David E. Schwartz

Dana-Farber Cancer Institute

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Tse Nga Ng

University of California, San Diego

Neal H. Cohen

University of California, San Francisco

Richard D. Minshall

University of Illinois Chicago

János Veres

NextFlex

Sergei M. Danilov

University of Illinois Chicago

P. Mei

Palo Alto Research Center

Randal O. Dull

University of Arizona

B. S. Krusor

Palo Alto Research Center

Gregory L. Whiting

University of Colorado Boulder

Guochang Hu

Illinois College

Cooperative Institutions

University of Illinois Chicago

Illinois College

Palo Alto Research Center

University of Illinois Urbana-Champaign

Northwestern University

University of Chicago

University of California, San Francisco

Harvard University

University of Zurich

The University of Texas Health Science Center at Houston

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ACE phenotyping in Gaucher disease

Molecular Genetics and Metabolism (2018)

Sergei M. Danilov Victoria Tikhomirova Roman Metzger Irina A. Naperova Т. М. Букина

10.1016/j.ymgme.2018.02.007

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Citations (37)

Hematopoiesis on cellulose ester membranes (CEM). XII. Effect of membrane enrichment by purified matrix proteins

The International Journal Of Cell Cloning (1990)

William H. Knospe Salah Husseini David E. Schwartz

Journal Article Hematopoiesis on cellulose ester membranes (CEM). XII. Effect of membrane enrichment by purified matrix proteins Get access William H. Knospe, M.D., William H. Knospe, M.D. Section of Hematology, Departments of Medicine and Biochemistry, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois, USA Correspondence: William H. Knospe, M.D., Director, Section of Hematology, Rush-Presbyterian-St. Luke's Medical Center, 1653 West Congress Parkway, Chicago, IL 60612, USA. Search for other works by this author on: Oxford Academic Google Scholar Salah G. Husseini, Salah G. Husseini Section of Hematology, Departments of Medicine and Biochemistry, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois, USA Search for other works by this author on: Oxford Academic Google Scholar David Schwartz David Schwartz Section of Hematology, Departments of Medicine and Biochemistry, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois, USA Search for other works by this author on: Oxford Academic Google Scholar The International Journal Of Cell Cloning, Volume 8, Issue 6, 1990, Pages 425–430, https://doi.org/10.1002/stem.5530080645 Published: 01 January 1996 Article history Received: 14 May 1990 Accepted: 06 July 1990 Published: 01 January 1996

Section (typography)

10.1002/stem.5530080645

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Propofol increases morbidity and mortality in a rat model of sepsis

Critical Care (2015)

Martin Schläpfer Tobias Piegeler Randal O. Dull David E. Schwartz Mao Mao

Abstract Introduction Severe sepsis is associated with approximately 50% mortality and accounts for tremendous healthcare costs. Most patients require ventilatory support and propofol is commonly used to sedate mechanically ventilated patients. Volatile anesthetics have been shown to attenuate inflammation in a variety of different settings. We therefore hypothesized that volatile anesthetic agents may offer beneficial immunomodulatory effects during the course of long-term intra-abdominal sepsis in rats under continuous sedation and ventilation for up to 24 hours. Methods Sham operation or cecal ligation and puncture (CLP) was performed in adult male Wistar rats followed by mechanical ventilation. Animals were sedated for 24 hours with propofol (7 to 20 mg/kg/h), sevoflurane, desflurane or isoflurane (0.7 minimal alveolar concentration each). Results Septic animals sedated with propofol showed a mean survival time of 12 hours, whereas >56% of all animals in the volatile groups survived 24 hours ( P <0.001). After 18 hours, base excess in propofol + CLP animals (−20.6 ± 2.0) was lower than in the volatile groups (isoflurane + CLP: -11.7 ± 4.2, sevoflurane + CLP: -11.8 ± 3.5, desflurane + CLP -14.2 ± 3.7; all P <0.03). Plasma endotoxin levels reached 2-fold higher levels in propofol + CLP compared to isoflurane + CLP animals at 12 hours ( P <0.001). Also blood levels of inflammatory mediators (tumor necrosis factor-α, interleukin-1β, interleukin-10, CXCL-2, interferon-γ and high mobility group protein-1) were accentuated in propofol + CLP rats compared to the isoflurane + CLP group at the same time point ( P <0.04). Conclusions This is the first study to assess prolonged effects of sepsis and long-term application of volatile sedatives compared to propofol on survival, cardiovascular, inflammatory and end organ parameters. Results indicate that volatile anesthetics dramatically improved survival and attenuate systemic inflammation as compared to propofol. The main mechanism responsible for adverse propofol effects could be an enhanced plasma endotoxin concentration, leading to profound hypotension, which was unresponsive to fluid resuscitation.

