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Dennis Lo

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https://www.readbyqxmd.com/read/28077575/effector-attenuating-substitutions-that-maintain-antibody-stability-and-reduce-toxicity-in-mice
#1
Megan Lo, Hok Seon Kim, Raymond K Tong, Travis W Bainbridge, Jean-Michel Vernes, Yin Zhang, Yuwen Linda Lin, Shan Chung, Mark S Dennis, Y Joy Yu Zuchero, Ryan J Watts, Jessica A Couch, Y Gloria Meng, Jasvinder K Atwal, Randall J Brezski, Christoph Spiess, James A Ernst
The antibody Fc region regulates antibody cytotoxic activities and serum half-life. In a therapeutic context however, the cytotoxic effector function of an antibody is often not desirable and can create safety liabilities by activating native host immune defenses against cells expressing the receptor-antigens. Several amino acid changes in the Fc region have been reported to silence or reduce the effector function of antibodies. These earlier studies focused primarily on the interaction of human antibodies with human Fc-Gamma; receptors, and it remains largely unknown how such changes to the Fc might translate in the context of a murine antibody...
January 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27974386/combined-count-and-size-based-analysis-of-maternal-plasma-dna-for-noninvasive-prenatal-detection-of-fetal-subchromosomal-aberrations-facilitates-elucidation-of-the-fetal-and-or-maternal-origin-of-the-aberrations
#2
Stephanie C Y Yu, Peiyong Jiang, K C Allen Chan, Brigitte H W Faas, Kwong W Choy, Wing C Leung, Tak Y Leung, Y M Dennis Lo, Rossa W K Chiu
BACKGROUND: Noninvasive prenatal detection of fetal subchromosomal copy number aberrations (CNAs) can be achieved through massively parallel sequencing of maternal plasma DNA. However, when a mother herself is a carrier of a CNA, one cannot discern if her fetus has inherited the CNA. In addition, false-positive results would become more prevalent when more subchromosomal regions are analyzed. METHODS: We used a strategy that combined count- and size-based analyses of maternal plasma DNA for the detection of fetal subchromosomal CNAs in 7 target regions for 10 test cases...
December 14, 2016: Clinical Chemistry
https://www.readbyqxmd.com/read/27932412/universal-haplotype-based-noninvasive-prenatal-testing-for-single-gene-diseases
#3
Winnie W I Hui, Peiyong Jiang, Yu K Tong, Wing-Shan Lee, Yvonne K Y Cheng, Maria I New, Rezan A Kadir, K C Allen Chan, Tak Y Leung, Y M Dennis Lo, Rossa W K Chiu
BACKGROUND: Researchers have developed approaches for the noninvasive prenatal testing of single gene diseases. One approach that allows for the noninvasive assessment of both maternally and paternally inherited mutations involves the analysis of single nucleotide polymorphisms (SNPs) in maternal plasma DNA with reference to parental haplotype information. In the past, parental haplotypes were resolved by complex experimental methods or inferential approaches, such as through the analysis of DNA from other affected family members...
December 8, 2016: Clinical Chemistry
https://www.readbyqxmd.com/read/27799561/second-generation-noninvasive-fetal-genome-analysis-reveals-de-novo-mutations-single-base-parental-inheritance-and-preferred-dna-ends
#4
K C Allen Chan, Peiyong Jiang, Kun Sun, Yvonne K Y Cheng, Yu K Tong, Suk Hang Cheng, Ada I C Wong, Irena Hudecova, Tak Y Leung, Rossa W K Chiu, Yuk Ming Dennis Lo
Plasma DNA obtained from a pregnant woman was sequenced to a depth of 270× haploid genome coverage. Comparing the maternal plasma DNA sequencing data with the parental genomic DNA data and using a series of bioinformatics filters, fetal de novo mutations were detected at a sensitivity of 85% and a positive predictive value of 74%. These results represent a 169-fold improvement in the positive predictive value over previous attempts. Improvements in the interpretation of the sequence information of every base position in the genome allowed us to interrogate the maternal inheritance of the fetus for 618,271 of 656,676 (94...
