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Biomedical subjects

M F Wu

Publications and source records attributed to M F Wu.

At least 55 records · Page 3Linked to original sources
PubMed1995

Establishment and characterization of TSGH9201, a human gastric carcinoma cell line that is growth inhibited by epidermal growth factor.

A human signet ring gastric carcinoma cell line TSGH9201 was established in vitro. The cells grew in vitro as a monolayer with polygonal morphology and had a population doubling time of 34 hours. The cells secreted tumor markers CEA and CA 125. They were, however, not tumorigenic in athymic nude mice. Karyotypic analysis demonstrated a near tetraploidy with a modal chromosome number of 98. Northern blotting and immunocytochemical analysis revealed the expression of both transforming growth factor alpha and high levels of epidermal growth factor receptor. Cell growth was inhibited by the epidermal growth factor in vitro. The cell line may be a useful tool to study autocrine growth regulation through the epidermal growth factor receptor.

Animals↗
PubMed1995

Inhibitory effects of class I molecules on murine NK cells: speculations on function, specificity and self-tolerance.

This review addresses the physiological role of class I-mediated inhibition of NK cell lysis. It is suggested that several distinct activating receptors can stimulate NK lysis, all of which can be inhibited by class I molecules on the target cell. Evidence that most or all peptides that bind a class I molecule can cause inhibition is discussed, supporting a model in which NK cells detect loss of class I molecules, rather than loss of specific peptide/class I complexes. Finally, the acquisition of self-tolerance among NK cells is addressed with respect to data suggesting that autoaggressive NK cells are not deleted but rather exhibit altered characteristics which may render them unable to lyse autologous cells.

Animals↗
PubMed1995

Phosphorylation of dense-plaque proteins talin and paxillin during tracheal smooth muscle contraction.

Reorganization of cytoskeletal-membrane interactions during contractile stimulation may contribute to the regulation of airway smooth muscle contraction. We investigated the effect of contractile stimulation on the phosphorylation of the actin-membrane attachment proteins talin, vinculin, and paxillin. Stimulation of 32P-labeled canine tracheal smooth muscle strips with acetylcholine (ACh; 10(-3) M) resulted in a rapid 2.6-fold increase in phosphorylation of serine and/or threonine residues, compared with resting levels of 0.22 mol PO4(3-)/mol talin. After stimulation with ACh, phosphorylation of tyrosine residues on paxillin increased approximately threefold. Two-dimensional phosphopeptide mapping of in vivo labeled talin and paxillin indicated phosphorylation on a limited number of sites. Vinculin phosphorylation was undetectable in either resting or ACh-stimulated muscle. We conclude that phosphorylation of talin and paxillin occurs during ACh-stimulated contraction of tracheal smooth muscle and that distinct signaling pathways activate a serine/threonine kinase that phosphorylates talin and a tyrosine kinase that phosphorylates paxillin. The pharmacological activation of airway smooth muscle cells might involve the anchoring of contractile filaments to the membrane.

Acetylcholine↗
PubMed1995

Mechanisms for the mechanical plasticity of tracheal smooth muscle.

In smooth muscle tissues, the relationship between muscle or cell length and active force can be modulated by altering the cell or tissue length during stimulation. Mechanisms for this mechanical plasticity were investigated by measuring muscle stiffness during isometric contractions in which contractile force was graded by changing stimulus intensity or muscle length. Stiffness was significantly higher in contracted than in resting muscles at comparable forces; however, the relationship between stiffness and force during force development was curvilinear and independent of muscle length and stimulus intensity. This suggests that muscle stiffness during force development reflects properties of cellular components other than cross bridges which contribute to the series elasticity only during activation. During the tonic phase of isometric contraction, muscle stiffness increased while force remained constant. A step decrease in the length of a contracted muscle resulted in a high level of stiffness relative to force during isometric force redevelopment following the length step. We propose that the arrangement of the cytoskeleton can adjust to changes in the conformation of resting smooth muscle cells but that the organization of the cytoskeleton becomes more fixed upon contractile activation and is modulated very slowly during a sustained contraction. This may provide a mechanism for optimizing force development to the physical conformation of the cell at the time of activation.

Animals↗
PubMed1993

Cholinergic mechanisms in startle and prepulse inhibition: effects of the false cholinergic precursor N-aminodeanol.

