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Biomedical subjects

D N Jones

Publications and source records attributed to D N Jones.

At least 73 records · Page 4Linked to original sources

Patterns of cytokeratin expression by neoplastic and non-neoplastic epithelium.

Eighty-one epithelial lesions were studied immunohistologically for cytokeratin protein expression using three anticytokeratins CAM 5.2, NCL5D3 and RCK102. Consistent differences were noted between squamous and glandular neoplasms. Squamous and cutaneous carcinomas were found to preferentially express higher molecular weight cytokeratins than adenocarcinomas. In addition, tumours of similar morphology from different sites showed differences in expression of these markers. Differences in pattern were also found between benign and malignant lesions in the case of liver and urinary bladder. Thus the value of cytokeratin profile analysis in characterisation of epithelial neoplasms is confirmed and may be useful in distinguishing benign from malignant tumours in some instances.

Antibodies, Monoclonal↗

Effects of naloxone infusion upon spontaneous and amphetamine-induced activity.

Naloxone-filled (1.0 mg/kg per h) or sham pumps were implanted subcutaneously (s.c.) in rats on day 0 and removed on day 7. Spontaneous locomotor activity was lower in naloxone-infused rats on day 3 only. Cumulative dose-response curves to D-amphetamine were constructed in separate groups on day 6 or day 8 (0.0-6.4 mg/kg s.c.). On day 6, naloxone infusion attenuated the gross movement response to D-amphetamine, but not the fine movement response. There were no differences in the response of naloxone- or sham-infused rats to D-amphetamine on day 8. Therefore, withdrawal from continuous naloxone infusion had no influence upon spontaneous or D-amphetamine-stimulated activity.

Animals↗

Long term kappa-opioid receptor blockade following nor-binaltorphimine.

This study determined the influence of nor-binaltorphimine (nor-BNI, 10 micrograms intracisternally), 1, 7 and 21 days post-administration, upon spiradoline-induced antinociception measured in the hot-plate test. On each test day, nor-BNI prevented the spiradoline-induced increase in the latency of rats to paw-lick without affecting the antinociceptive response to morphine. These data suggest that a single administration of nor-BNI can cause a long term blockade of kappa-opioid receptors in rats.

Analgesics↗

The distribution of 5-HT3 recognition sites in the marmoset brain.

The distribution of the binding of [3H]GR65630 (0.2 nM) to putative 5-HT3 recognition sites in the brain of the common marmoset was assessed using autoradiography. Specific binding was heterogeneously distributed with the highest densities found in discrete nuclei of the lower medulla (nucleus tractus solitarii, dorsal motor nucleus of the vagus nerve, nucleus of spinal trigeminal nerve tract and the area postrema). In forebrain areas, relatively high binding densities were located in the medial habenula nucleus and the hippocampus (CA3, CA4 and fascia dentata). Low levels of specific binding in the rest of the forebrain hindered quantification.

Animals↗

Naloxone reduces amphetamine-induced stimulation of locomotor activity and in vivo dopamine release in the striatum and nucleus accumbens.

This study tested the possibility that naloxone (NX), an opioid antagonist, reduces the behavioral effects of amphetamine (AMPH) in rats by attenuating the dopaminergic response to AMPH. In the first experiment, adult, male rats were injected SC with either NX (5.0 mg/kg) or saline and 30 min later received doses of AMPH (0.0, 0.1, 0.4, 1.6, and 6.4 mg/kg) cumulatively at 30-min intervals. Gross locomotor counts following AMPH administration were significantly lower for rats pretreated with NX than for rats pretreated with saline. In the second experiment, the same drug treatments were given while performing microdialysis in either the striatum (STR) or nucleus accumbens (NACC). STR rats treated with vehicle showed a larger percentage increase in DA levels following AMPH treatment than did NACC rats treated with vehicle. NX pretreatment did not affect dopamine concentrations in either brain region. However, compared to pretreatment with saline pretreatment with NX significantly decreased the dopaminergic response to AMPH in the STR. There was no difference between the two groups in the peak dopaminergic response to AMPH in the NACC, but there was a significant AMPH x treatment x time interaction due to differences between the groups during the later portion of the response to 6.4 mg/kg AMPH. There was also a difference in locomotor activity following AMPH treatment between NX- and saline-treated subjects during dialysis. These findings suggest that a decrease in the dopaminergic response to AMPH is the mechanism by which NX attenuates behavioral stimulant effects of AMPH. In addition, there is a difference between the STR and NACC in dopaminergic responsiveness to AMPH.

Animals↗

Ondansetron and arecoline prevent scopolamine-induced cognitive deficits in the marmoset.

