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Biomedical subjects

D N Jones

Publications and source records attributed to D N Jones.

At least 55 records · Page 3Linked to original sources

Influence of prefeeding and scopolamine upon performance in a delayed matching-to-position task.

The present study compared the influence of prefeeding (0, 10, 20 g or an unlimited amount of food pellets for a 90 min period prior to testing) with the effects of scopolamine (0, 0.03, 0.075 or 0.1 mg/kg s.c.) and scopolamine methylbromide (0.1 mg/kg s.c.) upon performance in the food reinforced delayed matching-to-position (DMTP) task. In preliminary studies using separate groups of rats, both scopolamine (but not scopolamine methylbromide) and prefeeding impaired choice accuracy in a seemingly delay-independent manner. Both treatments also increased omissions. However, while prefeeding increased all task latencies, scopolamine only increased sample latency. In a subsequent experiment, an intermediate dose of scopolamine (0.075 mg/kg s.c.) was directly compared with prefeeding in the same animals. Both treatments impaired choice accuracy, however, the effects of scopolamine were significantly larger than prefeeding. Conversely, prefeeding caused significantly greater omissions and larger increases in task latencies compared with scopolamine. These findings demonstrate some dissociation between the effects of scopolamine and prefeeding in the DMTP task, suggesting that the actions of scopolamine are not entirely due to reduction in motivation. Furthermore, the effects of scopolamine are likely to be centrally mediated.

Animals↗

Age-associated impairments in a test of attention: evidence for involvement of cholinergic systems.

We trained three groups of rats, young (Y; 3 months at the start of study), middle aged (MA; 15 months), and aged (AG; 22 months), in the serial five-choice serial reaction time task, a test of attention. There were clear age-related differences in task acquisition: Y acquired the task quicker than MA rats, which learned faster than AG rats. A subgroup of AG rats [AG(I)] could not reach criterion (> 80% correct, < 20% omissions under standard conditions of 0.5 sec stimulus duration, 5 sec limited hold). Accordingly, they were tested under conditions of 1 sec stimulus duration. Having acquired the task, under standard conditions both MA and AG groups were slower to make a correct response but not to collect the food reward. Furthermore, parameter changes, particularly reductions in stimulus duration and intensity, revealed further age-related changes in accuracy. Following completion of these studies, animals were trained in a simpler one-choice task. Importantly, reducing stimulus duration/intensity in this task revealed no differences between Y and MA/AG groups, although AG(I) rats were impaired. This dissociation between MA/AG impairments in the one- and five-choice task suggests that these animals may show attentional deficits compared with Y rats, which are independent of changes in sensory (visual), motor function, or motivation. Finally, the MA deficit in attention was partially reversed by tacrine pretreatment (3 mg/kg). Also scopolamine (0.01-0.075 mg/kg) and mecamylamine (0.3-5 mg/kg) pretreatment impaired choice accuracy of MA but not Y rats. Taken together, the drug studies imply that the attentional deficits may at least be partially due to changes in cholinergic function.

Aging↗

Trypanosoma cruzi in wild raccoons, opossums, and triatomine bugs in southeast Georgia, U.S.A.

The prevalence of Trypanosoma cruzi infection among wild opossums and raccoons live-trapped in 6 southeast Georgia counties was determined. Epimastigotes typical of T. cruzi were observed in liver infusion tryptose medium cultures of blood from 6 of 39 opossums (15.4%) and 12 of 54 raccoons (22.2%). Trypomastigotes (6,000/ml) were observed in a wet mount of blood from 1 of the animals, a raccoon trapped on St. Catherines Island in Liberty County. In addition, T. cruzi parasites were observed in the gut contents of 3 of 5 specimens of the triatomine bug Triatoma sanguisuga (Leconte) collected near human dwellings in Bulloch County. This is the first report of T. cruzi-infected triatomine bugs in Georgia.

Animals↗

The solution structure and dynamics of the DNA-binding domain of HMG-D from Drosophila melanogaster.

