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Biomedical subjects

C Foley

Publications and source records attributed to C Foley.

At least 19 recordsLinked to original sources
PubMed2000

Modeling zymogen protein C.

A solution structure for the complete zymogen form of human coagulation protein C is modeled. The initial core structure is based on the x-ray crystallographic structure of the gamma-carboxyglutamic acid (Gla)-domainless activated form. The Gla domain (residues 1-48) is modeled from the x-ray crystal coordinates of the factor VII(a)/tissue factor complex and oriented with the epidermal growth factor-1 domain to yield an initial orientation consistent with the x-ray crystal structure of porcine factor IX(a). The missing C-terminal residues in the light chain (residues 147-157) and the activation peptide residues 158-169 were introduced using homology modeling so that the activation peptide residues directly interact with the residues in the calcium binding loop. Molecular dynamics simulations (Amber-particle-mesh-Ewald) are used to obtain the complete calcium-complexed solution structure. The individual domain structures of protein C in solution are largely unaffected by solvation, whereas the Gla-epidermal growth factor-1 orientation evolves to a form different from both factors VII(a) and IX(a). The solution structure of the zymogen protein C is compared with the crystal structures of the existing zymogen serine proteases: chymotrypsinogen, proproteinase, and prethrombin-2. Calculated electrostatic potential surfaces support the involvement of the serine protease calcium ion binding loop in providing a suitable electrostatic environment around the scissile bond for II(a)/thrombomodulin interaction.

1-Carboxyglutamic Acid↗
PubMed2000

A multimedia approach to raising awareness of information and communications technology amongst healthcare professionals.

This study is concerned with the application of advanced multimedia technology to the development of a programme aimed at raising awareness of information and communications technology (ICT) amongst health professionals in Ireland. The programme is delivered in the form of a symposium supplemented by a multimedia CD and associated web site. It examines how ICT can be used effectively in healthcare across all sectors - primary, secondary and tertiary - with a strong emphasis on supporting shared care. The aim is to empower users to make informed technological choices and to actively participate in the exploitation of ICT in the health sector. The programme was successfully completed and delivered to over 2300 health professionals across Ireland and follow-up activities include the active encouragement of leaders and champions within the sector. This will be supported by interactive web-based education and training material focused on specialised topics of particular interest within the broader context of continuing medical education (CME).

Computer Literacy↗
PubMed2000

The role of differential activation of p38-mitogen-activated protein kinase in preconditioned ventricular myocytes.

Activation of protein kinase C (PKC) and more recently mitogen-activated protein kinases (MAPKs) have been associated with the cardioprotective effect of ischemic preconditioning. We examined the interplay between these kinases in a characterized model of ischemic preconditioning in cultured rat neonatal ventricular cardiocytes where ectopic expression of active PKC-delta results in protection. Two members of the MAPK family, p38 and p42/44, were activated transiently during preconditioning by brief simulated ischemia/reoxygenation. Overexpression of active PKC-delta, rather than augmenting, completely abolished this activation. We therefore determined whether a similar process occurred during lethal prolonged simulated ischemia. In contrast to ischemia, brief, lethal-simulated ischemia activated only p38 (2.8+/-0.45 vs. basal, P<0.01), which was attenuated by expression of active PKC-delta or by preconditioning (0.48+/-0.1 vs. ischemia, P<0.01). To determine whether reduced p38 activation was the cause or an effect of protection, we used SB203580, a p38 inhibitor. SB203580 reduced ischemic injury (CK release 38.0+/-3.1%, LDH release 77.3+/-4.0%, and MTT bioreduction 127.1+/-4.8% of control, n=20, P<0.05). To determine whether p38 activation was isoform selective, myocytes were infected with adenoviruses encoding wild-type p38alpha or p38beta. Transfected p38alpha and beta show differential activation (P<0.001) during sustained simulated ischemia, with p38alpha remaining activated (1.48+/-0.36 vs. basal) but p38beta deactivated (0.36+/-0.1 vs. basal, P<0.01). Prior preconditioning prevented the activation of p38alpha (0.65+/-0.11 vs. ischemia, P<0.05). Moreover, cells expressing a dominant negative p38alpha, which prevented ischemic p38 activation, were resistant to lethal simulated ischemia (CK release 82.9+/-3.9% and MTT bioreduction 130.2+/-6.5% of control, n=8, P<0.05). Thus, inhibition of p38alpha activation during ischemia reduces injury and may contribute to preconditioning-induced cardioprotection in this model.

