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C Barton

Publications and source records attributed to C Barton.

At least 37 records · Page 2Linked to original sources
PubMed1997

Effect of enterostatin and kappa-opioids on macronutrient selection and consumption.

Enterostatin, the activation peptide of pancreatic procolipase, suppresses consumption of high-fat diets and selectively suppresses fat consumption over carbohydrate consumption. Kappa-opioid subtype agonists stimulate feeding whereas antagonists suppress feeding. We investigated the effects of enterostatin, the kappa-opioid agonist U50488, and the kappa-opioid antagonist nor-binaltorphimine (nor-BNI) on macronutrient selection and food consumption in rats adapted to choose between a high-fat (HF) diet or a low-fat-high-carbohydrate (LF) diet. In fasted rats, lateral cerebro-ventricular injection (LV) of enterostatin selectively suppressed consumption of the HF diet, with no effect on LF diet consumption. Nor-BNI also selectively suppressed consumption of the HF diet without affecting LF diet consumption. Additionally, U50488 prevented the suppression of consumption of the HF diet in response to enterostatin. In food-sated rates, U50488 preferentially increased consumption of the HF diet and had no effect on consumption of the LF diet. Combined infusions of subthreshold doses of enterostatin and nor-BNI also inhibited consumption of the HF but not the LF diet, whereas combined infusions of maximal doses of enterostatin and nor-BNI had no additive effects. Collectively, these data suggest that a kappa-opioid pathway modulates selection and consumption of diets high in fat and that enterostatin modulates consumption of dietary fat by interacting with this pathway.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗
PubMed1996

Opioid receptor subtype control of galanin-induced feeding.

This study examined the effects of specific antagonists to kappa- and mu-opioid receptors on the feeding induced by injecting galanin into the lateral cerebral ventricle (LCV). Galanin injected into the lateral cerebral ventricle of sated rats stimulated the consumption of high-fat diet when compared to controls injected with saline vehicle. The mu-opioid receptor antagonist, CTOP, completely abolished galanin-induced feeding in sated rats whereas the kappa-opioid receptor antagonist, nor-BNI, had no effect on galanin-induced feeding. Neither CTOP nor nor-BNI alone produced any change in food consumption in sated rats. In fasted rats, on the other hand, nor-BNI significantly decreased consumption of a high-fat diet (> 83%) when compared to animals treated with the saline vehicle, whereas CTOP had no significant effect. These findings suggest that galanin-induced feeding of a high-fat diet is selectively modulated by a pathway involving mu-opioid receptors whereas feeding induced by fasting is dependent on a pathway mediated by kappa-opioid receptors. These data also suggest that galanin does not mediate the feeding response after fasting.

Animals↗
PubMed1996

Effect of selective aortic arch perfusion on median frequency and peak amplitude of ventricular fibrillation in a canine model.

STUDY OBJECTIVE: To determine whether the computer-derived measures of median frequency or peak amplitude of ventricular fibrillation (VF), obtained by fast Fourier transform of the VF waveform, change during selective aortic arch perfusion in a canine model of cardiac arrest. METHODS: Eight mongrel dogs (including 4 control animals) were sedated, intubated, catheterized, and instrumented to record the electrocardiogram (digitally at 100 Hz, filtered with a finite impulse response filter at 2 Hz), right atrial pressure, and aortic pressure during resuscitation in a model of VF-induced cardiac arrest. After 10 minutes of VF-induced arrest, cardiopulmonary resuscitation (CPR) with a mechanical chest compression device was initiated. Beginning 2 minutes later, the 4 study animals received, every 2 minutes, 45 seconds of selective aortic arch perfusion (SAAP) with autologous blood infusions under high pressure. Defibrillation was attempted after 3 minutes of CPR and every minute thereafter. Both study and control groups received standard-dose epinephrine (.01 mg/kg) every 3 minutes by means of an intraaortic catheter. The median frequency, peak amplitude, and coronary perfusion pressure (CPP) during the 5-second period just before defibrillation were obtained with the use of computer algorithms. RESULTS: All SAAP animals and 1 control animal were resuscitated. Baseline measures of median frequency (8.4 +/- 1.5 versus 6.6 +/- 1.0 Hz) and peak amplitude (.18 +/- .05 versus .36 +/- .13 mV) were not different between the SAAP and control groups, respectively, at the start of CRP. SAAP infusion resulted in significant increases in the SAAP group compared with the control group: median frequency, 9.6 +/- .4 versus 7.3 +/- 1.4 Hz; peak amplitude, .74 +/- .21 versus .39 +/- .15 mV; and CPP, 40.5 +/- 7.1 versus 18.0 +/- 15.0 mm Hg, respectively. Median frequency correlated with CPP (r2 = .67). Peak amplitude did not correlate with CPP (r2 = .06). CONCLUSION: Median frequency and peak amplitude increase with SAAP during cardiac arrest in a canine model. This method of resuscitation was reliable in allowing restoration of a stable perfusing rhythm after defibrillation. Changes in measures of peak amplitude and median frequency may reflect interventions that enhance the likelihood of successful defibrillation and may thereby offer a noninvasive means of monitoring interventions during cardiac arrest.

