481 research outputs found
Genetics and cellular expression of human apolipoproteins.
No full textThe purpose of this dissertation was to investigate the genetics and cellular expression of human apolipoproteins. The genetics aspect was an investigation of the Hind III apolipoprotein B gene DNA polymorphism and its association with lipids and lipoprotein parameters in a selected Canadian Caucasian population with documented coronary artery disease, and a healthy control population. To carry out this project, a simple and rapid method for the purification of human DNA from whole blood was developed. Typical 260 nm/280 nm absorbance ratio and yield for DNA so purified were 1.84 and 24.5 g/mL, respectively. Patients had significantly (p < 0.05) higher levels of cholesterol, triglycerides, LDL-cholesterol, apolipoprotein B, and lower level of apoAI compared to the controls. Restriction fragment length polymorphism analysis detected 9 hybridizable fragments denoted as H1 to H9. The H1, H2, H3, and H7 alleles were polymorphic. The (H4-H9) genotype was detected in 69% of the control group while the (H1-H9) genotype was observed in 68% of the patients. In the second phase of the studies the effects of insulin and thyroid hormone on apolipoprotein B, E, and AI mRNA expression were investigated using hepatoma cell-line. Thyroid hormone increased apolipoprotein B mRNA levels by about 25-36% as determined by slot- and Northern-blot analysis of total cellular RNA. No change in the amount of apolipoprotein B mRNA, measured by either slot- or Northern-blot analysis of total RNA was found in insulin treated cells. Both insulin and thyroid hormone were found to have no significant effect on apoE mRNA levels. The levels of apolipoprotein AI mRNA were found to be decreased by thyroid hormone and increased by insulin by about 19% and 30% respectively. A competitive chemiluminescent immunoassay was also developed for the sensitive measurement of apolipoprotein B. The lower limit of detection was 2.17 g/L (4.0 pmol/L). Comparison of the assay with an immunoturbidimetric assay gave a slope of 0.84, y-intercept at 0.94 and a correlation coefficient of 0.86. In summary, the observed mutations in apolipoprotein B gene may not affect the rate of apolipoprotein B synthesis, clearance or the affinity of low-density lipoprotein for structural elements on the arterial wall. Furthermore, thyroid hormone appears to regulate apolipoprotein B and AI transcription while insulin modulates only apoAI mRNA levels.Dept. of Chemistry and Biochemistry. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis1993 .O42. Source: Dissertation Abstracts International, Volume: 56-01, Section: B, page: 0223. Adviser: K. Adeli. Thesis (Ph.D.)--University of Windsor (Canada), 1994
Expression of apolipoprotein B in human hepatocytes: Studies onmRNA translation and posttranslational degradation.
No full textThe objectives of my research program were: (i) to develop a mRNA-dependent cell-free system capable of translation of apoB mRNA, since common in vitro translation systems are unable to synthesize apoB 100 because of its unusually large size; (ii) to study the effect of hypolipidemic drugs including a newly developed HMG-CoA reductase inhibitor, atorvastatin, on intracellular degradation of apoB in HepG2 cells; and (iii) to study degradation of different intracellular apoB pools in HepG2 cells in order to elucidate factors regulating apoB degradation. An mRNA-dependent cell-free system was developed from HepG2 cells which can accommodate in vitro translation of apoB mRNA. Upon addition of cytoplasmic RNA extracted from HepG2 cells, the HepG2 cell-free system was capable of synthesis of the full length apoB100, with a size of 550 kDa. The HepG2 cell-free system also proved to be sensitive to heterologous mRNAs and actively translated Brome Mosaic Virus RNA. Studies on apoB degradation in HepG2 cells were also performed by using a permeabilized HepG2 system developed in our laboratory. Degradation of apoB was studied under the influence of a battery of hypolipidemic drugs including the fibrate derivatives, nicotinic acid, probucol, as well as the HMG-CoA reductase inhibitors lovastatin and atorvastatin. The fibrates, nicotinic acid, probucol, and lovastatin did not influence apoB degradation. However atorvastatin appeared to stimulate apoB degradation by approximately 25%. Atorvastatin showed this stimulatory effect under different conditions in which the HepG2 cells were provided with oleate or low density lipoprotein (LDL) as a source of