorders
