Jonathan D Daniels | North Carolina State University (original) (raw)

Papers by Jonathan D Daniels

Infection Control & Hospital Epidemiology, 2020

Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a frequent cause of healthcare-... more Background: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a frequent cause of healthcare-associated infections (HAIs). The CDC Emerging Infections Program (EIP) conducted population and laboratory-based surveillance of CRPA in selected areas in 8 states from August 1, 2016, through July 31, 2018. We aimed to describe the molecular epidemiology and mechanisms of resistance of CRPA isolates collected through this surveillance. Methods: We defined a case as the first isolate of P. aeruginosa resistant to imipenem, meropenem, or doripenem from the lower respiratory tract, urine, wounds, or normally sterile sites identified from a resident of the EIP catchment area in a 30-day period; EIP sites submitted a systematic random sample of isolates to CDC for further characterization. Of 1,021 CRPA clinical isolates submitted, 707 have been sequenced to date using an Illumina MiSeq. Sequenced genomes were classified using the 7-gene multilocus sequence typing (MLST) scheme, and a core ...

1 Jonathan Daniels Biografi the Man of Independence Jonathan Daniels, 1950

NeuroRehabilitation, 2011

Bone loss is a common and often debilitating condition that accompanies spinal cord injury. Becau... more Bone loss is a common and often debilitating condition that accompanies spinal cord injury. Because bone loss after spinal cord injury is multifactorial, it can be difficult to assess and treat. This process becomes even more complex as secondary conditions associated with aging are introduced. There are two purposes of this literature review. The first is to summarize information concerning the mechanisms of bone loss and osteoporosis after spinal cord injury. The second is to summarize existing data concerning the effects of exercise on bone loss after spinal cord injury. Literature was reviewed concerning the bone loss process and the non-pharmacological treatment options for ameliorating bone loss after spinal cord injury. (Part One) Osteoporosis is universal in persons with chronic complete spinal cord injury, which increases the risk of bone fracture. Bone loss after spinal cord injury is both sublesional and regional with the greatest areas of bone demineralization being in t...

The Journal of Spinal Cord Medicine, 2012

Background: Functional electrical stimulation (FES) has been regularly used to offset several neg... more Background: Functional electrical stimulation (FES) has been regularly used to offset several negative body composition and metabolic adaptations following spinal cord injury (SCI). However, the outcomes of many FES trials appear to be controversial and incoherent. Objective: To document the potential consequences of several factors (e.g. pain, spasms, stress and lack of dietary control) that may have attenuated the effects on body composition and metabolic profile despite participation in 21 weeks of FES training. Participant: A 29-year-old man with T6 complete SCI participated in 21 weeks of FES, 4 days per week. Methods: Prior to and following training, the participant performed arm-crank-graded exercise testing to measure peak VO 2. Tests conducted included anthropometrics and dual energy X-ray absorptiometry body composition assessments, resting energy expenditure, plasma lipid profiles and intravenous glucose tolerance tests. Results: The participant frequently reported increasing pain, stress and poor eating habits. VO 2 peak decreased by 2.4 ml/kg/minute, body mass increased by 8.5 kg, and body mass index increased from 25 to 28 kg/m 2. Waist and abdominal circumferences increased by 2-4 cm, while %fat mass increased by 5.5%. Absolute increases in fat mass and fat-free mass of 8.4 and 1 kg, respectively, were reported. Fasting and peak plasma glucose increased by 12 and 14.5%, while lipid panel profiles were negatively impacted. Conclusion: Failure to control for the listed negative emerging factors may obscure the expected body composition and metabolic profile adaptations anticipated from FES training.

Molecular Endocrinology, 2002

Nuclear receptors form strong dimers that are essential for their function as transcription facto... more Nuclear receptors form strong dimers that are essential for their function as transcription factors, and it is thought that ligand binding can affect dimer stability. In this report, we describe convenient fluorescence resonance energy transfer (FRET)-based methods for measuring the thermodynamic and kinetic stability of dimers of the estrogen receptor-␣ ligand-binding domain (ER␣-LBD). We have developed receptors that are chemically labeled with a single fluorophore in a site-specific manner. These fluorophore-labeled ERs are functional and can be used to measure directly the affinity and stability of ER␣-LBD dimers. Our results indicate that unligan-ded ER␣-LBDs exist as very stable dimers and that the dissociation rate of these dimers is slow (t 1/2 ‫؍‬ 39 ؎ 3 min at 28 C) and is further slowed (≤7-fold) by the addition of various ligands. Estrogen antagonists provide greater kinetic stabilization of the ER dimers than agonists. In addition, coactivator peptides containing the LXXLL motif selectively stabilize agonistbound ER␣-LBD dimers. These fluorescence-based assays for measuring the kinetic and thermodynamic stability of ER dimers provide a functional in vitro method for assessing the agonist or antagonist character of novel ligands. (Molecular Endocrinology 16: 2706-2719, 2002) RESULTS ER Mutants Having a Single Reactive Cysteine Can Be Labeled with a Cysteine-Specific Fluorophore in a Site-Specific Manner Proteins can be covalently labeled in a site-specific manner through a reactive cysteine residue (11).