The cognitive-enhancing potential of the 5-hydroxytryptamine (5-HT) selective 5-HT3 receptor antagonist, ondansetron, was investigated in a model of cognitive impairment induced by the muscarinic receptor antagonist, scopolamine. For this purpose, marmosets were trained in an object discrimination task utilizing the Wisconsin General Test Apparatus. Administration of scopolamine (0.01-0.04 mg/kg, SC) caused a dose-dependent impairment in the acquisition of the object discrimination task in that marmosets required more trials to reach criterion, made more errors, and took longer to choose the objects. Administration of arecoline (0.06-0.1 mg/kg, SC) or 1,2,3,9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol- 1-yl)methyl]-4H-carbazol-4-one,HCl.2H2O (ondansetron) (0.1-1 micrograms/kg, SC) prevented the scopolamine-induced impairment in task acquisition in that the performance of marmosets was indistinguishable from that of saline-treated animals and was significantly better than that following scopolamine/saline. From these studies, we conclude that ondansetron prevents impairment in the cognitive performance of marmosets induced by administration of scopolamine.

Animals↗

Behavioural effects of anxiogenic agents in the common marmoset.

The effects of the anxiogenic agents FG7142, caffeine, pentylenetetrazole, and amphetamine were assessed in two anxiety situations in the marmoset, first in an "anxiogenic" test based on the animal's response to a human observer standing in front of the home cage and second in a low-anxiety situation where animals behaviour was videotaped in the absence of the observer. In response to the human observer, the anxiolytic agent diazepam (0.1-2.5 mg/kg, SC) was shown to reduce the intensity of behaviours such as postures, while increasing time spent on the cage front. In this test, with the exception of amphetamine, which only modified responding at stereotypic doses, the anxiogenic agents failed to modify marmoset behaviour. In contrast, in the low-anxiety filming protocol the anxiogenic agents consistently reduced measures of locomotor activity while increasing the amount of time animals spent in the nest box. It is suggested that the low-anxiety protocol may be useful to evaluate drug-induced anxiogenesis and in studies of withdrawal from chronic anxiolytic treatment or drugs of abuse.

Amphetamine↗

The role of hemodynamics and duplex ultrasound in the diagnosis of peripheral arterial disease.

Recent reports have suggested that duplex ultrasound should replace hemodynamic measurements and the use of the ankle-to-arm systolic blood pressure ratio in evaluating patients with peripheral arterial disease. Measurement of peripheral hemodynamics in patients with peripheral arterial disease is well established and can be used for screening populations at risk for peripheral arterial disease; the finding of an abnormal ankle-to-arm ratio is associated with a high risk of cardiovascular morbidity and mortality. With the ankle-to-arm ratio, the diagnosis of vascular disease can be established in symptomatic patients and initial treatment plans can be formulated. In contrast, duplex ultrasound provides accurate information on vessel morphology and changes in blood-flow velocity in specific areas of stenosis. The test is noninvasive, and in some situations the duplex instrument may be superior to an angiogram in detecting patent distal vessels. Because it is more expensive and time-intensive than measuring peripheral pressures, duplex ultrasound should be used in selected patients in whom the knowledge of actual vessel morphology is critical to the patient's treatment.

Ankle↗

Bilateral spondylolysis and associated dysplasia of C6.

Cervical spondylolysis is a rare condition, characterised by the presence of a corticated cleft between the superior and inferior articular facets of the articular mass (1). This defect involves the cervical equivalent of the pars interarticularis of the lumbar spine. Associated dysplastic changes are present, suggesting that the lesion is congenital (1 and 2). This case report describes bilateral spondylolysis and associated dysplasia of C6 in an 18 year old female. The importance of this lesion lies in its differentiation from the more serious articular mass fracture or dislocation (1).

Adolescent↗

Interaction between opioid antagonists and amphetamine: evidence for mediation by central delta opioid receptors.

Naloxone, the opioid receptor antagonist, attenuates the effects of amphetamine in a wide range of behavioral paradigms. To determine the role of the opioid receptor subtypes in this phenomenon, subtype-selective opioid receptor antagonists were administered intracisternally to rats either as a 15-min [naloxone methiodide (NX.M) and naltrindole (NTI)] or a 24-hr [beta-funaltrexamine (beta-FNA) and norbinaltorphimine (nBNI)] pretreatment. Cumulative dose-response curves to amphetamine were constructed (saline, 0.1, 0.4, 1.6 and 6.4 mg/kg s.c.) with dosing every 30 min. Motor activity (gross and fine movements) was recorded for 20 min, commencing 10 min postinjection. Amphetamine dose-dependently increased both fine and gross movements. NX.M (30 micrograms) and NTI (10 and 30 micrograms) attenuated the gross activity response to amphetamine but did not alter the increase in fine movements. Lower doses of NX.M (2.0 and 10 micrograms) potentiated the fine activity response to amphetamine without any effect on the gross movements. Pretreatment with beta-FNA (1.25-20 micrograms), nBNI (10 and 30 micrograms) or NX.M (5.0 mg/kg s.c.) did not influence the response to amphetamine. However, beta-FNA and nBNI blocked the antinociceptive effects of morphine and spiradoline, respectively, indicating that these antagonists were tested under appropriate conditions for opioid receptor blockade. These data indicate a central site of action for the opioid antagonist-amphetamine interaction. The ability of NX.M (i.c.) and NTI, but not beta-FNA or nBNI, to influence the motor activity response to amphetamine implicates delta receptors in the opioid-mediated modulation of the behavioral stimulant effects of amphetamine.

