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Biomedical subjects

J G Phillips

Publications and source records attributed to J G Phillips.

At least 37 records · Page 2Linked to original sources
PubMed1998

Frontostriatal deficits in unipolar major depression.

Recent accounts of major depression have tended to focus on dysfunction of frontothalamic-striatal reentrant circuits as a possible source of the disorder. Evidence of frontostriatal involvement in unipolar major depression from lesion and neuropsychological studies, and functional and structural imaging studies is examined. The high incidence of depressive symptomatology following left frontal and basal ganglia lesions implicate these as possible sites of dysfunction. Neuropsychological evidence indicates similar deficits in patients with major depression, perhaps with dorsolateral prefrontal deficits most prominent. Structural imaging studies report frontal and basal ganglia (BG) abnormalities particularly in cases of late-age onset depression. Resting state functional imaging studies show deficits in dorsolateral, anterior cingulate (medial frontal), and BG structures. Activation imaging studies show less consistent evidence of dorsolateral deficit, while anterior cingulate deficit is more consistently demonstrated. Variability in findings across studies may reflect differences between subtypes of depression and differences in methodology. Possible involvement of the BG in the psychomotor retardation of depression is examined. It is concluded that, while there is evidence of frontostriatal deficit in major depression, the exact nature of such deficits is uncertain. Issues such as component vs. system dysfunction need to be addressed.

Clinical Trials as Topic↗
PubMed1998

Development of a sensitive and quantitative analytical method for 1H-4-substituted imidazole histamine H3-receptor antagonists utilizing high-performance liquid chromatography and dabsyl derivatization.

A sensitive and versatile analytical method utilizing high-performance liquid chromatography (HPLC) and precolumn derivatization of 1H-4-substituted imidazole compounds is described. A HPLC method using 4-dimethylaminoazobenzene-4'-sulfonyl chloride (dabsyl chloride) and ultraviolet (UV) detection was developed for the analysis of histamine (HA) H3-selective compounds in human plasma, rat plasma, or homogenized rat cortical tissue. The average intra- and inter-assay variability, over a range of 10 to 0.01 microg/ml, was determined to be acceptable. The lower limit of detection for the dabsylated ligands was estimated to be <1.0 ng/ml while the lower limit of quantitation (LLOQ) was determined to be 10 ng/ml of conjugate. This assay has demonstrated it's suitability for the sensitive quantitation of several structurally diverse 1H-4-substituted imidazole HA H3-receptor antagonists in biological matrices for pharmacokinetic and biodistribution studies.

Animals↗
PubMed1998

High antagonist potency of GT-2227 and GT-2331, new histamine H3 receptor antagonists, in two functional models.

GT-2227 (4-(6-cyclohexylhex-cis-3-enyl)imidazole) and GT-2331 ((1R,2R)-4-(2-(5,5-dimethylhex-1-ynyl)cyclopropyl)imidazole) were developed as new potent histamine H3 receptor antagonists. The functional activity of these ligands on the histamine H3 receptor-mediated inhibition of neurogenic contraction of the guinea-pig jejunum and histamine H3 receptor-mediated inhibition of norepinephrine release from guinea-pig heart synaptosomes were investigated. GT-2227 and GT-2331 both antagonized the inhibitory effects of (R)-alpha-methylhistamine on the contraction induced by electrical field stimulation in the guinea-pig jejunum with pA2 values of 7.9+/-0.1 and 8.5+/-0.03, respectively. In addition, GT-2227 and GT-2331 antagonized the inhibition of norepinephrine release in cardiac synaptosomes by GT-2203 ((1R,2R)-trans-2-(1H-imidazol-4-yl)cyclopropylamine), a histamine H3 receptor agonist. The current results demonstrate the antagonist activity for both GT-2227 and GT-2331 in two functional assays for histamine H3 receptors.

Animals↗
PubMed1998

Revised model for aerobic growth of Shigella flexneri to extend the validity of predictions at temperatures between 10 and 19 degrees C.

Although Shigella is a major foodborne pathogen, its growth in foods has received little attention. Growth of S. flexneri 5348 inoculated into commercially available sterile foods (canned broths, meat, fish, UHT milk, baby foods) was studied at 10 to 37 degrees C. S. flexneri was enumerated by surface-plating on Tryptic Soy Agar and growth curves were fitted by means of the Gompertz equation. Observed growth kinetics values and values calculated using a previously developed response surface model compared favorably for growth at 19 to 37 degrees C, but not at < 19 degrees C. To refine the model, additional data were collected for growth at 10 to 19 degrees C. A total of 844 tests in BHI broth, representing 197 variable combinations of temperature (10-37 degrees C), pH (5.0-7.5), NaCl (0.5-5.0%) and NaNO2 (0-1000 ppm) was used for the revised model. The revised model, developed in BHI, gave significantly better agreement of calculated growth kinetics values with those observed in foods at 10 to 19 degrees C.