We examined the effects of cholinergic deficiency on prepulse inhibition (PPI) of the acoustic startle. Rats treated with a choline-free diet that contained the false cholinergic precursor N-aminodeanol showed great deficit in PPI. This deficit does not appear to be secondary to an increase of stereotyped behaviors. Startle threshold was also greatly reduced, as these rats startled to the 70-dB prepulse and the baseline startle amplitude was increased by 60% over the control rats. Arecoline (4 mg/kg) partially reversed the deficit in PPI. This improvement persisted beyond the period of drug treatment. On the other hand, scopolamine (1 mg/kg) reduced PPI in the control rats. These results suggest that cholinergic systems play a major role in both the elicitation and prepulse inhibition of startle.

Acoustic Stimulation↗
PubMed1993

Contraction history modulates isotonic shortening velocity in smooth muscle.

The effect of contraction history on the isotonic shortening velocity of canine tracheal smooth muscle was investigated. Muscles were contracted isometrically for 20 s at initial lengths of L(o) (length of maximal active force), 85% L(o), or 70% L(o) using electrical field stimulation. Muscles were then allowed to shorten isotonically under different afterloads either with or without first being subjected to a step decrease in length to 70% L(o). Instantaneous velocities were plotted against instantaneous muscle length during isotonic shortening. Regardless of protocol, the velocity at any muscle length during shortening was lower when the muscle was initially activated at a longer length. The isotonic shortening velocity decreased progressively during shortening at a nearly linear rate with respect to instantaneous muscle length under all conditions. Results suggest that a longer muscle length at the time of activation leads to the development of higher loads on the contractile element during subsequent shortening, resulting in a slower shortening velocity. This plasticity of the force-velocity relationship may result from cytostructural reorganization of the smooth muscle cells in response to contractile activation at different muscle lengths.

Animals↗
PubMed1993

Midazolam pharmacokinetics and electroencephalographic changes in eight Chinese men.

Eight Chinese healthy male volunteers aged 27 +/- s 4 a were injected i.v. midazolam (Mid) 15 mg. Blood samples were collected at 0, 2, 5, 7, 10, 20, 30, 45, 60, 90, 120, 180, and 240 min. A HPLC method was established for determining the Mid concentrations in serum. The concentration-time data was fitted with biexponential curve. Pharmacokinetic parameters were: T1/2 alpha = 6.8 +2- 2.5 min, T1/2 beta = 118 +/- 27 min, Vc = 25 +/- 7 L, Cl = 393 +/- 79 ml.min-1, Vdss = 59 +/- 13 L, AUC0-infinity = 39.6 +/- 8.6 g.min.L-1. The electroencephalogram (EEG) showed a decrease in alpha activity and an increase in beta activity. The EEG pattern reverted toward baseline after 2-3 h. Pharmacokinetic and EEG findings suggest that Mid is a preferable anesthesia inducing agent.

Adult↗
PubMed1991

REM sleep deprivation reduces auditory evoked inhibition of dorsolateral pontine neurons.

In many dorsolateral pontine neurons, auditory stimulation produces an initial excitation followed by a sustained inhibition. We now report that rapid eye movement (REM) sleep deprivation, for periods of from 22-48 h, reduced this auditory evoked inhibition of unit discharge. Inhibition returned to baseline levels after recovery REM sleep. Prior work indicates that the auditory evoked inhibition seen in noradrenergic cells in this region is partially mediated by norepinephrine. We hypothesize that the reduction in inhibition that we see is a consequence of either downregulation/desensitization of norepinephrine receptors or reduced norepinephrine release resulting from REM sleep deprivation.

Acoustic Stimulation↗
PubMed1990

Facilitation of the acoustic startle reflex by ponto-geniculo-occipital waves: effects of PCPA.

The relationship between ponto-geniculo-occipital (PGO) waves and motor activity during waking and non-rapid eye movement (non-REM) sleep stages was studied in cats treated with the serotonin synthesis inhibitor p-chlorophenylalanine (PCPA). PGO waves appeared in waking after daily treatment with PCPA. The magnitude of the acoustic startle elicited in the absence of prior PGO waves was increased (by a mean of 555%) by the PCPA treatment as compared to that of the pre-drug level. When startle-eliciting stimuli were presented shortly after the occurrence of the PGO wave, the response amplitude was further enhanced as compared to that of the baseline startle. The effect was maximal 50 ms following the peak of the PGO wave (average 192% of the baseline level), with return to the baseline startle level within 200 ms. A similar effect could also be seen with waking eye-movement potentials (EMPs) in drug-naive animals. Over half of the spontaneous PGO waves were found to be preceded or followed by discrete head-body movements. After PCPA, the amplitude of auditory-evoked LGN PGO waves increased during quiet waking (QW) while those in non-REM and REM sleep states did not change. It was concluded that serotonergic systems produce a tonic suppression of startle response and PGO amplitude in waking. PGO spikes in waking are associated with a phasic facilitation of the sensorimotor mechanisms involved in startle.

