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Biomedical subjects

B Woodward

Publications and source records attributed to B Woodward.

At least 37 records · Page 2Linked to original sources
PubMed1999

Acidosis-induced coronary constriction in the rat heart: evidence for the activation of L-type calcium channels.

Perfused rat hearts were used to study the effects of acidosis on coronary tone. When pH was decreased, over the range pH 7.4 to pH 6.2, by reducing perfusate bicarbonate levels, under constant flow conditions, there was a transient decrease in coronary perfusion pressure (CPP), followed by a sustained acidosis-dependent increase in CPP, which reversed when pH was returned to pH 7.4. This increase in CPP was seen at perfusion rates of 5, 10, and 20 ml/min(-1). When using constant pressure perfusion acidosis reduced coronary flow. In a HEPES-buffered bicarbonate-free solution, acidosis did not cause a transient fall in CPP but it did produce a sustained increase in CPP. Addition of ammonium chloride (10 mM) reduced CPP, while washout of ammonium chloride increased CPP. The acidosis-induced increase in CPP was not affected by indomethacin, nitro-L-arginine, the nonselective adenosine receptor antagonist, 8-phenyl theophylline, or the thromboxane receptor antagonist, ZD 1542. The acidosis-induced increase in CPP was independent of the myocardial depressant effects of acidosis, but was attenuated by three different L-type calcium channel blockers. These results demonstrate that the coronary circulation of the rat constricts in response to acidosis. Experiments performed with L-type calcium channel blockers, and the calcium channel activator BAY K8644, suggest that constriction occurs via activation of L-type calcium channels. This would not be expected on the basis of electrophysiological studies, which have shown an inhibition of L-type calcium channels by acidosis.

Acidosis↗
PubMed1999

Effects of tumour necrosis factor-alpha on left ventricular function in the rat isolated perfused heart: possible mechanisms for a decline in cardiac function.

1. The cardiac depressant actions of TNF were investigated in the isolated perfused rat heart under constant flow (10 ml min(-1)) and constant pressure (70 mmHg) conditions, using a recirculating (50 ml) mode of perfusion. 2. Under constant flow conditions TNF (20 ng ml(-1)) caused an early (< 25 min) decrease in left ventricular developed pressure (LVDP), which was maintained for 90 min (LVDP after 90 min: control vs TNF; 110 +/- 4 vs 82 +/- 10 mmHg, P < 0.01). 3. The depression in cardiac function seen with TNF under constant flow conditions, was blocked by the ceramidase inhibitor N-oleoylethanolamine (NOE), 1 microM, (LVDP after 90 min: TNF vs TNF with NOE; 82 +/- 10 vs 11 +/- 5 mmHg, P < 0.05). 4. In hearts perfused at constant pressure, TNF caused a decrease in coronary flow rate (change in flow 20 min after TNF: control vs TNF; -3.0 +/- 0.9 vs -8.7 +/- 1.2 ml min(-1), P < 0.01). This was paralleled by a negative inotropic effect (change in LVDP 20 min after TNF: control vs TNF; -17 +/- 7 vs -46 +/- 6 mmHg, P < 0.01). The decline in function was more rapid and more severe than that seen under conditions of constant flow. 5. These data indicate that cardiac function can be disrupted by TNF on two levels, firstly via a direct, ceramidase dependant negative inotropic effect, and secondly via an indirect coronary vasoconstriction.

Animals↗
PubMed1999

T cells with a quiescent phenotype (CD45RA+) are overabundant in the blood and involuted lymphoid tissues in wasting protein and energy deficiencies.

The objective of this investigation was to determine the influence of distinct forms of acute weight loss on the expression of the quiescence marker, CD45RA, by T cells in several lymphoid compartments including the blood. Male and female weanling mice, CBA/J and C57BL/6J strains, were allocated to the following groups: ad libitum intake of a complete purified diet; restricted intake of the complete diet; and ad libitum intake of an isocaloric low-protein diet. The restricted intake protocol produced weight loss through energy deficiency (marasmic-type malnutrition), whereas the low-protein diet caused wasting through inadequate protein nitrogen and induced a condition mimicking incipient kwashiorkor. In one experiment, weanling mice of both strains were maintained for 14 days according to each of these dietary protocols and, in a supplementary study, C57BL/6J weanlings consumed either the complete diet or the low-protein diet ad libitum for 21 days. Zero-time control groups (19-days old and 23-days old in C57BL/6J and CBA/J strains, respectively) were included in the first experiment to control for ontogeny-related change. Expression of CD45RA was assessed by two-colour flow cytometry in CD4+ and CD8+ T cells from the spleen, mesenteric lymph nodes and blood. Within 14 days, energy-restricted mice exhibited a high percentage of CD4+ T cells expressing CD45RA in all three lymphoid compartments in both mouse strains (an average of 50% CD45RA+ versus 9% in well-nourished controls), and a similar outcome was apparent in the CD8+ subset (93% CD45RA+ versus 63%). Mice fed the low-protein diet required up to 21 days to exhibit the same imbalance within the CD4+ T-cell subset (33% CD45RA+ versus 4% in well-nourished controls). A shift toward a quiescent phenotype occurs throughout the peripheral T-cell system in acute wasting disease. Consequently, the quiescence-activation phenotype of blood T cells reflects the same index in secondary lymphoid organs in such pathologies. Naive-type quiescence among T cells is implicated as a component of depressed adaptive immunocompetence in the advanced stages of diverse forms of acute weight loss.

