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Elaine T Lam, S Gail Eckhardt, Wells Messersmith, Antonio Jimeno, Cindy L O'Bryant, Ramesh K Ramanathan, Glen J Weiss, Manpreet Chadha, Abbie Oey, Han Ting Ding, Patricia A Culp, Stephan F Keller, Vivian Y Zhao, L Claire Tsao, Anil Singhal, Kyle D Holen, Daniel D Von Hoff
This phase I study evaluates the safety, maximum tolerated dose (MTD), pharmacokinetics (PK), pharmacodynamics, and preliminary anticancer activity of enavatuzumab, a humanized IgG1 antibody to the TWEAK receptor, in patients with advanced solid malignancies. Patients received escalating doses of enavatuzumab given intravenously over 60 minutes every 2 weeks. Blood was obtained for PK and biomarker assessment. Three patients were enrolled per dose level in a standard 3+3 design with response assessment by RECIST version 1...
October 20, 2017: Molecular Cancer Therapeutics
Hua Zhao, Peng Wang, Chengliang Zhu, Ramanathan Subramanian, Hongpu Li
Through analyzing the structure of the phase-shifted helical long-period fiber grating (HLPG), which is fabricated based on the thermally twisting method, we have shown that there exists a phase-diffusion effect when the thermal region is larger than the grating period itself, i.e., the inserted phase preset at particular period will be diffused to several neighboring periods, which causes a large distortion in the transmission spectrum. We have analytically proved that this kind of phase-diffusion effect can be quantified by doing the convolution between the preset phase function and the phase-diffusion function in spatial domain...
August 7, 2017: Optics Express
Anand Ramanathan, Thekkeparambil Chandrabose Srijaya, Prema Sukumaran, Rosnah Binti Zain, Noor Hayaty Abu Kasim
OBJECTIVES: Homeobox genes are a group of conserved class of transcription factors that function as key regulators during the embryonic developmental processes. They act as master regulator for developmental genes, which involves coordinated actions of various auto and cross-regulatory mechanisms. In this review, we summarize the expression pattern of homeobox genes in relation to the tooth development and various signaling pathways or molecules contributing to the specific actions of these genes in the regulation of odontogenesis...
October 4, 2017: Archives of Oral Biology
Mani Ramanathan, Yi-Hung Liu, Shie-Ming Peng, Shiuh-Tzung Liu
A transition metal-free synthesis of multisubstituted quinazolin-4(3H)-imines has been realized by the direct reaction of aryldiazonium salts, nitriles, and 2-cyanoanilines in a one-pot fashion. This strategy utilizes the in situ formation of reactive N-arylnitrilium intermediate, which undergoes further tandem cyclization with consecutive formation of N-C bonds. Broad functional group compatibility, mild conditions, shorter time, and operational simplicity are the notable features of this report.
October 13, 2017: Organic Letters
Ashleigh Scott, Nicholas Weber, Campbell Tiley, Kerry Taylor, John Taper, Simon Harrison, Kah-Lok Chan, Richard Stark, Cindy Lee, Kirk Morris, P Joy Ho, Anthony Dodds, Sundra Ramanathan, Raj Ramakrishna, Anne-Marie Watson, Bradley Auguston, Fiona Kwok, Hang Quach, Pauline Warburton, Philip Rowlings, Peter Mollee
No abstract text is available yet for this article.
October 12, 2017: Leukemia & Lymphoma
Peter Barr, John Ormiston, Jim Stewart, Parma Nand, Tharumenthiran Ramanathan, Mark Webster
BACKGROUND: As the indications for transcatheter aortic valve implantation (TAVI) have expanded, so to have the demands on interventionists to allow as many patients to access this technology as possible. METHODS: We retrospectively reviewed our TAVI database for patients who had received a 29mm SAPIEN 3 valve despite having an annular area greater than the manufacturer-recommended upper limit of 683mm(2), as determined by multi-detector computed tomography (MDCT)...
September 28, 2017: Heart, Lung & Circulation
Raghu Ramanathan, Karthikeyan Sivanesan
The HIV-infected patients are co-infected with many bacterial infections in which tuberculosis is most common found worldwide. These patients are often administered with combined therapy of anti-retroviral and anti-tubercular drugs which leads to several complications including hepatotoxicity or adverse drug interactions. The drug-drug interactions between the anti-retroviral and anti-tubercular drugs are not clearly defined and hence, this study was conducted to evaluate the pharmacokinetic drug-drug interactions of Zidovudine (AZT) with Isoniazid (INH) and its hepatotoxic metabolites...
