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Biomedical subjects

J R James

Publications and source records attributed to J R James.

At least 19 recordsLinked to original sources
PubMed2000

Individual variability of dopamine release from nucleus accumbens induced by nicotine.

Effects of subcutaneous administration of vehicle, amphetamine (1 mg/kg) or nicotine (0.4 mg/kg, injected twice, 90 min apart) on extracellular dopamine (DA) concentration in the nucleus accumbens (ACC) and ventral tegmental area (VTA) of the Sprague-Dawley rat were studied using microdialysis. Experiments were conducted at least 10 days following implantation of guide cannulae, and at least 2 h following insertion of microdialysis probes into the guides on the morning of each experiment. Probes were perfused at 2.5 microl/min and several fractions were collected every 10 min before and after the two test injections. Samples were analyzed by high-performance liquid chromatography with electrochemical detection for the major neurotransmitters and their metabolites. Significant DA release following nicotine administration was observed in ACC but not in VTA. By classifying ACC DA responses of individual rats, three major subgroups were identified which exhibited more robust responses. Nicotine appeared to be acting as a modulator of ACC DA, increasing DA output if baseline was <5 nM, but slowing release when the baseline exceeded 5 nM. These data are consistent with previous reports of modulation of arousal level by nicotine via DA.

Animals↗
PubMed1999

Discriminative stimulus (DS) properties of nicotine in the C57BL/6 mouse.

Previous research conducted in this and other laboratories has examined the role of genetic factors in determining sensitivity to (-)-nicotine in a variety of behavioral and physiological measures in the rat. More recent research further indicates that genetic factors can also influence the level of sensitivity to (-)-nicotine when serving as a discriminative stimulus (DS) in different rat strains. However, there has been little work examining the influence of genotype on the discriminative stimulus (DS) properties of (-)-nicotine in mice, a species that has played a major role in understanding the relationship between genetics and (-)-nicotine pharmacological effects. To further our understanding of the role of genetics and the ability of (-)-nicotine to exert DS control of behavior in the mouse, a group of C57BL/6 mice was trained to discriminate 0.4 mg/kg (-)-nicotine from saline using a two-lever operant procedure. (-)-Nicotine's discriminative stimulus in C57BL/6 mice appears to be similar to that generated in the rat. Results from behavioral tests with other drugs indicated that d-amphetamine exhibited a partial generalization, while (+)-nicotine fully generalized with nicotine. Tests of antagonism with mecamylamine and scopolamine further showed the cholinergic specificity of the (-)-nicotine DS in the mouse; mecamylamine but not scopolamine completely antagonized the (-)-nicotine DS. This work lays the groundwork for future comparisons of different mouse strain's sensitivities to (-)-nicotine's discriminative stimulus as well as using this behavioral model to search for new nicotinic receptor agonists and antagonists.

Analysis of Variance↗
PubMed1997

Pharmacological investigation of (+)- and (-)-cis-2,3,3a,4,5,9b-hexahydro-1-methyl-1H-pyrrolo-[3,2-h]isoq uinoline, a bridged-nicotine analog.

We recently synthesized a bridged-nicotine (BN) analog and its enantiomers. They failed to compete for [3H]nicotine binding in rat brain homogenates, yet they produced nicotine-like effects by decreasing locomotor activity and producing antinociception in the tail-flick, hot-plate and PPQ tests in mice. Therefore, additional in vivo and in vitro studies were undertaken to determine whether these compounds are indeed acting independently of the nicotinic system. Although these analogs did not produce nicotine-like responding when evaluated in rat drug discrimination, the racemate augmented the cue when administered in conjunction with nicotine. Moreover, the antinociceptive measured in the different tests and hypothermic effects of (+)-BN, the more potent enantiomer, were not blocked by the nicotinic antagonists mecamylamine and dihydro-beta-erythroidine. Acute tolerance developed to (+)-BN-induced antinociception but not to hypothermia after subcutaneous administration. In addition, no cross-tolerance was observed between (+)-BN and nicotine in the different tests. The absence of generalization in the discrimination test suggests that the BN analogs do not possess nicotine-like activity. In addition, the failure of mecamylamine and dihydro-beta-erythroidine to antagonize the antinociceptive and hypothermic effects of (+)-BN, on one hand, and the inability of the bridge analogs to stimulate 86Rb+ efflux in brain synaptosomes, on the other hand, provide further evidence that BN analog agonist effects are not mediated by the alpha-4, beta-2 receptor subunit combination. It is unlikely that alpha-7 subunits mediate the agonists effects of BN analogs because their affinity to neuronal [125I]alpha-bungarotoxin binding sites is in the higher micromolar range. Other nicotinic receptor subtypes remain possible candidates because (+/-)-BN augments the generalization of nicotine in drug discrimination and produces some nicotine-like pharmacological effects. BN analogs could represent a novel class of nicotinic analgesics because naloxone and atropine failed to alter the antinociceptive effects of (+)-BN. Alternatively, their actions may be entirely independent of the nicotinic system.