Acute Disease↗
PubMed1999

The comparative performance of mobile telemedical systems based on the IS-54 and GSM cellular telephone standards.

The performance of mobile telemedical communications links based on the IS-54 and GSM cellular telephone standards (the most widely used commercial systems in North America and Europe, respectively) was studied by computer simulations. A photoplethysmography signal was used to investigate the transmission of medical data over simulated mobile phone channels. Various conditions were simulated in the communications path between a mobile transmitter and receiver, from perfect to distorted conditions. The results showed successful transmission, with bit error rates of better than 10(-7) at the receiver for the IS-54 standard. The performance of the IS-54 standard was superior to that of GSM in terms of minimum path delay variations, especially in built-up (urban) areas.

Computer Simulation↗
PubMed1998

Effects of prostaglandin F2 alpha on intracellular pH, intracellular calcium, cell shortening and L-type calcium currents in rat myocytes.

OBJECTIVE: We have studied the mechanisms underlying the positive inotropic action of prostaglandin F2 alpha (PGF2 alpha) by monitoring intracellular calcium transients, intracellular pH, L-type calcium currents and cell shortening in isolated ventricular myocytes. METHODS: Rat myocytes were loaded with fura-2AM for intracellular calcium measurements, or BCECF-AM for pH measurements. Cell shortening was recorded using an edge detection system, and L-type calcium currents measured using whole cell patch clamping. RESULTS: PGF2 alpha (3 nmol l-1-3 mumol l-1 increased single myocyte shortening and reduced resting cell length in a concentration-dependent manner. While myocyte shortening was increased by PGF2 alpha, this was not associated with any change in the amplitude of intracellular calcium transients, diastolic calcium, or L-type calcium currents. However, the same myocytes were capable of responding to catecholamines with increases in calcium transient amplitude and L-type calcium currents. PGF2 alpha (3 mumol l-1 caused a reversible rise in intracellular pH of 0.08 +/- 0.01 pH units (n = 5, p < 0.05). The Na(+)-H+ exchanger inhibitor, HOE 694 (10 mumol l-1, abolished the PGF2 alpha-induced rise in pH and the increase in cell shortening. PGF2 alpha-induced increases in cell shortening and intracellular pH were also attenuated by the protein kinase C (PKC) inhibitor, chelerythrine (2 mumol l-1. CONCLUSION: The positive inotropic action of PGF2 alpha appears to be mediated via activation of the Na(+)-H+ exchanger with the possible involvement of PKC. This suggests that PGF2 alpha-produces intracellular alkalosis, which then sensitizes cardiac myofilaments to calcium.

Alkaloids↗
PubMed1998

Effects of tumour necrosis factor-alpha on the coronary circulation of the rat isolated perfused heart: a potential role for thromboxane A2 and sphingosine.

1. The actions of tumour necrosis factor-alpha (TNF-alpha) on the coronary circulation were investigated in the rat isolated heart, perfused under constant flow, recirculating conditions. 2. An early increase in coronary perfusion pressure (CPP) was observed upon treatment with TNF-alpha (increase in CPP 10 min after TNF-alpha treatment: 45+/-12 mmHg vs control: 15+/-4 mmHg, P<0.05). The role of sphingosine, prostanoids and endothelins, in this coronary constrictor action, was investigated with the use of pharmacological inhibitors and antagonists. 3. The TNF-alpha induced increase in coronary tone was blocked by indomethacin, 10 microM (increase in CPP after 10 min: 13+/-4 mmHg vs TNF-alpha alone, P<0.05). 4. The thromboxane receptor antagonist GR32191, 10 microM, attenuated the TNF-alpha induced coronary constriction (12+/-2 mmHg vs TNF-alpha alone, P<0.05), as did the joint thromboxane A2 synthesis inhibitor and receptor antagonist ZD1542, 10 microM (8+/-1 mmHg vs TNF-alpha alone, P<0.05). 5. The ceramidase inhibitor N-oleoylethanolamine (NOE), 1 microM, also blocked the TNF-alpha induced response (8+/-4 mmHg vs TNF-alpha alone, P<0.05). 6. In contrast, the coronary constrictor action of TNF-alpha was not inhibited by the endothelinA/B receptor antagonist bosentan, 3 microM (38+/-9 mmHg vs TNF-alpha, P=NS). 7. These data indicated that the early coronary vasoconstriction induced by TNF-alpha was mediated by both thromboxane A2 and sphingosine, suggesting an interaction between both the sphingomyelinase and phospholipase A2 metabolic pathways.

