Biomedical subjects

K T Ng

Publications and source records attributed to K T Ng.

At least 55 records · Page 3Linked to original sources

PubMed1995

Combination chemotherapy with carmustine and cisplatin before, during, and after radiotherapy for adult malignant gliomas.

Twenty-two patients, aged 16 to 67, who had malignant gliomas after surgical resection were treated with carmustine and cisplatin intravenous infusion before, during, and after radiotherapy. All patients had subtotal or total resection, or biopsy as the initial procedure. Twenty-one patients who had at least 2 cycles of chemotherapy and finished the whole course of radiotherapy were considered to be evaluable for responses. Among them, 5 had glioblastoma multiforme, 16 had anaplastic astrocytoma. The median time to tumor progression was 35 weeks (range 12-130 weeks) and median survival time was 66 weeks (range 10-156 weeks). Early progression occurred more frequently in patients with biopsy only and subtotal resection, and in patients with glioblastoma than in those with anaplastic astrocytoma. This combined modality treatment program was associated with reversible hematologic toxicity which was severe in 2 patients, and with ototoxicity in 1 patient, nephrotoxicity in 2 patients. Combination of carmustine and cisplatin with cranial irradiation for malignant gliomas is moderately toxic and appears to offer no obvious survival advantage compared with radiation therapy plus BCNU alone.

Adolescent↗

PubMed1995

Three-dimensional uniform grid modeling of electrical defibrillation on a data parallel computer.

Finite element modeling has played an increasingly important role in the study of defibrillation. In order to model well the complex anatomical details, a large number of elements are required in the finite element grid, leading to a large set of equations that often cannot be solved effectively with the computational power of conventional computers. In this paper, we describe the use of a data parallel computer to provide the memory and reduction in solution time for solving these large finite element problems. Using a uniform grid and a nodal assembly technique, the discretized problem domain can be mapped efficiently to the parallel computer, allowing the solution of problems with over two million unknowns. The finite element algorithm for a three-dimensional inhomogeneous anisotropic body is described together with its parallel implementation. Test results for a canine torso model constructed from CT images are also presented.

Algorithms↗

PubMed1995

Passive avoidance learning induced change in GAP43 phosphorylation in day-old chicks.

Day-old chicks trained on a single trial passive discriminated avoidance task demonstrated a significant increase in in vitro phosphorylation of a 50 kDa protein in P2M fractions of total forebrain. The increase occurred 30 min posttraining, at a time when previous reports suggest that mechanisms for triggering protein synthesis-dependent long-term memory consolidation are activated. These changes in phosphorylation rates were accompanied by a substantial enhancement of total kinase activity. Immunoblotting studies with monoclonal anti-GAP43 antibody indicate that this protein is GAP43. These results contradict previous reports of a decrease in in vitro GAP43 phosphorylation following the same learning paradigm. A number of procedural differences may account for this discrepancy. The results suggest that changes in the phosphorylation state may be associated with mechanisms triggering long-term memory consolidation.

Animals↗

PubMed1995

Phosphorylation changes following weakly reinforced learning and ACTH-induced memory consolidation for a weak learning experience.

The formation of a protein synthesis-dependent long-term memory stage in day-old chicks trained on a passive discriminated avoidance task has been shown to occur only with an adequate level of reinforcement, and is preceded by a significant change in the phosphorylation state of the forebrain synaptosomal membrane protein GAP43 protein. In the present study, it is shown that weakly reinforced training did not lead to formation of a long-term memory stage or to any change in phosphate incorporation into forebrain P2M protein bands. However, administration of ACTH immediately posttraining led to both the formation of the long-term memory stage and a preceding significant increase in the phosphorylation of GAP43. These findings are consistent with the view that a reinforcement-dependent neurohormone-mediated change to the phosphorylation of this synaptosomal membrane protein may be implicated in the triggering of long-term memory consolidation.

Animals↗

PubMed1995

Blockade of metabotropic glutamate receptors prevents long-term memory consolidation.