Desflurane

10.1186/s13054-015-0751-x

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Citations (54)

Peel-and-Stick Sensors Powered by Directed RF Energy

Christopher Lalau-Keraly George Daniel Joseph Lee David E. Schwartz

PARC, a Xerox Company, is developing a low-cost system of peel-and-stick wireless sensors that will enable widespread building environment sensor deployment with the potential to deliver up to 30% energy savings. The system is embodied by a set of RF hubs that provide power to automatically located sensor nodes, and relay data wirelessly to the building management system (BMS). The sensor nodes are flexible electronic labels powered by rectified RF energy transmitted by an RF hub and can contain multiple printed and conventional sensors. The system design overcomes limitations in wireless sensors related to power delivery, lifetime, and cost by eliminating batteries and photovoltaic devices. Sensor localization is performed automatically by the inclusion of a programmable multidirectional antenna array in the RF hub. Comparison of signal strengths while the RF beam is swept allows for sensor localization, reducing installation effort and enabling automatic recommissioning of sensors that have been relocated, overcoming a significant challenge in building operations. PARC has already demonstrated wireless power and temperature data transmission up to a distance of 20m with less than one minute between measurements, using power levels well within the FCC regulation limits in the 902–928 MHz ISM band. The sensor’s RF energy harvesting antenna achieves high performance with dimensions below 5cm × 9cm.

ISM band

Electro-optical sensor

10.1115/ipack2017-74150

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Molecular characteristics of the inhibition of human neutrophil elastase by nonsteroidal antiinflammatory drugs

Experimental & Molecular Medicine (2000)

Kooil Kang Sung Jun Bae Woo Mi Kim Dae-Heui Lee Unsuck Cho

Nonsteroidal antiinflammatory drugs(NSAIDs) are known as clinically effective agents for treatment of inflammatory diseases. Inhibition of cyclooxygenase has been thought to be a major facet of the pharmacological mechanism of NSAIDs. However, it is difficult to ascribe the antiinflammatory effects of NSAIDs solely to the inhibition of prostaglandin synthesis. Human neutrophil elastase (HNElastase; HNE, EC 3.4.21.37) has been known as a causative factor in inflammatory diseases. To investigate the specific relationship between HNElastase inhibition and specificity of molecular structure of several NSAIDs, HNElastase was purified by Ultrogel AcA54 gel filtration, CM-Sephadex ion exchange, and HPLC (with TSK 250 column) chromatography. HNElastase was inhibited by aspirin and salicylate in a competitive manner and by naproxen, ketoprofen, phenylbutazone, and oxyphenbutazone in a partial competative manner, but not by ibuprofen and tolmetin. HNElastase-phenylbutazone-complex showed strong Raman shifts at 200, 440, 1124, 1194, 1384, 1506, and 1768 cm(-1). The Raman bands 1194, 1384, and 1768 cm(-1) may represent evidences of the conformational change at -N=N-Φ radical, pyrazol ring, and -C=O radical of the elastase-drug complex, respectively. Phenylbutazone might be bound to HNElastase by ionic and hydrophobic interaction, and masked the active site. Inhibition of HNElastase could be another mechanism of action of NSAIDs besides cyclooxygenase inhibition in the treatment of inflammatory diseases. Different inhibition characteristics of HNE-lastase by NSAIDs such as aspirin, phenylbutazone-like drugs and ineffective drugs could be important points for drawing the criteria for appropriate drugs in clinical application.