Animals↗
PubMed1996

Generation and characterisation of stable cell lines expressing recombinant human N-methyl-D-aspartate receptor subtypes.

Transfection of mouse L(tk-) cells with human N-methyl-D-aspartate (NMDA) receptor subunit cDNAs under the control of a dexamethasone-inducible promoter has been used to generate two stable cell lines expressing NR1a/NR2A receptors and a stable cell line expressing NR1a/NR2B receptors. The cell lines have been characterised by northern and western blot analyses, and the pharmacology of the recombinant receptors determined by radioligand binding techniques. Pharmacological differences were identified between the two NMDA receptor subtypes. The glutamate site antagonist D, L-(epsilon)-2-[3H]amino-4-propyl-5-phosphono-3-pentanoic acid ([3H]CGP 39653) had high affinity for NR1a/NR2A receptors (KD = 3.93 nM) but did not bind to NR1a/NR2B receptors. Glycine site agonists showed a 2.6-5.4-fold higher affinity for NR1a/NR2B receptors. Data from radioligand binding studies indicated that one of the cell lines, NR1a/NR2A-I, expressed a stoichiometric excess of the NR1a subunit, which may exist as homomeric assemblies. This observation has implications when interpreting data from pharmacological analysis of recombinant receptors, as well as understanding the assembly and control of expression of native NMDA receptors.

2-Amino-5-phosphonovalerate↗
PubMed1995

Differential effects of enterostatin, galanin and opioids on high-fat diet consumption.

Enterostatin, the activation peptide of pancreatic procolipase, suppresses high-fat diet consumption both centrally and peripherally. kappa-opioid agonists are also known to stimulate fat intake. These experiments were conducted to determine if an opioidergic central pathway might mediate the effects of enterostatin and galanin on fat intake. Male Sprague-Dawley rats were adapted to a high-fat diet (56% energy) and were implanted with cannulae aimed at the lateral cerebral ventricle (LV) or third cerebral ventricle (3V). Injection of enterostatin (1 nmol, LV) suppressed high-fat diet consumption in fasted (20 h) rats. This inhibition of high-fat intake by enterostatin was attenuated by central injection of the specific kappa-agonist U50488 (2.15, 21.5 and 215 nmol, LV) in a dose-dependent manner in fasted rats while only the highest dose of U50488 (215 nmol, LV) independently produced stimulation of high-fat diet consumption in sated rats. Galanin (0.1 nmol, 3V) induced consumption of high-fat diet in sated rats similar to that seen with U50488 and this stimulation was attenuated by peripheral injection of naloxone (1.0 mg/kg i.p.). We present a model which integrates the present data, as well as previous findings, in explaining a potential common opioid pathway modulating fat consumption.

Animals↗
PubMed1995

Identification of 3,5-dihydro-2-aryl-1H-pyrazolo[3,4-c]quinoline-1,4(2H)-diones as novel high-affinity glycine site N-methyl-D-aspartate antagonists.

Almost all of the existing known antagonists at the glycine site of the N-methyl-D-aspartate (NMDA) receptor have a low propensity for crossing the blood-brain barrier. It has been suggested that in many cases this may be due to the presence of a carboxylic acid which is a common feature of most of the potent full antagonists at this receptor. In this study, 2-aryl-1H-pyrazolo[3,4-c]quinoline-1,4(2H)-diones were found to have high-affinity binding at the glycine receptor. In particular, structure-activity studies identified 7-chloro-3,5-dihydro-2-(4-methoxyphenyl)-1H-pyrazolo[3,4-c]quinoline- 1,4(2H)-dione as the most potent of a series of analogues with an IC50 of 3.3 nM. The measured pKa values in this class of compounds (typically 4.0) indicate they are of equivalent acidity to carboxylic acids. Functional antagonism was demonstrated by inhibition of NMDA-evoked responses in rat cortical slices. Anticonvulsant activity in DBA/2 mice was achieved after dosing by direct injection into the cerebral ventricles, but no activity was seen after systemic administration, suggesting low brain penetration with this class of antagonists.