December 13, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27784706/dried-blood-spot-reference-intervals-for-steroids-and-amino-acids-in-a-neonatal-cohort-of-the-national-children-s-study
#5
Dennis J Dietzen, Michael J Bennett, Stanley F Lo, Vijay L Grey, Patti M Jones
BACKGROUND: Reference intervals from children are limited by access to healthy children and their limited blood volumes. In this study we set out to fill gaps in pediatric reference intervals for amino acids and steroid hormones using dried blood spots (DBS) from a cohort of the National Children's Study. METHODS: Deidentified DBS annotated with age, birthweight, sex, and geographic location were obtained from 310 newborns aged 0-4 days and analyzed for 25 amino acids and 4 steroid hormones using LC-MS/MS...
December 2016: Clinical Chemistry
https://www.readbyqxmd.com/read/27774548/a-biotin-conjugated-glutathione-responsive-fret-based-fluorescent-probe-with-a-ferrocenyl-bodipy-as-the-dark-quencher
#6
Wen-Jing Shi, Pui-Chi Lo, Shirui Zhao, Roy C H Wong, Qiong Wang, Wing-Ping Fong, Dennis K P Ng
An efficient ferrocenyl BODIPY based dark quencher has been developed and employed to construct a FRET-based fluorescent probe that contains a biotin moiety as a potential directing ligand for cancer cells and a glutathione-cleavable disulfide linker connecting the quencher and a distyryl BODIPY fluorophore. This molecular probe is deactivated in the native form through FRET followed by intramolecular charge transfer due to the ferrocenyl unit. However, upon interaction with glutathione in phosphate buffered saline and inside cancer cells, the fluorescence emission is significantly increased due to detachment of the fluorophore from the quencher...
October 24, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/27620950/cell-free-dna-in-maternal-plasma-and-serum-a-comparison-of-quantity-quality-and-tissue-origin-using-genomic-and-epigenomic-approaches
#7
Felix C K Wong, Kun Sun, Peiyong Jiang, Yvonne K Y Cheng, K C Allen Chan, Tak Y Leung, Rossa W K Chiu, Yuk Ming Dennis Lo
OBJECTIVES: The objectives of this study were to compare the concentrations, size profiles and major tissue contributors of cell-free DNA (cfDNA) in plasma and in serum. DESIGN AND METHODS: Thirteen pregnant women in the third trimester were recruited for this study. We collected EDTA-plasma and serum samples using various collection tubes. We determined their cfDNA concentrations and fetal cfDNA fractions using a zinc-finger X (ZFX)/zinc-finger Y (ZFY) droplet digital polymerase chain reaction (ZFX/ZFY ddPCR) assay...
December 2016: Clinical Biochemistry
https://www.readbyqxmd.com/read/27525383/tracing-the-tissue-of-origin-of-plasma-dna-feasibility-and-implications
#8
Yuk Ming Dennis Lo, Wai Kei Jacky Lam
Scientists have been exploring cell-free DNA in plasma for a wider clinical application in addition to noninvasive prenatal testing. Tracing the tissue of origin of plasma DNA is the next important step. In this perspective, we discuss different approaches recently reported for tracing the tissue of origin of plasma DNA and the implications.
July 2016: Annals of the New York Academy of Sciences
https://www.readbyqxmd.com/read/27396392/an-acid-cleavable-phthalocyanine-tetramer-as-an-activatable-photosensitiser-for-photodynamic-therapy
#9
Sun Y S Chow, Pui-Chi Lo, Dennis K P Ng
An acetal-linked self-quenched zinc(ii) phthalocyanine tetramer has been prepared. In an acidic environment in phosphate buffered saline or inside tumour cells, the phthalocyanine units of the tetramer are separated thereby restoring the fluorescence emission and singlet oxygen production. This response enables this compound to serve as a promising activatable photosensitiser for photodynamic therapy.