Medicine & Science in Sports & Exercise, 2011

Critical assessment of SCAT2 as a clinical office tool, measuring it's contents and format agains... more Critical assessment of SCAT2 as a clinical office tool, measuring it's contents and format against current concussion assessment methodology and international consensus. A tool better suited to further evaluation of the concussed athlete and addressing the deficiencies of SCAT2 is proposed. RESULTS: SCAT2 has limitations as an office tool; the newly-devised SCOAT incorporates more information useful to accurate clinical concussion management. CONCLUSIONS: The Sports Concussion Office Assessment Tool (SCOAT) is an appropriate clinical evaluation tool that complements the SCAT2 and better allows the clinician to evaluate clinical and cognitive concussion recovery.

Carcinogenesis, 1990

Aflatoxin B1 (AFB1) is a potent hepatotoxic and hepatocarcinogenic mycotoxin that requires bioact... more Aflatoxin B1 (AFB1) is a potent hepatotoxic and hepatocarcinogenic mycotoxin that requires bioactivation to AFB1-2,3-oxide for activity. In addition to epoxidation, microsomal monooxygenases biotransform AFB1 to the less toxic metabolites, aflatoxin M1 (AFM1) and aflatoxin Q1 (AFQ1). The lung is at risk from AFB1 both via inhalation and via the circulation. In the present study, we have characterized rabbit lung and liver microsomal AFB1-DNA binding (an index of AFB1-2,3-oxide formation), AFM1 formation and AFQ1 formation. Vmax values for AFB1-DNA binding were not different between lung and liver when expressed per mg microsomal protein (1.06 +/- 0.13 and 2.12 +/- 1.30 nmol/mg/h for lung and liver respectively), but lung values were greater than liver when expressed per nmol cytochrome P450 (3.64 +/- 0.31 and 1.29 +/- 0.70 nmol/nmol P450/h for lung and liver respectively). Km values for this reaction were not different between lung and liver. Vmax values for AFM1 formation in liver microsomes were greater than in lung when expressed per mg protein, but not when expressed per nmol P450. No differences were detected for the Km for AFM1 formation between lung and liver microsomes. For AFQ1 formation, no differences were detected between Vmax values of lung and liver, regardless of whether results were expressed per mg protein or per nmol P450, while the Km for AFQ1 formation was lower in liver. SKF-525A inhibited these reactions by 63-74% in lung microsomes and 90-96% in liver microsomes. These results indicate that the lung is capable of activating AFB1, and that rabbit lung microsomes contain high activity for this reaction. Furthermore, little AFM1 and AFQ1 are formed in lung microsomes, leading to minimal shunting of AFB1 from the activation pathway.

Canadian Journal of Physiology and Pharmacology, 1990

Amiodarone is a potent and efficacious antiarrhythmic agent, yet associated with its use are life... more Amiodarone is a potent and efficacious antiarrhythmic agent, yet associated with its use are life-threatening pulmonary fibrosis and hepatotoxicity. We have investigated the susceptibility of the male Sprague–Dawley rat to pulmonary and hepatic toxicity after repeated exposure to amiodarone and the effects of such exposure on hepatic and extrahepatic drug metabolizing enzymes. Animals received amiodarone (200 mg∙kg−1∙day−1 i.p., 5 days/week) for 1 week followed by 150 mg∙kg−1∙day−1 (5 days/week) for 3 additional weeks. No signs of pulmonary fibrosis or hepatotoxicity were observed, based on histological examination, lung hydroxyproline content, and plasma alanine aminotransferase activity. Analysis of tissues revealed extensive accumulation of amiodarone and desethylamiodarone in lung and liver, but concentrations were significantly lower in animals treated for 4 weeks than for 1 week. In a separate experiment, rats received amiodarone 150 mg∙kg−1∙day−1 i.p. (5 days/week) for 1 or 4...