BACKGROUND: The HMG-box is a conserved DNA-binding motif that has been identified in many high mobility group (HMG) proteins. HMG-D is a non-histone chromosomal protein from Drosophila melanogaster that is closely related to the mammalian HMG-box proteins HMG-1 and HMG-2. Previous structures determined for an HMG-box domain from rat and hamster exhibit the same global topology, but differ significantly in detail. It has been suggested that these differences may arise from hinge motions which allow the protein to adapt to the shape of its target DNA. RESULTS: We present the solution structure of HMG-D determined by NMR spectroscopy to an overall precision of 0.85 A root mean squared deviation (rmsd) for the backbone atoms. The protein consists of an extended amino-terminal region and three alpha-helices that fold into a characteristic 'L' shape. The central core region of the molecule is highly stable and maintains an angle of approximately 80 degrees between the axes of helices 2 and 3. The backbone dynamics determined from 15N NMR relaxation measurements show a high correlation with the mean residue rmsd determined from the calculated structures. CONCLUSIONS: The structure determined for the HMG-box motif from HMG-D is essentially identical to the structure determined for the B-domain of mammalian HMG-1. Since these proteins have significantly different sequences our results indicate that the global fold and the mode of interaction with DNA are also likely to be conserved in all eukaryotes.

Amino Acid Sequence↗

Influence of naloxone upon motor activity induced by psychomotor stimulant drugs.

Naloxone, an opioid receptor antagonist, attenuates a wide range of behavioral effects of d-amphetamine, such as the stimulation of motor activity. To investigate the pharmacological selectivity of the naloxone/amphetamine interaction, we assessed the effects of naloxone (5.0 mg/kg SC) upon motor activity induced in rats by a range of psychomotor stimulant drugs with a mechanism of action either similar to or different from that of d-amphetamine. Each of the drugs tested caused dose-dependent increases in both gross and fine activity. Naloxone attenuated the gross but not the fine activity response to d- and l-amphetamine, but had no influence upon the other catecholamine-releasing drugs, methamphetamine and phendimetrazine. In contrast, naloxone increased the gross but not the fine activity response to the catecholamine uptake inhibitors cocaine and mazindol, but had no effects upon the motor response to methylphenidate. The responses to other stimulant drugs (apomorphine, caffeine, scopolamine) were unaffected by naloxone pretreatment. The present findings extend the range of conditions under which naloxone and, by inference, endogenous opioid systems, modulate the behavioral response to psychomotor stimulants. However, the differential effects of naloxone upon the motor response to individual stimulant drugs support previous suggestions of fundamental differences in mechanisms of action among these compounds.

Animals↗

Individual differences in behavior following amphetamine, GBR-12909, or apomorphine but not SKF-38393 or quinpirole.

Subjects that respond more to a novel environment show a greater locomotor response to drugs of abuse such as cocaine and amphetamine. The current study was performed to examine differences between high (HR) and low (LR) responding rats to a novel environment following administration of amphetamine, a selective dopamine uptake blocker (GBR-12909), a nonselective dopamine agonist (apomorphine), and selective dopamine D1 and D2/D3 agonists. A behavioral checklist and a rating scale were used to determine the behavioral arousal caused by administration of amphetamine (0, 0.5, 2.0, and 8.0 mg/kg), GBR-12909 (0, 1.25, 5.0, and 20.0 mg/kg), apomorphine (0, 0.1, 0.3, and 1 mg/kg), SKF 39393 (0, 2.5, 10, and 40 mg/kg), or quinpirole (0, 0.05, 0.5, and 5.0 mg/kg). The five drugs produced behavioral activation profiles distinct from each other. Following amphetamine administration, both HR and LR subjects showed dose dependent increases in behavioral arousal. The behaviors primarily affected were sniffing, locomotor activity, rearing, and oral activity. HR rats showed a greater overall behavioral response to amphetamine administration compared with LR rats and there were differences in specific behaviors between the two groups. Following GBR-12909 administration, all subjects showed dose dependent increases in sniffing, locomotor activity, and rearing. Differences between HR and LR were observed in sniffing, locomotor activity, and rearing behaviors. HR and LR both showed dose dependent increases in behavior following apomorphine administration. HR showed greater behavioral activation after apomorphine than LR.(ABSTRACT TRUNCATED AT 250 WORDS)

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Behavioral effects of systemically administered mu and kappa opioid agonists in the squirrel monkey: peptides versus alkaloids.

This study compared the effects of receptor-selective peptide and nonpeptide opioid agonists administered intramuscularly to squirrel monkeys responding under a fixed-interval 3-min schedule of stimulus termination. The mu opioid receptor agonist morphine (0.1-3.0 mg/kg) increased response rate at low doses and decreased it and quarter-life at higher doses. [D-Ala2,N-Me-Phe4,Gly-ol]Enkephalin (DAMGO; 0.3-3.0 mg/kg) reduced quarter-life at the highest dose. The kappa dose. The kappa opioid receptor agonist U50,488H (0.1-1.0 mg/kg) elevated response rate transiently and dose-dependently decreased quarter-life. Dynorphin A(1-13) (0.3-10 mg/kg), a purported endogenous ligand of the kappa opioid receptor, decreased response rate slightly but significantly at 3.0 mg/kg and had no effect on quarter-life. Thus, the behavior of squirrel monkeys was affected by systemically administered peptide as well as by nonpeptide opioid drugs. The two alkaloids were much more effective than the two peptides, presumably because of greater ability to penetrate the blood-brain barrier. Quarter-life was often a more sensitive measure of drug effects than was response rate.