Animals↗
PubMed1998

Design of mobile telemedicine systems using GSM and IS-54 cellular telephone standards.

This paper presents an overview of the design of mobile telemedical systems using cellular telephone channels. A mobile telemedicine communication system was studied using both the GSM and the IS-54 standards, which are the most widely used commercial cellular telephone systems in Europe and North America, respectively. A simulation using a photoplethesmography signal showed successful transmission of data with bit error rates of less than 10(-7) at the receiver for the IS-54 standard and less than 10(-5) for the GSM standard, depending on the mobile channel conditions used.

Equipment Design↗
PubMed1998

Depression in the quantity of intestinal secretory IgA and in the expression of the polymeric immunoglobulin receptor in caloric deficiency of the weanling mouse.

The objective of this investigation was to determine the influence of weanling caloric restriction on the expression of the polymeric immunoglobulin receptor (pIgR) in the liver and intestine and on the levels of IgA in the blood and intestinal secretions. Male C57BL/6J mice were allocated to a zero-time control group (19 days of age) or to groups fed for 14 days as follows: ad libitum intake of a complete purified diet (19% crude protein, 17 kJ/g gross energy) or restricted intake of a complete diet. Enzyme-linked immunosorbent assays revealed a low concentration of gut luminal immunoglobulin A (IgA) despite a normal concentration of serum IgA in the malnourished mice. The concentration and total quantity per organ of the pIgR were assessed in the liver and intestine by means of Western immunoblotting using an antiserum raised against the secretory component portion of rat pIgR. Malnourished animals exhibited low quantities of hepatic and intestinal pIgR relative to well-nourished controls (8% and 40% of control, respectively) and also exhibited a low concentration (soluble protein basis) of hepatic pIgR (39% of control). The concentration of biliary secretory component was also low in the malnourished animals (20% of well nourished). Despite the low quantity of hepatic pIgR, Western blotting revealed no change in the concentration of monomeric, dimeric, and polymeric forms of serum IgA in the malnourished group relative to well-nourished animals. Caloric deficiency in an experimental system that closely resembles human marasmus results in a decrease in the quantity of the pIgR that is sufficient to account for the low concentration of IgA in the mucous secretions of the intestine. Considered together with recent evidence pertaining to weanling protein deficiency, these results permit the conclusion that the pIgR is a focal point of the impact exerted by metabolically diverse forms of protein-energy malnutrition on mucosal humoral immunocompetence.

Animals↗
PubMed1997

Reduction in the quantity of the polymeric immunoglobulin receptor is sufficient to account for the low concentration of intestinal secretory immunoglobulin A in a weanling mouse model of wasting protein-energy malnutrition.

The main objective of this investigation was to determine the influence of protein-energy malnutrition (PEM) in weanling mice on the expression of the hepatic and intestinal polymeric immunoglobulin receptor (pigR), a molecule that transports mucosal immunoglobulin A (IgA) into the intestinal lumen. An experimental system was used that produces systemic wasting (loss of approximately 1.9% of initial body weight per day) and that exhibits fidelity to human PEM in its influence on the concentration of IgA in critical biological fluids as well as in its influence on lymphoid involution and thymus-dependent immunocompetence. Male C57BL/6J mice were allocated to a zero-time control group (19 d of age) or to groups fed for 14 d as follows: free access to a complete purified diet (19% crude protein, 17 kJ/g gross energy) or free access to a low protein diet (0.5% crude protein). The concentration and total quantity per organ of the pIgR were assessed in the liver and intestine by Western immunoblotting using an antiserum raised against the secretory component portion of rat pIgR. Malnourished mice exhibited low quantities of hepatic and intestinal pIgR relative to well-nourished controls (0.4% and 36% of control, respectively) and also exhibited a low concentration (soluble-protein basis) of hepatic pIgR (2% of control). The concentration of biliary secretory component also was low in the malnourished mice (4% of the value for well-nourished controls). Finally, Western blotting revealed an eightfold increase in serum concentration of dimeric IgA in the malnourished group relative to well-nourished mice, whereas the levels of the monomeric form and of the higher order polymers of IgA were elevated by factors of three and two, respectively. In this experimental system, decreased expression of the pIgR is sufficient to account for the low concentration of IgA that is maintained in the mucous secretions of the intestine.

