Biomedical subjects

J D Allen

Publications and source records attributed to J D Allen.

At least 55 records · Page 3Linked to original sources

PubMed1995

Perturbed development of T and B cells in mice expressing an Hlx homeobox transgene.

Within the lymphoid compartment of mice, the Hlx homeobox gene is expressed only at early stages of B-lymphoid differentiation. To determine whether Hlx influences lymphopoiesis, transgenic mice were developed to enforce Hlx expression throughout the B and T cell lineages. The strain with the highest transgene expression in both cell types (Hlx-94) exhibited marked perturbations in both B and T cell development. In these mice, the thymus lacked almost all mature CD4+8- and CD8+4- cells and the medulla was greatly shrunken, whereas nearly one-half the T cells in the periphery were CD4+8+, a cell type normally confined to the thymus. The peripheral CD4+8+ cells had some features of mature T cells, including responsiveness to mitogens. Presumably these cells had emigrated prematurely from the thymus and generated mature T cells in the periphery. Bone marrow transplantation experiments indicated that the defects was intrinsic to the Hlx-94 hematopoietic cells rather than support cells. Although thymocyte development in Hlx-94 mice was blocked at the stage when selection normally occurs, analysis of lymphocyte populations in the progeny of crosses with mice transgenic for an anti-HY T cell receptor indicated that neither positive nor negative selection of T cells was markedly affected. In addition to T cell defects, Hlx-94 mice had subnormal numbers of B lymphoid cells in the bone marrow and spleen, and their surface phenotype suggested that B cell development after the pro-B stage was impeded. Furthermore, the B cell response to stimulation with LPS was impaired. These striking developmental defects suggest that the Hlx gene may help to govern lymphoid maturation.

Animals↗

PubMed1995

Effects of hostility on alcohol stress-response-dampening.

The purpose of this study was to compare the stress-response-dampening (SRD) effect of alcohol in hostile and nonhostile men based on a combined score of four subscales of the Cook-Medley Hostility Scale. Subjects were 72 male social drinkers. Subjects' cardiac interbeat-interval, and systolic and diastolic blood pressure reactivity to a situational stressor were measured following the consumption of either alcohol, no alcohol, or an active placebo beverage. Results demonstrated that hostile men evinced lower heart rate and systolic blood pressure (SBP) reactivity to the stressor when given alcohol, compared with intoxicated nonhostile subjects, and lower reactivity relative to all other groups, with the exception of SBP in the nonhostile controls. These results allow for speculation that hostile men may be more likely than controls to experience possible SRD effects of alcohol and thus, perhaps, be predisposed to increased alcohol consumption when under stress.

Adult↗

PubMed1995

Esophageal countershock: anthropometric determinants of impedance.

OBJECTIVE: To examine the use of a novel esophageal electrode system for countershock of atrial and ventricular tachyarrhythmias, with particular regard to the measurement of transesophageal and transthoracic impedances and their association with anthropometric variables. METHODS: Transesophageal cardioversion was attempted during 131 episodes of arrhythmia in 105 patients (including 109 episodes of atrial fibrillation). The esophageal system also used in 29 patients undergoing electrophysiologic studies for investigation of ventricular tachyarrhythmias. Transesophageal and transthoracic impedances were estimated during passage of a high-frequency, low-amplitude current between the respective electrodes. Impedance estimates were associated with anthropometric measurements using linear regression (least-squares method). RESULTS: In the group of patients undergoing attempted transesophageal cardioversion, the mean estimated transesophageal impedance of 52.6 +/- 11.7 omega was significantly lower than the mean estimated transthoracic impedance of 63.1 +/- 16.4 omega (n = 104, p < 0.01). For all the patients, transesophageal impedance was associated with weight, body mass index, and chest circumference (all r > or = 0.65, p < 0.01). Transthoracic impedance was associated with the same factors (all r > or = 0.55, p < 0.01). CONCLUSION: This esophageal electrode system results in lower impedance values for countershock between the esophagus and the cutaneous cardiac apex in comparison with standard transthoracic cutaneous electrode placement. Both techniques are dependent on anthropometric factors.