January 1, 2017: Journal of Pharmacy Practice
Elizabeth M Parzych, Kazutoyo Miura, Aarti Ramanathan, Carole A Long, James M Burns
Challenges with the production and suboptimal immunogenicity of malaria vaccine candidates have slowed the development of a Plasmodium falciparum multi-antigen vaccine. Attempting to resolve these issues, we focused on the use of the highly immunogenic merozoite surface protein 8 (MSP8) as a vaccine carrier protein. Previously, we showed that genetic fusion of the C-terminal 19 kDa fragment of merozoite surface protein 1 (MSP119) to PfMSP8 facilitated antigen production, folding and induction of neutralizing antibodies to conformational B cell epitopes of MSP119 Here, using the PfMSP1/8 construct, we further optimized the rPfMSP8 carrier by introduction of two cysteine to serine substitutions (CΔS) to improve the yield of monomeric product...
October 9, 2017: Infection and Immunity
Nyall R London, Murugappan Ramanathan
The sinonasal epithelial barrier is comprised of tight and adherens junction proteins. Disruption of epithelial barrier function has been hypothesized to contribute to allergic disease such as allergic rhinitis through increased passage of antigens and exposure of underlying tissue to these stimuli. Several mechanisms of sinonasal epithelial barrier disruption include antigen proteolytic activity, inflammatory cytokine-mediated tight junction breakdown, or exacerbation from environmental stimuli. Mechanisms of sinonasal epithelial barrier stabilization include corticosteroids and nuclear erythroid 2-related factor 2 (Nrf2) cytoprotective pathway activation...
October 5, 2017: Otolaryngologic Clinics of North America
Christopher R Roxbury, J Trent Magruder, Murugappan Ramanathan, Michael Lim, Gary L Gallia, Masaru Ishii, Douglas D Reh
BACKGROUND: Sellar pathology is increasingly addressed using the expanded endonasal approach (EEA). Although avascular graft reconstruction is an acceptable means to prevent cerebrospinal fluid leak, there are few data regarding sinonasal morbidity in these patients. In this study we compare rates of persistent postoperative crusting (PPC) and rhinosinusitis in patients undergoing sellar reconstruction with mucosal autografting and acellular dermal allografting (ADA). METHODS: Patients undergoing the EEA between 2008 and 2014 were categorized into 2 subgroups: mucosal reconstruction and ADA reconstruction...
October 6, 2017: International Forum of Allergy & Rhinology
Samantha J Mikals, Austin M McCuiston, Murugappan Ramanathan
No abstract text is available yet for this article.
October 5, 2017: JAMA Otolaryngology—Head & Neck Surgery
Tom Kupfer, Joerg Lehmann, Duncan J Butler, Ganesan Ramanathan, Tracy E Bailey, Rick D Franich
PURPOSE: This study investigates a large-area plane-parallel ionization chamber (LAC) for measurements of dose-area product in water (DAPw ) in megavoltage (MV) photon fields. METHODS: Uniformity of electrode separation of the LAC (PTW34070 Bragg Peak Chamber, sensitive volume diameter: 8.16 cm) was measured using high-resolution microCT. Signal dependence on angle α of beam incidence for square 6 MV fields of side length s = 20 cm and 1 cm was measured in air...
October 4, 2017: Journal of Applied Clinical Medical Physics
Ragu Ramanathan, Amanda J King-Ahmad, Christopher L Holliman, A David Rodrigues
AIM: Coproporphyrin-I (CP-I) and coproporphyrin-III (CP-III) in plasma and urine have been proposed as biomarkers for assessing drug-drug interactions involving hepatic drug transporters such as organic anion-transporting peptides (OATP), 1B1 and 1B3. Materials & methods: Plasma and urine extracts were analyzed for CP-I/CP-III using a TripleTOF API6600 HRMS. Results: Previously unreported, CP-I/CP-III doubly charged ions (m/z 328.14) were used as precursor ions to improve the assay sensitivity and selectivity over the singly charged precursor ions (m/z 655...
October 5, 2017: Bioanalysis
Binnu Gangadharan, Margaret S Sunitha, Souhrid Mukherjee, Ritu Roy Chowdhury, Farah Haque, Narendrakumar Sekar, Ramanathan Sowdhamini, James A Spudich, John A Mercer
Point mutations in genes encoding sarcomeric proteins are the leading cause of inherited primary cardiomyopathies. Among them are mutations in the TNNT2 gene that encodes cardiac troponin T (TnT). These mutations are clustered in the tropomyosin (Tm) binding region of TnT, TNT1 (residues 80-180). To understand the mechanistic changes caused by pathogenic mutations in the TNT1 region, six hypertrophic cardiomyopathy (HCM) and two dilated cardiomyopathy (DCM) mutants were studied by biochemical approaches. Binding assays in the absence and presence of actin revealed changes in the affinity of some, but not all, TnT mutants for Tm relative to WT TnT...