Animals↗
PubMed1997

Microcontroller-based underwater acoustic ECG telemetry system.

This paper presents a microcontroller-based underwater acoustic telemetry system for digital transmission of the electrocardiogram (ECG). The system is designed for the real time, through-water transmission of data representing any parameter, and it was used initially for transmitting in multiplexed format the heart rate, breathing rate and depth of a diver using self-contained underwater breathing apparatus (SCUBA). Here, it is used to monitor cardiovascular reflexes during diving and swimming. The programmable capability of the system provides an effective solution to the problem of transmitting data in the presence of multipath interference. An important feature of the paper is a comparative performance analysis of two encoding methods, Pulse Code Modulation (PCM) and Pulse Position Modulation (PPM).

Acoustics↗
PubMed1997

Retroviral marking identifies grafted autologous keratinocytes in porcine wounds receiving cultured epithelium.

Cultured epithelial autografts are often applied to wounds with a capacity for regeneration from dermal appendages. It is unclear in these circumstances whether the cultured autografts act merely as a biologic dressing or whether they become incorporated into the new epithelium. We have used retroviral gene transfer techniques to identify autologous keratinocytes in an established porcine model of cultured epidermal (CE) grafting. Porcine keratinocytes were transduced with an MFG-lacZ nls vector produced by the amphotropic packaging line GP+EnvAm12. Transduction rates of 15.1%, in the absence of selection, were achieved by a single passage on gamma-irradiated retroviral producers as a feeder layer. Full-thickness wounds were created on Large White pigs and isolated from the surrounding skin by a polytetrafluoroethylene chamber. Wounds were grafted initially with autologous de-epidermized dermis (DED), followed 7 d later by sheets of retrovirally marked or unmarked CE autografts. Two weeks after grafting, the mean area of epithelium was 48.4% in wounds that received CE grafts and 32.3% in wounds that were left as DED alone. The epithelium on DED represents regeneration from dermal appendages. The contribution made by the autograft cells to the new epidermis was demonstrated unequivocally, however, by lacZ-positive areas visible macroscopically on the surface of the excised wound. In cryostat sections through the lacZ-positive areas, retrovirally marked cells were present at both superficial and basal positions in the new epithelium.

Animals↗
PubMed1997

Use of neural networks in telemedical monitoring of divers.

An artificial neural network (ANN) has been developed to predict and classify the risk of medical disorders for certain dive profiles. The telemedical data applied to the ANN represent different physiological and physical parameters that are transmitted acoustically from a diver to a remote receiver. The telemetered data include dive time, maximum depth and decompression stop times and depths. Preliminary tests demonstrated the successful performance of the ANN where classical mathematical and statistical methods had failed due to the complex nature and variability of the parameters involved.

Diving↗
PubMed1997

Evidence for endothelin involvement in the pulmonary vasoconstrictor response to systemic hypoxia in the isolated rat lung.

We investigated the effect of systemic hypoxia (Krebs-Henseleit solution gassed with 5% CO2/95% N2) on an isolated, perfused rat lung. Hypoxia resulted in a slowly developing sustained increase in pulmonary perfusion pressure (PPP) accompanied by an increase in lung weight (LW). The endothelin (ET) receptor antagonists BQ123 (3 and 10 microM), BQ788 (3 microM) and bosentan (1.5 and 5 microM) all attenuated the hypoxia-induced increases in LW and PPP. In addition, phosphoramidon (1 microM), an ET-converting enzyme inhibitor, also significantly attenuated the hypoxia-induced increases in PPP and LW. The use of two agents that alter peptide secretion, phalloidin (10 and 50 nM) and colchicine (100 nM), and the peptide synthesis inhibitor cycloheximide (5 microM) all significantly attenuated the hypoxia-induced increases in PPP and LW. The increase in PPP and LW after the onset of hypoxia was accompanied by an increase in perfusate levels of ET-1 compared with normoxic time-matched controls. The results show that in this model, systemic hypoxia is capable of causing a sustained vasoconstriction and increased LW. The fact that these increases can be attenuated by an ET-converting enzyme inhibitor, ET receptor antagonists and agents that block peptide synthesis and secretion, together with the increase in perfusate levels of ET-1, suggests that ET production and release contribute to the changes seen.

Animals↗