Analgesics↗
PubMed1995

Genetic and environmental aspects of the role of nicotinic receptors in neurodegenerative disorders: emphasis on Alzheimer's disease and Parkinson's disease.

As neurodegenerative disorders are better characterized, the importance of genetic and environmental interactions is becoming more evident. Among the neurodegenerative disorders, Alzheimer's disease and Parkinson's disease are both characterized by large losses of nicotinic binding sites in brain. In addition, losses in nicotinic receptors occur during normal aging. Chronic administration of nicotine in man or experimental animals increases the number of nicotinic receptors in brain. Nicotine has been shown to possess some neuroprotective properties for both cholinergic and dopaminergic neurons. These neuroprotective properties, when better understood, may provide important information on normal aging and neurodegenerative disorder related neuronal cell death. Understanding the functional aspects of neuronal nicotinic receptor subtypes may lead to successful therapeutic treatments or disease preventative strategies for neurodegenerative disorders.

Aging↗
PubMed1994

Evidence that nicotine can acutely desensitize central nicotinic acetylcholinergic receptors.

Current concepts concerning nicotine's CNS mechanism(s) of action suggest that this drug produces its effects via an interaction at nicotinic-cholinergic receptors (nAChRs) sensitive to acetylcholine. In vitro research further suggests that, following its initial agonist effect, this cholinergic drug may also induce a rapid desensitization of the nAChR similar to that of acetylcholine, resulting in termination of its pharmacological effect. Research described in this paper provides evidence of this secondary desensitization process in vivo by demonstrating nicotine's ability to induce acute tolerance in a Discriminative Stimulus (DS) paradigm. The ability of nicotine (400 micrograms/kg, SC) to elicit DS control of behavior in a two-lever operant procedure was significantly reduced via a challenge dose (800 micrograms/kg, SC) of nicotine administered 15-180 min before the training dose. Twenty-three of 52 rats demonstrated this phenomenon. The time to develop acute tolerance varied, providing additional evidence that these effects may be contingent upon individual rat variability. In addition, physostigmine was also observed to induce a similar desensitization in a random population of desensitizing rats. Lastly, there were no differences between desensitizers and non-desensitizers in relation to the ability of mecamylamine (1000 micrograms/kg, SC) to antagonize the DS, while in both populations of rats scopolamine (100 micrograms/kg, SC) failed to antagonize the DS.

Animals↗
PubMed1994

Restructuring the CNS role for a managed care environment.

The CNS role in a large northeast teaching hospital was the focus of a major organizational change process in response to a tightening fiscal environment. CNSs worked with the nurse executive team to restructure their role from expert consultant to case manager, nurse manager partner, and resource and consultant to the Department of Nursing. Development needs of the CNSs were assessed before and after role revision to evaluate the process and provide evidence of learning and change. The change and learning process evidenced in this article exemplifies the CNSs' ability to adapt and respond to the rapidly changing needs of today's managed care setting.

Hospital Restructuring↗
PubMed1993

Development needs of advance practice nurses in a managed care environment.

The authors describe an organizational change process driven by a critical cost containment effort in a teaching hospital in the northeastern United States. This process resulted in a major shift in the role of the clinical nurse specialist. Development priorities of clinical nurse specialists before and after redesign of the role are described.

Cost Control↗
PubMed1990

Withdrawal from chronic nicotine fails to produce a conditioned taste aversion to saccharin in rats.

