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Biomedical subjects

Y H Shih

Publications and source records attributed to Y H Shih.

At least 37 records · Page 2Linked to original sources

Leached components from dental composites in oral simulating fluids and the resultant composite strengths.

The aim of this study was to analyse the leached moieties of dental composites after storage in ethanol and organic acids of plaque and further evaluate the resultant effect on the diametral tensile strength (DTS) of the composites. Three commercial composites were used: Bis-GMA-based Z100, Bis-GMA/UDMA-based Heliomolar, and Bis-MPEPP-based Marathon One. The solutions used were: 99.9% acetic acid, 99% propionic acid and 75% ethanol. Specimens (4 mm diam. x 2 mm thick) were stored at 37 degrees C in 3 mL of solution for up to 30 days. Gas chromatography/mass spectrometry was used to characterize the leached moieties and DTS of the specimens after immersion was evaluated. Data were analysed using ANOVA and Tukey LSD test. The eluted substances were not all the same in different solutions and composites but mostly increased with immersion time, and included diluents (TEGDMA and decamethacrylate) and some additives, such as an ultra-violet stabilizer (TINUVINP), plasticizers (dicyclohexyl phthalate and bis(2-ethylhexyl) phthalate), initiator (triphenyl stibine), coupling agent (gamma-methacryloxypropyl trimethoxysilane), and phenyl benzoate. The chief polymerizing monomers were not found. More kinds of components were found in the acetic acid and ethanol groups studied. The fewest kinds and quantities of leached moieties were found for Bis-GMA specimens and then Bis-GMA/UDMA ones, most of which are diluent agents. Bis-MPEPP specimens leached the most substances, which were composed mostly of a short phenyl group chain structure. The BisGMA composite showed the highest DTS (54.8 +/- 5.7 MPa), which was not greatly affected by the length of storage. Bis-GMA/UDMA (36.2 +/- 6.8 MPa) and Bis-MPEPP (26.1 +/- 4.5 MPa) composites were significantly reduced (P < 0.05) after 30 days storage in the ethanol (35-50%), in the propionic acid (25-30%), and in the acetic acid (40-60%). Irreversible processes such as the leaching of components occur in fluids simulating an oral environment, which may contribute to irreversible material degradation, especially for non-Bis-GMA-based composites.

Acetates↗

Cloning of porcine neuron growth inhibitory factor (metallothionein III) cDNA and expression of the gene in Saccharomyces cerevisiae.

Growth inhibitory factor (GIF), a member of the metallothionein (MT) family, is also known as MTIII. This protein distinguishes itself from other MT isoforms by exerting an inhibitory effect on cortical neuron growth instead of metal ion buffering. In this work, we cloned MTIII genes from a porcine brain cDNA library. Two species of clones were isolated that vary with respect to one nt in the coding sequence. This discrepancy results in the translation of two MTIII primary structures having a different amino acid at residue 46. Herein, both MTIII cDNAs were constructed into an expression vector and transformed into yeast cells, respectively. The yeast carrying either MTIII gene displayed a similar metal tolerance when cultured in a medium containing metal. The resistance to metal toxicity was attributed to the expression of MTIII gene which was confirmed by RNA and protein analyses. The characteristics of the protein stability, metal binding affinity and ultraviolet absorption spectrum of the yeast produced MTIII are also compared with those of MTII. The comparison reveals that both MTs have similar physical characteristics. Moreover, circular dichroism spectrum of Cd saturated MTIII was analyzed as well. Typical Cys-Cd bands for MTII appear in the spectrum, indicating similar metal-thiol interactions for MTIII to those for other MT isoforms.

Alzheimer Disease↗

Cloning, expression and CNS distribution of Kv4.3, an A-type K+ channel alpha subunit.

A full-length K+ channel cDNA of Kv4.3, with an open reading frame of 611 amino acids, was isolated from rat hippocampus. Functional expression of Kv4.3 cDNA in Xenopus oocytes revealed an A-type K+ channel. In the central nervous system, Kv4.3 is most prominently expressed in the retrosplenial cortex, medial habenula, anterior thalamus, hippocampus, cerebellum, as well as lateral geniculate and superior colliculus, which are important for vision. The abundant expression of Kv4.3 in many CNS neurons supports its important role as a major component of subthreshold A currents in the control of action potentials and thus neuronal excitability.

