Jeff Shenberger - Academia.edu (original) (raw)

Papers by Jeff Shenberger

Research paper thumbnail of Proliferative and antiproliferative effects of interferon-'Y and tumor necrosis factor-α. on cell lines derived from cervical and ovarian malignancies

American Journal of Obstetrics and Gynecology, 1990

Four human cell lines derived from cervical carcinomas (ME-180, SiHa, HT-3, and MS751) and three ... more Four human cell lines derived from cervical carcinomas (ME-180, SiHa, HT-3, and MS751) and three human cell lines derived from ovarian carcinomas (SK-OV-3, Caov-3, and NIH:OVCAR-3) were analyzed in vitro to determine the effect of recombinant interferon-gamma and recombinant human tumor necrosis factor-alpha on cell growth and survival. The effects of interferon-gamma, tumor necrosis factor-alpha, and both interferon-gamma and tumor necrosis factor-alpha on cell growth were measured after 24 and 72 hours of incubation by the incorporation of chromium 51. The results of this analysis showed that all seven cell lines were resistant to the antiproliferative action of tumor necrosis factor-alpha, that the growth of most cell lines was inhibited by interferon-gamma by 72 hours of incubation, and that after 72 hours of incubation all cell lines demonstrated a synergistic antiproliferative response to the combination of interferon-gamma and tumor necrosis factor-alpha. However, the effects of these cytokines on cell growth were found to differ among cell lines and varied with the concentration and the duration of incubation. The growth of one cell line (Caov-3) was stimulated by both tumor necrosis factor-alpha and interferon-gamma. These results suggest that the clinical effects of these cytokines on the growth of gynecologic cancers may be more complex than previously supposed.

Research paper thumbnail of Proliferative and antiproliferative effects of interferon-'Y and tumor necrosis factor-α. on cell lines derived from cervical and ovarian malignancies

American Journal of Obstetrics and Gynecology, 1990

Four human cell lines derived from cervical carcinomas (ME-180, SiHa, HT-3, and MS751) and three ... more Four human cell lines derived from cervical carcinomas (ME-180, SiHa, HT-3, and MS751) and three human cell lines derived from ovarian carcinomas (SK-OV-3, Caov-3, and NIH:OVCAR-3) were analyzed in vitro to determine the effect of recombinant interferon-gamma and recombinant human tumor necrosis factor-alpha on cell growth and survival. The effects of interferon-gamma, tumor necrosis factor-alpha, and both interferon-gamma and tumor necrosis factor-alpha on cell growth were measured after 24 and 72 hours of incubation by the incorporation of chromium 51. The results of this analysis showed that all seven cell lines were resistant to the antiproliferative action of tumor necrosis factor-alpha, that the growth of most cell lines was inhibited by interferon-gamma by 72 hours of incubation, and that after 72 hours of incubation all cell lines demonstrated a synergistic antiproliferative response to the combination of interferon-gamma and tumor necrosis factor-alpha. However, the effects of these cytokines on cell growth were found to differ among cell lines and varied with the concentration and the duration of incubation. The growth of one cell line (Caov-3) was stimulated by both tumor necrosis factor-alpha and interferon-gamma. These results suggest that the clinical effects of these cytokines on the growth of gynecologic cancers may be more complex than previously supposed.

Research paper thumbnail of Partnering with parents to improve outcomes for substance exposed newborns—a pilot program

Research paper thumbnail of Neurodevelopmental Outcomes of Neonates Randomized to Morphine or Methadone for Treatment of Neonatal Abstinence Syndrome

The Journal of Pediatrics

Research paper thumbnail of The role of recombinant human CC10 in the prevention of chronic pulmonary insufficiency of prematurity

Pediatric Research

BACKGROUND: Preterm neonates can develop chronic pulmonary insufficiency of prematurity (CPIP) la... more BACKGROUND: Preterm neonates can develop chronic pulmonary insufficiency of prematurity (CPIP) later in infancy. Recombinant human CC10 protein (rhCC10) is an anti-inflammatory agent that could potentially prevent CPIP. METHODS: The safety and efficacy of a single intratracheal dose of rhCC10 in reducing CPIP at 12 months corrected gestational age (CGA) was evaluated in a Phase II double-blind, randomized, placebo-controlled, multisite clinical trial. Eighty-eight neonates were randomized: 22 to placebo and 22 to 1.5 mg/kg rhCC10 in the first cohort and 21 to placebo and 23 to 5 mg/kg rhCC10 in the second cohort. Neonates were followed to 12 months CGA. RESULTS: With CPIP defined as signs/symptoms, medical visits, hospital readmissions, and use of medications for respiratory complications at 12 months CGA, no significant differences were observed between rhCC10 or placebo groups. Only 5% of neonates had no evidence of CPIP at 12 months CGA. CONCLUSIONS: A single dose of rhCC10 was not effective in reducing CPIP at 12 CGA. Since most neonates had evidence of CPIP using these exploratory endpoints, it is essential to develop more robust outcome measures for clinical trials of respiratory medications in high-risk premature neonates.