Metabotropic glutamate receptor activation has been shown to be essential for establishment of long-term potentiation, a phenomenon increasingly thought to be associated with the laying down of permanent memory. However, these receptors may also play a part in the initiation of protein kinase C activity, which has been demonstrated to be involved in prelong-term memory processes. Blockade of the metabotropic glutamate receptors by the specific antagonist, (RS)-alpha-Methyl-4-carboxyphenylglycine (500 microM) is shown to induce amnesia during a long-term memory stage in day-old chicks trained on a passive avoidance task, and to have no effect on prelong-term stages. The results suggest a specific role for these receptors in a possibly LTP associated mechanism of memory processing.

Amnesia↗

PubMed1995

Administration of glutamate following a reminder induces transient memory loss in day-old chicks.

Monosodium glutamate (4.0 mM) administered immediately after a visual reminder presented to day-old chickens between 7.5 min and 24 h following a single trial passive avoidance learning task produced transient losses of memory on retention test, an effect not observed in the absence of a reminder or when the reminder was given 48 h post-learning. The duration of the transient deficit decreased with increasing interval between the training and the reminder trial. The time of onset of memory loss after the reminder trial appeared to increase with increasing interval between the training and the reminder trials. The results suggest that, for a period of at least up to 24 h after passive avoidance training, retrieval of memory may lead to processes which are sensitive to inhibition by glutamate, with the duration of sensitivity post-retrieval decreasing as the period of memory consolidation increases. The results extend previously reported findings with rodents and suggest the possibility that consolidation of a stable memorial representation of a learning experience may take place over several days and may entail the concurrent laying down of a stable retrieval mechanism.

Animals↗

PubMed1995

Numerical analysis of electrical defibrillation. The parallel approach.

Numerical modeling offers a viable tool for studying electrical defibrillation, allowing the behavior of field quantities to be observed easily as the different system parameters are varied. One numerical technique, namely the finite-element method, has been found particularly effective for modeling complex thoracic anatomies. However, an accurate finite-element model of the thorax often requires a large number of elements and nodes, leading to a large set of equations that cannot be solved effectively with the computational power of conventional computers. This is especially true if many finite-element solutions need to be achieved within a reasonable time period (eg, electrode configuration optimization). In this study, the use of massively parallel computers to provide the memory and reduction in solution time for solving these large finite-element problems is discussed. Both the uniform and unstructured grid approaches are considered. Algorithms that allow efficient mapping of uniform and unstructured grids to data-parallel and message-passing parallel computers are discussed. An automatic iterative procedure for electrode configuration optimization is presented. The procedure is based on the minimization of an objective function using the parallel direct search technique. Computational performance results are presented together with simulation results.

Algorithms↗

PubMed1995

Control of high common mode voltage during transthoracic defibrillation.

A high common mode voltage (Vcm) relative to earth ground is produced on the myocardium during the delivery of a defibrillator pulse and can generate a differential error signal when potential gradients are recorded with bipolar electrodes and isolation amplifiers. The error signal is proportional to Vcm, and therefore, a reduction in Vcm improves the accuracy of the potential gradient data. Experiments were conducted on 5 dogs to determine whether Vcm can be controlled using a bridge circuit. The bridge circuit consisted of a 5 k omega power rheostat in parallel with the transthoracic resistance of the dog. The variable contact of the rheostat was connected to earth ground, and by adjusting the rheostat, Vcm on the myocardium could be varied. In each dog, 20 A shocks were delivered through stainless steel transthoracic electrodes. Point contact electrodes sutured to the epicardium were used to measure Vcm. It was determined that Vcm could be reduced to approximately zero at a given electrode on the heart. In addition, for the 5 dogs studied, the maximum measured Vcm on the heart was only 10% of the transthoracic voltage when the bridge circuit was balanced for an interior point in the heart.

Animals↗

PubMed1995

Cisplatin and 5-fluorouracil as neoadjuvant chemotherapy: predicting response in head and neck squamous cell cancer.