Amino Acid Sequence↗

Cloning, expression and characterization of a human dopamine D4.2 receptor (CHO K1 cells) and various D4.2/D2L chimeras (COS-7 cells).

1. Using the gene splicing technique a synthetic human dopamine (DA) D4.2 gene was constructed and subsequently stably expressed in CHO K1 cells. 2. Binding of [3H]spiperone to membranes prepared from human DA D4.2 CHO K1 cells was saturable with a Kd of 93 +/- 0.51 pM and a Bmax of 768 +/- 22 fmol per mg protein. 3. Clozapine, apomorphine, and S(+)-NPA were more selective for D4.2 than for D2L receptors, with D2L/D4.2 ratios of 5.7, 7.1, and 19.6, respectively. 4. Functional studies indicated that DA D4.2 receptors expressed in CHO K1 cells inhibited forskolin stimulated cAMP levels showing coupling to G-proteins. 5. Two reciprocal human D2L and D4.2 chimeric receptors (D2L/D4.2 and D4.2/D2L) were constructed by exchanging the amino-terminal end to the third transmembrane (TM) of one receptor with the counter part of the other receptor and expressing them transiently into COS-7 cells. The chimeric D2L/D4.2 receptor displayed non-detectable specific binding of [3H] spiperone and other ligands. The chimeric D4.2/D2L receptor binding affinities of DA agonists were more affected than that of antagonists, suggesting that binding affinities of agonists are more sensitive to changes in receptor conformation than that of antagonists. 6. This study characterized the pharmacology of a novel synthesized DA D4.2 receptor that provides a useful model for screening of potential D4.2 receptor agonist and antagonist.

Animals↗

Effects of the dopamine D3 antagonist PD 58491 and its interaction with the dopamine D3 agonist PD 128907 on brain dopamine synthesis in rat.

The dopamine (DA) D3 receptor antagonist PD 58491 [3-[4-[1-[4-[2-[4-(3-diethylaminopropoxy)phenyl]benzoimidazol++ +-1-yl-butyl]-1H-benzoimidazol-2-yl]phenoxy]propyl]diethylamine] bound with high affinity and selectivity to recombinant human DA D3 versus D2L and D4.2 receptors transfected into Chinese hamster ovary cells: Ki values of 19.5 nM versus 2,362 and >3,000 nM, respectively. In contrast, the putative DA D3 receptor antagonist (+)-AJ76 displayed low affinity and selectivity for D3 versus D2L and D4.2 receptors (91 nM vs. 253 and 193 nM, respectively). In vitro, PD 58491 (1 nM-1 microM) exhibited D3 receptor antagonist activity, reversing the quinpirole (10 nM)-induced stimulation of [3H]thymidine uptake in D3 CHOpro-5 cells, but did not have any significant intrinsic activity by itself in this assay. PD 58491 did not decrease the gamma-butyrolactone-induced increase in DA synthesis (L-3,4-dihydroxyphenylalanine accumulation) in rat striatum, indicating that the compound possessed no in vivo DA D2/D3 receptor agonist action at DA autoreceptors. PD 58491 (3-30 mg/kg, i.p.) generally did not alter DA or serotonin synthesis in either the striatum or mesolimbic region of rat brain. The D3-preferring agonist PD 128907 decreased DA synthesis in striatum and mesolimbic regions, and this effect was attenuated by pretreatment with PD 58491. These findings support the hypothesis that DA D3 autoreceptors may in part modulate the synthesis and release of DA in striatum and mesolimbic regions.

5-Hydroxytryptophan↗

A nationwide epidemiological study of spinal cord injuries in Taiwan from July 1992 to June 1996.