Research paper thumbnail of Comparison of Safety and Efficacy of Methadone vs Morphine for Treatment of Neonatal Abstinence Syndrome

JAMA Pediatrics

IMPORTANCE Although opioids are used to treat neonatal abstinence syndrome (NAS), the best pharma... more IMPORTANCE Although opioids are used to treat neonatal abstinence syndrome (NAS), the best pharmacologic treatment has not been established. OBJECTIVE To compare the safety and efficacy of methadone and morphine in NAS. DESIGN, SETTING, AND PARTICIPANTS In this randomized, double-blind, intention-to-treat trial, term infants from 8 US newborn units whose mothers received buprenorphine, methadone, or opioids for pain control during pregnancy were eligible. A total of 117 infants were randomized to receive methadone or morphine from February 9, 2014, to March 6, 2017. Mothers who declined randomization could consent to data collection and standard institutional treatment. INTERVENTIONS Infants were assessed with the Finnegan Neonatal Abstinence Scoring System every 4 hours and treated with methadone or placebo every 4 hours or morphine every 4 hours. Infants with persistently elevated Finnegan scores received dose increases. Infants who exceeded a predetermined opioid dose received phenobarbital. Dose reductions occurred every 12 to 48 hours when signs of NAS were controlled with therapy, stopping at 20% of the original dose. MAIN OUTCOMES AND MEASURES The primary end point was length of hospital stay (LOS). The secondary end points were LOS attributable to NAS and length of drug treatment (LOT). RESULTS A total of 183 mothers consented to have their infants in the study; 117 infants required treatment. Because 1 parent withdrew consent, data were analyzed on 116 infants (mean [SD] gestational age, 39.1 [1.1] weeks; mean [SD] birth weight, 3157 [486] g; 58 [50%] male). Demographic variables and risk factors were similar except for more prenatal cigarette exposure in infants who received methadone. Adjusting for study site and maternal opioid type, methadone was associated with decreased mean number of days for LOS by 14%

Research paper thumbnail of Essential Expectations-Avoiding Hypocapnia and Hyperoxemia in Neonatal Encephalopathy

Journal of Pediatrics & Neonatal Care

Research paper thumbnail of New body composition reference charts for preterm infants

The American journal of clinical nutrition, 2017

The American Academy of Pediatrics (AAP) has recommended that nutritional management of the prete... more The American Academy of Pediatrics (AAP) has recommended that nutritional management of the preterm infant should aim to achieve body composition that replicates the in utero fetus, but intrauterine body composition reference charts for preterm infants are lacking. Our objective was to create body composition reference curves for preterm infants that approximate the body composition of the in utero fetus from 30 to 36 wk of gestation. A total of 223 ethnically diverse infants born at 30 + 0 to 36 + 6 wk of gestation were enrolled. Inclusion and exclusion criteria were specified so that the sample would represent healthy appropriately growing fetuses (e.g., singleton, birth weight appropriate for their gestational age, and medically stable). Cross-sectional reference values were generated for fat mass (FM), fat-free mass (FFM), and percentage body fat (PBF) by gestational age (GA), with the use of air-displacement plethysmography (ADP) and the lambda-mu-sigma method for percentile es...

Research paper thumbnail of Rapamycin-sensitive Co-localization of mTOR to the Mitotic Spindle

The Faseb Journal, Apr 1, 2010

Research paper thumbnail of Upregulation of p21WAF1 Is Not Essential for Oxygen-Induced Growth Arrest

Research paper thumbnail of Forearm training attenuates sympathetic responses to prolonged rhythmic forearm exercise

Journal of applied physiology (Bethesda, Md. : 1985), 1996

We previously demonstrated that nonfatiguing rhythmic forearm exercise at 25% maximal voluntary c... more We previously demonstrated that nonfatiguing rhythmic forearm exercise at 25% maximal voluntary contraction (12 2-s contractions/min) evokes sympathoexcitation without significant engagement of metabolite-sensitive muscle afferents (B.A. Batman, J.C. Hardy, U.A. Leuenberger, M.B. Smith, Q.X. Yang and L.I. Sinoway. J. Appl. Physiol. 76: 1077-1081, 1994). This is in contrast to the sympathetic nervous system responses observed during fatiguing static forearm exercise where metabolite-sensitive afferents are the key determinants of sympathetic activation. In this report we examined whether forearm exercise training would attenuate sympathetic nervous system responses to rhythmic forearm exercise. We measured heart rate, mean arterial blood pressure (MAP), muscle sympathetic nerve activity (microneurography), plasma norepinephrine (NE), and NE spillover and clearance (tritiated NE kinetics) during nonfatiguing rhythmic forearm exercise before and after a 4-wk unilateral forearm training...