Acoustic Stimulation↗
PubMed1990

Lesions producing REM sleep without atonia disinhibit the acoustic startle reflex without affecting prepulse inhibition.

This study determined whether the brainstem motor inhibition system that mediates muscle atonia during rapid eye movement (REM) sleep is involved in the elicitation and prepulse inhibition of the acoustic startle reflex. Electrolytic or neurotoxic (glutamate) lesions were made in the dorsolateral pontine tegmentum or the medial medulla, respectively, to produce the syndrome of REM sleep without atonia. Startle responses were released during REM sleep following the lesions. However, the amount of startle suppression produced by auditory prepulse after the lesion did not differ from that seen in intact controls. We conclude that REM sleep suppression of the acoustic startle responses is mediated by the system responsible for tonic motor inhibition, but auditory prepulse inhibition of the acoustic startle is not.

Animals↗
PubMed1990

Counterproductive transcriptional and translational regulation of elongation factor 1-alpha synthesis during early development in sea urchins.

We have isolated a cDNA clone encoding elongation factor 1-alpha (EF1-alpha) and used probes prepared from this cDNA to measure levels of EF1-alpha transcripts during early development. We also determined the fraction of EF1-alpha transcripts in polysomes during this time period. Following the blastula stage there is a sharp increase in the amount of EF1-alpha mRNA. This pattern of accumulation is similar to other previously described sea urchin mRNAs. However, while the level of EF1-alpha mRNA is increasing, the fraction of EF1-alpha mRNA in polysomes decreases. Thus, there is an apparently counter-productive decrease in efficiency of recruitment into polysomes occurring concurrently with an increase in the overall amount of EF1-alpha mRNA.

Animals↗
PubMed1989

Mechanisms of seizure suppression during rapid-eye-movement (REM) sleep in cats.

REM sleep is the most antiepileptic state in the sleep-wake cycle for human generalized epilepsy, yet the neural mechanism is unknown. This study verified the antiepileptic properties of REM sleep in feline generalized epilepsy and also isolated the responsible factors. Conclusions are based on 20 cats evaluated for generalized EEG and motor seizure susceptibility before and after dissociation of specific REM sleep components. Bilateral electrolytic lesions of the medial-lateral pontine tegmentum created a syndrome of REM sleep without atonia. Systemic atropine created a syndrome of REM sleep without thalamocortical EEG desynchronization. Identical results were obtained in two seizure models, systemic penicillin epilepsy and electroconvulsive shock. (1) Normal REM sleep retarded the spread of EEG seizure discharges and had even more potent anticonvulsant effects. (2) Selective loss of 'sleep paralysis' (skeletal muscle atonia) during REM abolished REM sleep protection against myoclonus and convulsions without affecting generalized EEG paroxysms. (3) Conversely, selective loss of thalamocortical EEG desychronization abolished REM sleep protection against generalized EEG seizures without affecting clinical motor accompaniment. These results suggest that the descending brainstem pathways which mediate lower motor neuron inhibition also protect against generalized motor seizures during REM sleep. Protection against spread of EEG paroxysms is governed by a separate mechanism, presumably the ascending brainstem pathways mediating intense thalamocortical EEG desynchronization during REM sleep.

Animals↗
PubMed1989

Lateral geniculate spikes, muscle atonia and startle response elicited by auditory stimuli as a function of stimulus parameters and arousal state.

We have investigated the motor and ponto-geniculo-occipital (PGO) wave response to startle eliciting stimuli in the unanesthetized cat. We found that the amplitude of the PGO spike recorded in the lateral geniculate nucleus (LGN) increases monotonically with increasing intensities of auditory stimuli. In contrast, the motor response to low intensity (less than 75 dB) stimuli is characterized by electromyographic (EMG) suppression, while at higher intensities an EMG excitation is superimposed on this suppression. Thus PGO elicitation is accompanied by EMG suppression at low intensities and by a net EMG excitation at high intensities. While the amplitude of the auditory elicited PGO response is a graded function of stimulus intensity, somatic stimuli tend to elicit the PGO response in all-or-none fashion. Both the motor and PGO responses to sensory stimulation change with behavioral state. The EMG suppression by auditory stimulation increases in duration during the transition to rapid eye movement (REM) sleep. Elicited PGO amplitude is highest in transitional sleep, lower in quiet waking and REM sleep and lowest in active waking. Prepulse inhibition of PGO spikes is greatly attenuated during transitional and REM sleep. We hypothesize the existence of 3 phasic response systems, a motor suppression system, a motor excitation (startle) system and a PGO elicitation system. While these systems are triggered concurrently by intense phasic stimuli in waking, they are modulated independently by stimulus intensity and behavioral state, and have different rates of habituation. These systems act in concert to produce behavioral responses to sudden onset stimuli.