Adult↗

PubMed1994

Intertarget interval does not affect P300 within oddball series.

Increasing interstimulus interval or decreasing target probability of an oddball series increases P300 amplitude. These findings serve as one of the key underpinnings for the context updating hypothesis of P300. This hypothesis argues that by increasing the average amount of time elapsing between targets, decay of the neural model occurs and there is greater need for updating the model's accuracy. The amount of updating is reflected by increased P300 amplitude. To date, most comparisons have been made between P300 elicited by targets in different oddball series which vary in their mean intertarget interval. The current study examined P300 responses to within-series targets grouped according to how much time had elapsed since the previous target. No differences were found between P300 responses elicited by targets occurring 5-20 s since the previous target. This indicates that P300 amplitude does not vary with the amount of time passing between targets. Therefore, the context updating hypothesis may require some revision.

Adolescent↗

PubMed1994

Assessment of ability of levcromakalim and sodium nitroprusside to reverse the cardiovascular effects of nitric oxide synthase inhibition in the anaesthetised pig.

OBJECTIVE: The aim was to test the ability of levcromakalim, a potassium channel opener, and sodium nitroprusside, a nitric oxide donor, to reverse the systemic and pulmonary vasoconstrictor actions of NG-nitro-L-arginine methyl ester (L-NAME), and thus to restore cardiac output in anaesthetised pigs. METHODS: In separate groups of pigs administration of a bolus of L-NAME (10 mg.kg-1) was followed either by no further agent (control group; n = 8) or by increasing bolus doses of levcromakalim (10, 20, and 40 micrograms.kg-1; n = 8) or by increasing infused doses of sodium nitroprusside (1, 2, and 4 micrograms.kg-1.min-1 for 15 min at each dose). The same doses of levcromakalim and sodium nitroprusside were also given to pigs (n = 6 in each group) which had been pretreated with saline rather than L-NAME. The changes in systemic and pulmonary haemodynamic indices and cardiac output as a result of each intervention were measured at each stage and compared between and within drug groups. RESULTS: In each group, the bolus of L-NAME caused increases in systemic vascular resistance, mean arterial pressure, pulmonary vascular resistance, and mean pulmonary artery pressure, and a reduction in cardiac output. These effects were significantly different from pretreatment values at 15 min, and were maintained for at least 60 min when no further agent was given. The subsequent administration of levcromakalim caused significant reductions in systemic vascular resistance and mean arterial pressure, the effects being greater than in animals that had been pretreated with saline rather than L-NAME. Pulmonary vascular resistance and mean pulmonary artery pressure were also reduced, but to a lesser degree. Cardiac output was partially but significantly restored. The subsequent administration of sodium nitroprusside caused significant reductions in systemic vascular resistance, mean arterial pressure, pulmonary vascular resistance, and mean pulmonary artery pressure. These effects were significantly greater than those in animals that had been pretreated with saline rather than L-NAME. Cardiac output was weakly, though significantly restored. CONCLUSIONS: Increased systemic vascular resistance following a bolus of L-NAME (10 mg.kg-1) is reversed by subsequent administration of levcromakalim (10-40 micrograms.kg-1) or sodium nitroprusside (1-4 micrograms.kg-1.min-1) associated with partial restoration of cardiac output. The degree to which cardiac output is restored by these two agents is limited by a concomitant reduction in preload.

Amino Acid Oxidoreductases↗

PubMed1994

Comparison of the ability of nicardipine, theophylline and zaprinast to restore cardiovascular haemodynamics following inhibition of nitric oxide synthesis.