Research paper thumbnail of A 30-day forearm work protocol increases maximal forearm blood flow

Journal of applied physiology (Bethesda, Md. : 1985), 1987

To evaluate the local circulatory changes that accompany chronic localized work, we studied the e... more To evaluate the local circulatory changes that accompany chronic localized work, we studied the effects of a 4-wk handgrip work protocol on maximal forearm work-related blood flow (ml X min-1 X 100 ml-1) in the nondominant forearms of six normal subjects. The reactive hyperemic blood flow response (RHBF) was also evaluated pre- and posttraining in both forearms of each subject to determine whether maximal vasodilatory capacity would be enhanced. In addition, maximal O2 consumption (VO2max) was measured. We found that chronic handgrip work led to an increase in work-related blood flow (before, 22.4; after, 32.1; P less than 0.05); a drop in work-related minimal resistance (R) (before, 6.4; after, 4.1; P less than 0.05). RHBF rose in the chronically exercised extremity by 30% (before, 33.5; after, 43.7; P less than 0.05) as minimal R fell (before, 3.2; after, 2.2; P less than 0.05). RHBF and R in the unstimulated dominant forearm remained unchanged (blood flow: before, 33.5; after, 31...

Research paper thumbnail of Sympathetic tone affects human limb vascular resistance during a maximal metabolic stimulus

The American journal of physiology, 1988

To evaluate the relationship between heightened sympathetic tone and maximal metabolic vasodilati... more To evaluate the relationship between heightened sympathetic tone and maximal metabolic vasodilation, peak forearm blood flow (ml.min-1.100 ml-1) was measured plethysmographically in 18 volunteers after the release of 10 min of arterial occlusion (the peak reactive hyperemic blood flow response, RHBF) both before and after a stimulus to induce heightened sympathetic tone. The stimulus was the application of ice to the forehead for 90 s just before and during RHBF measurements. Mean arterial cuff blood pressure (MAP; mmHg) was calculated, and corresponding resistance (R; mmHg.ml-1.min.100 ml) was derived from blood pressure divided by RHBF. During ice application, blood pressure rose (pre 92 vs. post 115 ml/mmHg; P less than 0.05), peak RHBF was unchanged (pre 38.8 vs. post 36.4 ml.min-1.100 ml-1; not significant), but R during the maximal metabolic stimulus rose (pre 2.5 vs. post 3.2 mmHg.ml-1.min.100 ml; P less than 0.05). To examine the effects of heightened sympathetic tone on con...

Research paper thumbnail of Muscle acidosis during static exercise is associated with calf vasoconstriction

Journal of applied physiology (Bethesda, Md. : 1985), 1989

In this study we measured (n = 6) the phosphocreatine-to-inorganic phosphate ratio (PCr/Pi), Pi, ... more In this study we measured (n = 6) the phosphocreatine-to-inorganic phosphate ratio (PCr/Pi), Pi, and pH with 31P-nuclear magnetic resonance (31P-NMR) in the human forearm during static work at 30% of maximal voluntary contraction (MVC) for 2 min followed immediately by 3 min of circulatory arrest (forearm arterial occlusion). Static exercise, with its central volitional and skeletal muscle metabolic and mechanical afferent components, caused a rise in heart rate (HR, 32%), blood pressure (BP, 29%), and calf vascular resistance (calf R, 30%). During forearm occlusion after static exercise, HR returned to base line, the increase in BP was attenuated by 30%, and calf R remained elevated and unchanged. The percent change in calf R was correlated with forearm cellular pH (R = 0.56, P less than 0.001) but only weakly associated with PCr/Pi (R = 0.33, P less than 0.042). 30% MVC for 1 min followed by arterial occlusion (3 min) reduced PCr/Pi by 65% and pH by 0.16 U (P less than 0.05). Calf...

Research paper thumbnail of Roles of mitogen-activated protein kinase signal-integrating kinases 1 and 2 in oxidant-mediated eIF4E phosphorylation