August 16, 2016: Dalton Transactions: An International Journal of Inorganic Chemistry
https://www.readbyqxmd.com/read/27383789/corrigendum-sfrp2-in-the-aged-microenvironment-drives-melanoma-metastasis-and-therapy-resistance
#10
Amanpreet Kaur, Marie R Webster, Katie Marchbank, Reeti Behera, Abibatou Ndoye, Curtis H Kugel, Vanessa M Dang, Jessica Appleton, Michael P O'Connell, Phil Cheng, Alexander A Valiga, Rachel Morissette, Nazli B McDonnell, Luigi Ferrucci, Andrew V Kossenkov, Katrina Meeth, Hsin-Yao Tang, Xiangfan Yin, William H Wood, Elin Lehrmann, Kevin G Becker, Keith T Flaherty, Dennie T Frederick, Jennifer A Wargo, Zachary A Cooper, Michael T Tetzlaff, Courtney Hudgens, Katherine M Aird, Rugang Zhang, Xiaowei Xu, Qin Liu, Edmund Bartlett, Giorgos Karakousis, Zeynep Eroglu, Roger S Lo, Matthew Chan, Alexander M Menzies, Georgina V Long, Douglas B Johnson, Jeffrey Sosman, Bastian Schilling, Dirk Schadendorf, David W Speicher, Marcus Bosenberg, Antoni Ribas, Ashani T Weeraratna
No abstract text is available yet for this article.
September 8, 2016: Nature
https://www.readbyqxmd.com/read/27379603/group-relationships-in-early-and-late-sessions-and-improvement-in-interpersonal-problems
#11
Gianluca Lo Coco, Salvatore Gullo, Carla Di Fratello, Cecilia Giordano, Dennis M Kivlighan
Groups are more effective when positive bonds are established and interpersonal conflicts resolved in early sessions and work is accomplished in later sessions. Previous research has provided mixed support for this group development model. We performed a test of this theoretical perspective using group members' (actors) and aggregated group members' (partners) perceptions of positive bonding, positive working, and negative group relationships measured early and late in interpersonal growth groups. Participants were 325 Italian graduate students randomly (within semester) assigned to 1 of 16 interpersonal growth groups...
July 2016: Journal of Counseling Psychology
https://www.readbyqxmd.com/read/27139139/ph-and-thiol-responsive-bodipy-based-photosensitizers-for-targeted-photodynamic-therapy
#12
Xiong-Jie Jiang, Janet T F Lau, Qiong Wang, Dennis K P Ng, Pui-Chi Lo
A diiodo distyryl boron dipyrromethene (BODIPY) core was conjugated to two ferrocenyl quenchers through acid-labile ketal and/or thiol-cleavable disulfide linkers, of which the fluorescence and photosensitizing properties were significantly quenched through a photoinduced electron-transfer process. The two symmetrical analogues that contained either the ketal or disulfide linkers could only be activated by a single stimulus, whereas the unsymmetrical analogue was responsive to dual stimuli. Upon interaction with acid and/or dithiothreitol (DTT), these linkers were cleaved selectively...
June 6, 2016: Chemistry: a European Journal
https://www.readbyqxmd.com/read/27129983/the-long-and-short-of-circulating-cell-free-dna-and-the-ins-and-outs-of-molecular-diagnostics
#13
REVIEW
Peiyong Jiang, Y M Dennis Lo
The discovery of cell-free tumor and fetal DNA molecules in the plasma of cancer patients and pregnant women, respectively, has opened up exciting opportunities in molecular diagnosis. The understanding of the biological properties of circulating cell-free DNA (cfDNA) molecules would be essential for us to make the best use of such molecules in different clinical settings. In this review we start by exploring the technologies that have been used for analyzing the size profiles of cfDNA in plasma. We then review the size profiles of cfDNA in different clinical scenarios, including cancer, pregnancy, transplantation, and autoimmune diseases...