1. The use of pharmacological inhibitors of nitric oxide (NO) synthesis to treat patients with septic shock is limited by the observation that they cause a fall in cardiac output in some subjects. The aim of this work was to investigate this fall and to test whether it was reversible by subsequent administration of nicardipine, theophylline or the cyclic GMP-selective phosphodiesterase inhibitor, zaprinast (M&B 22948). 2. In pentobarbitone-anaesthetized pigs, haemodynamic indices were measured before and after intravenous administration of NG-nitro-L-arginine methyl ester (L-NAME) in a dose-response protocol (0.2-20 mg kg-1; n = 6) and as a single bolus of 10 mg kg-1 either alone or followed by increasing doses of nicardipine, theophylline or zaprinast (n = 8 in each group). 3. L-NAME caused a dose-dependent rise in systemic vascular resistance and mean systemic arterial pressure and a dose-dependent fall in cardiac output. A single bolus of L-NAME (10 mg kg-1) produced these effects within 15 min. 4. Subsequent administration of nicardipine (0.05-0.2 mg kg-1) caused complete reversal of systemic vasoconstriction and hypertension and in doing so completely restored cardiac output. Theophylline (7.5-10 mg kg-1) partially reversed the rise in systemic vascular resistance and partially restored cardiac output but the effect was small compared to that of nicardipine. Zaprinast (1-5 mg kg-1) had no significant effect on any of these variables. 5. These results suggest that reduced cardiac output following inhibition of NO synthesis is an effect of increased afterload on the heart and is reversible by nicardipine and to a lesser extent by theophylline.These findings may have potential value for those using NO synthase inhibitors to treat patients with septic shock.

3',5'-Cyclic-GMP Phosphodiesterases↗

PubMed1994

Alcohol and aggression: effects of personal threat on human aggression and affective arousal.

Theorists have attempted to account for the relationship between alcohol intoxication and a wide range of aggressive behaviors by ascribing alcohol-related aggression to the disinhibiting effects of alcohol and to its disruptive effects on cognitive processes. Allocation of attention and situational threat have been thought to mediate alcohol-related aggression. In the present study, 72 male social drinkers received either alcohol, a placebo, or a nonalcoholic beverage and were exposed to either threatening or nonthreatening personal information. Measuring levels and duration of aggressive responses on a Taylor-Buss aggression machine, intoxicated subjects were found to be generally more aggressive under threatening than under nonthreatening information conditions. Intoxicated subjects also reported relatively large increases in anger, depression, and tension following the aggression task, which appeared to be affected by the type of information received. These findings concur with and refine previous models suggesting that alcohol focuses the drinker's attention to salient cues in threatening circumstances, thus increasing the likelihood of aggressive behavior.

Adult↗

PubMed1994

Transesophageal electroventilation. Optimization and improvement.

For electroventilation, short duration pulse trains (0.1 ms) were applied between two axillary pads (transchest) and compared with transesophageal electroventilation where pulses passed between the same pads to an esophageal electrode in apneic, pentobarbitone-anesthetized pigs. Significantly greater tidal volumes were produced by transesophageal electroventilation in comparison with transchest. As measured by maintained tidal volumes, duration of inspiratory air flow, peak flow, percentage hemoglobin oxygen saturation (%SaO2), and end tidal carbon dioxide concentration (ETCO2), the optimal requirements for transesophageal electroventilation were pulse frequency 40 Hz, 0.7 s duration pulses, at 60 to 100 V, pulse width 0.1 ms, with the esophageal electrode proximal to the gastroesophageal junction without producing brachial plexus stimulation. The efficiency of transesophageal electroventilation falls off rapidly following ventricular fibrillation. Thus, the application of this technique would be in respiratory arrest with maintained circulation, eg, in drug-induced respiratory depression, severe smoke inhalation, severe emphysema, high cervical cord lesion, and weaning from prolonged mechanical ventilation.

Animals↗

PubMed1994

Hemisphericity and information processing in North American Native (Ojibwa) and non-native adolescents.

Thirty-two male and female adolescents of native ancestry (Ojibwa) and 32 controls were tested using (1) four WISC-R subtests and (2) two dichotic listening tasks which employed a focused-attention paradigm for processing consonant-vowel combinations (CVs) and musical melodies. On the WISC-R, natives scored higher than controls on Block Design and Picture Completion subtests but lower on Vocabulary and Similarities subtests. On laterality measures more native males showed a left ear advantage on the CV task and the melody task. For CVs the left ear advantage was due to native males' lower right ear (i.e., left hemisphere) involvement. For melodies, the laterality index pointed to less left hemisphere involvement for native males, however, the raw scores showed that natives were performing lower overall. The findings are consistent with culturally-based strategy differences, possibly linked to "hemisphericity," but additional clarifying research regarding the cause and extent of such differences is warranted. Thus, implications for education are premature but a focus on teaching "left hemisphere type" strategies to all individuals not utilizing such skills, including many native males, may prove beneficial.