The International Journal of Biochemistry & Cell Biology, 2007

Oxidative stress alters cellular metabolic processes including protein synthesis. The eukaryotic ... more Oxidative stress alters cellular metabolic processes including protein synthesis. The eukaryotic initiation factor, eIF4E, acts in the rate-limiting steps of initiation and promotes nuclear export. Phosphorylation of eIF4E by mitogen activated protein kinase signalintegrating kinases 1 and 2 (Mnk) influences the affinity of eIF4E for the 5-mRNA cap and fosters nuclear export activity. Although phosphorylation of eIF4E on Ser 209 is observed following oxidant exposure, the contribution of Mnk isoforms and the significance of phosphorylation remain elusive. Using a Mnk inhibitor and fibroblasts derived from Mnk knockout mice, we demonstrate that that H 2 O 2 enhances eIF4E phosphorylation in cells containing Mnk1. In contrast, cells containing only Mnk2 show little change or a decrease in eIF4E phosphorylation in response to H 2 O 2. H 2 O 2 also shifted eIF4GI protein from the nucleus to the cytoplasm suggesting that the increases in eIF4E phosphorylation may reflect enhanced substrate availability to cytoplasmic Mnk1. In Mnk1 +/+ cells, H 2 O 2 also enhanced eIF4E phosphorylation in the nucleus to a greater degree than in the cytoplasm, an effect not observed in cells containing Mnk2. In response to H 2 O 2 , all MEFs showed increased eIF4E:4E-BP1 and 4E-BP2:eIF4E binding and reduced eIF4E:eIF4GI binding. We also observed a dramatic increase in the amount of Mnk1 associated with eIF4E following affinity chromatography. These changes coincided with a smaller reduction in global protein synthesis in response to H 2 O 2 in the DKO cells. These findings suggest that changes in eIF4GI distribution may enhance eIF4E phosphorylation and that the presence of either Mnk1 or 2 or any degree of eIF4E phosphorylation negatively regulates global protein synthesis in response to oxidant stress.

Research paper thumbnail of Regulation of Fibroblast Growth Factor 2 Expression in Oxygen-Induced Retinopathy

Investigative Ophthalmology & Visual Science, 2014

Fibroblast growth factor (FGF) 2 is a potent endothelial cell mitogen and survival factor that is... more Fibroblast growth factor (FGF) 2 is a potent endothelial cell mitogen and survival factor that is postulated to participate in the pathogenesis of retinopathy of prematurity (ROP). The purpose of the current study was to determine the transcriptional and translational regulation of FGF2 expression in oxygen-induced retinopathy (OIR), the animal model of ROP. We examined FGF2 protein and mRNA expression and optokinetic visual responses in transgenic mice possessing a dual-luciferase bicistronic transgene containing a 5'-internal ribosome entry site (IRES) of FGF2. We found that retinal FGF2 protein isoform expression varies with age but not in response to OIR. Analysis of luciferase, protein, and mRNA data indicate that FGF2 protein expression is translationally repressed during the vaso-obliterative phase of OIR, possibly by inhibiting elongation. At the transition from vaso-obliteration to neovascularization, heightened FGF2 protein expression corresponds to maintenance of IRES activity and diminished cap-dependent translational activity. During neovascularization, FGF2 expression is primarily regulated by transcription. Mice recovering from OIR display alterations in visual optokinetic responses and increased FGF2 protein expression at 6 weeks of age. In total, these findings illustrate the complexity of translational and transcriptional regulation of FGF2 protein expression in OIR. The augmentation of FGF2 expression and reduced optokinetic responses during the resolution of surface vasculopathy may indicate a role for FGF2 in the maintenance of neuroretinal function in OIR/ROP.

Research paper thumbnail of Relaxation of porcine tracheal smooth muscle by parathyroid hormone-related protein

Respiration Physiology, 1997

Parathyroid hormone-related protein (PTHrp) has been shown to relax uterine and gastrointestinal ... more Parathyroid hormone-related protein (PTHrp) has been shown to relax uterine and gastrointestinal smooth muscles, but the mechanisms underlying its effects have not been characterized. Furthermore, its effect on pulmonary smooth muscle is unknown. Therefore we designed the present study to determine the PTHrp dose-response; the interaction of PTHrp and PTH; and the role of cyclic nucleotides and potassium channels in the PTHrp response in porcine tracheal smooth muscle (TSM). Our results indicate that, (1-34)PTHrp causes dose-dependent relaxation of TSM; that (1-34)PTHrp and (1-34)PTH demonstrate cross-tachyphylaxis to one another; that phosphodiesterase inhibition augments and phosphodiesterase stimulation attenuates the relaxation response while guanylate cyclase blockade has little effect, and that charybdotoxin and iberiotoxin, inhibitors of large conductance, Ca 2 +-activated, K + channels, diminish the relaxation response. These findings suggest that (1-34)PTHrp-induced relaxation of TSM is mediated through a common PTHrp/PTH pathway or receptor, stimulation of cAMP and activation of large conductance, Ca 2 +-activated, K + channels.