October 2, 2017: Proceedings of the National Academy of Sciences of the United States of America
Raghu Ramanathan, Secunda Rupert, Sakthivel Selvaraj, Jeswanth Satyanesan, Rosy Vennila, Surendran Rajagopal
BACKGROUND/AIM: Mesenchymal stem cells (MSCs) are multipotent precursor cells having self-renewal ability making them a candidate for use in regenerative medicine. Acute liver injury results in sudden loss of hepatic function leading to organ failure. Liver transplantation is often required to salvage patients with acute liver failure. Due to shortage of organs, identification of alternate method is the need of the hour. In view of this, an attempt has been made to check the regenerative ability of WJ-MSCs (wharton's jelly derived MSC) in mice models for acute liver injury...
September 2017: Journal of Clinical and Experimental Hepatology
(no author information available yet)
No abstract text is available yet for this article.
October 2017: Pediatrics
Patrick Younan, Mathieu Iampietro, Andrew Nishida, Palaniappan Ramanathan, Rodrigo I Santos, Mukta Dutta, Ndongala Michel Lubaki, Richard A Koup, Michael G Katze, Alexander Bukreyev
Ebola virus (EBOV) disease (EVD) results from an exacerbated immunological response that is highlighted by a burst in the production of inflammatory mediators known as a "cytokine storm." Previous reports have suggested that nonspecific activation of T lymphocytes may play a central role in this phenomenon. T-cell immunoglobulin and mucin domain-containing protein 1 (Tim-1) has recently been shown to interact with virion-associated phosphatidylserine to promote infection. Here, we demonstrate the central role of Tim-1 in EBOV pathogenesis, as Tim-1(-/-) mice exhibited increased survival rates and reduced disease severity; surprisingly, only a limited decrease in viremia was detected...
September 26, 2017: MBio
Jeffrey R Infante, Ronald L Korn, Lee S Rosen, Patricia LoRusso, Samuel S Dychter, Joy Zhu, Daniel C Maneval, Ping Jiang, H Michael Shepard, Gregory Frost, Daniel D Von Hoff, Mitesh J Borad, Ramesh K Ramanathan
BACKGROUND: Hyaluronan accumulation in tumour stroma is associated with reduced survival in preclinical cancer models. PEGPH20 degrades hyaluronan to facilitate tumour access for cancer therapies. Our objective was to assess safety and antitumour activity of PEGPH20 in patients with advanced solid tumours. METHODS: In HALO-109-101 (N=14), PEGPH20 was administered intravenously once or twice weekly (0.5 or 50 μg kg(-1)) or once every 3 weeks (0.5-1.5 μg kg(-1))...
September 26, 2017: British Journal of Cancer
Taimur Ahmed, Sumeet Walia, Jeeson Kim, Hussein Nili, Rajesh Ramanathan, Edwin L H Mayes, Desmond W M Lau, Omid Kavehei, Vipul Bansal, Madhu Bhaskaran, Sharath Sriram
Transparent non-volatile memory devices are desirable for realizing visually-clear integrated systems for information storage. Optical transparency provides advantages in applications such as smart glass electronic devices and wearable electronics. However, achieving high transparency limits the choice of active layers as well as the electrodes; thereby, constraining device processing and performance. Here, we demonstrate bilayer transparent memory cells using room temperature deposited amorphous strontium titanate as the functional material and indium tin oxide electrodes...
October 5, 2017: Nanoscale
Manoj Biniwale, Angela Weiner, Smeeta Sardesai, Rowena Cayabyab, Lorayne Barton, Rangasamy Ramanathan
OBJECTIVE: The objective of this study is to validate the reliability of early postnatal weight gain as an accurate predictor of type 1 retinopathy of prematurity (ROP) requiring treatment in a large predominantly Hispanic US cohort with the use of an online tool called WINROP (weight, neonatal retinopathy of prematurity (IGF-1), neonatal retinopathy of prematurity). STUDY DESIGN: Retrospective cohort study consisted of preterm infants <32 weeks gestation and birth weight <1500 g...
October 1, 2017: Journal of Maternal-fetal & Neonatal Medicine
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