Animals↗
PubMed1997

Sleep problems of elementary school children. A community survey.

OBJECTIVE: To examine the prevalence, co-occurrence, and correlates of sleep problems among elementary school children. DESIGN: Survey. SETTING: General community. PARTICIPANTS: The parents of 987 children aged 5 to 12 years completed an anonymous survey distributed in their children's schools. MAIN OUTCOME MEASURES: The survey form asked about background characteristics, children's sleep environment, sleep habits, adult interventions, sleep history, and specific sleep problems. RESULTS: Bedtime resistance was the most prevalent sleep problem (27%). Sleep-onset delays (11.3%), night waking (6.5%), morning wake-up problems (17%), and fatigue complaints (17%) were also common. Among children with sleep-onset problems, 80% displayed bedtime resistance, while 34% of bedtime resisters had onset problems. Onset problems correlated with more fears, night waking, psychiatric and medical conditions, the need for reassurance and caregiver proximity, and history of sleep problems. Bedtime resistance was associated with an inconsistent bedtime and falling asleep away from bed. Those who display delayed sleep onset and bedtime resistance also wake later, suggesting that sleep-phase delays may maintain these problems. CONCLUSIONS: The results confirm bedtime resistance as parents principal sleep-related complaint for this age group but reveal a subgroup more prone to insomnia, night waking, and anxiety-related features. Phase delay findings suggest the importance of limits around wake-up time as well as bedtime. The results highlight the importance of distinctly evaluating bedtime resistance, sleep onset, sleep maintenance, waking, and emotional adjustment.

Child↗
PubMed1997

Steady-state auditory evoked responses to pulsed frequency modulations in children.

This study investigated steady-state auditory evoked responses to pulsed frequency modulations (FM) of a continuous tone in normal children ranging in age from 6 to 12 years. We examined variations in response amplitude and phase as a function of age, recording site, and FM pulse duration. The surface topography of these evoked potentials suggested a relatively broad distribution with maximal responses observed at frontal electrode sites, smaller responses from parietal leads and the smallest responses were evident at the temporal lobe placements. Response parameters varied significantly as a function of pulse duration. Fifty milliseconds pulses elicited responses that were on average 20% larger than 100 ms FM pulses. Mean phase differences suggested that responses to the 100 ms pulses also lagged behind responses to the 50 ms pulses by the equivalent of 20 ms. There were no significant age-related variations in response amplitude. Phase varied with age only in response to the 50 ms FM pulses. The findings indicated that steady-state responses are sensitive to temporal parameters of frequency change present in pulsed modulations. The possibility is raised that this paradigm may be clinically useful in detecting dysfunction of specialized auditory mechanisms involved in frequency modulation analysis.

Acoustic Stimulation↗
PubMed1997

Fellowship training.

Explore the source record for details and available documents.

Fellowships and Scholarships↗
PubMed1996

Excretory fate of estradiol and progesterone in the African elephant (Loxodonta africana) and patterns of fecal steroid concentrations throughout the estrous cycle.

We developed and validated a noninvasive method to quantify fecal estrogens and progestins as a tool for monitoring long-term ovarian activity in free-ranging African elephants. The lag times between iv injection of [(3)H]estradiol and [(14)C]progesterone and peak excretion of radioactivity in urine and feces were approximately 4 hr and 48 hr, respectively. The majority of progesterone metabolites recovered was excreted in feces (55%) versus urine (45%), whereas comparatively little of the recovered estradiol metabolites were excreted in feces (5%) compared to urine (95%). Intrasample variation in fecal hormone concentrations was extremely high but could be substantially reduced by extracting well-mixed fecal powder from freeze-dried samples, taken from the central or premixed portion of the wet sample. This method resulted in a close correspondence between matched serum and fecal progestins (mean correlation = 0.81, range 0.61-0.94) collected from five nonpregnant adult females over a 7-month period. Fecal estrogen profiles were more ambiguous, tending to overlap with those of fecal progestins. We conclude that analyses of fecal progestins can provide an effective, noninvasive means of characterizing ovarian activity in free-ranging African elephants.

Animals↗
PubMed1996

Perfluorocarbon-associated gas exchange in normal and acid-injured large sheep.

