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F C Chang

Publications and source records attributed to F C Chang.

At least 91 records · Page 5Linked to original sources
PubMed1991

Bursting discharges in disinhibited amygdala slices: the role of excitatory amino acid receptors.

The involvement of N-methyl-D-aspartate (NMDA) and non-NMDA receptors in the epileptiform activity, induced by bicuculline, was studied in slices of amygdala in the rat, using intracellular recording techniques. Stimulation of the ventral endopyriform nucleus evoked an excitatory postsynaptic potential (EPSP). After exposure to bicuculline (20 microM), the same stimulus evoked burst firing. Occasionally, spontaneous bursts similar in waveform to synaptically triggered bursts also occurred in disinhibited slices. Superfusion of DL-2-amino-5-phosphonovalerate (DL-APV, 50 microM) or 3-((+)-2-carboxypiperazin-4-yl)-propyl-1-phosphonic acids (CPP, 10 microM), rapidly blocked the late component of the paroxysmal depolarizing shift. The spontaneous and evoked bursts were never completely abolished in the presence of DL-APV or CPP. These results suggest that NMDA receptors may contribute to but are not required for the generation of these bursts. In contrast, application of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 10 microM) largely abolished the bursts, indicating that activation of non-NMDA receptors is of primary importance in this model of epilepsy.

2-Amino-5-phosphonovalerate↗
PubMed1991

Potential bile acid metabolites. 17. Synthesis of 2 beta-hydroxylated bile acids.

The 2 beta-hydroxylated derivatives of lithocholic, chenodeoxycholic, deoxycholic, and cholic acids were synthesized from the respective parent bile acids by established procedures. The principal reactions involved were (1) bromination of 3-oxo formylated bile acids in N,N-dimethylformamide, (2) rearrangement and substitution of the resulting 4 beta-bromo-3-oxo derivatives to the 2 beta-acetoxy-3-oxo compounds with potassium acetate, and (3) reduction to the 2 beta-acetoxy-3 alpha-hydroxy compounds with tert-butylamine-borane complex. As for the prepared 2 beta-hydroxylated bile acids with a diequatorial trans-glycol structure, proton and carbon-13 nuclear magnetic resonance spectroscopic and gas-liquid chromatographic/mass spectrometric properties are discussed.

Acetates↗
PubMed1991

Effects of pentobarbital on respiratory functional dynamics in chronically instrumented guinea pigs.

Respiratory effects of sodium pentobarbital (35 mg/kg; IP) were studied in guinea pigs chronically instrumented to permit concurrent recordings of bulbar respiratory-related units (RRUs), diaphragmatic electromyogram (DEMG), and electrocorticogram (ECoG). RRU activities were recorded from either the Bötzinger Complex (BOT; expiratory) or Nucleus para-Ambiguus (NpA; inspiratory). Pentobarbital-induced changes in respiratory-related activities were evaluated before, throughout the course of, and during recovery from, anesthesia. The most notable development following pentobarbital was a state of progressive bradypnea which was accompanied by a variety of complex changes in the amplitude and temporal attributes of RRU, DEMG and ECoG activities. As anesthetic effects progressed, the activity profiles of both BOT and NpA units underwent striking transformations from a behavioral and state-dependent wakefulness pattern to an activity profile characterized by i) a significantly augmented RRU cycle duration, burst duration and spike frequency; and, ii) an alteration to the pattern of within-burst spike frequency modulation. Along with changes in RRU activity, pentobarbital also produced a marked attenuation of the amplitudes of diaphragmatic activity as well as a discrete, time-dependent alteration in the amplitude and spectral characters of ECoG activities. Differences in BOT and NpA unit responses to alveolar CO2 loading (ramp; 2% and 5%) across wakefulness and anesthesia states were also considerable. In addition to a depressed responsiveness to CO2, the temporal attributes of BOT and NpA activity profiles also indicated an asymmetrical change under pentobarbital anesthesia. Taken together, these findings indicate that pentobarbital causes not only a fundamental alteration in bulbar rhythmogenic mechanisms, but also a differential influence on bulbar respiratory system components that are involved in the definition of the shape and the amplitude of central respiratory drive. In conclusion, this study offers, for the first time, direct evidence from physiologically and structurally intact preparations that the functional dynamics of respiratory system components are profoundly altered during pentobarbital anesthesia.

Animals↗
PubMed1991

Ketamine suppresses synchronized discharges in the disinhibited amygdala slice.

