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Biomedical subjects

J R Bailey

Publications and source records attributed to J R Bailey.

At least 19 recordsLinked to original sources
PubMed2006

Oncogenic Vav1 induces Rac-dependent apoptosis via inhibition of Bcl-2 family proteins and collaborates with p53 deficiency to promote hematopoietic progenitor cell proliferation.

Vav1 is an hematopoietic-specific Rho guanine nucleotide exchange factor coupling tyrosine kinase receptors and Rac GTPases, and has been implicated in transformation of fibroblasts and pancreas. To determine the biologic effect and oncogenic potential of Vav1 in hematopoietic lineages, we stably express oncogenic mutant of Vav1 in primary bone marrow cells using retrovirus-mediated gene transfer. Contrary to the growth stimulatory effects observed in fibroblasts, oncogenic Vav1 inhibits hematopoietic stem cell/progenitor engraftment in vivo and progenitor cell expansion in vitro via inducing apoptosis. The oncogenic Vav1-induced apoptosis is associated with reduced expression of Bcl-2 and Bcl-xL proteins and effectively suppressed by transgenic overexpression of Bcl-2, suggesting Vav1-mediated signaling via Bcl-2 in apoptosis. Also, oncogenic Vav1 stimulates sustained activation of Rac GTPases and the biologic effects of oncogenic Vav1 are Rac-dependent. Further, when expressed in the p53-deficient cells, which express elevated Bcl-2 and Bcl-xL and are resistant to the apoptosis, oncogenic Vav1 enhances both proliferation and self-renewal of hematopoietic progenitor cells. These results demonstrate clear phenotypic differences between wild-type and p53(-/-) hematopoietic cells expressing oncogenic Vav1, and suggest oncogenic potential of Vav1-mediated pathways in primary hematopoietic cell when they collaborate with additional genetic hits that affect the p53 pathway.

Animals↗
PubMed2002

A fluorescent compound for glucose uptake measurements in isolated rat cardiomyocytes.

A focus of current diabetes research is the development of insulinomimetic compounds for oral treatment of diabetes and its associated cardiac complications. Screening compounds for their potential insulinomimetic effects usually involves the use of radioactive isotopes. The focus of this study was to investigate a nonradioactive fluorescent compound for its use in screening insulinomimetic compounds. The indicator 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG) has been used by some workers to measure glucose uptake in Escherichia coli and Candida albicans. We propose that 2-NBDG will also be a suitable indicator for mammalian cell lines, in particular rat cardiomyocytes. We found that the indicator could give a reliable reproducible standard curve following appropriate dilution and is taken up by isolated cardiomyocytes. The insulinomimetic compounds vanadyl sulfate and sodium molybdate showed rates of glucose uptake similar to that of insulin. Furthermore, the rate of uptake measured for insulin using this technique (0.04 +/- 0.003 nmol x min(-1) x 10(6) cells(-1) is comparable with previous literature using 2-deoxyglucose uptake measurements on isolated myocytes (0.040 nmol x min(-1) x 10(6) cells(-1), demonstrating the validity of this fluorescent compound for glucose uptake studies.

4-Chloro-7-nitrobenzofurazan↗
PubMed2001

One-time gene gun or intramuscular rabies DNA vaccination of non-human primates: comparison of neutralizing antibody responses and protection against rabies virus 1 year after vaccination.

We have previously shown that Macaca fascicularis (Cynomologus) monkeys receiving a primary and either one or two booster rabies DNA vaccinations are protected against rabies virus. In this study, we determined whether monkeys that had been vaccinated only once via gene gun or intramuscularly (i.m.) with different concentrations of DNA would be protected against rabies virus challenge. Neutralizing antibody responses were assayed for 1 year before the monkeys were challenged. Neutralizing antibody was detected at least 50 days earlier in gene gun vaccinated as compared to i.m. vaccinated animals. Prior to viral challenge, all (6/6, 100%) gene gun vaccinated animals, but only 3/6 (50%) i.m. vaccinated animals seroconverted. In general, antibody titers of the gene gun vaccinated animals were higher than the titers of the i.m. vaccinated animals. There was no correlation between the concentration of DNA used for vaccination, the neutralizing antibody responses elicited and protection against viral challenge. Seven days after viral challenge, a rapid and strong anamnestic antibody response was elicited in 100% of the gene gun vaccinated monkeys and in four i.m. vaccinated monkeys. Neutralizing antibody remained undetectable in two i.m. vaccinated monkeys. Overall, 60% (3/5) of the gene gun vaccinated animals and 87% (5/6) of the i.m. vaccinated monkeys survived viral challenge. This study is the first, to our knowledge, to show long-term protection of non-human primates against a human viral pathogen using a DNA vaccination protocol that did not include a booster immunization.