In order to prospectively evaluate the efficacy, toxicity and predictive factors of response to neoadjuvant chemotherapy, a total of 120 patients with head and neck squamous cell cancer diagnosed from January 1992 to November 1993 were enrolled in this study. There were 118 male and 2 female patients, with a median age of 51 years (range 30-74 years). The primary sites were the oral cavity (77), oropharynx (15), hypopharynx (25) and larynx (3). Betel quid chewing was habitual in 91% of patients. All patients were previously untreated, and 94% had stage III or IV disease. Chemotherapy was given in two or three courses to 96 patients who were then assessed for response rate and predictive factors. The chemotherapy regimen consisted of cisplatin 100 mg/m2/day on day 1 and 5-fluorouracil (5-FU) 1 g/m2/day intravenous infusion continuously for 4 to 5 days for 4 weeks. The overall chemotherapy response rate was 56%, with a 3% complete response. By univariate analysis, both the T-stage and tumor volume were significant for predicting the response of the primary site. The age, histologic differentiation, tumor location and N-stage were unpredictive for response. The nodal response (43%) was less than that of the primary site (68%). By multivariate analysis, only the tumor volume (> or = 50 cm3) and the presence of nodal metastases were predictive for the combined TN response. Based on the World Health Organization toxicity criteria, 49 patients experienced grade 3 to 4 mucositis, and 24 patients had grade 3 to 4 vomiting.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1994

Astrocytic glycogenolysis energizes memory processes in neonate chicks.

In previous pharmaco-behavioural experiments, we have shown that three sequential stages can be distinguished in discrimination memory for a single trial passive avoidance experience in neonate chicks: a short-term (STM) stage, available for 10 min following learning; an intermediate (ITM) stage, operating between 20 and 50 min (ITMB) post-learning; and a long-term (LTM) stage formed by 60 min after learning. The ITM stage can be divided into two parts: a first phase (ITMA) which is susceptible to inhibition by the uncoupler of oxidative phosphorylation (and thus of oxidative metabolism), 2,4-dinitrophenol (DNP), and a second DNP-insensitive phase (ITMB). ITMA occurs between 20 and 30 min post-training and ITMB between 30 and 50 min. In the present study we have shown: (1) that day-old chicks trained in the passive avoidance task and immediately thereafter injected with the glycolytic inhibitor iodoacetate show retention deficits that are first evident 30 min post-training, and (2) that glycogenolysis, i.e. breakdown of glycogen, a high-molecular carbohydrate energy store localized in astrocytes, occurs in the forebrains of trained, but otherwise untreated birds, between 35 and 55 min after learning. These findings strongly suggest that glycolysis, including astrocytically localized glycogenolysis, is essential to provide energy for active processes occurring during ITMB and that these processes are indispensable for subsequent development of long-term memory.

2,4-Dinitrophenol↗

PubMed1994

Effect of PKC inhibitors and activators on memory.

Changes in the activity of the enzyme protein kinase C (PKC) have been implicated in learning and memory consolidation, and in the induction of long-term potentiation. The precise role of PKC in memory processing is still unknown. Using 1-day-old chicks trained on a single-trial passive avoidance task, we demonstrate that inhibition of PKC activity by melittin induced retention loss, in a dose-dependent manner, in the second stage of a three-stage sequence of memory processing. The effect was lateralized to the left hemisphere of the chick forebrain. This effect of melittin was prevented by high concentrations (16-320 microM) of the PKC activator, phorbol 12-myristate 13-acetate (PMA). Furthermore, concentrations of PMA in the range 1.6 to 40 microM were shown to induce long-term memory consolidation following a weakly reinforced version of the learning task, which normally does not lead to formation of long-term memory. That these actions of PMA are attributable to PKC activation is supported by the further finding that the inactive phorbol ester 4 alpha-PDD had no effect either on melittin-induced amnesia or on memory consolidation following weakly reinforced learning. Paradoxically, concentrations of 16 microM or higher of PMA inhibited memory consolidation for the normal strongly reinforced learning trial, an effect again not observed with 40 alpha-PDD. The results are consistent with the view that PKC activity may be implicated in a pre-long-term stage of memory processing.