Adolescent↗

PubMed1994

Fms-like tyrosine kinase 3 catalytic domain can transduce a proliferative signal in FDC-P1 cells that is qualitatively similar to the signal delivered by c-Fms.

A full length clone of murine fms-like tyrosine kinase 3 [flt3, also known as fetal liver kinase 2 (flk2)] was constructed from sequences obtained from a brain complementary DNA (cDNA) library and from cDNA prepared from the cell line Tikaut. In the absence of a ligand to study the function of Flt3, a chimeric molecule was constructed comprising the extracellular domain of murine c-Fms and the transmembrane and cytoplasmic domains of Flt3. A plasmid encoding the chimeric receptor was cotransfected along with a plasmid conferring neomycin resistance into FDC-P1 cells that do not normally express c-fms or flt3 and require granulocyte-macrophage colony-stimulating factor (GM-CSF) or interleukin 3 for growth. Two types of clones were obtained following selection in GM-CSF and G418. Two of seven clones had the capacity for M-CSF-dependent colony formation in semisolid medium, indicating that the cytoplasmic domain of Flt3 can transduce a proliferative signal. From the remaining clones, M-CSF-dependent clonogenic cells could be selected by prior bulk liquid culture in M-CSF. It has been shown previously that the GM-CSF-dependent proliferative capacity is strongly inhibited by M-CSF in FDC-P1 cells engineered to express full length c-fms. This phenomenon was also observed with FD/fms-flt3 cells that were clonogenic in M-CSF. Stimulation of FD/fms or FD/fms-flt3 cells in liquid culture by M-CSF caused differentiation of a small proportion of cells along the myelomonocytic pathway which was enhanced by the combination of M-CSF and GM-CSF.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1993

Enforced expression of Hlx homeobox gene prompts myeloid cell maturation and altered adherence properties of T cells.

Within the hematopoietic compartment, the murine Hlx homeobox gene is expressed in myeloid cells, most prominently in macrophages and granulocytes, and in immature B-lymphoid cells but not in erythroid, mast, or T-lymphoid cells. The level of Hlx mRNA increased with induced differentiation of the promyelocytic lines WEHI-3B and HL-60. To address its biologic action more directly, Hlx expression vectors were introduced into seven mouse hematopoietic cell lines representing several lineages. Although four lines did not tolerate stable Hlx expression, high-level expression was achieved in the early myeloid line FDC-P1 and in the immature T-cell lines Tikaut and WEHI-707. Overexpression of Hlx in FDC-P1 cells downregulated two markers of myeloid immaturity, Thy-1 and CD34, and also promoted changes in cellular and colony morphology, indicative of limited differentiation. Ectopic Hlx expression in the T-cell lines induced changes in cellular and colony morphology and adhesiveness, concomitant with decreased expression of adhesion molecules ICAM-1 (CD54) and Pgp-1 (CD44) and increased expression of heat-stable antigen. These results implicate Hlx in the control of myeloid maturation and the regulation of lymphoid adhesion processes.

Animals↗

PubMed1993

Transesophageal cardioversion.

