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Biomedical subjects

Byung H Lee

Publications and source records attributed to Byung H Lee.

8 recordsLinked to original sources

Visual search pattern during the line quadrisection task in normal subjects.

A common test for the assessment of hemispatial neglect is the line bisection test. A recent modification of the task has been reported wherein subjects place a mark at either 25% or 75% of line length ('quadrisection'). In a previous study, we suggested that line quadrisection might entail iteration of two steps involved in standard line bisection: (1) finding the midpoint of the entire line, and then (2) bisecting the half-line segment between the adjudged midpoint and the line end ipsilateral to the target quadrisection point. The present study investigated eye movement patterns during line quadrisection in order to test this hypothesis. Twenty normal volunteers determined the left or right quadrisection point of a horizontal line while their eye movements were recorded using two-dimensional video-oculography. Analysis revealed that, like the results of previous studies on bisection, most normal subjects fixate the central portion of the line segment before reaching the target area during the quadrisection task. Normal subjects' eye movements during quadrisection performance share a number of features with line bisection and provide support for the two-step processing hypothesis.

Adult↗

Dose-dependent pharmacokinetics of KR-31378, a new neuroprotective agent for ischaemia-reperfusion damage in dogs.

Dose-dependent pharmacokinetic parameters of KR-31378, a new neuroprotective agent for ischaemia-reperfusion damage, were evaluated after intravenous and oral administration of the drug at doses of 5, 10 and 25 mg/kg to male beagle dogs. After intravenous administration, the dose-normalized (based on 5 mg/kg) areas under the plasma concentration-time curve from time zero to time infinity (AUC values, 725, 1450 and 2300 micro g min/ml for 5, 10 and 25 mg/kg, respectively) were significantly different among the three dose ranges studied; the value increased more proportionally as the dose increased. This could be due to slower total body clearance (Cl) with increasing doses (6.90, 3.46 and 2.17 ml/min/kg). The slower Cl value with increasing doses may be due to saturable metabolism of KR-31378 in dogs. After oral administration, the dose-normalized (based on 5 mg/kg) AUC values (833, 1450 and 1920 micro g min/ml) at 5 mg/kg were significantly smaller than those at 10 and 25 mg/kg. Note that the AUC values were comparable (not significantly different) between intravenous and oral administration at all doses studied, indicating that the absorption of KR-31378 from the gastrointestinal tract was essentially complete and the first-pass (gastric, intestinal and/or hepatic first-pass) effects were almost negligible in dogs.

Administration, Oral↗

Length perception and production of normal subjects in proximal versus distal peripersonal space.

We investigated whether the perception or production of a given line length in normal subjects varies according to where in peripersonal space the line is perceived or produced. We also investigated the influence of the direction of movement used to make the line. In Experiment 1, blindfolded normal subjects were asked to estimate distances while the examiner moved the subject's hand in proximal (medial) or distal (lateral) space, moving centripetally or centrifugally. The subjects showed a spatial effect, perceiving the same length as shorter in proximal space than distal space. This result could be related to either a proximal spatial attentional bias or an anisometric representation of spatial distances. In Experiment 2, we attempted to dissociate these hypotheses by studying blindfolded normal subjects, who were requested to produce horizontal lines of a given length (100 or 200 mm) in proximal versus distal peripersonal space using centripetal or centrifugal movements. Centrifugal movements in proximal space were the longest; centrifugal movements in distal space were the shortest: in between were the proximal centripetal and distal centripetal movements which did not differ from each other. These results suggest that in peripersonal space the perception of length in normal subjects is most consistent with anisometric mental representation where the size of mental representations of length units decreases as a function of the distance from the subject's midsagittal plane. Length production, however, may depend on an interaction of the anisometric mental representation and the premotor/intentional factors.

Adult↗

Restricted conformation analogues of an anthelmintic cyclodepsipeptide.

Six analogues of the anthelmintic cyclodepsipeptide PF1022A were prepared, each containing a small ring fused to the macrocycle to restrict the number of conformations the larger ring can adopt. It was anticipated that such conformational changes could lead to enhanced biological activity and selectivity. The analogues form two series of three members each. In one series, a carbon-based molecular bridge joins the methyl of a leucine residue with the methyl of its closest lactic acid residue to form five-, six-, and seven-membered lactam rings. In the second series, a leucine residue is replaced with five-, six-, and seven-membered nitrogen heterocycles. Decreasing the size of the small ring in the lactam series increasingly distorts the macrocycle and consistently decreases activity relative to PF1022A. In the leucine series, a similar trend is observed. Molecular modeling of PF1022A along with the analogues described herein suggests that the ability to exist in a highly symmetrical conformational state is a necessary condition for biological activity.