The effect of ketamine on the paroxysmal depolarizing shift (PDS) induced by bicuculline was studied in rat amygdala slices using intracellular recording techniques. Stimulation of the ventral endopyriform nucleus evoked an excitatory postsynaptic potential (EPSP). After exposure to bicuculline (20 microM), the same stimulus intensity evoked burst firing. Superfusion of ketamine reversibly reduced the duration of PDS. Pretreatment of amygdala slices with DL-2-amino-5-phosphonovaleate (DL-APV, 50 microM) occluded the effect of ketamine suggesting that ketamine shortened the burst duration via its blocking action on the NMDA receptors. In all neurons tested, a large depolarizing shift remained in the presence of ketamine. The ketamine-resistant component was blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX, 8 microM) indicating its mediation by the non-NMDA receptors.

2-Amino-5-phosphonovalerate↗
PubMed1991

Characterization of a monoclonal antibody (RJ5) against the immunodominant 41-kD antigen of Candida albicans.

A 41-kD component of Candida albicans was identified to be the major antigen radioimmunoprecipitated by antibodies with increased titers in the sera of patients with invasive candidiasis. A mouse monoclonal antibody (RJ5) was generated which, by immunoblotting, showed positive reactivity to the immunoprecipitated 41-kD component. By two-dimensional gel electrophoresis and immunoblotting, MoAb RJ5 was shown to react with different isoforms of the 41-kD component with pI values from 6.1 to 6.9. Furthermore, MoAb RJ5 showed positive reactivity to cytoplasmic antigens of C. albicans by frozen section and immunoperoxidase staining. By SDS-polyacrylamide gel electrophoresis and immunoblotting, MoAb RJ5 showed no cross-reactivity to antigens of Candida tropicalis and Candida parapsilosis. The epitope of the 41-kD molecule recognized by MoAb RJ5 was susceptible to treatment of proteinase K at concentrations of greater than or equal to 5 micrograms/ml, and was relatively resistant to periodate oxidation with concentration of NaIO4 up to 20 mM. This MoAb may be useful in the purification and characterization of the immunodominant 41-kD antigen of C. albicans, and as a probe in the detection of Candida antigens in the sera of patients with invasive candidiasis.

Antibodies↗
PubMed1991

Potential bile acid metabolites. XVIII. Synthesis of stereoisomeric 3,6,12 alpha-trihydroxy-5 beta-cholanoic acids.

Two new 6-hydroxylated bile acids, 3 beta, 6 alpha, 12 alpha- and 3 beta, 6 beta, 12 alpha-trihydroxy-5 beta-cholanoic acids, were synthesized from deoxycholic acid. In addition, their C-3 epimers, 3 alpha, 6 alpha, 12 alpha- and 3 alpha, 6 beta, 12 alpha-trihydroxy acids, were prepared by a new route. The principal reactions used were 1) 6 beta-hydroxylation of 3-methoxy-3,5-dienes with m-chloroperbenzoic acid in aqueous dioxane; 2) catalytic hydrogenation of the resulting 6 beta-hydroxy-3-oxo-4-enes to the 6 beta-hydroxy-3-oxo-5 beta compounds with palladium on calcium carbonate catalyst in ethanol; and 3) stereoselective reduction of appropriate 3-oxo derivatives with potassium tri-sec-butylborohydride and tert-butylamine-borane complex. The thin-layer chromatographic, gas-liquid chromatographic, and high performance liquid chromatographic mobilities, and 1H- and 13C-nuclear magnetic resonance spectroscopic data of the four stereoisomers are presented. With this work all the 6-hydroxylated derivatives of lithocholic, deoxycholic, chenodeoxycholic, ursodeoxycholic, and cholic acids in the 5 beta series are now known and have been synthesized.

Bile Acids and Salts↗
PubMed1990

Respiratory and cardiovascular effects of tetrodotoxin in urethane-anesthetized guinea pigs.