OBJECTIVES: We hypothesized that a) perfluorocarbon-associated gas exchange could be accomplished in normal large sheep; b) the determinants of gas exchange would be similar during perfluorocarbon-associated gas exchange and conventional gas ventilation; c)in large animals with lung injury, perfluorocarbon-associated gas exchange could be used to enhance gas exchange without adverse effects on hemodynamics; and d) the large animal with lung injury could be supported with an FIO2 of <1.0 during perfluorocarbon-associated gas exchange. DESIGN: Prospective, observational animal study and prospective randomized, controlled animal study. SETTING: An animal laboratory in a university setting. SUBJECTS: Thirty adult ewes. MEASUREMENT AND MAIN RESULTS: Five normal ewes (61.0 +/- 4.0 kg) underwent perfluorocarbon-associated gas exchange to ascertain the effects of tidal volume, end-inspiratory pressure, and positive end-expiratory pressure (PEEP) on oxygenation. Respiratory rate, tidal volume, and minute ventilation were studied to determine their effects on CO2 clearance. Sheep, weighing 58.9 +/- 8.3 kg, had lung injury induced by instilling 2 mL/kg of 0.05 Normal hydrochloric acid into the trachea. Five minutes after injury, PEEP was increased to 10 cm H2O. Ten minutes after injury, sheep with Pao2 values of <100 torr (<13.3 kPa) were randomized to continue gas ventilation (control, n=9) or to institute perfluorocarbon-associated gas exchange (n=9) by instilling 1.6 L of unoxygenated perflubron into the trachea and resuming gas ventilation. Blood gas and hemodynamic measurements were obtained throughout the 4-hr study. Both tidal volume and end-inspiratory pressure influenced oxygenation in normal sheep during perfluorocarbon-associated gas exchange. Minute ventilation determined CO2 clearance during perfluorocarbon-associated gas exchange in normal sheep. After acid aspiration lung injury, perfluorocarbon-associated gas exchange increased PaO2 and reduced intrapulmonary shunt fraction. Hypoxia and intrapulmonary shunting were unabated after injury in control animals. Hemodynamics were not influenced by the institution of perfluorocarbon-associated gas exchange. CONCLUSIONS: Tidal volume and end-inspiratory pressure directly influence oxygenation during perfluorocarbon-associated gas exchange in large animals. Minute ventilation influences clearance of CO2. In adult sheep with acid aspiration lung injury, perfluorocarbon-associated gas exchange at an FIO2 of <1.0 supports oxygenation and improves intrapulmonary shunting, without adverse hemodynamic effects, when compared with conventional gas ventilation.

Analysis of Variance↗
PubMed1995

Expression and activity of the newt Msx-1 gene in relation to limb regeneration.

The Msx-1 homeobox gene is expressed in various contexts during vertebrate development, including the progress zone of the avian and mouse limb bud. Expression of mouse Msx-1 in a cultured myogenic cell line conferred a transformed phenotype and inhibited fusion into myotubes. It has been proposed that Msx-1 expression is required to maintain certain cells in a proliferating and undifferentiated state and may be associated with the ability to regenerate limbs. Urodele amphibians such as the newt regenerate their limbs by formation of a growth zone or blastema, and we have isolated and sequenced newt Msx-1 (NvMsx-1) from a limb blastemal cDNA library. NvMsx-1 expression was detectable in RNA preparations from both limb and tail and their regeneration blastemas, although cultured cells established from limb blastemal mesenchyme gave negative results. When either COS cells or cultured newt blastemal cells were cotransfected with an expression vector for NvMsx-1 and reporter plasmids containing multiple homeobox protein binding sites, NvMsx-1 repressed reporter expression. If NvMsx-1 was expressed together with a marker enzyme in cultured newt blastemal cells, no significant difference in DNA synthesis was observed relative to control transfectants. When myogenic mononucleate cells were transfected with NvMsx-1 and subsequently exposed to low serum to promote fusion, the fraction of Msx-1 positive cells in myotubes was comparable to a control transfected population analysed in the same culture. These results indicate that although Msx-1 expression could be important for limb regeneration, it does not exert a cell-autonomous effect on proliferation or myogenic differentiation of cultured blastemal cells.

Amino Acid Sequence↗
PubMed1995

Homology modeling and molecular dynamics simulation of human prothrombin fragment 1.

The crystallographic structure of bovine prothrombin fragment 1 bound with calcium ions was used to construct the corresponding human prothrombin structure (hf1/Ca). The model structure was refined by molecular dynamics to estimate the average solution structure. Accommodation of long-range ionic forces was essential to reach a stable solution structure. The gamma-carboxyglutamic acid (Gla) domain and the kringle domain of hf1/Ca independently equilibrated. Likewise, the hydrogen bond network and the calcium ion coordinations were well preserved. A discussion of the phospholipid binding of the vitamin K-dependent coagulation proteins in the context of the structure and mutational data of the Gla domain is presented.