Animals↗

PubMed1994

Na+,K(+)-ATPase activity in young chicks after taste stimulation.

The activity of specific ouabain-sensitive Na+,K(+)-ATPase was studied in crude membrane fraction of the brain of 1- to 3-day-old chicks after the administration of a chemical aversant methylanthranilate (MeA), shown in previous behavioral studies to induce avoidance of pecking of an otherwise attractive stimulus. Enzyme activity was dramatically decreased (by 40-50%) in the time interval between 10 min-2 h after MeA administration onto the tongue of awake chicks. It was possible to localize these changes in Na+,K(+)-ATPase activity into forebrain structures contained within the dorsal ventricular ridge comprising the hyperstriatum accessorium (HA), hyperstriatum ventrale (HV), hyperstriatum dorsale (HD), and parts of neostriatum (N). In contrast, Na+,K(+)-ATPase activity in the ectostriatum (E), the medial neostriatum (NM), and the paleostriatal complex were unaffected. Results from experiments involving preincubation of membrane fractions and with partial purification using detergents, suggest that some substances with inhibitory effects were produced under the effect of MeA and bound to membrane fractions in their respective areas. A similar decrease of Na+,K(+)-ATPase activity as after MeA administration in vivo was observed when inhibitory mediators (GABA, glycine) were added to membrane fractions in vitro. These findings may have implications for memory processing in chicks following aversive learning using MeA as the aversant.

Animals↗

PubMed1994

Astrocytes implicated in the energizing of intermediate memory processes in neonate chicks.

Day-old chicks trained in a single trial passive avoidance task develop three sequentially dependent stages of discrimination memory. The second intermediate stage is made up of two phases: the initial A phase being susceptible to inhibition of oxidative metabolism in the tricarboxcylic acid (TCA) system with 2,4-dinitrophenol (DNP), and a second DNP-insensitive B phase. The studies reported in this paper found that doses of the metabolic toxins fluoroacetate (0.2 mM) and fluorocitrate (0.1 mM) previously reported to disrupt the astrocytic TCA cycle only, also disrupt the A (but not the B) phase of intermediate memory, suggesting an interaction between the astrocytic and neuronal oxidative systems may be required to meet the metabolic demands of this earlier phase. The B phase, on the other hand, was not expressed in the presence of the glycolytic inhibitor iodoacetate (1 mM), suggesting that glycolysis (known to be more efficient in astrocytes) and glycogenolysis (which may be exclusive to astrocytes) may support this second phase of intermediate memory. In this regard, the rise in forebrain noradrenaline levels previously reported to occur before the appearance of the B phase is particularly relevant. Given that noradrenaline has been shown to be capable of enhancing glycogenolysis in astrocyte-enriched cell cultures, it is conceivable that noradrenaline exerts an effect on memory by stimulating the glycolytic system in astrocytes, thereby providing energy or metabolites (e.g. pyruvate) needed to sustain the cellular processes operating during the B phase of intermediate memory.

Animals↗

PubMed1994

2-deoxygalactose interferes with an intermediate processing stage of memory.

The effect of 2-deoxygalactose (2-D-gal), an inhibitor of glycoprotein synthesis, on memory formation was investigated with the day-old chick trained on a single-trial passive discrimination task. 2-D-gal (10 mumol/chick) was shown to inhibit memory formation at a time before the emergence of an antibiotic-sensitive long-term memory stage. The amnestic effect of 2-D-gal was successfully prevented by galactose, and more significantly by noradrenaline. In contrast, anisomycin-induced amnesia was resistant to challenge by either galactose or noradrenaline. The results are consistent with the view that some glycoprotein involvement in memory formation occurs prior to the formation of protein synthesis-dependent long-term memory, and this role of glycoproteins may be associated with the triggering of long-term memory formation by noradrenaline.