Animals↗
PubMed2001

Putative behavioral history effects and aggression maintained by escape from therapists.

Differentially higher rates of aggression in treatment sessions occurred in the presence of two staff members who had previously worked with the participant at another facility. Adding an edible reinforcer for compliance and the absence of aggression in sessions conducted by these two staff members decreased aggression to rates similar to those obtained with less familiar therapists. Results suggest that embedding positive reinforcement within a demand context may reduce the aversiveness of therapists correlated with a history of demand situations.

Adolescent↗
PubMed2000

Verocytotoxin-producing Escherichia coli O157 on a farm open to the public: outbreak investigation and longitudinal bacteriological study.

Verocytotoxin-producing Escherichia coli (VTEC) O157 phage type 2 (PT2) was isolated from three calves and two goats on a farm open to the public. Phenotypic and DNA-based typing showed that the strains were identical or very closely related to those obtained from an outbreak of VTEC O157 infection in two separate family groups who visited the farm. No VTEC O157 PT2 was isolated again from the farm during a 12-month longitudinal bacteriological study undertaken after the infected animals had been removed. However, phenotypically and genotypically indistinguishable VTEC O157 PT2/28 strains were detected in two of 474 faecal samples collected at monthly visits from 15 species of animals of various ages. The two isolates were obtained from calves from different sources sampled 146 days apart, suggesting that the infection had persisted on the farm although it was not detected in the other species. The same strain was subsequently isolated from another calf housed in the same pen as one of the infected calves. The longest period during which the organism was excreted was seven days. No VTEC O157 was isolated either from 204 replacement animals (including 138 orphan lambs and 10 calves) brought in from various sources, and sampled while they were kept in isolation for two weeks before being introduced to the farm, or from environmental samples. During the study a visitor became ill with VTEC O157 PT2. However, the isolate was distinct from those recovered from the farm and there was no evidence to suggest that the visit was the source of the infection.

Agriculture↗
PubMed2000

Maintenance of resting tension in the american eel (Anguilla rostrata L.) heart is dependent upon exogenous fuel and the sarcoplasmic reticulum.

The relationship between extracellular glucose and management of cell Ca(2+) in the heart of the American eel (Anguilla rostrata) was indirectly assessed by monitoring the performance of isolated ventricular strips at 20 degrees C. Twitch force increased in ventricular strips under specific conditions of 30 bpm pacing and an extracellular Ca(2+) challenge from 1.5 to 9.5 mM. The response was independent of any exogenous metabolic fuel in the medium. Resting tension was maintained when glucose was available, but in the absence of a metabolic fuel, resting tension increased in response to the increase in extracellular Ca(2+) level. When ventricular strips were treated with iodoacetate to inhibit glycolysis, a Ca(2+) challenge resulted in a decrease in twitch force in association with an approximately equivalent increase in resting tension even in the presence of exogenous glucose. However, when pyruvate (5 mM) was substituted as a metabolic fuel, twitch force increased as a function of extracellular Ca(2+), and resting tension was maintained in the presence of iodoacetate. Therefore, there is a need for an extracellular fuel but not a specific metabolic requirement for glucose to maintain the performance characteristics, which are presumably related to the management of intracellular Ca(2+) levels. Ventricular strips were treated with ryanodine to inhibit Ca(2+) release and uptake by the sarcoplasmic reticulum (SR). Ryanodine treatment impaired postrest potentiation at high extracellular Ca(2+) levels. In the presence of ryanodine, the protective effect of glucose on the increase in resting tension in the face of an extracellular Ca(2+) challenge was eliminated. Considered together, the results reveal that the heart of the American eel has a requirement for an extracellular fuel to manage intracellular Ca(2+) at high Ca(2+) loads, and that the SR plays a role in the beat-to-beat regulation of Ca(2+) at a frequency of 30 bpm, high Ca(2+) load, and 20 degrees C.

Anguilla↗
PubMed2000

Anoxic performance of the american eel (Anguilla rostrata L.) heart requires extracellular glucose.