1-Carboxyglutamic Acid↗
PubMed1995

Binding-protein expression is subject to temporal, developmental and stress-induced regulation in terminally differentiated soybean organs.

Binding protein (BiP) is a widely distributed and highly conserved endoplasmic-reticulum luminal protein that has been implicated in cotranslational folding of nascent polypeptides, and in the recognition and disposal of misfolded polypeptides. Analysis of cDNA sequences and genomic blots indicates that soybeans (Glycine max L. Merr.) possess a small gene family encoding BiP. The deduced sequence of BiP is very similar to that of other plant BiPs. We have examined the expression of BiP in several different terminally differentiated soybean organs including leaves, pods and seed cotyledons. Expression of BiP mRNA increases during leaf expansion while levels of BiP protein decrease. Leaf BiP mRNA is subject to temporal control, exhibiting a large difference in expression in a few hours between dusk and night. The expression of BiP mRNA varies in direct correlation with accumulation of seed storage proteins. The hybridization suggests that maturing-seed BiP is likely to be a different isoform from vegetative BiPs. Levels of BiP protein in maturing seeds vary with BiP mRNA. High levels of BiP mRNA are detected after 3 d of seedling growth. Little change in either BiP mRNA or protein levels was detected in maturing soybean pods, although BiP-protein levels decrease in fully mature pods. Persistent wounding of leaves by whiteflies induces massive overexpression of BiP mRNA while only slightly increasing BiP-protein levels. In contrast single-event puncture wounding only slightly induces additional BiP expression above the temporal variations. These observations indicate that BiP is not constitutively expressed in terminally differentiated plant organs. Expression of BiP is highest during the developmental stages of leaves, pods and seeds when their constituent cells are producing seed or vegetative storage proteins, and appears to be subject to complex regulation, including developmental, temporal and wounding.

Adaptation, Psychological↗
PubMed1994

Children's behavioral adaptation early in psychiatric hospitalization.

Behavioral patterns over time were assessed during the first 24 days of hospitalization for 98 child psychiatric inpatients. Staff completed daily behavioral monitoring and ratings. Patients were categorized as improved, unchanged or deteriorated during this time. Thirty-four percent of patients initially exhibited well-controlled behavior, but then significantly worsened after a period averaging 6.8 days. This result empirically supports the "honeymoon" phenomenon. Other patients showed either improvement during the initial period (15%), no change (30%), or could not be reliably classified (21%). Therefore, many child inpatients show rapid symptom stabilization after admission, but a large number then worsen. Clinical, scientific and administrative implications of these results are discussed.

Adaptation, Psychological↗
PubMed1993

Technetium 99mTc-HMPAO SPECT in children and adolescents with neurologic disorders.

We evaluated regional cerebral blood flow with technetium 99mTc hexamethylpropyleneamineoxime single photon emission computed tomography (SPECT) in 20 children and adolescents with neurologic dysfunction of varied etiology and abnormal electroencephalograms (EEGs). All patients were also examined with computed tomography (CT) and magnetic resonance imaging (MRI). Abnormal perfusion was found in 17 (85%) of 20 SPECT scans. Abnormal CT or MRI scans were noted in nine (45%) and in 10 (50%) of 20 cases, respectively. In eight (73%) of 11 cases with normal CT scans and in seven (70%) of 10 with normal MRI scans, the SPECT scan was abnormal. Abnormal regional cerebral blood flow on SPECT scans correlated better with EEG abnormalities than with neurologic examination or CT or MRI scan findings. We conclude that in children and adolescents with a spectrum of neurologic diseases and abnormal EEGs, abnormalities of brain structure or function are more likely to be documented by SPECT than by CT or MRI scans. SPECT findings correlate well with the location and type of EEG abnormality.

Adolescent↗
PubMed1991

Three years of a required geriatrics module for third-year medical students.

The Parker Jewish Geriatric Institute, a teaching nursing home at which an accredited internal medicine geriatrics fellowship is based, co-developed with the Department of Family Practice of the medical school at the State University of New York at Stony Brook a mandatory geriatrics module for third-year medical students. The module's implementation over a three-year period (1985-1987) with 278 medical students is described. The authors conclude that if time and effort are given to the development of a geriatrics curriculum, and if appropriate instructors are chosen, then learning geriatrics in long-term-care settings can be as rewarding and exciting an experience for medical students as their experiences in other clinical settings, even when that learning is required.

Adult↗