Cardiorespiratory effects of tetrodotoxin (TTX) (15 micrograms/kg, i.p.) were investigated in urethane-anesthetized guinea pigs acutely instrumented for the recording of medullary respiratory-related units (RRUs), diaphragm electromyogram (DEMG), electrocorticogram (ECoG), electrocardiogram (ECG), blood pressure (BP), endtidal CO2, and arterial O2 and CO2. Respiratory system responses showed a hyperventilatory profile during the initial stage of intoxication. This was followed by an abrupt onset of a progressive decrease in the respiratory frequency, and a respiratory rate depression-related respiratory failure. The average time to TTX-induced respiratory arrest and death was 10.3 +/- 4.2 min. Concurrently recorded inspiratory and expiratory RRU activities indicated that respiration invariably failed in an end-expiratory position as manifested by a sustained period of expiratory RRU discharge. The progressive rate depression prior to respiratory arrest was temporally correlated only to a concomitantly augmenting expiratory RRU discharge duration. Inspiratory RRU discharge duration, on the other hand, did not display any significant change throughout the course of intoxication. The asymmetry in RRU response patterns indicates either an expiratory network component's particular sensitivity to perturbation by TTX or a dissociative trend in some bulbar respiratory rhythmogenic mechanisms. Peripheral cardiorespiratory changes were also quite profound. These included a gradual and steadfast decline in BP, a steadily decreasing amplitude in DEMG oscillations, and a state of progressive hypercapnia and hypoxemia. Changes in heart rate and ECG waveform attributes prior to respiratory arrest were not appreciable. In conclusion, in addition to a variety of TTX-induced peripheral cardiorespiratory effects, findings from this study have revealed a central respiratory system component that appears to show an unusual sensitivity to perturbation by TTX. The significance of this unique phenomenon as it relates to the nature and extent of TTX-induced central respiratory depression is discussed.

Anesthesia, General↗
PubMed1990

Epileptiform activity induced by 4-aminopyridine in rat amygdala neurons: the involvement of N-methyl-D-aspartate receptors.

The involvement of the N-methyl-D-aspartate (NMDA) receptor in the epileptiform activity induced by 4-aminopyridine (4-AP) was studied in rat amygdala slices using intracellular recording techniques. Stimulation of the ventral endopyriform nucleus evoked an excitatory postsynaptic potential (EPSP). After exposure to 4-AP (200 microM) the amygdala slices usually exhibited spontaneous and evoked epileptiform activity. The epileptiform events had an average duration of 522 +/- 78 ms with a frequency of 0.5-8.5 bursts/min. Superfusion of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a selective non-NMDA receptor antagonist, practically abolished the epileptiform bursting. However, there remained a residual depolarizing component in 13 out of 18 neurons. This CNQX-resistant component was markedly enhanced both in amplitude and duration when extracellular Mg2+ was removed and could be reversibly blocked by the specific NMDA receptor antagonist, DL-2-amino-5-phosphonovaleate (DL-APV). Compared with the CNQX-sensitive component, the APV-sensitive component had a much smaller amplitude shorter duration. These data suggest that the NMDA receptor is likely to play only a minor role, and activation of the NMDA receptor may contribute to but is not required, for the generation of these bursts.

2-Amino-5-phosphonovalerate↗
PubMed1990

Potential bile acid metabolites. 16. Synthesis of stereoisomeric 3 alpha,6,7,12 alpha-tetrahydroxy-5 beta-cholanoic acids.

New synthetic routes to the four possible stereoisomeric 3 alpha,6,7,12 alpha-tetrahydroxy-5 beta-cholanoic acids (and their methyl esters), one of which (3 alpha,6 alpha 7 beta,12 alpha) is new, and some related compounds are described. In addition, the 5 alpha-epimer of the new acid was obtained. The final products were obtained in high purity for use as reference compounds in the analysis of bile acids in human biologic samples. The results of analysis of the prepared stereoisomers by proton and carbon 13 nuclear magnetic resonance spectroscopies are briefly discussed along with the thin-layer and gas-liquid chromatographic properties.

Bile Acids and Salts↗
PubMed1990

Neurophysiological concomitants of soman-induced respiratory depression in awake, behaving guinea pigs.

Soman-induced respiratory failure was investigated in awake, behaving guinea pigs chronically instrumented to allow concurrent recordings of medullary respiratory-related unit (RRU) activity, diaphragm electromyogram (DEMG), and electrocorticogram. Responses to soman typically began with hyperpnea. Loss of consciousness, as indicated by the development of seizure activities, took place shortly after the onset of hyperpnea. This was followed by dyspnea, hypopnea, and finally, respiratory failure. The most profound respiratory dysfunctions were seen during the development of dyspnea characterized by a progressively degenerative RRU-DEMG phase relationship (phase anomalies) and mixed patterns of ataxic breathing. Electrophysiographic records indicated that the anomalous RRU-DEMG phase phenomenon is attributable to a state of functional dissociation in some brainstem mechanisms that are normally involved in the orchestration of a synchronous respiratory drive. The failure of bulbar rhythmogenic mechanisms to maintain an orderly and synchronous recruitment of respiratory drive, which led to untimely and chaotic activations of respiratory muscles, was apparently the underlying cause of various ataxic breathing patterns and a reduced ventilatory efficiency. Spectral analyses of DEMG activities showed that, despite episodic muscle fasciculations and signs of fatigue, the functional integrity of the diaphragm was not significantly compromised by soman at a dose sufficient to produce respiratory failure. These findings not only support the notion of a relatively more important involvement of central respiratory mechanisms in soman-induced respiratory failure, but also identify a state of functional dissociation of central respiratory timing mechanisms as being a significant component in soman intoxication.