This prospective epidemiological survey of spinal cord injury (SCI) in Taiwan was carried out by recruiting patients attended by physicians from various medical centers and general hospitals all over Taiwan from July 1992 to June 1996. A total of 6,410 cases of traumatic spinal fracture were registered among which were 1,586 new cases of SCI. The results represented 70% of the scope of SCI in Taiwan. The observed average annual incidence of SCI in Taiwan was 18.8 per million population. The mean age was 46.1 years-old with a plateau distribution for over 20 years and older. Geriatric victims are a major group of SCI in Taiwan. The male to female ratio was 3 to 1. The leading causes of SCI were traffic accidents and accidental falls. Motorcycle collisions accounted for 62% of the traffic accidents, and as most of the motorcycle riders were not helmet users, head injury became the major associated injury of SCI in Taiwan. The effectiveness of the comprehensive care system for SCI patients in Taiwan is relatively good, as reflected by the low rates of complications of SCI, the low mortality rate (6.6%) and the high percentage (67.4%) of SCI patients achieving self-care ultimately at home after rehabilitation. The analysis of person days healthy life loss and quality adjusted survival time revealed that SCI patients in Taiwan required 4 years to cope with the morbidity, and on average, could return to the main stream of life for another 30 years.

Accidental Falls↗

A nationwide epidemiological study of spinal cord injury in geriatric patients in Taiwan.

This prospective epidemiological survey of spinal cord injury (SCI) in Taiwan was carried out among patients attended by physicians from various medical centers and general hospitals all over Taiwan from July 1992 to June 1996. In all, 1,586 new cases of SCI were registered, representing about 70% of all possible SCI cases in Taiwan. The observed average annual incidence of SCI in Taiwan was 18.8 per million people, whereas it was 47.5 for the geriatric section. The mean age was 46.1 years with a plateau distribution after 20 years and older. Geriatric victims (297 cases, 18.7%, group II) formed a major section of SCI cases in Taiwan. Another group of younger SCI patients (15-64 years old, 1,232 cases, group I) was selected for comparison. The results showed that the male-to-female ratio, pattern of neurological deficits, and causes of injury and death of geriatric SCI patients differed significantly from those of the younger SCI group. Elderly women were exposed to a higher risk of SCI than younger women (M/F ratio 1.7:1). Falls were the leading cause of geriatric SCI, and two thirds of them occurred on level ground. Traffic accidents accounted for a third of SCI cases, half of which involved motorcycle accidents, a fifth of them pedestrians. Quadriplegia and quadriparesis occurred more frequently among elderly cases of SCI than in the younger group and a higher proportion of them died of SCI complications. Two thirds of elderly SCI patients recovered well enough after comprehensive treatment to be able to take care of themselves at home. The government should initiate programs of prevention to reduce the prevalence of geriatric SCI in Taiwan.

Age Factors↗

Relationship between mesial temporal seizure focus and elevated serum prolactin in temporal lobe epilepsy.

We evaluated the relationship between mesial temporal seizure focus and serum prolactin (PRL) in patients before and after they underwent anterior temporal lobectomy (ATL) for medically intractable temporal lobe epilepsy (TLE). These patients had a confirmed unilateral epileptogenic focus in mesial temporal structures, a postictal rise in serum PRL 15 to 20 minutes after onset of complex partial seizures, and were refractory for more than 2 years to antiepileptic drugs. Presurgical interictal serum PRL levels were significantly elevated (16.47 +/- 0.85 ng/mL, n = 62) and declined after ATL to normal values (patients, 9.63 +/- 0.55 ng/mL, n = 54; normal subjects, 8.99 +/- 0.57 ng/mL, n = 52). Serial evaluations indicated that normalization was seen 3 months after surgery (9.42 +/- 1.22 ng/mL, n = 9). The postsurgical reduction in serum PRL was similar in men and women, in patients with epileptogenic focus on either side of mesial temporal structures, and was unaffected by antiepileptic medication. We conclude that PRL is elevated following seizures and that a seizure focus in mesial temporal structures may exert a sustained excitatory influence on PRL release in patients with medically intractable TLE.

Adolescent↗

Role of foramen ovale electrodes in presurgical evaluation of intractable complex partial seizures.