Colony Count, Microbial↗
PubMed1998

Sequence heterogeneity in Parkinsonian speech.

Parkinson's disease (PD) is a neurodegenerative movement disorder primarily due to basal ganglia dysfunction. While much research has been conducted on Parkinsonian deficits in the traditional arena of musculoskeletal limb movement, research in other functional motor tasks is lacking. The present study examined articulation in PD with increasingly complex sequences of articulatory movement. Of interest was whether dysfunction would affect articulation in the same manner as in limb-movement impairment. In particular, since very similar (homogeneous) articulatory sequences (the tongue twister effect) are more difficult for healthy individuals to achieve than dissimilar (heterogeneous) gestures, while the reverse may apply for skeletal movements in PD, we asked which factor would dominate when PD patients articulated various grades of artificial tongue twisters: the influence of disease or a possible difference between the two motor systems. Execution was especially impaired when articulation involved a sequence of motor program heterogeneous in terms of place of articulation. The results are suggestive of a hypokinesic tendency in complex sequential articulatory movement as in limb movement. It appears that PD patients do show abnormalities in articulatory movement which are similar to those of the musculoskeletal system. The present study suggests that an underlying disease effect modulates movement impairment across different functional motor systems.

Aged↗
PubMed1998

The effects of competition and motor reprogramming on visuomotor selection in unilateral neglect.

Patients with unilateral neglect following right hemisphere damage may have difficulty in moving towards contralesional targets. To test the hypothesis that this impairment arises from competing motor programs triggered by irrelevant ipsilesional stimuli, we examined 16 right hemisphere patients, eight with left visual neglect and eight without, in addition to eight healthy control subjects. In experiment 1 subjects performed sequences of movements using their right hand to targets on the contralesional or ipsilesional side of the responding limb. The locations of successive targets in each sequence were either predictable or unpredictable. In separate blocks of trials, targets appeared either alone or with a simultaneous distractor located at the immediately preceding target location. Neglect patients were significantly slower to execute movements to contralesional targets, but only for unpredictable movements and in the presence of a concurrent ipsilesional distractor. In contrast, healthy controls and right hemisphere patients without neglect showed no directional asymmetries of movement execution. In experiment 2 subjects were required to interrupt a predictable, reciprocating sequence of leftward and rightward movements in order to move to an occasional, unpredictable target that occurred either in the direction opposite to that expected, or in the same direction but twice the extent. Neglect patients were significantly slower in reprogramming the direction and extent of movements towards contralesional versus ipsilesional targets, and they also made significantly more errors when executing such movements. Right hemisphere patients without neglect showed a similar bias in reprogramming direction (but not extent) for contralesional targets, whereas healthy controls showed no directional asymmetry in either condition. On the basis of these findings we propose that neglect involves a competitive bias in favour of motor programs for actions directed towards ipsilesional versus contralesional events. We suggest that programming errors and increased latencies for contralesional movements arise because the damaged right hemisphere can no longer effectively inhibit the release of inappropriate motor programs towards ipsilesional events.

Aged↗
PubMed1998

Response programming in patients with schizophrenia: a kinematic analysis.

Schizophrenia may involve disturbed subcortical mechanisms or anomalous functional asymmetries. We therefore examined any anomalies of functional asymmetry in a kinematic analysis of a cued sequential movement task previously found to be sensitive to basal ganglia dysfunction. Twenty patients with schizophrenia and 20 matched controls used preferred or non-preferred hand to connect a series of targets on a WACOM SD420 graphics tablet, in response to the pattern of illumination of light emitting diodes (LEDs). Movements were to be initiated with or without an external cue as to target location. Patients with schizophrenia exhibited relatively normal functional asymmetries, but had programming deficits, taking longer to initiate (i.e. self generate) movements in the absence of an external cue. The movements of patients with schizophrenia were more variable and less efficient, resembling those seen in Huntington's disease. Results supported a hypothesis of disturbance at some level in fronto-subcortical circuitry in schizophrenia.

Adolescent↗
PubMed1998

Inter-limb coupling in coordinated bimanual movement: attention and asymmetries.

Inter-limb coupling, a phenomenon whereby each of the upper limbs tends to take on characteristics of the intended movement of the other, represents a limitation on the ability to perform asymmetrical bimanual movements. Two experiments each employing 16 dextral and 16 sinistral normal subjects are reported. In the first experiment evidence of inter-limb coupling was observed during a continuous bimanual rotary task. This coupling appeared to be asymmetrical, with the nonpreferred hand contributing more to coupling than the preferred hand, especially in dextrals. In the second experiment asymmetries in inter-limb coupling were found to be modified by the conscious direction of attention to one or other hand. This suggests that the often reported strong inter-limb asymmetry associated with dextrality, and the weaker assymetry associated with sinistrality, may be partly due to an underlying inter-limb attentional asymmetry in the former, and a relative lack of attentional asymmetry in the latter.