With the use of a novel quadripolar esophageal electrode system, we have attempted 131 transesophageal cardioversions in 105 patients: 109 episodes were atrial fibrillation, 16 episodes were atrial flutter, 2 episodes were supraventricular tachycardia, and 4 episodes were ventricular tachycardia. The mean predicted transesophageal impedance (+/- SEM) of 52.6 +/- 1.1 omega was significantly lower than the mean predicted transthoracic impedance (+/- SEM) of 63.1 +/- 1.6 omega (n = 104; p < 0.01). Of the 88 patients who presented with atrial fibrillation as the initial arrhythmia, successful transesophageal cardioversion (maximal delivered transesophageal energy of 100 J in 84 patients and 200 J in 4 patients) was recorded in 70 (79.5%); transesophageal cardioversion required a mean delivered energy of 63.1 +/- 4.2 J and a mean peak current of 20.3 +/- 0.6 A. Transthoracic countershock (maximal delivered energy of 360 J) was attempted in 17 of 18 patients when the transesophageal approach had been unsuccessful; countershock was successful in 10 patients, which yielded an overall success rate of 92.0% (mean successful delivered energy [transesophageal and transthoracic] of 85.3 +/- 7.8 J). All episodes of atrial flutter, supraventricular tachycardia, and ventricular tachycardia were successfully terminated with the use of the esophagus. This esophageal electrode system permits low-energy countershock of atrial and ventricular tachyarrhythmias.

Adult↗

PubMed1993

Attention allocation: effects of alcohol and information salience on attentional processes in male social drinkers.

The purpose of this study was to examine the interactive effects of alcohol and salience of social cues (personality traits) on allocation of attention in the intoxicated male social drinker. It was expected that inebriated subjects would preferentially attend to high threat relative to low threat information contingent on the information's personal relevance. Seventy-six participants received either alcohol or a placebo, or were in a control condition, and were given the opportunity to attend to personally salient or nonsalient positive, negative, and neutral information. Intoxicated participants viewed negative traits longer than did nonintoxicated subjects and attended to these traits longer in the salient than in the nonsalient condition. Findings are compared to the attention allocation model, and their implications for alcohol-mediated cognitive processes are discussed.

Adult↗

PubMed1993

Altered cardiac oxygen extraction, lactate production and coronary blood flow after large dose transthoracic DC countershocks.

Although problems such as hypotension and pulmonary edema complicate the use of transthoracic DC countershocks, the mechanisms are not clear. In anesthetized dogs at 1 minute after only two defibrillator shocks there was a brief rise in coronary sinus lactate, exceeding arterial concentrations. Larger rises in lactate were seen after five shocks, indicating myocardial production of lactate. By contrast in eight animals given dummy shocks the heart always extracted lactate. At 2 minutes after five shocks mean myocardial oxygen extraction (6.5 +/- 0.6 mL/100 mL/100 mL blood; n = 4; P < 0.001), and remained so until 3 minutes after shocks, without significant increase in the lipid peroxidation product malondialdehyde in coronary sinus or arterial blood. Great cardiac venous blood flow, measured by thermodilution, rose after five shocks, and the heart rate pressure product also increased at 1-2 minutes. This transient failure of oxygen extraction, in the presence of arterial normoxia, hyperemia, and increased cardiac work, is best accounted for by a central effect of countershocks on myocardial cellular respiration.

Animals↗

PubMed1992

Failure of countershock-type pulses in vitro to adversely alter mitochondrial oxidative phosphorylation.

STUDY OBJECTIVE: The aim of the study was to investigate a potential mechanism of myocardial injury after DC countershock. The effect of countershock-type electrical discharges on rabbit heart mitochondrial oxygen consumption was measured in vitro using a novel respiration cell. MEASUREMENTS AND MAIN RESULTS: Mitochondria were isolated from the hearts of adult Dutch and New Zealand White rabbits. Single rectangular shocks (voltage gradients 20 to 80 V/cm; 5 ms duration) caused no significant changes in state 3 oxygen consumption in standard incubation medium. Single and multiple defibrillator shocks (critically damped sine waveform; 5 ms duration) with peak voltage gradients of 242 to 659 V/cm similarly had no significant effect on state 3 oxygen consumption. CONCLUSION: At voltage gradients similar to and greater than those causing myocardial cell injury and necrosis, electrical discharges do not directly depress mitochondrial function. Therefore, the reduction in mitochondrial oxygen consumption observed following transthoracic shocks in vivo may invoke other mechanisms (eg, intracellular calcium influx, high circulating noradrenaline, or free radical formation in the intact heart).

Animals↗

PubMed1992

Oxidative metabolism and myocardial blood flow changes after transthoracic DC countershocks in dogs.