BACKGROUND: The value of intracranial electrodes such as depth electrodes and subdural grids for intracranial electroencephalographic (EEG) recording in patients with intractable epilepsies has been well recognized. A new technique, foramen ovale electrode (FOE) implantation, was first introduced by Wieser in 1984 for the lateralization of bilateral mesiotemporal lobe (MTL) onset of seizures. METHODS: Since October 1993, a multipolar, three-contact FOE has been used in 12 intractable epileptic patients for presurgical evaluation. The reasons for FOE implantation included bilateral MTL onset of seizures recorded by extracranial EEGs in nine patients, and extracranial EEG abnormalities inconsistent with the results of magnetic resonance imaging (MRI), positron emission tomogram (PET) or Wada test in three patients. Under general anesthesia, the FOEs were implanted according to the technique introduced by Kirschner, using Barters landmarks. RESULTS: After long-term telemetry recording with FOE, seven patients revealed clear onset of seizures originating from one side of the MTL and underwent anterior temporal lobectomy (ATL). Two patients had seizures of bilateral MTL onset. However, they received ATL due to predominantly unilateral interictal epileptiform discharges (EDs) and/or MRI and PET abnormalities. Seven (78%) of the nine operated patients became seizure-free after ATL. Three patients were considered not operable because two had multifocal onset of seizures and one had seizures with independent bilateral MTL onset. No serious complication resulted from implantation of FOE in this series. CONCLUSIONS: The semi-invasive technique of FOE is reliable for lateralization of bilateral MTL onset of seizures which are often not clearly recorded by extracranial EEGs. This procedure is safe and can be an alternative to invasive implantation of depth electrodes and subdural grids.

Adult↗

Antisense vasopressin oligonucleotides: uptake, turnover, distribution, toxicity and behavioral effects.

The uptake, turnover, distribution, toxicity and behavioral effects of antisense vasopressin oligonucleotides were investigated to define how these compounds interact with neural tissue to inhibit translation of a target mRNA. Both phosphorothioate modified and unmodified oligonucleotides are rapidly taken up by mammalian neural tissue. Turnover of the unmodified oligonucleotide was found to be fast (t1/2 < 1 h) relative to the phosphorothioate modified oligonucleotide (t1/2 = 12 h). The phosphorothioate vasopressin antisense oligonucleotide suppressed vasopressin synthesis in vivo at concentrations below the toxic threshold of approximately 5 microM. Intracranial injections of phosphorothioate antisense oligonucleotide into the region of the SON in vivo, resulted in a small decrease in vasopressin mRNA and a compensatory drinking response within the first 24 h, consistent with a deficit in vasopressin translation with kinetics similar to those observed in vitro. Water intake returned to normal by the second day indicating relatively rapid clearance of the oligonucleotide and minimal side effects. Although the mechanisms of accumulation and details of the molecular interactions are still unknown, our observation of preferential uptake and/or retention of oligonucleotide within a subset of neurons in vitro suggests some process of selective targeting. Thus, low concentrations of oligonucleotides targeted to the untranslated 5' end of vasopressin mRNA can be effective for the acute and reversible control of vasopressin synthesis in mammalian CNS with relatively rapid onset of behavioral effects and minimal side effects.

Animals↗

CI-1007, a dopamine partial agonist and potential antipsychotic agent. I. Neurochemical effects.