Sprague-Dawley rats were maintained on a daily regimen of nicotine, morphine or saline administration for 28 days. Following the discontinuation of the daily drug regimen, rats were given a choice of tap water or a saccharin-water solution. The rats previously receiving morphine drank significantly less saccharin-water solution than did the rats receiving nicotine or saline injections. The failure of the nicotine rats to display a conditioned aversion to the novel saccharin flavor suggests that nicotine did not produce a physiological withdrawal syndrome analogous to morphine withdrawal in this paradigm.

Animals↗
PubMed1989

Osteopenia in extremely low birthweight infants.

Fifteen extremely low birthweight (ELBW) white infants (those weighing 1000 g or less) were observed at birth, within eight weeks of birth and near 40 weeks postconception. On the second and third occasions, weight, crown-heel length, and bone mineral content of their forearms were measured. Fifteen infants born at full term on whom similar measurements were made soon after birth acted as controls. Between 32 and 39 weeks the median weight of ELBW infants increased from 970 g to 1850 g and crown-heel length from 35.7 cm to 41.0 cm. There was no evidence, however, of bone mineral accretion in the measurement region; initial and final median measurements of bone mineral content were 76 mg/cm and 86 mg/cm, the median individual difference being only 4 mg/cm with an interquartile range of 25 mg/cm. Median weight, crown-heel length, and bone mineral content of the control group were 3270 g, 50.6 cm, and 196 mg/cm, respectively. Compared with the controls, ELBW infants at 39 weeks were a median (interquartile range) of 1420 (525) g lighter, 9.9 (3.9) cm shorter, and had a bone mineral content deficit of 108 (32) mg/cm. In terms of weight and crown-heel length ELBW infants at 39 weeks were comparable with infants born and observed at 32 weeks' gestation; compared with these infants the bone mineral content deficit in the ELBW group was about 33%.

Body Height↗
PubMed1987

Bone mineral content in bronchopulmonary dysplasia.

Fourteen preterm infants who developed bronchopulmonary dysplasia diagnosed radiologically were compared with a group of similar infants who did not. The two groups were of comparable maturity and birth weight. The clinical histories indicated that those infants with bronchopulmonary dysplasia had had longer periods of supplemental oxygen, more frequent treatment with dexamethasone, and a higher mean total dosage of frusemide. Bone mineral content in the mid-forearm was measured by photon absorptiometry at or near the postconceptional age of 40 weeks in all cases; no significant difference was found between the two groups, although both were severely undermineralised when compared with infants born at full term. In both groups mean daily calcium intake (about 70 mg/kg/day) was about half the daily intrauterine accretion of calcium.

Absorption↗
PubMed1986

Measurement of bone mineral content in the human fetus by photon absorptiometry.

A photon absorptiometer designed to measure the bone mineral content (BMC) of the radius and ulna in premature or term babies was used to examine 34 forearm specimens obtained from 25 male and 9 female babies dying before or up to 13 weeks after birth. Gestational age, foot and crown-heel lengths and birth weight were recorded. Radiographic measurements showed that the midshaft of the radius can be located with a positioning error of +/- 1.28 mm (+/- 2 S.E.E.) from the distance between the distal ulnar styloid process and proximal tip of the olecranon, both of which can be palpated in vivo. Scanning at 5 sites showed that effects of positioning errors on BMC measurements are least at the midshaft site. Subsequent measurements of the ash weight of sections of the radius and ulna, centred on the midshaft of the radius, showed that ash weight/unit length can be estimated with a standard error 2.99 mg/cm from scan data.

Birth Weight↗
PubMed1986

Osteopenia of prematurity.

Bone mineral content of the forearm was measured by photon absorptiometry in 17 preterm infants at a postconceptional age of 40 weeks. Radiographs of the forearm were assessed by Koo's method and plasma alkaline phosphatase activity was also measured at this time. Bone mineral content was significantly but weakly correlated with Koo score and was not significantly correlated with alkaline phosphatase activity. Neither of these two commonly used investigations accurately predicts the presence of underlying bone disease. Compared with 15 full term infants the preterm infants had significantly lower values of bone mineral content, palpated ulnar length, and crown-heel length. After adjusting for weight and ulnar length the preterm group still had a significantly lower mean value of bone mineral content than the full term group. Accurate diagnosis of osteopenia of prematurity requires photon absorptiometry, with bone mineral content assessed relative to body weight or ulnar length.

Anthropometry↗