Toxicology, Aug 1, 1992

Aflatoxin B1 (AFB1) is a carcinogenic mycotoxin that requires activation to the corresponding 8,9... more Aflatoxin B1 (AFB1) is a carcinogenic mycotoxin that requires activation to the corresponding 8,9-epoxide for activity. In addition to being present in foodstuffs, AFB1 can contaminate respirable grain dusts and thus the respiratory system is a potential target for carcinogenesis. In the present study, we have investigated the role of polycyclic aromatic hydrocarbon-inducible forms of cytochrome P-450 in the pulmonary and hepatic microsomal activation ([3H]AFB1-DNA binding) and detoxification ([3H]AFM1 and [3H]AFQ1 formation) of [3H]AFB1. In rabbit lung microsomes, the apparent Vmax for [3H]AFM1 formation was increased significantly when values were expressed per mg microsomal protein or per nmol P-450 present. In liver microsomes, the apparent Vmax for DNA binding and [3H]AFM1 formation were increased by beta-naphthoflavone (BNF) treatment (to 2.3 and 3.3 times control, respectively) when expressed per mg protein, but when expressed per nmol P-450, only AFM1 formation was significantly increased. The apparent Km values for both these reactions were unaffected. The apparent Vmax for [3H]AFQ1 formation was not affected by BNF treatment, but the apparent Km was increased to 4.5 times control. Boiling of microsomes or omitting the NADPH-generating system decreased DNA binding, AFM1 formation and AFQ1 formation by 89-97%, while addition of 1.0 mM SKF-525A inhibited these reactions by 46-57%. Addition of 1.0 mM alpha-naphthoflavone (ANF) had no effect on the biotransformation of [3H]AFB1 in lung microsomes of control rabbits, but significantly decreased AFM1 formation (by 31%) in lung microsomes from BNF-treated animals (other reactions were unaffected). In liver microsomes from BNF treated rabbits, 1.0 mM ANF inhibited DNA binding of [3H]AFB1 by 68%, while there was no effect in control microsomes. ANF significantly inhibited AFM1 formation in liver microsomes from both control and BNF-treated animals (by 87-97% and 67-78% at 1.0 mM and 2.0 microM, respectively), but had no effect on AFQ1 formation in liver microsomes from animals in either treatment group. These results indicate an important role for the 1A subclass of P-450 isozymes in the biotransformation of AFB1 to AFM1 in rabbit lung and liver, and a minor role in AFB1 activation in liver.

Carcinogenesis, Nov 1, 1990

In order to study the mechanism of cancer production by aflatoxin B1 (AFB1) in extrahepatic tissu... more In order to study the mechanism of cancer production by aflatoxin B1 (AFB1) in extrahepatic tissues which have relatively low cytochrome P450 monooxygenase (P450) activity, we have examined prostaglandin H synthase (PHS)-mediated AFB1 activation [( 3H]AFB1-DNA binding). [3H]AFB1 was activated by both purified PHS and microsomal PHS from guinea-pig kidney and liver, as well as by P450 in lung, kidney and liver microsomes, though P450-mediated [3H]AFB1-DNA binding in lung and liver was much higher than that catalyzed by PHS. Arachidonic acid (AA)-dependent [3H]AFB1-DNA binding could be inhibited by the PHS inhibitor indomethacin (0.1 mM), but was enhanced by the P450 inhibitor SKF-525A (3 mM), confirming that the reaction was independent of P450. Pulmonary PHS-mediated [3H]AFB1--DNA binding was less than 0.1 pmol [3H]AFB1/mg protein/min. HPLC analysis showed only minimal formation of [3H]AFM1 and [3H]AFQ1 by PHS, confirming that the low rate of PHS-dependent [3H]AFB1-DNA adduct formation was not due to conversion of AFB1 to other metabolites by PHS. The omission of AA did not diminish [3H]AFB1-DNA binding. In AA-free incubates, indomethacin inhibited, and SKF-525A enhanced, [3H]AFB1-DNA binding to a similar degree as in complete incubates, indicating that DNA binding in AA-free incubates was catalyzed by PHS. This reaction was also inhibited by 4-bromophenacyl bromide, a phospholipase A2 inhibitor, by 92%. These data are consistent with previous reports indicating the ability of AFB1 to stimulate the release of endogenous AA from membranes, presumably by stimulating phospholipase A2 activity, which may lead to enhanced bioactivation of AFB1 by PHS in vivo.

American Historical Review, 1972