Journal Article↗
PubMed1998

Bimanual co-ordination in Parkinson's disease.

The basal ganglia may be involved in bimanual co-ordination. Parkinson's disease (which impairs basal ganglia output) is clinically reported to cause difficulties in the performance of co-ordinated bimanual movements. Nevertheless, any bimanual co-ordination difficulties may be task specific, as experimental observations are equivocal. To infer the role of the basal ganglia in co-ordinating the two arms, this study investigated the bimanual co-ordination of patients with Parkinson's disease. Sixteen Parkinson's disease patients and matched control subjects performed a bimanual cranking task, at different speeds (1 and 2 Hz) and phase relationships. All subjects performed the required bimanual in-phase movement on a pair of cranks, at fast (2 Hz) and slow (1 Hz) speeds. However, the Parkinson's disease patients were unable to perform the asymmetrical anti-phase movement, in which rotation of the cranks differed by 180 degrees, at either speed; but instead reverted to the in-phase symmetrical movement. For Parkinson's disease patients, performance of the in-phase movement was more accurate and stable when an external timing cue was used; however, for anti-phase movement, the external cue accentuated the tendency for patients to revert to more symmetrical, in-phase movements.

Aged↗
PubMed1998

Response (re-)programming in aging: a kinematic analysis.

BACKGROUND: Age-related motor slowing may reflect either motor programming deficits, poorer movement execution, or mere strategic preferences for online guidance of movement. We controlled such preferences, limiting the extent to which movements could be programmed. METHODS: Twenty-four young and 24 older adults performed a line drawing task that allowed movements to be prepared in advance in one case (i.e., cue initially available indicating target location) and not in another (i.e., no cue initially available as to target location). Participants connected large or small targets illuminated by light-emitting diodes upon a graphics tablet that sampled pen tip position at 200 Hz. RESULTS: Older adults had a disproportionate difficulty initiating movement when prevented from programming in advance. Older adults produced slower, less efficient movements, particularly when prevented from programming under greater precision requirements. CONCLUSIONS: The slower movements of older adults do not simply reflect a preference for online control, as older adults have less efficient movements when forced to reprogram their movements. Age-related motor slowing kinematically resembles that seen in patients with cerebellar dysfunction.

Adult↗
PubMed1998

Provision of external cues and movement sequencing in Parkinson's disease.

The basal ganglia (BG) may play a part in motor sequencing. Individuals with Parkinson's disease (PD) may exhibit progressive slowing (sequence effect) during motor sequences such as writing (micrographia) and gait. In the present study, a serial two-way choice reaction time (CRT) task was employed, in which advance information about each next movement was not provided until the participant began moving, thereby assessing the participant's ability to utilize advance information. Participants were 13 individuals with idiopathic PD and 13 age-matched controls. Both PD subjects and controls showed a significant sequence effect in the absence of advance information, possibly reflecting difficulty in initiating and maintaining movement without external cues. PD subjects and controls both exhibited a sequence effect at moderate levels of advance information. At high levels of advance information, PD subjects showed the effect but controls did not, suggesting that controls, unlike PD subjects, were able to use the extra information to facilitate performance, perhaps reflecting more frontal aspects of impairment in PD.

Adult↗
PubMed1998

Cue dependent right hemineglect in schizophrenia: a kinematic analysis.

OBJECTIVES: Schizophrenia may result from disturbed attentional processes and/or defective internal cueing. Attention for subsequent action within a cued movement task was therefore studied, testing specific hypotheses of hemispheric dysfunction and of impaired interhemispheric communication. METHOD: Fifteen patients with schizophrenia and 15 matched controls were either cued or uncued when moving a pen to a target on their right or left side with their right or left hand. Pen tip position was sampled at 200 Hz on a WACOM SD420 graphics tablet for subsequent kinematic analysis. RESULTS: Patients with schizophrenia were slower initiating rightwards movements without a cue. Patients also exhibited reduced abductive/adductive differences in the shape of their movement trajectories, implying differences in interhemispheric communication. CONCLUSIONS: It is speculated that schizophrenia is a form of cue dependent right hemineglect.

Adolescent↗
PubMed1997

Impairments of movement kinematics in patients with Huntington's disease: a comparison with and without a concurrent task.