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

Ectoparasites of opossums and raccoons in southeastern Georgia.

Twelve species of ectoparasites (four fleas, three ticks, three chiggers, one macronyssid mite, and one atopomelid mite) were recovered from 42 opossums, Didelphis virginiana Kerr, live-trapped from September 1992 through April 1994 in southeastern Georgia. The fleas, Ctenocephalides felis (Bouché) (prevalence = 19%) and Polygenis gwyni (C. Fox) (36%); the ticks, Dermacentor variabilis (Say) (40%) and Ixodes scapularis Say (19%); and the macronyssid mite, Ornithonyssus wernecki (Fonseca) (21%), exhibited the highest infestation prevalences on opossums. The atopomelid mite, Didelphilichus serrifer Fain, and the chigger mite Leptotrombidium peromysci Vercammen-Grandjean & Langston, both ectoparasites of opossums, are reported from Georgia for the first time. Six species of ectoparasites (one chewing louse, four ticks, and one macronyssid mite) were collected from 58 raccoons, Procyon lotor (L.), examined between October 1992 and September 1993 in the same region. The chewing louse, Trichodectes octomaculatus Paine (prevalence = 24%); and the ticks, Amblyomma americanum (L.) (69%), D. variabilis (55%), and Ixodes texanus Banks (24%), exhibited the highest infestation prevalences on raccoons. Three species of ticks, A. americanum, D. variabilis, and I. scapularis, were the only ectoparasites recovered from both host species. Several of the ectoparasites collected are proven vectors of pathogenic agents that affect humans and animals.

Animals↗

Choledochal cyst.

A case of a choledochal cyst occurring in a 21-year-old woman is presented. The spectrum of congenital dilatation of the biliary tree and the contributions of various imaging modalities and procedures in the condition are discussed, including the use of nuclear medicine biliary imaging.

Adult↗

Cryptogenic organizing pneumonia with atypical histopathological features.

A case report of cryptogenic organizing pneumonia (COP); also known as bronchiolitis obliterans organizing pneumonia (BOOP) is presented. The histopathologic findings of COP are well documented in the literature and typically consist of organizing pneumonia of uniform appearance. This case report describes, in addition to the classic findings, more acute exudative inflammation not usually associated with this condition. Variation in the evolution of the pneumonic process is one of the reasons for reporting this case. The promotion of awareness of this treatable condition is the other reason for reporting this case. When multifocal areas of consolidation are demonstrated radiologically, particularly when peripheral and basal, and in the correct clinical setting, the possibility of COP should be entertained. This condition responds dramatically to steroid therapy, and has a good prognosis.

Bronchiolitis Obliterans↗

Bone scan demonstration of progression of sacral insufficiency stress fracture.

This case documents the progression of a sacral insufficiency stress fracture, initially involving the lateral left ala and later extending across the body of the sacrum to the right ala. The 'H' shaped distribution of increased uptake on radionuclide bone scanning is characteristic of this type of fracture, although variations of this pattern are also seen according to the severity of the sacral trauma. While the differing bone scan patterns of this particular fracture type are well established, it is unusual to document the progression of this fracture on bone scan in any one patient.

Aged↗

Imaging of the absent cervical pedicle syndrome.

Three cases of congenital absence of a cervical spine pedicle are described. This anomaly comprises a radiological triad of (i) the absent pedicle producing an apparently 'giant' neural foramen; (ii) a dorsally displaced ipsilateral articular mass and lamina with a dysplastic and reversed facet joint; and (iii) deficiency or absence of the ipsilateral transverse process. Recognition of this anomaly is particularly important in the context of acute injury to avoid misdiagnosis as a traumatic facet joint fracture-dislocation. The giant foramen must also be differentiated from expansion due to a neurofibroma. A correct plain radiographic diagnosis is usually possible, but in doubtful cases appearances on computed tomography are pathognomonic. Magnetic resonance imaging, performed in two of the cases, was helpful in elucidating the contents of the giant foramen, but should rarely be necessary in clinical practice.

Adult↗

Multifocal osteonecrosis following chemotherapy and short-term corticosteroid therapy in a patient with small-cell bronchogenic carcinoma.