The receptor binding and biochemical effects of the putative dopamine (DA) partial agonist CI-1007 ([R(+)-1,2,3,6-tetrahydro-4-phenyl- 1-[(3-phenyl-3-cyclohexen-1-yl)methyl]pyridine] maleate) and potential antipsychotic were evaluated with a variety of biochemical methods. In receptor binding studies, CI-1007 bound to rat striatal DA receptors exhibiting a Ki of 3 nM as assessed by inhibition of [3H]N-propylnorapomorphine binding. CI-1007 also exhibited high affinity for cloned human D2L (Ki = 25.5 nM) and D3 (Ki = 16.6 nM) receptors with less affinity for D4.2 receptors (Ki = 90.9 nM). The affinity for serotonin-1A (5-HT-1A), alpha-2 adrenergic and 5-HT-2 receptors was moderate (submicromolar range) and slight or negligible for alpha-1, DA D1 and various other receptors. Unlike dopamine, the inhibition of [3H]spiperone binding was monophasic for CI-1007 and only slightly affected by the addition of Gpp-(NH)p. In vitro CI-1007 antagonized the forskolin-induced increases in cyclic AMP levels in GH4C1 cells expressing the human D2L receptor, having an intrinsic activity of 53% of that seen with the full agonist quinpirole. In vivo CI-1007 antagonized the gamma-butyrolactone (GBL)-induced accumulation of L-3,4-dihydroxyphenylalanine in striatum and mesolimbic regions of rat brain, causing a maximal 64% reversal in striatum, consistent with a partial agonist profile. In microdialysis studies it decreased DA overflow in both striatum and nucleus accumbens, indicating decreased release of DA. CI-1007 also reduced brain DA synthesis (DOPA accumulation), metabolism (DOPAC and HVA) and utilization (after tyrosine hydroxylase inhibition with alpha-methyl-p-tyrosine). CI-1007 did not affect striatal acetylcholine levels indicating lack of potent postsynaptic DA actions. CI-1007 seemed to be selective for DA neurons as it did not alter rat brain norepinephrine (NE) synthesis in the NE-enriched brainstem or NE utilization in the mesolimbic region. In addition, it did not affect in general 5-HT synthesis and metabolism in striatum and mesolimbic regions. These neurochemical results demonstrate that CI-1007 is a selective potent brain dopamine partial agonist with limited agonist activity at postsynaptic DA receptors.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗

Clinical experience of neurosurgical reconstruction in anterior skull base lesions.

BACKGROUND: Surgery of the anterior skull base confronts with the life-threatening risks of infection and cerebrospinal fluid (CSF) leakage, especially after extensive tumor resection. Avoidance of these complications demands a good intraoperative reconstruction. The technical feasibility has been demonstrated in previous reports. A judicious rationale of surgical principle is investigated in review of our patients and other series. METHODS: Fourteen cases underwent neurosurgical procedures involving the anterior skull base by the authors between June 1992 and January 1994. Five patients with trauma, 1 with inflammation, and 8 with space-occupying lesion were included. The modality of skull base reconstruction and patients' outcome were evaluated. RESULTS: Eleven of these cases accepted reconstructive procedures to some extent including pericranium, lyodura, tissue glue, bone graft and muscle flaps. Four cases of traumatic CSF leakage were successfully repaired after anterior skull base reconstruction. One case with traumatic optic neuropathy restored vision after surgical optic nerve decompression. A rhinogenic infected discharging sinus was cured with pedicle island flap obliteration. Space-occupying lesions in 8 cases were totally removed without postoperative wound infection, CSF leakage, or meningitis, of which 2 cases of malignancy recurred 7 and 5 months after operation respectively. The follow-up period was from 5 to 26 months with a mean of 14 months. CONCLUSIONS: Meticulous reconstruction with different possibilities of closure is the cornerstone of anterior skull base surgery, in spite of its difficulties and needs for extensive resection. Combined craniofacial resection could achieve "en bloc" or radical excision of "inoperable" anterior skull base lesions confidently with low morbidity and mortality based on skillful reconstructive techniques.

Adolescent↗

Neurochemical and functional characterization of the preferentially selective dopamine D3 agonist PD 128907.