Flurbiprofen

Ketoprofen

Oxyphenbutazone

Ibuprofen

Anti-inflammatory

Sulindac

Mechanism of Action

Acetaminophen

10.1038/emm.2000.25

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Citations (5)

An RF-Powered Self-Locating Flexible Building Environment Sensor System

David E. Schwartz Shabnam Ladan Vijay Karthik Venkatasubramanian Joseph Lee P. Mei

Wireless, battery-free, peel-and-stick sensors can enable many new capabilities in the Internet-of-Things(IoT). Low-cost sensor hardware and manufacturing together with no-skill installation and commissioning and low maintenance requirements can allow widely distributed sensors for continuous, comprehensive monitoring for structural health, physical health, safety, and industrial and environmental applications. This paper presents a system of RF-powered flexible sensors for building environment sensing with the potential to deliver up to 30% energy savings through improved HVAC controls. The system utilizes a set of electronic hubs that both provide remote power to the sensors and wirelessly relay sensor data to the building management system (BMS). The sensors are flexible electronic labels powered by rectified RF energy received from a hub and can contain multiple printed and conventional sensors including for temperature, humidity, and air quality. The electronic hub includes a programmable multidirectional beam-steering antenna that allows arbitrarily-placed sensors to be automatically located by the system through monitoring of received RF power as a function of transmission angle. The system has achieved extremely low-power operation, wireless sensor data transmission over > 10 meters, remote power delivered across >7 meters and sensor localization to within 0.5 meters.

10.1109/wptc45513.2019.9055560

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Citations (1)

Identifying S100B as a Biomarker and a Therapeutic Target For Brain Injury and Multiple Diseases

Current Medicinal Chemistry (2016)

Zhao Zhong Chong Benjarat Changyaleket Hao‐Liang Xu Randy O. Dull David E. Schwartz

The calcium binding protein S100B has attracted great attention as a biomarker for a variety of diseases. S100B is mainly expressed in glial cells and functions through intracellular and extracellular signaling pathways. The biological roles of S100B have been closely associated with its concentrations and its physiological states. The released S100B can bind to the receptor of advanced glycation end products and induce the initiation of multiple cell signaling transductions. The regulation of S100B bioactivities has been suggested through phosphoinositide 3 kinase/Akt, p53, mitogen-activated protein kinases, transcriptional factors including nuclear factor-kappaB, and cyclic adenosine monophosphate. The levels of S100B in the blood may function to predict the progress or the prognosis of many kinds of diseases, such as cerebrovascular diseases, neurodegenerative diseases, motor neuron diseases, traumatic brain injury, schizophrenia, depression, diabetes mellitus, myocardial infarction, cancer, and infectious diseases. Given that the activity of S100B has been implicated in the pathological process of these diseases, S100B should not be simply regarded as a biomarker, it may also function as therapeutic target for these diseases. Further elucidation of the roles of S100B may formulate innovative therapeutic strategies for multiple diseases. Keywords: RAGE, PI3K, MAPK, neurodegeneration, stroke, diabetes, biomarker.

RAGE

10.2174/0929867323666160406121117

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Citations (32)

Mapping of Conformational mAb Epitopes to the C Domain of Human Angiotensin I-Converting Enzyme

Journal of Proteome Research (2008)

Irina A. Naperova Irina V. Balyasnikova David E. Schwartz Jean M. Watermeyer Edward D. Sturrock