Animals↗

Manual approach during hand gesture imitation.

BACKGROUND: Patients' tendency to draw near or into the target when copying figures, a phenomenon termed closing-in, has been previously described. That the closing-in could occur when copying hand gestures has also been noted. OBJECTIVES: To study a patient with corticobasal degeneration to quantify his manual approach behavior and to test a possible working memory hypothesis. METHODS: The subject of this study is a patient with severe ideomotor apraxia from probable corticobasal degeneration. Fluorine 18-labeled deoxyglucose-positron emission tomographic findings revealed a hypometabolism involving the bilateral parietotemporal and the right frontal lobes. When asked to copy an examiner's (J.C.K.) hand gesture, the patient approached, touched, or grasped the examiner's hand, a behavior mostly consistent with the closing-in behavior previously proposed. To investigate the frequency and severity of closing-in, the patient was asked to copy 20 meaningless hand gestures (10 simple and 10 complex). Copying the 20 hand gestures was performed with either the left or the right hand while the patient was seated opposite the examiner (across condition) or on the same side of the examiner (lateral condition). RESULTS: Of the 80 trials, closing-in occurred in 43 (53.8%) (35 with approaching, 6 with touching, and 2 with grasping). The closing-in was more frequent and more severe when gesturing with the left than the right hand, but it did not differ between the lateral and across conditions and between simple and complex gestures. CONCLUSIONS: Corticobasal degeneration might be associated with aberrant manual approach behavior. Although our results do not support the working memory hypothesis, frontal dysfunction might have led to a loss of voluntary control of ontologically primitive propensity to move the forelimb in the direction to which one attends.

Aged↗

Anthelmintic paraherquamides are cholinergic antagonists in gastrointestinal nematodes and mammals.

Oxindole alkaloids in the paraherquamide/marcfortine family exhibit broad-spectrum anthelmintic activity that includes drug-resistant strains of nematodes. Paraherquamide (PHQ), 2-deoxoparaherquamide (2DPHQ), and close structural analogs of these compounds rapidly induce flaccid paralysis in parasitic nematodes in vitro, without affecting adenosine triphosphate (ATP) levels. The mechanism of action of this anthelmintic class was investigated using muscle tension and microelectrode recording techniques in isolated body wall segments of Ascaris suum. None of the compounds altered A. suum muscle tension or membrane potential. However, PHQ blocked (when applied before) or reversed (when applied after) depolarizing contractions induced by acetylcholine (ACh) and the nicotinic agonists levamisole and morantel. These effects were mimicked by the nicotinic ganglionic blocker mecamylamine, suggesting that the anthelmintic activity of PHQ and marcfortines is due to blockade of cholinergic neuromuscular transmission. The effects of these compounds were also examined on subtypes of human nicotinic ACh receptors expressed in mammalian cells with a Ca2+ flux assay. 2DPHQ blocked nicotinic stimulation of cells expressing alpha3 ganglionic (IC50 approximately 9 microm) and muscle-type (IC50 approximately 3 microm) nicotinic cholinergic receptors, but was inactive at 100 microm vs. the alpha7 CNS subtype. PHQ anthelmintics are nicotinic cholinergic antagonists in both nematodes and mammals, and this mechanism appears to underlie both their efficacy and toxicity.

Animals↗

Marcfortine and paraherquamide class of anthelmintics: discovery of PNU-141962.

Three distinct chemical classes for the control of gastrointestinal nematodes are available: benzimidazoles, imidazothiazoles, and macrocyclic lactones. The relentless development of drug resistance has severely limited the usefulness of such drugs and the search for a new class of compounds preferably with a different mode of action is an important endeavor. Marcfortine A (1), a metabolite of Penicillium roqueforti, is structurally related to paraherquamide A (2), originally isolated from Penicillium paraherquei. Chemically the two compounds differ only in one ring; in marcfortine A, ring G is six-membered and carries no substituents, while in paraherquamide A, ring G is five-membered with methyl and hydroxyl substituents at C14. Paraherquamide A (2) is superior to marcfortine A as a nematocide. 2-Desoxoparaherquamide A (PNU-141962, 53) has excellent nematocidal activity, a superior safely profile, and is the first semi-synthetic member of this totally new class of nematocides that is a legitimate candidate for development. This review describes the chemistry, efficacy and mode of action of PNU-141962.

Animals↗