lipid. Fractionation of different apoB pools in HepG2 cells showed that atorvastatin enhanced degradation of apoB bound to the ER membrane as well as apoB present in the lumen of the ER. Subsequent fractionation of luminal apoB into dense (HDL) and light (LDL-VLDL like) particles revealed that apoB in the HDL-like particles is more sensitive to the degradation under the influence of atorvastatin. Characterization of degradation of different intracellular apoB pools in permeabilized HepG2 cells showed that degradation of membrane bound apoB occurs at a faster rate and to a larger extent compared to the luminal apoB. Degradation of apoB in the membrane pool was also not sensitive to N-acetylleucylleucylnorleucinal (ALLN), a cysteine protease inhibitor which repressed luminal apoB degradation. (Abstract shortened by UMI.)Dept. of Chemistry and Biochemistry. Paper copy at Leddy Library: Theses & Major Papers - Basement, West Bldg. / Call Number: Thesis1996 .M635. Source: Dissertation Abstracts International, Volume: 59-08, Section: B, page: 3909. Adviser: K. Adeli. Thesis (Ph.D.)--University of Windsor (Canada), 1997
A rapid HPLC-mass spectrometry cyclosporin method suitable for current monitoring practices
No full textObjectives: Cyclosporin is an immunosuppressant drug with a narrow therapeutic window. Trough and 2-h post-dose blood samples are currently used for therapeutic drug monitoring in solid organ transplant recipients. The aim of the current study was to develop a rapid HPLC-tandem mass spectrometry (HPLC-MS) method for the measurement of cyclosporin in whole blood that was not only suitable for the clinical setting but also considered a reference method. Methods: Blood samples (50 mu L) were prepared by protein precipitation followed by C-18 solid-phase extraction while using d(12) cyclosporin as the internal standard. Mass spectrometric detection was by selected reaction monitoring with an electrospray interface in positive ionization mode. Results: The assay was linear from 10 to 2000 mu g/L (r(2) > 0.996, n = 9). Inter-day,analytical recovery and imprecision using whole blood quality control samples at 10, 30, 400, 1500, and 2000 mu g/L were 94.9-103.5% an
The Microbiome-Gut-Brain Axis and Resilience to Developing Anxiety or Depression under Stress
No full textEpisodes of depression and anxiety commonly follow the experience of stress, however not everyone who experiences stress develops a mood disorder. Individuals who are able to experience stress without a negative emotional effect are considered stress resilient. Stress-resilience (and its counterpart stress-susceptibility) are influenced by several psychological and biological factors, including the microbiome-gut-brain axis. Emerging research shows that the gut microbiota can influence mood, and that stress is an important variable in this relationship. Stress alters the gut microbiota and plausibly this could contribute to stress-related changes in mood. Most of the reported research has been conducted using animal models and demonstrates a relationship between gut microbiome and mood. The translational evidence from human clinical studies however is rather limited. In this review we examine the microbiome-gut-brain axis research in relation to stress resilience.fals
Matching Knowledge Supply and Demand of Expertise: A Case Study by Patent Analysis
No full textTechnology transfer has the aim to analyze the mechanisms behind the value raised by knowledge in the long trip from labs to society and markets. It is a demanding task due to the potential of its refinement on one hand and the challenging mission of understanding it with detail on the other. The complication arises in terms of availability of structured data and on the complexity of the mechanisms behind the osmosis of knowledge through a heterogeneous society. This article analyzes the potentiality of a correlation paradigm between patents supply and companies’ purpose of business to outline a potential hint of value through this complexity. © The Author(s), under exclusive license to Springer Nature Switzerland AG 2024
Molecular, serological, and biochemical diagnosis and monitoring of COVID-19: IFCC taskforce evaluation of the latest evidence