Angiotensin I-converting enzyme (ACE, CD143) has two homologous domains, each having a functional active site. Fine epitope mapping of 8 mAbs to the C-terminal domain of human ACE was carried out using plate precipitation assays, mAbs' cross-reactivity with ACE from different species, site-directed mutagenesis, and antigen- and cell-based ELISAs. Almost all epitopes contained potential glycosylation sites. Therefore, these mAbs could be used to distinguish different glycoforms of ACE expressed in different tissues or cell lines. mAbs 1B8 and 3F10 were especially sensitive to the composition of the N-glycan attached to Asn 731; mAbs 2H9 and 3F11 detected the glycosylation status of the glycan attached to Asn 685 and perhaps Asn1162; and mAb 1E10 and 4E3 recognized the glycan on Asn 666. The epitope of mAb 1E10 is located at the N-terminal end of the C domain, close to the unique 36 amino acid residues of testicular ACE (tACE). Moreover, it binds preferentially to tACE on the surface of human spermatozoa and thus may find application as an immunocontraceptive drug. mAb 4E3 was the best mAb for quantification of ACE-expressing somatic cells by flow cytometry. In contrast to the other mAbs, binding of mAb 2B11 was not markedly influenced by ACE glycosylation or by the cell culture conditions or cell types, making this mAb a suitable reference antibody. Epitope mapping of these C-domain mAbs, particularly those that compete with N-domain mAbs, enabled us to propose a model of the two-domain somatic ACE that might explain the interdomain cooperativity. Our findings demonstrated that mAbs directed to conformational epitopes on the C-terminal domain of human ACE are very useful for the detection of testicular and somatic ACE, quantification using flow cytometry and ELISA assays, and for the study of different aspects of ACE biology.

Epitope mapping

10.1021/pr800142w

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Citations (27)

Utilizing high resolution and reconfigurable patterns in combination with inkjet printing to produce high performance circuits

Applied Physics Letters (2014)

P. Mei Tse Nga Ng R. Lujan David E. Schwartz Siv Kor

Inkjet printing on pre-fabricated high-resolution substrate is developed to improve the operational speed of printed organic transistors. The high-resolution features are designed to define transistor critical dimensions, while maintaining the flexibility to incorporate different circuit constructions. Logic gate and ring oscillator circuits fabricated by inkjet printing on the high-resolution substrate are demonstrated, to show that the same high resolution pattern can be adapted for constructing different electronic circuits.

Printed Electronics

Inkjet Printing

Ring oscillator

10.1063/1.4896547

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A Novel Angiotensin I-Converting Enzyme Mutation (S333W) Impairs N-Domain Enzymatic Cleavage of the Anti-Fibrotic Peptide, AcSDKP

PLoS ONE (2014)

Sergei M. Danilov Michael S. Wade Sylva L. U. Schwager Ross G. Douglas Andrew B. Nesterovitch

Background Angiotensin I-converting enzyme (ACE) has two functional N- and C-domain active centers that display differences in the metabolism of biologically-active peptides including the hemoregulatory tetrapeptide, Ac-SDKP, hydrolysed preferentially by the N domain active center. Elevated Ac-SDKP concentrations are associated with reduced tissue fibrosis. Results We identified a patient of African descent exhibiting unusual blood ACE kinetics with reduced relative hydrolysis of two synthetic ACE substrates (ZPHL/HHL ratio) suggestive of the ACE N domain center inactivation. Inhibition of blood ACE activity by anti-catalytic mAbs and ACE inhibitors and conformational fingerprint of blood ACE suggested overall conformational changes in the ACE molecule and sequencing identified Ser333Trp substitution in the N domain of ACE. In silico analysis demonstrated S333W localized in the S1 pocket of the active site of the N domain with the bulky Trp adversely affecting binding of ACE substrates due to steric hindrance. Expression of mutant ACE (S333W) in CHO cells confirmed altered kinetic properties of mutant ACE and conformational changes in the N domain. Further, the S333W mutant displayed decreased ability (5-fold) to cleave the physiological substrate AcSDKP compared to wild-type ACE. Conclusions and Significance A novel Ser333Trp ACE mutation results in dramatic changes in ACE kinetic properties and lowered clearance of Ac-SDKP. Individuals with this mutation (likely with significantly increased levels of the hemoregulatory tetrapeptide in blood and tissues), may confer protection against fibrosis.

Tetrapeptide

10.1371/journal.pone.0088001

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Citations (20)