Animals↗
PubMed1995

Bombesin-induced hypothermia in rats tested at normal ambient temperatures: contribution of the sympathetic nervous system.

Rats infused centrally with bombesin become hypothermic at normal ambient temperatures when acutely deprived of food, but not while allowed unrestrained access to food. Ad lib-fed rats, tested at normal ambient temperatures, become hypothermic after receiving intracerebroventricular (ICV) bombesin when they have ventromedial hypothalamic lesions or when administered insulin or 2-deoxy-D-glucose peripherally. All of these conditions have been linked to reductions of sympathetic nervous system activity to brown adipose tissue (BAT), a major thermogenic mechanism of many homeotherms. A between group design was used to examine the effects of ICV bombesin infusions on the response to peripheral injections of a) the sympathetic ganglionic blocker chlorisondamine (2.5 mg/kg, IP) in ad lib-fed rats, b) the nonspecific beta-agonist isoproterenol (30 mg/kg, IP) in food-deprived rats, and c) the combination of isoproterenol and chlorisondamine in ad lib-fed rats. Ad lib-fed rats receiving ICV bombesin (100 ng/5 microliters), in combination with peripheral chlorisondamine injection, became hypothermic 60 min postbombesin administration (-2.84 +/- 0.33 degrees C), while ad lib-fed rats receiving ICV bombesin infusion and peripheral injections of saline did not (-0.08 +/- 0.37 degrees C). Isoproterenol blocked hyperthermia in ad lib-fed rats injected with chlorisondamine and ICV bombesin. Food-derived rats receiving ICV bombesin infusion and peripheral saline injection exhibited hypothermia 60 min postbombesin administration (-2.51 +/- 0.29 degrees C). Peripheral injections of isoproterenol prevented bombesin-induced hypothermia in food-deprived rats. These data suggest that bombesin induces hypothermia at normal ambient temperatures when the sympathetic nervous system drive to BAT cannot be (or is not) activated.

Adipose Tissue, Brown↗
PubMed1995

t(8;21) myelodysplasia, an early presentation of M2 AML.

The reciprocal translocation of genetic material between chromosomes 8 and 21, t(8;21), is usually restricted to cases of acute myeloid leukaemia (AML). Cases of AML with t(8;21) exhibit characteristic dysplastic features in myeloid and erythroid lineages with reduction in megakaryocytes. We report details of three patients presenting with myelodysplastic features; two had a typical t(8;21), and the third had a variant t(8;21) translocation. We discuss the significance of t(8;21) in the aetiology of myelodysplastic syndrome (MDS) and implications for the management of such patients.

Adult↗
PubMed1995

Lack of a fast-acting effect of erythropoietin on arterial blood pressure and endothelin level.

Recombinant erythropoietin (EPO) has been shown to induce vascular smooth muscle contraction in vitro suggesting a rapid acting pressor effect. In addition its chronic administration has been shown to raise plasma endothelin. This study was designed to explore the presence, if any, of fast-acting effects of EPO on the arterial blood pressure and endothelin level in vivo. Nine stable patients with end-stage renal disease (ESRD) were included in a double-blind, crossover, placebo-controlled study using IV bolus injections of either EPO or saline solution administered to patients while they were comfortably seated in reclining chairs and undisturbed in individual climate-controlled rooms. After a 15-min resting period, the bolus injection was given, and blood pressure (BP) and heart rate were measured and recorded automatically every 5 min for 60 min using an electronic device to avoid operator bias/error. In addition, blood samples were obtained for plasma endothelin determination at time 0 and at 5, 30, and 60 min after injection. Patients were studied approximately 2 h before their regularly scheduled dialysis session. The EPO dosage given (50-60 U/kg) was equal to the maintenance dose, routinely administered during dialysis. No significant change was observed in arterial BP, heart rate, or plasma endothelin concentration relative to the baseline values after either EPO or placebo administration. Thus, the results have excluded a rapid effect on BP, heart rate, and endothelin concentration of EPO at therapeutic doses which, when chronically administered, can clearly raise arterial blood pressure in ESRD patients.