June 2016: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/27126326/screening-for-depression-in-older-people-on-acute-medical-wards-the-validity-of-the-edinburgh-depression-scale
#14
Collins Esiwe, Sarah Baillon, Aniruddha Rajkonwar, James Lindesay, Nelson Lo, Michael Dennis
BACKGROUND: depression is common in people with poor physical health, particularly within the acute medical in-patient setting. Co-morbid depression contributes to poor outcomes, and screening for depression in acute medical in-patients has been advocated. The Edinburgh Depression Scale (EDS) has been validated in a variety of general hospital patient groups, but not previously in older acute medical in-patients. METHODS: one hundred and eighteen patients aged 65 and older on acute medical wards were assessed using a standardised diagnostic interview (Present State Examination-Schedules for Clinical Assessment in Neuropsychiatry) to identify depression according to ICD-10 criteria...
July 2016: Age and Ageing
https://www.readbyqxmd.com/read/27042933/sfrp2-in-the-aged-microenvironment-drives-melanoma-metastasis-and-therapy-resistance
#15
Amanpreet Kaur, Marie R Webster, Katie Marchbank, Reeti Behera, Abibatou Ndoye, Curtis H Kugel, Vanessa M Dang, Jessica Appleton, Michael P O'Connell, Phil Cheng, Alexander A Valiga, Rachel Morissette, Nazli B McDonnell, Luigi Ferrucci, Andrew V Kossenkov, Katrina Meeth, Hsin-Yao Tang, Xiangfan Yin, William H Wood, Elin Lehrmann, Kevin G Becker, Keith T Flaherty, Dennie T Frederick, Jennifer A Wargo, Zachary A Cooper, Michael T Tetzlaff, Courtney Hudgens, Katherine M Aird, Rugang Zhang, Xiaowei Xu, Qin Liu, Edmund Bartlett, Giorgos Karakousis, Zeynep Eroglu, Roger S Lo, Matthew Chan, Alexander M Menzies, Georgina V Long, Douglas B Johnson, Jeffrey Sosman, Bastian Schilling, Dirk Schadendorf, David W Speicher, Marcus Bosenberg, Antoni Ribas, Ashani T Weeraratna
Cancer is a disease of ageing. Clinically, aged cancer patients tend to have a poorer prognosis than young. This may be due to accumulated cellular damage, decreases in adaptive immunity, and chronic inflammation. However, the effects of the aged microenvironment on tumour progression have been largely unexplored. Since dermal fibroblasts can have profound impacts on melanoma progression, we examined whether age-related changes in dermal fibroblasts could drive melanoma metastasis and response to targeted therapy...
April 14, 2016: Nature
https://www.readbyqxmd.com/read/27021296/ccr5-t-bet-foxp3-effector-cd4-t-cells-drive-atherosclerosis
#16
Jie Li, Sara McArdle, Amin Gholami, Takayuki Kimura, Dennis Wolf, Teresa Gerhardt, Jacqueline Miller, Christian Weber, Klaus Ley
RATIONALE: CD4 T cells are involved in the pathogenesis of atherosclerosis, but atherosclerosis-specific CD4 T cells have not been described. Moreover, the chemokine(s) that regulates T-cell trafficking to the atherosclerotic lesions is also unknown. OBJECTIVE: In Apoe(-/-) mice with mature atherosclerotic lesions (5 months of high fat diet), we find that most aortic T cells express CCR5 and interferon-γ with a unique combination of cell surface markers (CD4(+)CD25(-)CD44(hi)CD62L(lo)) and transcription factors (FoxP3(+)T-bet(+))...