Research paper thumbnail of Increased p21 and p53 levels are associated with S phase growth arrest in hyperoxia-treated human bronchial smooth muscle cells † 1968

Research paper thumbnail of Hyperoxic Damage to Growth of Human Small Airway Epithelial Cells is not Attenuated by the Addition of Nitric Oxide 1959

Research paper thumbnail of Upregulation of p21WAF1 Is Not Essential for Oxygen-Induced Growth Arrest

Research paper thumbnail of Proliferative and antiproliferative effects of interferon-'Y and tumor necrosis factor-α. on cell lines derived from cervical and ovarian malignancies

American Journal of Obstetrics and Gynecology, 1990

Four human cell lines derived from cervical carcinomas (ME-180, SiHa, HT-3, and MS751) and three ... more Four human cell lines derived from cervical carcinomas (ME-180, SiHa, HT-3, and MS751) and three human cell lines derived from ovarian carcinomas (SK-OV-3, Caov-3, and NIH:OVCAR-3) were analyzed in vitro to determine the effect of recombinant interferon-gamma and recombinant human tumor necrosis factor-alpha on cell growth and survival. The effects of interferon-gamma, tumor necrosis factor-alpha, and both interferon-gamma and tumor necrosis factor-alpha on cell growth were measured after 24 and 72 hours of incubation by the incorporation of chromium 51. The results of this analysis showed that all seven cell lines were resistant to the antiproliferative action of tumor necrosis factor-alpha, that the growth of most cell lines was inhibited by interferon-gamma by 72 hours of incubation, and that after 72 hours of incubation all cell lines demonstrated a synergistic antiproliferative response to the combination of interferon-gamma and tumor necrosis factor-alpha. However, the effects of these cytokines on cell growth were found to differ among cell lines and varied with the concentration and the duration of incubation. The growth of one cell line (Caov-3) was stimulated by both tumor necrosis factor-alpha and interferon-gamma. These results suggest that the clinical effects of these cytokines on the growth of gynecologic cancers may be more complex than previously supposed.

Research paper thumbnail of Proliferative and antiproliferative effects of interferon-'Y and tumor necrosis factor-α. on cell lines derived from cervical and ovarian malignancies

American Journal of Obstetrics and Gynecology, 1990

Four human cell lines derived from cervical carcinomas (ME-180, SiHa, HT-3, and MS751) and three ... more Four human cell lines derived from cervical carcinomas (ME-180, SiHa, HT-3, and MS751) and three human cell lines derived from ovarian carcinomas (SK-OV-3, Caov-3, and NIH:OVCAR-3) were analyzed in vitro to determine the effect of recombinant interferon-gamma and recombinant human tumor necrosis factor-alpha on cell growth and survival. The effects of interferon-gamma, tumor necrosis factor-alpha, and both interferon-gamma and tumor necrosis factor-alpha on cell growth were measured after 24 and 72 hours of incubation by the incorporation of chromium 51. The results of this analysis showed that all seven cell lines were resistant to the antiproliferative action of tumor necrosis factor-alpha, that the growth of most cell lines was inhibited by interferon-gamma by 72 hours of incubation, and that after 72 hours of incubation all cell lines demonstrated a synergistic antiproliferative response to the combination of interferon-gamma and tumor necrosis factor-alpha. However, the effects of these cytokines on cell growth were found to differ among cell lines and varied with the concentration and the duration of incubation. The growth of one cell line (Caov-3) was stimulated by both tumor necrosis factor-alpha and interferon-gamma. These results suggest that the clinical effects of these cytokines on the growth of gynecologic cancers may be more complex than previously supposed.

Research paper thumbnail of Partnering with parents to improve outcomes for substance exposed newborns—a pilot program

Research paper thumbnail of Neurodevelopmental Outcomes of Neonates Randomized to Morphine or Methadone for Treatment of Neonatal Abstinence Syndrome

The Journal of Pediatrics

Research paper thumbnail of The role of recombinant human CC10 in the prevention of chronic pulmonary insufficiency of prematurity

Pediatric Research

BACKGROUND: Preterm neonates can develop chronic pulmonary insufficiency of prematurity (CPIP) la... more BACKGROUND: Preterm neonates can develop chronic pulmonary insufficiency of prematurity (CPIP) later in infancy. Recombinant human CC10 protein (rhCC10) is an anti-inflammatory agent that could potentially prevent CPIP. METHODS: The safety and efficacy of a single intratracheal dose of rhCC10 in reducing CPIP at 12 months corrected gestational age (CGA) was evaluated in a Phase II double-blind, randomized, placebo-controlled, multisite clinical trial. Eighty-eight neonates were randomized: 22 to placebo and 22 to 1.5 mg/kg rhCC10 in the first cohort and 21 to placebo and 23 to 5 mg/kg rhCC10 in the second cohort. Neonates were followed to 12 months CGA. RESULTS: With CPIP defined as signs/symptoms, medical visits, hospital readmissions, and use of medications for respiratory complications at 12 months CGA, no significant differences were observed between rhCC10 or placebo groups. Only 5% of neonates had no evidence of CPIP at 12 months CGA. CONCLUSIONS: A single dose of rhCC10 was not effective in reducing CPIP at 12 CGA. Since most neonates had evidence of CPIP using these exploratory endpoints, it is essential to develop more robust outcome measures for clinical trials of respiratory medications in high-risk premature neonates.