The present study determined the biochemical and pharmacological effects of PD 128907 [R-(+)-trans-3,4,4a,10b-tetrahydro-4-propyl-2H,5H- [1]benzopyrano[4,3-b]-1,4-oxazin-9-ol], a dopamine (DA) receptor agonist that shows a preference for the human D3 receptor. In transfected Chinese hamster ovary cells (CHO K1), PD 128907 displaced [3H]spiperone in a biphasic fashion which fit best to a two-site model, generating Ki values of 20 and 6964 nM for the high- and low-affinity sites for the D2L receptors and 1.43 and 413 nM for the corresponding sites for the D3 receptors. Addition of sodium and the GTP analog Gpp(NH)p to both the D2L and D3 caused a modest reduction in the affinity of the compound suggestive of an agonist type action. In agonist binding ([3H]N-0437), PD 128907 exhibited an 18-fold selectivity for D3 versus D2L, a selectivity similar to that found with antagonist binding to the high-affinity sites. PD 128907 exhibited only weak affinity for D4.2 receptors (Ki = 169 nM). No significant affinity for a variety of other receptors was observed. PD 128907 stimulated cell division (measured by [3H]thymidine uptake) in CHO p-5 cells transfected with either D2L or D3 receptors exhibiting about a 6.3-fold greater potency in activating D3 as compared to D2L receptors. In vivo the compound was active in reducing DA synthesis both in normal and gamma-butyrolactone (GBL) treated rats; in the GBL model, the decrease was greater in the higher D3-expressing mesolimbic region as compared with striatum which has a lower expression of D3 receptors. PD 128907 decreased DA release (as measured by brain microdialysis) both in rat striatum, nucleus accumbens and medial frontal cortex, as well as in monkey putamen. Behaviorally PD 128907 decreased spontaneous locomotor activity (LMA) in rats at low doses, whereas at higher doses stimulatory effects were observed. PD 128907 at high doses reversed the reserpine-induced decrease in LMA and induced stereotypy in combination with the D1 agonist SKF 38393 indicating postsynaptic DA agonist actions. It is unclear which of the subtypes of DA receptors might be mediating the pharmacological effects of PD 128907. However, the present findings indicating that PD 128907 shows a preference for DA D3 over D2L and D4.2 receptors indicates that its action at low doses may be due to interaction with D3 receptors and at higher doses, with both D2 and D3 receptors.

Animals↗

Characterization of the human dopamine D3 receptor expressed in transfected cell lines.

A full-length cDNA clone of the human dopamine D3 receptor was obtained by the polymerase chain reaction (PCR) using reverse-transcribed RNA from human brain as the template. The cDNA was inserted into an expression vector which was then stably transfected into either Chinese hamster ovary (CHO), SK-N-MC human epithelioma or mouse CCL1.3 fibroblast cell lines. Post-transfection, the Bmax for D3 receptor expression was 1.9, 1.1 and 0.4 pmol/mg protein in the CHO-K1, SK-N-MC and CCL1.3 cell lines, respectively. The D3 receptor expressed in CHO-K1 and CCL1.3 cells exhibited similar radioligand binding profiles, especially for the D3-selective compound, 7-hydroxy-2-(di-n-propylamino)tetralin (7-OH-DPAT). Radioligand-binding competition curves of presumed D3 agonists were shifted to the right by the addition of guanine nucleotides and Na+ to the assay buffer. Presumed D3-receptor agonists had no effect on cAMP accumulation in any of the D3-transfected cell lines although cAMP accumulation was inhibited by dopamine D2 receptor activation in D2-transfected CHO and CCL1.3 cells and by activation of the exogenously expressed neuropeptide Y receptor in SK-N-MC cells. Also, D3 receptor activation neither potentiated ATP-stimulated arachidonic acid release from CHO cells nor stimulated inositol phosphate production in CCL1.3-cells although both of these responses were elicited by D2 agonists in D2-transfected cells. We conclude that the signalling properties of the D3 receptor differ from those of its closest homolog, the D2 receptor.

Animals↗

Immunohistochemical expression of proliferating cell nuclear antigen (PCNA) in intracranial glioma and meningioma.

BACKGROUND: Immunohistochemical study of proliferating cells in normal or neoplastic tissues has its advantages over other methods in understanding cell kinetic information. Proliferating cell nuclear antigen (PCNA) immunolocalization in paraffin section was reported as an index for cellular proliferation and well-correlated with the histopathological grading of certain systemic malignancies. METHODS: By using immunohistochemical staining of PCNA on formalin-fixed, paraffin-embedded sections, the anti-PCNA monoclonal antibody (PC10) staining scores were counted in 32 intracranial gliomas and 32 intracranial meningiomas. RESULTS: The PC10 scores ranged from 7.8% to 24.1% (m = 15.7 +/- 4.5%) in 12 anaplastic astrocytomas, and from 15.1% to 51.3% (m = 38.4 +/- 11.7%) in 9 glioblastomas. The difference in between was significant. The mean PC10 scores of benign meningiomas, malignant meningiomas, and hemangiopericytomas were 13.8%, 50.2%, and 50.8% respectively. The difference of PC10 scores was also significant between benign and malignant meningioma, as well as between benign meningioma and hemangiopericytoma. CONCLUSIONS: The PC10 scores have a good correlation with the histopathological grading of both intracranial glioma and meningioma.