The importance of extracellular glucose in the maintenance of performance of the heart of the American eel (Anguilla rostrata Le Sueur (L.) Under anoxia was assessed under a variety of experimental conditions. Ventricular strips, electrically paced at 36 bpm, in N(2)-gassed medium maintained the imposed pace rate and generated approximately 25% of the initial twitch force of contraction for at least 60 min when glucose was present in the medium. But ventricular strips challenged without glucose in the medium failed to maintain the pacing rate within 5-10 min. Isolated and intact, perfused hearts maintained pressure and followed an imposed pace rate of 24 bpm for at least 2 hr, under anoxic conditions, if glucose was present in the medium. But without glucose in the medium isolated hearts failed within 30 min. Endogenous glycogen stores were utilized in hearts perfused with medium containing NaCN to impair oxidative phosphorylation. The presence of glucose in the medium did not protect against glycogen mobilization. The data indicate that exogenous glucose is necessary to maintain performance under anoxia at high workloads and physiological Ca(2+) levels. Finally, ventricular strips treated with NaCN and forced to contract at 24 bpm lost 70% of initial twitch force. Increasing extracellular Ca(2+) concentration stepwise from 1.5 to 9.5 mM restored twitch force to approximately 50% of the initial level and this response was not dependent on exogenous glucose. However, glucose was required to maintain resting tension even under normoxic conditions in the face of a Ca(2+) challenge.

Anguilla↗
PubMed1998

Oxygen consumption in myoglobin-rich and myoglobin-poor isolated fish cardiomyocytes.

The function of myoglobin at the cellular level was investigated by comparing O2 consumption in isolated myoglobin-rich cardiac myocytes from the sea raven (Hemitripterus americanus) and myoglobin-poor myocytes from the ocean pout (Macrozoarces americanus). O2 consumption by sea raven myocytes, 0.21 +/- 0.04 microM O2/10(6) cells.min-1, was significantly higher than O2 consumption by ocean pout myocytes, 0.10 +/- 0.07 microM O2/10(6) cells.min-1 at high PO2. O2 consumption in sea raven myocytes treated with sodium nitrite was not significantly different than that in untreated myocytes at high PO2, but it was significantly lower than controls at low PO2. O2 consumption of sea raven myocytes treated with the mitochondrial uncoupler CCCP was not significantly different from that of control myocytes at high PO2, but it was significantly greater than untreated controls at low PO2. In ocean pout preparations, O2 consumption by nitrite-treated myocytes was significantly higher than that of untreated myocytes at high PO2, but it was not different from that of controls at low PO2. CCCP-treated ocean pout myocytes had a significantly higher oxygen consumption than that of untreated myocytes at high PO2, but oxygen consumption was not different from that of controls at low PO2. The CCCP-activated O2 consumption at low PO2 was myoglobin-dependent in that CCCP alone resulted in a threefold increase in sea raven cells over controls but had no impact on sea raven cells in the presence of nitrite or ocean pout cells treated with CCCP alone. This study further supports the contention that myoglobin only plays an important role in oxygen metabolism at low extracellular PO2's.

Animals↗
PubMed1998

National outbreak of Salmonella senftenberg associated with infant food.

Eight cases of Salmonella senftenberg infection in infants were identified in the first half of 1995 in England, five were indistinguishable S. senftenberg strains. A case-control study showed an association between illness and consumption of one brand of baby cereal (P = 0.03). The cereal manufacturer reported isolating S. senftenberg in June 1994 from an undistributed cereal batch. Outbreak strains and the cereal strain were all plasmid-free in contrast to other human isolates of S. senftenberg in the same period. Changes in the production process were implemented to prevent further contamination. Surveillance centres should strengthen the detection and investigation of outbreaks of gastrointestinal infection in susceptible groups, especially young children. In this outbreak, the study of only five cases led to identification of the vehicle of infection. Even when few cases are reported, epidemiological investigation in conjunction with molecular typing may lead to public health action which prevents continuing or future outbreaks.

Case-Control Studies↗
PubMed1997

Protein synthesis under conditions of anoxia and changing workload in ventricle strips from turtle heart.