Changes in oxidative metabolism and myocardial blood flow were investigated in adult greyhounds following transthoracic shocks from a DC cardiac defibrillator (400 Joules stored energy, damped sine wave, 0.5 min intervals). Myocardial lactate extraction became negative maximally at 1 min, following both two (mean -24% +/- SEM24) or five (-193% +/- 148) shocks and returned to baseline by 6-15 min. Transient reductions were also observed in myocardial extraction of pyruvate and free fatty acids but not glucose. Myocardial necrosis assessed at 4 h following the shocks was 0.05 g (+/- 0.03) after two shocks, 6.5 g (+/- 1.5) after five shocks and zero in controls. Mean peak noradrenaline levels in arterial (785 +/- 319 pg.ml-1) and coronary sinus (916 +/- 313 pg.ml-1) blood at 1 min after five shocks were higher than after 0 shocks (82 +/- 33 pg.ml-1 and 201 +/- 63 pg.ml-1 respectively), P < 0.05. Great cardiac venous blood flow was measured by a thermodilution technique, with continuous infusion of 0.9% saline, before, during and after five shocks. Mean blood flow fell from 47 +/- 13 ml.min-1 to a minimum of 36 +/- 7 ml.min-1 during shocks, and then rose to 83 +/- 17 ml.min-1 at 2 min after the fifth shock (P < 0.05). Following damaging countershocks, oxidative metabolism is depressed, in keeping with a primary disturbance of mitochondrial function. These metabolic changes are not secondary to ischaemia, since an increase in blood flow in the great cardiac vein (GCV) is observed. Vasodilatation of the coronary vascular bed must occur to account for this.

Analysis of Variance↗

PubMed1992

Failure of a single postpartum prostaglandin treatment to improve the reproductive performance of dairy cows.

A study was conducted to evaluate the effects of postpartum prostaglandin treatment on reproduction in 3 seasonal calving dairy herds. Recently calved lactating dairy cows were paired on herd, age, calving date and previous production index. One cow in each of the 196 pairs received a single intramuscular injection of 25 mg of the prostaglandin analogue, dinoprost, between 14 and 28 days after calving. Subsequent reproduction was monitored. Within each herd and overall, there was no significant effect of treatment on the intervals from calving to first service, mating start date to first service, calving to conception, mating start date to conception and first service to conception. Treatment also had no significant effect on 21-day submission and pregnancy rates, on the proportion of each group not pregnant at the end of mating, and on first service pregnancy rates. Responses to treatment did not vary between cows calving within 50 days of mating start date and earlier calving cows or between cows aged less than 5 years and older cows.

Animals↗

PubMed1992

Frequency analysis of ventricular fibrillation and resuscitation success.

In 56 patients, frequency analysis of the electrocardiogram of ventricular fibrillation exhibited power spectra with a distinct dominant frequency. The greatest success for resuscitation from ventricular fibrillation is recorded when ventricular fibrillation develops after the patient comes under coronary care. Of the 41 patients in whom the onset and first 8 s of ventricular fibrillation were artefact-free the mean dominant frequency of primary ventricular fibrillation (no cardiogenic shock or cardiac failure) in 21 patients was 6.2 +/- 0.2 Hz, significantly higher than the mean dominant frequency of the first 8 s of secondary ventricular fibrillation (cardiogenic shock or heart failure) (4.0 +/- 0.2 Hz, 20 patients, p = 0.0001). In these patients the peak-to-trough amplitude (ECG) of the first 8 s of ventricular fibrillation was similar in both primary and secondary ventricular fibrillation as was the mean duration of ventricular fibrillation prior to the first DC shock. There was a significantly lower success rate for resuscitation from secondary ventricular fibrillation (6 of 20 patients) compared with resuscitation from primary ventricular fibrillation (18 of 21 patients, chi 2 17.8, p = 0.001). Of the remaining 15 patients who were collapsed between 3 and 20 min before the arrival of the mobile coronary care unit, the dominant frequency of the first 8 s of ventricular fibrillation fell with increased duration of collapse (from 5.5 Hz at 3 min to a mean of 2.1 Hz at 20 min).(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