Research paper thumbnail of Comparison of Safety and Efficacy of Methadone vs Morphine for Treatment of Neonatal Abstinence Syndrome

JAMA Pediatrics

IMPORTANCE Although opioids are used to treat neonatal abstinence syndrome (NAS), the best pharma... more IMPORTANCE Although opioids are used to treat neonatal abstinence syndrome (NAS), the best pharmacologic treatment has not been established. OBJECTIVE To compare the safety and efficacy of methadone and morphine in NAS. DESIGN, SETTING, AND PARTICIPANTS In this randomized, double-blind, intention-to-treat trial, term infants from 8 US newborn units whose mothers received buprenorphine, methadone, or opioids for pain control during pregnancy were eligible. A total of 117 infants were randomized to receive methadone or morphine from February 9, 2014, to March 6, 2017. Mothers who declined randomization could consent to data collection and standard institutional treatment. INTERVENTIONS Infants were assessed with the Finnegan Neonatal Abstinence Scoring System every 4 hours and treated with methadone or placebo every 4 hours or morphine every 4 hours. Infants with persistently elevated Finnegan scores received dose increases. Infants who exceeded a predetermined opioid dose received phenobarbital. Dose reductions occurred every 12 to 48 hours when signs of NAS were controlled with therapy, stopping at 20% of the original dose. MAIN OUTCOMES AND MEASURES The primary end point was length of hospital stay (LOS). The secondary end points were LOS attributable to NAS and length of drug treatment (LOT). RESULTS A total of 183 mothers consented to have their infants in the study; 117 infants required treatment. Because 1 parent withdrew consent, data were analyzed on 116 infants (mean [SD] gestational age, 39.1 [1.1] weeks; mean [SD] birth weight, 3157 [486] g; 58 [50%] male). Demographic variables and risk factors were similar except for more prenatal cigarette exposure in infants who received methadone. Adjusting for study site and maternal opioid type, methadone was associated with decreased mean number of days for LOS by 14%

Research paper thumbnail of Essential Expectations-Avoiding Hypocapnia and Hyperoxemia in Neonatal Encephalopathy

Journal of Pediatrics & Neonatal Care

Research paper thumbnail of New body composition reference charts for preterm infants

The American journal of clinical nutrition, 2017

The American Academy of Pediatrics (AAP) has recommended that nutritional management of the prete... more The American Academy of Pediatrics (AAP) has recommended that nutritional management of the preterm infant should aim to achieve body composition that replicates the in utero fetus, but intrauterine body composition reference charts for preterm infants are lacking. Our objective was to create body composition reference curves for preterm infants that approximate the body composition of the in utero fetus from 30 to 36 wk of gestation. A total of 223 ethnically diverse infants born at 30 + 0 to 36 + 6 wk of gestation were enrolled. Inclusion and exclusion criteria were specified so that the sample would represent healthy appropriately growing fetuses (e.g., singleton, birth weight appropriate for their gestational age, and medically stable). Cross-sectional reference values were generated for fat mass (FM), fat-free mass (FFM), and percentage body fat (PBF) by gestational age (GA), with the use of air-displacement plethysmography (ADP) and the lambda-mu-sigma method for percentile es...

Research paper thumbnail of Rapamycin-sensitive Co-localization of mTOR to the Mitotic Spindle

The Faseb Journal, Apr 1, 2010

Research paper thumbnail of Upregulation of p21WAF1 Is Not Essential for Oxygen-Induced Growth Arrest

Research paper thumbnail of Forearm training attenuates sympathetic responses to prolonged rhythmic forearm exercise

Journal of applied physiology (Bethesda, Md. : 1985), 1996

We previously demonstrated that nonfatiguing rhythmic forearm exercise at 25% maximal voluntary c... more We previously demonstrated that nonfatiguing rhythmic forearm exercise at 25% maximal voluntary contraction (12 2-s contractions/min) evokes sympathoexcitation without significant engagement of metabolite-sensitive muscle afferents (B.A. Batman, J.C. Hardy, U.A. Leuenberger, M.B. Smith, Q.X. Yang and L.I. Sinoway. J. Appl. Physiol. 76: 1077-1081, 1994). This is in contrast to the sympathetic nervous system responses observed during fatiguing static forearm exercise where metabolite-sensitive afferents are the key determinants of sympathetic activation. In this report we examined whether forearm exercise training would attenuate sympathetic nervous system responses to rhythmic forearm exercise. We measured heart rate, mean arterial blood pressure (MAP), muscle sympathetic nerve activity (microneurography), plasma norepinephrine (NE), and NE spillover and clearance (tritiated NE kinetics) during nonfatiguing rhythmic forearm exercise before and after a 4-wk unilateral forearm training...