Antigens, Neoplasm↗

Temporal lobectomy in adults with intractable epilepsy.

We report on 30 adult patients with intractable complex partial seizure (CPS) of the temporal lobe origin who received anterior temporal lobectomy. The average follow-up period was 41 months. The age of onset was younger and the duration of epilepsy was longer in the non-mass lesion group than in the mass lesion group. Postoperatively, 21 patients (70%) were seizure-free, four patients (13%) had only rare seizures (less than three attacks per year), three patients (10%) achieved a remarkable reduction (more than 50%) of seizure frequency, and two patients (7%) showed no worthwhile improvement. Based on our experience, anterior temporal lobectomy is an effective and safe procedure for adult patients with intractable CPS. For diagnosis, magnetic resonance imaging (MRI) yielded a higher sensitivity rate than computed tomography (CT), especially in the group without mass lesions. Positron emission tomography using 18F-fluorodeoxyglucose (FDG-PET) was superior to single photon emission computed tomography (SPECT) which had a relatively high false localization rate. With high resolution MRI and FDG-PET, localization of the epileptogenic zone was more accurate. A preresection electrocorticogram (ECoG) was used to confirm the epileptogenic focus during the operation. The residual spikes on the postresection ECoG did not necessarily predict a poor seizure control outcome after anterior temporal lobectomy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Aromatic DNA adducts in brain tumors by 32P-postlabeling analysis.

DNA from human brain tumor samples was analysed by the 32P-postlabeling technique for the presence of aromatic DNA adducts. Thirteen out of 16 samples showed low levels of adducts at 0.14-3.53 adducts per 10(9) nucleotides. Inter-individual variations in the patterns of these aromatic adducts were observed. On the other hand, none of 5 brain samples from epilepsy patients revealed any evidence of such adducts. The data demonstrated the presence of low level, large molecule aromatic DNA adducts in malignant brain tissues and these adducts may either result from environmental exposure to an undetermined genotoxic agent or from the aging process.

Adenoma↗

Pharmacological profile of the dopamine partial agonist, (+/-)-PD 128483 and its enantiomers.

(+/-)-PD 128483, ((+/-)-4,5,5a,6,7,8-hexahydro-6-methylthiazolo[4,5-f]-quinolin+ ++-2-amine, maleate (1:1)), is a racemic compound that is a p.o. active dopamine (DA) partial agonist that has DA autoreceptor agonist effects and displays antipsychoticlike activity in preclinical tests. In in vitro receptor binding assays, (+/-)-PD 128483 and its enantiomers bound selectively to DA D-2 receptors vs. DA D-1 receptors and showed no affinity for adrenergic alpha-1 or serotonin1A receptors, but had affinity for adrenergic alpha-2 receptors. In tests of DA agonist effects, including reversal of the tau-butyrolactone-stimulated increase in brain dopa synthesis in striatum and inhibition of DA neuronal firing, the rank order of efficacy was (+)-PD 128483 > (+/-)-PD 128483 > (-)-PD 128483. (+/-)-PD 128483 and (+)-PD 128483 inhibited, whereas (-)-PD 128483 increased, brain DA synthesis in normal rats. (+/-)-PD 128483 and (-)-PD 128483 inhibited spontaneous locomotion in rats and did not produce locomotor stimulation or stereotypies. In contrast, (+)-PD 128483 inhibited locomotor activity at low doses, but at relatively high doses increased locomotion and induced stereotypy in rats. (-)-PD 128483 consistently inhibited Sidman avoidance responding in squirrel monkeys. (+/-)-PD 128483 inhibited Sidman avoidance responding in one group of monkeys, but had minimal effects in another group. (+)-PD 128483 did not inhibit avoidance responding. In squirrel or cebus monkeys sensitized to the acute dystonic effects of haloperidol, only (-)-PD 128483 induced extrapyramidal dysfunction. These results indicate that (+/-)-PD 128483 is a DA partial agonist which produces DA autoreceptor agonist effects and has a preclinical behavioral profile suggestive of antipsychotic activity.

4-Butyrolactone↗