Animals↗

PubMed1994

Both non-NMDA and NMDA glutamate receptors are necessary for memory consolidation in the day-old chick.

Day-old chicks (black Australorp-white Leghorn) trained to avoid an aversive stimulus will usually retain memory for this event indefinitely. The passive avoidance task used involves a period of pretraining where chicks peck freely at two differently colored glass beads, a single training trial where one of the beads is coated in a chemical aversant eliciting typical disgust reactions from the chicks, and a test trial where both beads are presented dry, and discrimination memory is demonstrated by avoidance of the previously aversive bead with continued pecking of the nonaversive bead. Intracranial administration of a N-methyl-D-aspartate glutamate receptor antagonist (50 microM 2-amino-5-phosphopentanoate) immediately after or prior to learning, or a non-N-methyl-D-aspartate glutamate receptor antagonist (100 microM 6,7-dinitro-quinoxaline-2,3-dione) between 10 and 25 min after learning, resulted in amnesia for this task at 80 to 90 min post-training. These data indicate that processes dependent on N-methyl-D-aspartate and non-N-methyl-D-aspartate glutamate receptor activation are necessary for memory consolidation of a passive avoidance task in the day-old chick. Since these agents must be administered during the earlier stages of memory formation to cause amnesia, the receptors are probably activated close to the time of learning. The delayed effect of these antagonists, however, suggests that memory is independent of these receptors until quite late in the memory consolidation process.

2-Amino-5-phosphonovalerate↗

PubMed1994

A nitric oxide agonist stimulates consolidation of long-term memory in the 1-day-old chick.

Chicks, age 1 to 2 days, that have been trained on a passive avoidance task with a strongly reinforced training trial yield a memory trace that is composed of 3 behaviorally and pharmacologically distinguishable stages, with the final long-term memory stage being dependent on protein synthesis. In contrast, chicks trained with a weakly reinforced learning trial typically do not demonstrate this final stage of memory. Sodium nitroprusside 150 microM intracranially administered immediately after a weak training trial promoted the formation of long-term memory, whereas saline did not. The results suggest that nitric oxide synthesis is either itself critical or stimulates other processes that are critical for the consolidation of long-term memory.

Age Factors↗

PubMed1994

Linearity of transthoracic conductance with respect to electrode force and area during high-voltage defibrillation shocks.

Canine transthoracic conductance (GT) was measured during high-voltage defibrillation shocks to test the hypothesis that (GT) is a linear function of electrode force (F) and electrode area (A). Symmetric protocols were used to compensate for changes in (GT) with respect to shock number (n). Stainless steel electrodes were employed with a force-control system for precise selection and control of both F and A at each shock. For a constant A = 60 cm2, GT was linear (r = 0.996, 0.995, 0.971, 0.992, 0.995) over five dogs for 30 N < or = F < or = 70 N. For a constant F = 50 N, GT was linear (r = 0.992, 0.998, 0.994, 0.992) over four dogs for 20 cm2 < or = A < or = 60 cm2, and in one dog (r = 0.996) for 40 cm2 < or = A < or = 90 cm2. The quantitative relationship demonstrated for GT and F and A can be used in the design of experiments and interpretation of results used for validation of numerical defibrillation models.

Animals↗

PubMed1993

Purified antichick Thy-1 IgG abolishes intermediate and long-term memory.

One- to 2-day-old chicks administered purified antichick Thy-1 IgG showed substantial amnesia for a single-trial passive discriminated avoidance task. Amnesia was clearly evident at 30 min after learning, during the intermediate stage of a three-stage model of memory processing, and persisted for at least 3 h. A similar effect was also observed with Fab and F(ab')2 fragments. Fc fragments, the non-IgG fraction of ascites, and saline yielded normal retention levels at all times. These results contrast with our earlier reports that both polyclonal and monoclonal antibodies to chick Thy-1 inhibited long-term memory formation only. The present findings are interpreted as possibly representing a dual effect of the purified IgG.

Animals↗