Research paper thumbnail of A 30-day forearm work protocol increases maximal forearm blood flow

Journal of applied physiology (Bethesda, Md. : 1985), 1987

To evaluate the local circulatory changes that accompany chronic localized work, we studied the e... more To evaluate the local circulatory changes that accompany chronic localized work, we studied the effects of a 4-wk handgrip work protocol on maximal forearm work-related blood flow (ml X min-1 X 100 ml-1) in the nondominant forearms of six normal subjects. The reactive hyperemic blood flow response (RHBF) was also evaluated pre- and posttraining in both forearms of each subject to determine whether maximal vasodilatory capacity would be enhanced. In addition, maximal O2 consumption (VO2max) was measured. We found that chronic handgrip work led to an increase in work-related blood flow (before, 22.4; after, 32.1; P less than 0.05); a drop in work-related minimal resistance (R) (before, 6.4; after, 4.1; P less than 0.05). RHBF rose in the chronically exercised extremity by 30% (before, 33.5; after, 43.7; P less than 0.05) as minimal R fell (before, 3.2; after, 2.2; P less than 0.05). RHBF and R in the unstimulated dominant forearm remained unchanged (blood flow: before, 33.5; after, 31...

Research paper thumbnail of Sympathetic tone affects human limb vascular resistance during a maximal metabolic stimulus

The American journal of physiology, 1988

To evaluate the relationship between heightened sympathetic tone and maximal metabolic vasodilati... more To evaluate the relationship between heightened sympathetic tone and maximal metabolic vasodilation, peak forearm blood flow (ml.min-1.100 ml-1) was measured plethysmographically in 18 volunteers after the release of 10 min of arterial occlusion (the peak reactive hyperemic blood flow response, RHBF) both before and after a stimulus to induce heightened sympathetic tone. The stimulus was the application of ice to the forehead for 90 s just before and during RHBF measurements. Mean arterial cuff blood pressure (MAP; mmHg) was calculated, and corresponding resistance (R; mmHg.ml-1.min.100 ml) was derived from blood pressure divided by RHBF. During ice application, blood pressure rose (pre 92 vs. post 115 ml/mmHg; P less than 0.05), peak RHBF was unchanged (pre 38.8 vs. post 36.4 ml.min-1.100 ml-1; not significant), but R during the maximal metabolic stimulus rose (pre 2.5 vs. post 3.2 mmHg.ml-1.min.100 ml; P less than 0.05). To examine the effects of heightened sympathetic tone on con...

Research paper thumbnail of Muscle acidosis during static exercise is associated with calf vasoconstriction

Journal of applied physiology (Bethesda, Md. : 1985), 1989

In this study we measured (n = 6) the phosphocreatine-to-inorganic phosphate ratio (PCr/Pi), Pi, ... more In this study we measured (n = 6) the phosphocreatine-to-inorganic phosphate ratio (PCr/Pi), Pi, and pH with 31P-nuclear magnetic resonance (31P-NMR) in the human forearm during static work at 30% of maximal voluntary contraction (MVC) for 2 min followed immediately by 3 min of circulatory arrest (forearm arterial occlusion). Static exercise, with its central volitional and skeletal muscle metabolic and mechanical afferent components, caused a rise in heart rate (HR, 32%), blood pressure (BP, 29%), and calf vascular resistance (calf R, 30%). During forearm occlusion after static exercise, HR returned to base line, the increase in BP was attenuated by 30%, and calf R remained elevated and unchanged. The percent change in calf R was correlated with forearm cellular pH (R = 0.56, P less than 0.001) but only weakly associated with PCr/Pi (R = 0.33, P less than 0.042). 30% MVC for 1 min followed by arterial occlusion (3 min) reduced PCr/Pi by 65% and pH by 0.16 U (P less than 0.05). Calf...

Research paper thumbnail of Roles of mitogen-activated protein kinase signal-integrating kinases 1 and 2 in oxidant-mediated eIF4E phosphorylation