This report describes the development of multiple-site, biopsy-proven osteonecrosis in a patient with small-cell bronchogenic carcinoma who had received chemotherapy and short-term administration of corticosteroid. Multifocal osteonecrosis has a wide variety of etiologies, but is most often encountered in the clinical setting of corticosteroid administration, connective tissue disorders, transplantation, hemoglobinopathies and dysbarism. In the oncology patient, chemotherapy, corticosteroids and bone marrow transplantation (with associated preparation therapy) have all been implicated as possible causes. There may be a synergistic effect when corticosteroids are used in combination with chemotherapy and radiation treatment. Multiple periarticular abnormalities appearing on serial radionuclide bone scanning of the cancer patient, particularly when symmetric and in a distribution not suggestive of osseous metastatic disease, raise the possibility of multifocal osteonecrosis. Also to be considered in the differential diagnosis are multifocal infection and polysynovitis/arthritis of other etiology. MRI has a high sensitivity and specificity in the diagnosis of osteonecrosis and should be used when this condition is suspected. Early diagnosis of osteonecrosis is important to prevent irreversible bone and joint destruction.

Antineoplastic Combined Chemotherapy Protocols↗

Delta-opioid receptor antagonists attenuate motor activity induced by amphetamine but not cocaine.

Naloxone and naltrindole attenuate the locomotor response to amphetamine, implicating delta-opioid receptors in the opioid-antagonist/amphetamine interaction. To determine the role of delta-opioid receptor subtypes in this phenomenon, rats were pretreated with the following selective antagonists administered intracisternally: naltrindole, [D-Ala2,Leu5,Cys6]enkephalin (DALCE, delta 1 receptor selective), naltrindole-5'-isothiocyanate (delta 2 receptor selective). Cumulative dose-response curves to amphetamine were constructed (saline, 0.1, 0.4, 1.6 and 6.4 mg/kg s.c.), with injections every 30 min. Naltrindole was also tested against cumulative doses of cocaine (saline, 3.0, 10, 30 and 56 mg/kg i.p.). Gross and fine motor activity were recorded for 20 min, commencing 10 min postinjection. Amphetamine and cocaine dose dependently increased both gross and fine movements. Naltrindole (10 micrograms) attenuated the gross but not fine activity response to amphetamine, but 10 or 30 micrograms failed to influence the response to cocaine. Naltrindole-5'-isothiocyanate (30 micrograms) attenuated slightly but significantly the gross activity response to amphetamine, whereas DALCE (30 micrograms) was without effect. However, a combination of 10 micrograms each of DALCE and naltrindole-5'-isothiocyanate markedly attenuated the amphetamine-induced increases in gross movements without altering fine activity. These data provide further evidence for the involvement of delta-opioid receptors in the modulation of behavioral effects of amphetamine; both delta 1- and delta 2-opioid receptors appear to play a role. The differential effects of opioid antagonists on locomotor activity stimulated by amphetamine and cocaine suggests differences in the mechanism of action of these drugs not previously appreciated.

Amphetamine↗

Assignment of the backbone 1H and 15N NMR resonances and secondary structure characterization of barstar.

Barstar, a polypeptide inhibitor of ribonucleases, has been studied by 2D and 3D NMR techniques using uniformly 15N-labeled protein. Backbone (15NH-C alpha H-C beta H) resonances were assigned for all but 5 of the 89 residues. Dihedral angle and deuterium exchange studies were used in conjunction with medium range inter-proton NOEs to characterize the secondary structure of barstar. The protein is composed of four alpha-helices and three short stretches of extended strand. By further analysis of the NOE data three of the helices were found to be parallel to each other with the single disulphide bond linking the second and fourth helices at their C-terminal ends.

Amino Acid Sequence↗

Identification of the barstar binding site of barnase by NMR spectroscopy and hydrogen-deuterium exchange.

The extracellular ribonuclease from Bacillus amyloliquifaciens, barnase, forms a tightly-bound one-to-one complex with its intracellular inhibitor barstar. The barstar binding site on barnase was characterized by comparing the differences in the chemical shift and hydrogen-deuterium exchange rates between free and bound barnase. Chemical shift assignments of barnase in the complex with barstar were determined from 3D NOESY-HMQC and TOCSY-HMQC spectra of a complex that had been prepared with uniformly 15N-labelled barnase and unlabelled barstar. Hydrogen exchange rates were obtained from an analysis of a series of [15N]HMQC spectra of a sample prepared in the same manner exchanged into D2O. The largest changes in either chemical shift or hydrogen-deuterium exchange rate are observed for residues located in the active-site and substrate binding loops indicating that barstar inhibits barnase activity by sterically blocking the active site.

Bacterial Proteins↗