An earlier study determined that protein synthesis in isolated perfused turtle (Trachemys [= Pseudemys] scripta elegans) hearts was three-fold lower under conditions of anoxia than under conditions of normoxia. However, the earlier study did not attempt to define the role of work in the isolated perfused preparation. In this study, the effects of varying workload, as defined by changing frequency of contraction, and anoxia on protein synthesis were examined. The ventricle strip preparation allows for comparison of multiple strips from a single heart, which aids in eliminating the variability found between individuals chosen from wild populations. Ventricle strips forced to contract at 24 contractions.min-1 under anoxic conditions failed more rapidly than strips forced to contract at 24 contractions.min-1 under normoxic conditions. Protein synthesis decreased by 32% when compared to normoxic controls. When stimulation was terminated after 2 hr of contraction, the rate of protein synthesis in strips under anoxic conditions was similar to that in strips under normoxic conditions. Also, returning strips to normoxic conditions after 2 hr of anoxia restored protein synthesis to the level of the normoxic controls. A significant correlation between pacing rate and protein synthesis was found under normoxic conditions but not under anoxic conditions when strips were paced at 12, 18 and 24 contractions.min-1. Protein synthesis increased by 30% at the 18 contractions.min-1 frequency and 45% at the 24 contractions.min-1 frequency over the rate at 12 contractions.min-1 frequency. Force-frequency studies revealed that under normoxic conditions force generation did not change until above 24 contractions.min-1, but under anoxic conditions there was a significant negative inotropic effect (20% decrease in force) at 24 contractions.min-1 and fell to 50% of initial at 36 contractions.min-1. These studies indicate that, in the turtle heart, anoxia per se is not the only determinant of protein synthesis but rather that work plays an important role in protein synthesis, as in the mammalian heart.

Animals↗
PubMed1996

Reprogramming pacemakers enhances longevity and is cost-effective.

BACKGROUND: Historically, the majority of pulse generators implanted in the United States remain at the nominal programmed settings from the time of implant. While these nominal settings typically allow a sufficient safety margin to prevent later loss of capture with potential chronic threshold rise, the pulse generator with significant use would not be expected to last longer than that predicted by the manufacturer. However, improvements in lead technology have resulted in significantly lower chronic capture thresholds, which would permit lower programmable output settings while still allowing acceptable safety margins. Such changes could result in a significant reduction in long-term battery drain and translate into longer generator life. METHODS AND RESULTS: One hundred eighty consecutive patients undergoing implantation of permanent pacemakers at our institution were studied to determine the impact of reprogramming on pulse generator longevity and cost. Of these patients, 122 completed 6 months of follow-up at our institution and had pulse generators implanted that were capable of measuring battery current. We compared the estimated longevity based on battery current at nominal settings with that based on settings achieved in follow-up. The final settings were determined by the patient's physician using standard safety margins. The predicted longevity was 6.95 +/- 1.59 years at nominal implant settings and 11.16 +/- 2.71 years at final programmed settings (P < .001). Therefore, reprogramming extends the estimated pulse generator longevity by 4.25 +/- 2.14 years (64%) at a mean cost of $110 per patient (+37 per year extended). CONCLUSIONS: Reprogramming of permanent pacemakers is efficacious and cost-effective.

Cost-Benefit Analysis↗
PubMed1996

Defibrillator twiddler's syndrome causing device failure in a subpectoral transvenous system.

Twiddler's syndrome is well described as a complication of cardiac pacing. Defibrillator twiddler's syndrome has been recently reported with abdominal implantations of epicardial and transvenous defibrillator systems. We report a case of a patient with a transvenous defibrillator system implanted with the pulse generator placed in the subpectoral plane. The patient developed twiddler's syndrome, which resulted in retraction of both leads. This caused inappropriate shocks due to sensing both the atrial and ventricular electrograms. While the subpectoral position leaves the generator deeper and more difficult for the patient to access, it may not lessen the chance of twiddler's syndrome. It is possible that the subpectoral position may actually predispose the patient to this malady.

Aged↗
PubMed1996

Effects of constant cardiac autonomic nerve stimulation on heart rate variability.

Heart rate variability is used to assess cardiac autonomic tone. We bought to determine the relationship of graded direct stimulation of efferent cardiac autonomic nerves on heart rate variability in an anesthetized canine model. Time and frequency domain variables were measured at denervated baseline and during electrical stimulation of the vagi and ansae subclaviae over a wide range of frequencies. Vagal and ansae stimuli produced significant changes in heart rate that correlated with the intensity of stimulation. Vagal stimulation resulted in small increases in time domain indexes of heart rate variability and in the power spectrum from 0.04 to 0.40 Hz, but with no correlation between stimulus intensity and changes in these indexes. By contrast, ansae stimulation had no effect on time or frequency domain measures. In the absence of central modulation of autonomic outflow, indexes of heart rate variability reflect the presence of vagal input but do not correlate with the level of vagal tone and are unaffected by changes in mean sympathetic tone.