Acoustic Stimulation↗
PubMed1989

Role of pontomedullary reticular formation neurons in horizontal head movements: an ibotenic acid lesion study in the cat.

Single-cell recording, electrolytic lesion and electrical stimulation studies have indicated that the pontomedullary reticular formation (PMRF) plays a role in head movement (HM) control. However, recent studies utilizing excitotoxin lesions of the PMRF have reported no effect on HM. In the present study, we have examined the acute and chronic motor effects of injecting ibotenic acid (IBO) into the nucleus reticularis pontis oralis, nucleus reticularis pontis caudalis and rostral medullary nucleus gigantocellularis of the feline PMRF. IBO injections in all of these regions induced tonic flexion of the head toward the ipsilateral side. This effect lasted 4-16 h. It was followed by a second phase in which head flexion and whole body circling were directed toward the contralateral side. Although this forced contralateral head turning disappeared within two days, the tendency to turn contralaterally and the impaired ability to make rapid ipsilateral HMs were present throughout survival periods lasting more than 4 months. Unilateral IBO PMRF lesions reduced the amplitude of vestibular induced quick phase (anti-compensatory) HMs toward the ipsilateral side and resulted in abnormally large and persistent slow compensatory HMs toward the contralateral side. Following IBO injections, the threshold intensity for HMs evoked by electrical stimulation at the injection site was elevated, and the amplitude and velocity of evoked HMs reduced. Histological data indicated that the reticular area involved in HM control was relatively large and probably extended beyond the PMRF region examined here. However, lesions including the nucleus reticularis pontis caudalis (NRPC) produced more severe and persistent HM deficits than those including the nucleus reticularis gigantocellularis. These data together with available anatomical and electrophysiological evidence indicate that PMRF neurons play a critical role in the generation of fast horizontal HMs toward the ipsilateral side.

Action Potentials↗
PubMed1988

Anatomical distribution and response patterns of reticular neurons active in relation to acoustic startle.

A population of reticulospinal neurons with short latency response to startle-inducing stimuli was identified in the nucleus reticularis pontis caudalis (NRPC) and nucleus gigantocellularis (NRGC) of the medial pontomedullary reticular formation. The threshold and magnitude of response to auditory stimuli was correlated in these cells and in the muscles mediating startle. Startle-related neurons were significantly more likely to have high conduction velocity spinal projections than adjacent cells not related to startle. Startle-related cells were not 'dedicated' to startle, but were active in relation to spontaneous movements. Both the unit response of the startle-related cells and the startle response recorded in muscles were suppressed by the prior presentation of a weak prepulse. Thus, prepulse inhibition of startle occurs at, or prior to, the medial pontomedullary reticular formation. We conclude that these reticulospinal cells convey the output of the brainstem system modulating and triggering startle.

Acoustic Stimulation↗
PubMed1985

Cutaneous and auditory function in rats following methyl mercury poisoning.

Rats were given a total dose of 50 mg/kg (Exp. 1), 13.3 or 40 mg/kg (Exp. 2), or 40 mg/kg (Exp. 3) of methyl mercury chloride subcutaneously over a course of 5 days. At varying times after the toxic exposure, up to 1 year, their sensory functioning was assessed by reflex modulation methods: stimuli of interest were presented just before an intense tone which elicited the startle reflex, and stimulus reception was measured by the inhibitory control of the stimuli over the amplitude of the reflex. In Experiment 1 cutaneous prestimuli (electric shock to the tail) and brief acoustic transients (silent periods in noise) were less effective inhibitors of reflex activity in poisoned animals, compared to controls, indicating that the poisoned animals had impairments in cutaneous sensitivity and audition. In Experiment 2 the time course of sensory loss and subsequent recovery was studied. Impaired auditory function was shown further by a deficit in the effectiveness of weak noise pulses, and, in addition, the cutaneous deficit for weak tail shocks was accompanied by an exaggerated or hyperpathic response to more intense tail shocks. Experiment 3 confirmed the finding that the loss of sensitivity to weak shock was accompanied by an enhancement of the response to more intense shock. These data were related to peripheral neuropathy and shown to be analogous to certain clinical symptoms of Minamata disease reported in humans.

Acoustic Stimulation↗