Amphetamine↗

Argon laser-assisted anastomoses in medium-size vessels: one-year follow-up.

Laser-assisted anastomosis of medium-size vessels can be performed with satisfactory short-term patency. This study was undertaken to evaluate patency and structural integrity up to 1 year. An argon laser was used to make bilateral femoral arteriovenous anastomoses in 12 dogs compared to conventional suture method in another 8 dogs. These anastomoses were evaluated for patency and aneurysm formation at 1 hour; 1, 2, 4, and 8 weeks; and 12 months after surgery. All anastomotic sites were patent and without aneurysmal change or luminal narrowing at all harvesting intervals. Histologic examination revealed that within 1 month laser anastomotic sites were almost completely healed and without intimal hyperplasia. In suture anastomoses, foreign-body reaction remained evident up to 1 year. Use of the argon laser for medium size vessel anastomoses resulted in excellent patency without aneurysm formation or intimal hyperplasia even in the long term. These data suggest promising clinical applications.

Anastomosis, Surgical↗

The effect of ondansetron on cognitive performance in the marmoset.

The 5-HT3 receptor antagonist, ondansetron, was administered to marmosets to determine its effect on their performance in a Wisconsin General Test Apparatus using an object discrimination reversal learning task. Briefly, this comprised a test situation in which marmosets were required to select a food rewarded object to reach criterion in performance (this was termed the initial discrimination task); the rewarded object was then changed (in the same test session) and the marmoset was required to abandon its recently learned strategy to gain reward by selection of the second object (this was termed the reversal task). At doses of 1-10 ng/kg SC b.i.d. ondansetron improved performance in both the initial discrimination and reversal tasks. This was indicated as a reduction in the number of trials required to reach criterion, a reduction in choice latency time and a reduction in the number of errors made in each test session. Higher doses of ondansetron impaired performance as measured by several criteria. The major conclusion of this study is, therefore, that ondansetron at low doses is able to improve the performance of marmosets in a cognitive task. This would support the concept that a 5-HT3 receptor antagonist can act as a cognitive enhancer.

Animals↗

Factors affecting the patency of small-caliber prostheses: Observations in a suitable canine model.

Lack of an endothelial surface is most often blamed for the relatively poor patency of polytetrafluoroethylene grafts used in infrageniculate bypass when compared to autogenous saphenous vein. Length, caliber, flow, and ability to withstand flexion are also acknowledged but have not been systematically examined. We report the results of our attempts to discriminate between the relative contributions of these factors and to develop a suitable canine model for evaluating small-caliber prostheses (4 mm x 10 cm thin-walled polytetrafluoroethylene). ASA/dipyridamole were given 1 week before and 4 weeks after operation. Patency was assessed by directional Doppler at frequent intervals (less than or equal to 3 days). The following were observed: (1) Iliac placement provided a useful patency reference point (40% to 50% patency at 60 days). (2) Carotid patency was not better than iliac patency. (3) Crossing a flexion crease decreased patency. (4) The low patencies were not technical but intrinsic to the graft. Iliofemoral vein grafts achieved 100% patency at 60 days. (5) External rings did not improve iliofemoral patency (equal in paired comparisons). (6) Neither baseline platelet aggregation nor platelet aggregation after ASA administration correlated with patency. This canine model is an excellent test for small caliber-low flow prostheses. It allows paired-site comparisons, which are essential, and meaningful patency data with reasonable numbers of subjects within 2 months' observation. Directional Doppler evaluation avoids need for angiography or serial postmortem analysis sacrifice.

Anastomosis, Surgical↗

Peripheral vascular assessment and its role in predicting wound healing potential.

Local perfusion is a critical factor in wound healing with substantially greater perfusion levels necessary to support healing than those required to maintain viable intact tissues. Clinical observations alone are not sufficiently reliable to assess healing potential particularly in the patient with known vascular compromise. This article reviews the more common noninvasive techniques for evaluating peripheral circulation and wound healing potential in the distal lower extremity.

Foot↗

A reverse approach to 1H-n.m.r. assignments of bacterial polysaccharides.

A new approach is reported for obtaining the assignment of the 1H-n.m.r. spectra of bacterial polysaccharides which are not amenable to analysis using conventional strategies. An unambiguous assignment of the 13C-n.m.r. spectrum is made by 13C-COSY of the polysaccharide labelled to a high level with 13C. Assignment of the 1H-n.m.r. spectrum is then made by proton-detected CH-correlation spectroscopy of material that is labelled at a low level. Using this approach, virtually complete assignments have been made for the Klebsiella K3 serotype polysaccharide under physiological conditions of temperature and pH.

Carbohydrate Conformation↗