This study aimed to quantify the efficiency and smoothness of voluntary movement in Huntington's disease (HD) by the use of a graphics tablet that permits analysis of movements profiles. In particular, we aimed to ascertain whether a concurrent task (digit span) would affect the kinematics of goal-directed movements. Twelve patients with HD and their matched controls performed 12 vertical zig-zag movements, with both left and right hands (with and without the concurrent task), to large or small circular targets over long or short extents. The concurrent task was associated with shorter movement times and reduced right-hand superiority. Patients with HD were overall slower, especially, with long strokes, and had similar peak velocities for both small and large targets, so that controls could better accommodate differences in target size. Patients with HD spent more time decelerating, especially with small targets, whereas controls allocated more nearly equal proportions of time to the acceleration and deceleration phases of movement, especially with large targets. Short strokes were generally less force inefficient than were long strokes, especially so for either hand in either group in the absence of the concurrent task, and for the right hand is its presence. With the concurrent task, however, the left hand's behavior changed differentially for the two groups; for patients with HD, it became more force efficient with short strokes and even less efficient with long strokes, whereas for controls, it became more efficient with long strokes. Controls may be able to divert attention away from the inferior left hand, increasing its automaticity, whereas patients with HD, because of disease, may be forced to engage even further online visual control under the demands of a concurrent task. Patients with HD may perhaps become increasingly reliant on terminal visual guidance, which indicates an impairment in constructing and refining an internal representation of the movement necessary for its effective execution. Basal ganglia dysfunction may impair the ability to use internally generated cues to guide movement.

Adrenergic Uptake Inhibitors↗
PubMed1997

Response programming in dementia of the Alzheimer type: a kinematic analysis.

Although planning is important for the functioning of patients with dementia of the Alzheimer Type (DAT), little is known about response programming in DAT. This study used a cueing paradigm coupled with quantitative kinematic analysis to document the preparation and execution of movements made by a group of 12 DAT patients and their age and sex matched controls. Participants connected a series of targets placed upon a WACOM SD420 graphics tablet, in response to the pattern of illumination of a set of light emitting diodes (LEDs). In one condition, participants could programme the upcoming movement, whilst in another they were forced to reprogramme this movement on-line (i.e. they were not provided with advance information about the location of the upcoming target). DAT patients were found to have programming deficits, taking longer to initiate movements, particularly in the absence of cues. While problems spontaneously programming a movement might cause a greater reliance upon on-line guidance, when both groups were required to guide the movement on-line, DAT patients continued to show slower and less efficient movements implying declining sensori-motor function; these differences were not simply due to strategy or medication status.

Aged↗
PubMed1997

Effect of directed attention in Huntington's disease.

This experiment sought to ascertain whether overt gaze (i.e., directed attention) would influence attentional performance in Huntington's disease (HD), via the use of a vibrotactile choice reaction time procedure involving biased probabilities of event occurrence. Subjects looked (i.e., direct gaze) either at the hand receiving the most (expected) vibrations, or the hand less often stimulated (the unexpected), for both crossed and uncrossed arm postures. Patients with HD showed performance advantages when directing attention (i.e., gaze) at the responding hand, especially for expected events. Patients with HD, however, were not sensitive to distributions of event probability in the uncrossed arm posture, nor when looking away from the responding hand. With the crossed arm posture, and when directing attention at the expected side, patients with HD became more sensitive to distributions of event probability. In HD, there may be a disruption of fronto-striatal circuitry on both cortical and subcortical levels which may account for impairments both in holding and shifting attention.

Adult↗
PubMed1997

Expanded models for the non-thermal inactivation of Listeria monocytogenes.

Previously developed four-variable response surface models for describing the effects of temperature, pH/lactic acid, sodium chloride and sodium nitrite on the time to achieve a 4-log, non-thermal inactivation (t4D) of Listeria monocytogenes in aerobic, acidic environments were expanded to five-variable models that distinguish the effects of pH and acidulant concentration. A total of 18 new variable combinations were evaluated and the inactivation kinetics data appended onto a consolidation of two data sets from earlier studies. The consolidated data set, which included 315 inactivation curves representing 209 unique combinations of the five variables, was analysed by response surface analysis. The quadratic model without backward elimination regression was selected for further evaluation. Three additional quadratic models were generated using the concentrations of undissociated lactic and/or nitrous acids as variables in place of percentage lactic acid and sodium nitrite concentration. Comparison of predicted t4D values against literature values for various food systems indicated that the models provide reasonable initial estimates of the inactivation of L. monocytogenes. The models based on the concentration of undissociated lactic and nitrous acids support the hypothesis that antimicrobial activity is associated with this form of the compounds. Evaluation of several examples suggests that these models may be useful for predicting the equivalent of the compounds' "minimal inhibitory concentrations' for accelerating inactivation under various conditions.

Aerobiosis↗