Adult↗
PubMed1994

Response of T-beta CD8+ lymphocytosis-associated neutropenia to G-CSF.

Only limited data are reported on the response to granulocyte-colony stimulating factor (G-CSF) of large granular lymphocytosis-associated neutropenia. We report features of such a case who developed a suppurating leg ulcer following a dog bite. G-CSF was used to increase the neutrophil count, allowing the ulcer to be successfully skin grafted.

Female↗
PubMed1994

Gram negative septicaemia diagnosed on peripheral blood smear appearances.

Buffy coat smears from febrile patients may contain visible bacteria and therefore detect bacteraemia before conventional blood cultures become positive. However, it is unusual to see micro-organisms in an otherwise untreated peripheral blood smear. The case of a febrile neutropenic patient is reported. A Wright's stained peripheral blood smear contained bacterial elements, thus making earlier diagnosis of septicaemia and identification of the causative bacterium possible.

Bacteremia↗
PubMed1993

Case-control study of leukaemia and non-Hodgkin's lymphoma among children aged 0-4 years living in west Berkshire and north Hampshire health districts.

OBJECTIVE: To investigate the relation between parental employment in the nuclear industry and childhood leukaemia and non-Hodgkin's lymphoma. DESIGN: Case-control study. SETTING-West Berkshire and Basingstoke and North Hampshire District Health Authorities. SUBJECTS: 54 children aged 0-4 years who had leukaemia or non-Hodgkin's lymphoma diagnosed during 1972-89, who were born in the study area and were resident there when cancer was diagnosed. Six controls were selected for each case: four from hospital delivery registers and two from livebirth registers maintained by the NHS central register. Controls were matched for sex, date of birth (within six months), and area of residence at birth and time of diagnosis. MAIN OUTCOME MEASURES: Parents' employment by the nuclear industry and exposure to ionising radiation at work. RESULTS: Five (9%) of the 54 cases and 14 (4%) of the 324 controls had fathers or mothers, or both, who had been employed by the nuclear industry (relative risk 2.2, 95% confidence interval 0.6 to 6.9). Nuclear industry employees who work in areas where exposure to radiation is possible are given film badges to monitor their exposure to external penetrating ionising radiation. Three fathers of cases and two fathers of controls (and no mothers of either) had been monitored in this way before their child was conceived (relative risk 9.0, 95% confidence interval 1.0 to 107.8). No father (of a case or control) had accumulated a recorded dose of more than 5 mSv before his child was conceived, and no father had been monitored at any time in the four years before his child was conceived. A dose-response relation was not evident among fathers who had been monitored. CONCLUSIONS: These results suggest that the children of fathers who had been monitored for exposure to external penetrating ionising radiation in the nuclear industry may be at increased risk of developing leukaemia before their fifth birthday. The finding is based on small numbers and could be due to chance. If the relationship is real the mechanisms are far from clear, except that the effect is unlikely to be due to external radiation; the possibility that it could be due to internal contamination by radioactive substances or some other exposure at work should be pursued. The above average rates of leukaemia in the study area cannot be accounted for by these findings.

Case-Control Studies↗
PubMed1993

Carboplatin-based chemotherapy for bladder cancer.

Urothelial cancer is common and the prognosis of patients with locally advanced tumors treated with conventional treatment is poor. In this trial we examined responses among 72 urothelial cancer patients referred for treatment with MVMJ (methotrexate/vinblastine/mitoxantrone/carboplatin) chemotherapy. Sixty-four evaluable patients, 37 with locally advanced and 27 with metastatic urothelial cancer, were treated. Twenty-nine (45%) of the 64 patients had a complete or partial response, 15 (23%) had stable disease, and 13 (20%) had disease progression. The median survival of the responding patients has not been reached (range, 114 to 1184+ days). Twelve patients (32%) with locally advanced disease had a complete response to treatment; their median survival has not been reached and ranges up to 1131+ days. Five patients (18%) with metastatic cancer had a complete response to treatment and their median survival was 497 days (range, 184 to 637+). There were seven deaths within the first treatment month.

Adult↗