Animals↗
PubMed1996

Decreased total ventricular and mitochondrial protein synthesis during extended anoxia in turtle heart.

The turtle heart provides a model system to study the effects of anoxia on protein synthesis without the potentially confounding factor of contractile failure and decreased ATP levels. Protein synthesis, as measured by 3H-labeled phenylalanine incorporation, was studied under conditions of normoxia and anoxia in isolated perfused turtle [Trachemys (= Pseudemys) scripta elegans] hearts at 15 degrees C. Heart rate, cardiac output, and ventricular pressure development were unaffected by 2 or 3 h of anoxia. Despite the anoxia, energy levels in the heart were presumably still high, since contractility was maintained. RNA content of ventricle decreased after anoxic perfusion. Rates of total protein synthesis rates in ventricle were threefold lower under anoxia than under normoxia. These findings suggest that the total level of RNA is one determinant of protein synthesis. Incorporation of label into protein extracted from mitochondria was also assessed. The ratio of mitochondrial to whole ventricular protein synthesis was significantly lower after anoxia, revealing preferential control mechanisms under anoxia between the synthesis of total cellular protein and protein destined for mitochondria. Isolated mitochondria were still coupled after 2 or 3 h of anoxia. In effect, the mitochondria enter into a state of hypometabolism in terms of rates of ATP synthesis and protein synthesis, but functional integrity is maintained. The decrease in protein synthesis in general and mitochondrial protein synthesis in particular may represent an adaptation to allow the partitioning of the available energy resources toward mechanical function during anoxia.

Animals↗
PubMed1995

Blockade of beta-adrenoceptor in control of blood pressure in fowl.

Several avian species show elevated blood pressure (BP) and spontaneous atherogenesis in the aorta and other large arteries. The BP appears to be influenced by age, sex (higher in males), environment, and diet in some species. We reported previously that mean aortic pressure and heart rate, but not plasma renin activity (PRA), of conscious female domestic fowl were markedly reduced by propranolol. In the present study, we aimed to determine in conscious roosters whether 1) hypotension evoked by atenolol or practolol, which selectively inhibit cardiac beta-receptors in mammals, is more potent than that evoked by propranolol, and 2) the renin-angiotensin (ANG) system and/or catecholamines are involved in beta-adrenoceptor antagonist-induced hypotension. Mean arterial pressure (171.2 +/- 3.5 mmHg) and heart rate (281 +/- 4 beats/min) of chronically cannulated roosters (n = 38) were markedly reduced by acute infusion or repeated injections (14 days) of propranolol, atenolol, or practolol, but not by SQ-14,225 (ANG-converting enzyme inhibitor) or [Sar1, Thr8]ANG II (nonselective ANG receptor antagonist). None of the beta-adrenoceptor blockers, however, showed cardioselectivity. The resting PRA of conscious roosters (1.27 +/- 0.09 ng.ml-1.h-1, n = 38) was low and did not change significantly after chronic or acute treatment with beta-adrenoceptor blockers except for a slight decrease induced by practolol. PRA increased after SQ-14,225. The plasma levels (pg/ml) of norepinephrine (701.9 +/- 76.0), epinephrine (337.2 +/- 57.1), and dopamine (299.1 +/- 39.0) of conscious roosters were further increased by propranolol. Practolol also increased dopamine significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMed1994

Apolipoprotein oxidation in the absence of lipid peroxidation enhances LDL uptake by macrophages.

A characteristic of the antioxidant, probucol, is its inability to inhibit apolipoprotein B fragmentation in low density lipoprotein (LDL), despite a pronounced ability to inhibit lipid oxidation on relatively lengthy exposure to Cu(II). Here we show that a short exposure of LDL to hydrogen peroxide and Cu(II) leads to 125I-labelled apolipoprotein B fragmentation, the production of malondialdehyde and hydroperoxides and leads to increased uptake by macrophages on subsequent culture. However, pre-loading LDL with probucol protects LDL from lipid oxidation but not protein fragmentation or macrophage uptake. The use of probucol to conduct studies on apolipoprotein B oxidation without extensive lipid oxidation may prove useful when studying LDL apolipoprotein damage on exposure to an aqueous free radical insult.

Apolipoproteins B↗