The International Journal of Biochemistry & Cell Biology, 2007

Oxidative stress alters cellular metabolic processes including protein synthesis. The eukaryotic ... more Oxidative stress alters cellular metabolic processes including protein synthesis. The eukaryotic initiation factor, eIF4E, acts in the rate-limiting steps of initiation and promotes nuclear export. Phosphorylation of eIF4E by mitogen activated protein kinase signalintegrating kinases 1 and 2 (Mnk) influences the affinity of eIF4E for the 5-mRNA cap and fosters nuclear export activity. Although phosphorylation of eIF4E on Ser 209 is observed following oxidant exposure, the contribution of Mnk isoforms and the significance of phosphorylation remain elusive. Using a Mnk inhibitor and fibroblasts derived from Mnk knockout mice, we demonstrate that that H 2 O 2 enhances eIF4E phosphorylation in cells containing Mnk1. In contrast, cells containing only Mnk2 show little change or a decrease in eIF4E phosphorylation in response to H 2 O 2. H 2 O 2 also shifted eIF4GI protein from the nucleus to the cytoplasm suggesting that the increases in eIF4E phosphorylation may reflect enhanced substrate availability to cytoplasmic Mnk1. In Mnk1 +/+ cells, H 2 O 2 also enhanced eIF4E phosphorylation in the nucleus to a greater degree than in the cytoplasm, an effect not observed in cells containing Mnk2. In response to H 2 O 2 , all MEFs showed increased eIF4E:4E-BP1 and 4E-BP2:eIF4E binding and reduced eIF4E:eIF4GI binding. We also observed a dramatic increase in the amount of Mnk1 associated with eIF4E following affinity chromatography. These changes coincided with a smaller reduction in global protein synthesis in response to H 2 O 2 in the DKO cells. These findings suggest that changes in eIF4GI distribution may enhance eIF4E phosphorylation and that the presence of either Mnk1 or 2 or any degree of eIF4E phosphorylation negatively regulates global protein synthesis in response to oxidant stress.

Research paper thumbnail of Regulation of Fibroblast Growth Factor 2 Expression in Oxygen-Induced Retinopathy

Investigative Ophthalmology & Visual Science, 2014

Fibroblast growth factor (FGF) 2 is a potent endothelial cell mitogen and survival factor that is... more Fibroblast growth factor (FGF) 2 is a potent endothelial cell mitogen and survival factor that is postulated to participate in the pathogenesis of retinopathy of prematurity (ROP). The purpose of the current study was to determine the transcriptional and translational regulation of FGF2 expression in oxygen-induced retinopathy (OIR), the animal model of ROP. We examined FGF2 protein and mRNA expression and optokinetic visual responses in transgenic mice possessing a dual-luciferase bicistronic transgene containing a 5'-internal ribosome entry site (IRES) of FGF2. We found that retinal FGF2 protein isoform expression varies with age but not in response to OIR. Analysis of luciferase, protein, and mRNA data indicate that FGF2 protein expression is translationally repressed during the vaso-obliterative phase of OIR, possibly by inhibiting elongation. At the transition from vaso-obliteration to neovascularization, heightened FGF2 protein expression corresponds to maintenance of IRES activity and diminished cap-dependent translational activity. During neovascularization, FGF2 expression is primarily regulated by transcription. Mice recovering from OIR display alterations in visual optokinetic responses and increased FGF2 protein expression at 6 weeks of age. In total, these findings illustrate the complexity of translational and transcriptional regulation of FGF2 protein expression in OIR. The augmentation of FGF2 expression and reduced optokinetic responses during the resolution of surface vasculopathy may indicate a role for FGF2 in the maintenance of neuroretinal function in OIR/ROP.

Research paper thumbnail of Relaxation of porcine tracheal smooth muscle by parathyroid hormone-related protein

Respiration Physiology, 1997

Parathyroid hormone-related protein (PTHrp) has been shown to relax uterine and gastrointestinal ... more Parathyroid hormone-related protein (PTHrp) has been shown to relax uterine and gastrointestinal smooth muscles, but the mechanisms underlying its effects have not been characterized. Furthermore, its effect on pulmonary smooth muscle is unknown. Therefore we designed the present study to determine the PTHrp dose-response; the interaction of PTHrp and PTH; and the role of cyclic nucleotides and potassium channels in the PTHrp response in porcine tracheal smooth muscle (TSM). Our results indicate that, (1-34)PTHrp causes dose-dependent relaxation of TSM; that (1-34)PTHrp and (1-34)PTH demonstrate cross-tachyphylaxis to one another; that phosphodiesterase inhibition augments and phosphodiesterase stimulation attenuates the relaxation response while guanylate cyclase blockade has little effect, and that charybdotoxin and iberiotoxin, inhibitors of large conductance, Ca 2 +-activated, K + channels, diminish the relaxation response. These findings suggest that (1-34)PTHrp-induced relaxation of TSM is mediated through a common PTHrp/PTH pathway or receptor, stimulation of cAMP and activation of large conductance, Ca 2 +-activated, K + channels.

Research paper thumbnail of Increased p21 and p53 levels are associated with S phase growth arrest in hyperoxia-treated human bronchial smooth muscle cells † 1968

Research paper thumbnail of Hyperoxic Damage to Growth of Human Small Airway Epithelial Cells is not Attenuated by the Addition of Nitric Oxide 1959

Research paper thumbnail of Upregulation of p21WAF1 Is Not Essential for Oxygen-Induced Growth Arrest