No full textThe global coronavirus disease 2019 (COVID-19) has presented major challenges for clinical laboratories, from initial diagnosis to patient monitoring and treatment. Initial response to this pandemic involved the development, production, and distribution of diagnostic molecular assays at an unprecedented rate, leading to minimal validation requirements and concerns regarding their diagnostic accuracy in clinical settings. In addition to molecular testing, serological assays to detect antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are now becoming available from numerous diagnostic manufacturers. In both cases, the lack of peer-reviewed data and regulatory oversight, combined with general misconceptions regarding their appropriate use, have highlighted the importance of laboratory professionals in robustly validating and evaluating these assays for appropriate clinical use. The International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) Task Force on COVID-19 has been established to synthesize up-to-date information on the epidemiology, pathogenesis, and laboratory diagnosis and monitoring of COVID-19, as well as to develop practical recommendations on the use of molecular, serological, and biochemical tests in disease diagnosis and management. This review summarizes the latest evidence and status of molecular, serological, and biochemical testing in COVID-19 and highlights some key considerations for clinical laboratories operating to support the global fight against this ongoing pandemic. Confidently this consolidated information provides a useful resource to laboratories and a reminder of the laboratory's critical role as the world battles this unprecedented crisis
Tinjauan Yuridis Penerapan Prinsip Perlindungan Merek Terkenal Pada Kasus Merek Bossini Dan Curesonic (Studi Putusan Ma No 211 K/Pdt.Sus-Hki/2015 Tentang Kasus Merek Bossini Dan Putusan Ma No 462 K/Pdt.Sus-Hki/2015 Tentang Kasus Merek Curesonic)
No full textPada skripsi ini mengangkat permasalahan Penerapan Prinsip Perlindungan Merek
Terkenal Pada Kasus Merek Bossini dan Curesonic dengan melakukan Studi Putusan
MA No 211 K/Pdt.Sus-HKI/2015 dan Putusan MA No 462 K/Pdt.Sus-HKI/2015. Hal
tersebut dilatar belakangi oleh banyaknya kasus pelanggaran merek terkenal dimana
banyak sekali merek lokal yang menggunakan nama merek terkenal asing untuk
mempromosikan barang dan/atau jasa yang dimilikinya. Namun yang terjadi, banyak
sekali dari sekian banyak kasus pelanggaran merek tersebut yang putusannya tidak
sesuai dengan penerapan prinsip perlindungan merek terkenal yang diberikan oleh
Undang-Undang Merek di Indonesia karena terdapat beberapa kelemahan-kelemahan
yang muncul baik dalam Undang-Undang Merek 2001 dan Undang-Undang Merek
2016. Konvensi Internasional TRIPs juga mengatakan bahwa sampai pada saat ini
belum ada satu negarapun yang bisa memberikan definisi tentang merek terkenal.
Penelitian ini menggunakan penelitian yuridis normatif. Dalam penelitian ini
ditemukan beberapa kelemahan dalam Undang-Undang Merek di Indonesia antara
lain tidak adanya pengertian merek terkenal, kedua tidak adanya pengertian tentang
teori reputasi, ketiga tidak dicantumkan syarat-syarat suatu merek dapat ditolak.
Sampai pada saat ini Pemerintah Republik Indonesia belum mempunyai upaya untuk
permasalahan ini. Rekomendasi atau saran untuk pemerintah dan pengadilan yang
berwenang: a) memperbaiki kelemahan-kelemahan dalam undang-undang merek, b)
mengetahui ciri-ciri dari merek terkenal, c) mengetahui reputasi merek terkenal di
masyarakat
Surface-Based Brain Morphometry for the Prediction of Fluid Intelligence in the Neurocognitive Prediction Challenge 2019
No full textBrain morphometry derived from structural magnetic resonance imaging is a widely used quantitative biomarker in neuroimaging studies. In this paper, we investigate its usefulness for the Neurocognitive Prediction Challenge 2019.
An in-depth analysis of the features provided by the challenge (anatomical segmentation and volumes for regions of interest according to the SRI24 atlas) motivated us to process the native T1-weighted images with FreeSurfer 6.0, to derive reliable brain morphometry including surface based metrics. A combination of subcortical volumes and cortical thicknesses, curvatures, and surface areas was used as features for a support-vector regressor (SVR) to predict pre-residualized fluid intelligence scores. Results performing only slightly better than the baseline (uniformly predicting the mean) were observed on two internally held-out validation sets, while performance on the official validation set was approximately the same as the baseline.
Despite a large dataset of a specific cohort available for training, this suggests that structural brain morphometry alone has limited power for this challenge, at least with today’s imaging and post-processing methods
- …