May 13, 2016: Circulation Research
https://www.readbyqxmd.com/read/26914591/congruence-of-group-therapist-and-group-member-alliance-judgments-in-emotionally-focused-group-therapy-for-binge-eating-disorder
#17
COMMENT
Angelo Compare, Giorgio A Tasca, Gianluca Lo Coco, Dennis M Kivlighan
We used West and Kenny's (2011) Truth-and-Bias (T&B) model to examine how accurately group therapists' judge their group members' alliances, and the effects of therapist-patient congruence in alliance ratings on patient outcomes. Were considered: (a) directional bias - therapists' tendency to over- or underrate their clients' alliances, (b) truth strength - clients' alliance ratings, and (c) bias strength - therapists' tendency to conflate their alliance ratings for a specific group member with the average alliance ratings for the other members of the group...
June 2016: Psychotherapy
https://www.readbyqxmd.com/read/26683339/noninvasive-prenatal-diagnosis-of-congenital-adrenal-hyperplasia
#18
REVIEW
Ahmed Khattab, Tony Yuen, Li Sun, Mabel Yau, Ariella Barhan, Mone Zaidi, Y M Dennis Lo, Maria I New
A major hallmark of classical congenital adrenal hyperplasia (CAH) is genital ambiguity noted at birth in affected females, which leads to psychological and psychosexual issues in adult life. Attempts to correct genital ambiguity through surgical intervention have been partially successful. Fetal hyperandrogenemia and genital ambiguity have been shown to be preventable by prenatal administration of low-dose dexamethasone initiated before the 9th week of gestation. In 7 of 8 at-risk pregnancies, the unaffected fetus is unnecessarily exposed to dexamethasone for weeks until the diagnosis of classical CAH is ruled out by invasive procedures...
2016: Endocrine Development
https://www.readbyqxmd.com/read/26541391/acquisition-analysis-and-sharing-of-data-in-2015-and-beyond-a-survey-of-the-landscape-a-conference-report-from-the-american-heart-association-data-summit-2015
#19
Elliott M Antman, Emelia J Benjamin, Robert A Harrington, Steven R Houser, Eric D Peterson, Mary Ann Bauman, Nancy Brown, Vincent Bufalino, Robert M Califf, Mark A Creager, Alan Daugherty, David L Demets, Bernard P Dennis, Shahram Ebadollahi, Mariell Jessup, Michael S Lauer, Bernard Lo, Calum A MacRae, Michael V McConnell, Alexa T McCray, Michelle M Mello, Eric Mueller, Jane W Newburger, Sally Okun, Milton Packer, Anthony Philippakis, Peipei Ping, Prad Prasoon, Véronique L Roger, Steve Singer, Robert Temple, Melanie B Turner, Kevin Vigilante, John Warner, Patrick Wayte
BACKGROUND: A 1.5-day interactive forum was convened to discuss critical issues in the acquisition, analysis, and sharing of data in the field of cardiovascular and stroke science. The discussion will serve as the foundation for the American Heart Association's (AHA's) near-term and future strategies in the Big Data area. The concepts evolving from this forum may also inform other fields of medicine and science. METHODS AND RESULTS: A total of 47 participants representing stakeholders from 7 domains (patients, basic scientists, clinical investigators, population researchers, clinicians and healthcare system administrators, industry, and regulatory authorities) participated in the conference...
November 2015: Journal of the American Heart Association
https://www.readbyqxmd.com/read/26473414/prenatal-diagnosis-innovation-genome-sequencing-of-maternal-plasma
#20
REVIEW
Felix C K Wong, Y M Dennis Lo
Noninvasive prenatal testing (NIPT) is accomplished by analysis of circulating cell-free fetal nucleic acids in maternal plasma. The advent of massively parallel sequencing (MPS) has enabled NIPT of chromosomal aneuploidies with unprecedented robustness, and these tests are now widely available for clinical use. Moreover, MPS-based NIPT of subchromosomal deletions/duplications and single-gene disorders has also been achieved, and the number of applications is growing. In addition to specific fetal genetic disorders, the whole fetal genome, transcriptome, and methylome have been revealed by deep sequencing of maternal plasma...
2016: Annual Review of Medicine
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