Animals↗
PubMed1989

A method for the simultaneous analysis of unconjugated and glycine-conjugated bile acids by capillary gas-liquid chromatography.

A method for the simultaneous analysis of unconjugated and glycine-conjugated bile acids by means of capillary gas-liquid chromatography without need for prior deconjugation is described. The method involves: i) the use of an aluminum-clad fused-silica capillary column coated with a very thin film (0.1 micron) of a highly thermostable bonded and crosslinked methyl polysiloxane, and ii) the analysis of the bile acids as their methyl ester-dimethylethylsilyl ether derivatives. This method, used to separate the major free and glycine-conjugated bile acids from human gall bladder bile, should be applicable for the analysis of other biological fluids.

Bile Acids and Salts↗
PubMed1989

A procedure for chronic recording of diaphragmatic electromyographic activity.

A simple procedure for recording of diaphragmatic electromyographic activity in awake, freely behaving animals is described. This procedure produces highly stable recording of muscle activity for very long periods. Because of its ease of use, the procedure has become the technique of choice for acute recording in our laboratories as well. The present procedure can also be adapted for chronic recording of electromyographic activities from nonrespiratory muscles. This option thus offers a variety of applications to those involved in investigations into the central neuromotor control of movement, pattern generation and autonomic functions.

Animals↗
PubMed1989

Potential bile acid metabolites. XV. Synthesis of 4 beta-hydroxylated bile acids; unique bile acids in human fetal bile.

The 4 beta-hydroxylated derivatives of lithocholic, deoxycholic, chenodeoxycholic, and cholic acids were synthesized from their respective parent compounds. The principal reactions employed were 1) beta-face cis-dihydroxylation of delta 3 intermediates with osmium tetroxide-N-methylmorpholine N-oxide, 2) selective cathylation of vicinal 3 beta,4 beta-diols followed by oxidation of the resulting 4 beta-monocathylates, or direct selective oxidation at C-3 of 3 beta,4 beta-diols with pyridinium chlorochromate, and 3) stereoselective reduction of the 3-oxo compounds with tert-butylamine-borane complex. The results of analysis of the prepared 4 beta-hydroxylated bile acids with a diequatorial trans-glycol structure and their 3 beta-epimers by proton and carbon-13 nuclear magnetic resonance spectroscopies are briefly discussed along with the mass spectrometric properties.

Bile↗
PubMed1989

Potential bile acid metabolites. 14. Hyocholic and muricholic acid stereoisomers.

The complete set of the eight theoretically possible stereoisomeric 3,6,7-trihydroxy-5 beta-cholanic acids, four of which are new, related to hyocholic and muricholic acids were prepared from chenodeoxycholic acid. The principal reactions used were 1) cis-dihydroxylation of delta 6-compounds with osmium tetroxide/N-methylmorpholine N-oxide; 2) trans-dihydroxylation of 6 alpha, 7 alpha-epoxy compounds with boron trifluoride etherate in N,N-dimethyl-formamide; 3) inversion of equatorial 3 alpha-hydroxylated compounds to the corresponding 3 beta-epimers with diethyl azodicarboxylate/triphenylphosphine/formic acid; and 4) stereoselective reduction of 7-keto derivatives with zinc borohydride (or sodium borohydride) and by metallic potassium/tert-amyl alcohol.

Bile Acids and Salts↗
PubMed1988

Dihydropyridine and phenylalkylamine receptors associated with cardiac and skeletal muscle calcium channels are structurally different.

We have purified putative L-type Ca2+ channels from chick heart by virtue of their associated high affinity receptors for the Ca2+ channel effectors, dihydropyridines (DHPs), and phenylalkylamines (PAAs). A peptide of 185,000-190,000 daltons was found to comigrate with the peak of DHP binding activity during purification through two successive cycles of lectin affinity chromatography and sucrose density gradient centrifugation. A previously described peptide of 140,000 daltons, whose Mr was increased to approximately 180,000 under nonreducing conditions, also copurified with the 185-kDa peptide and dihydropyridine binding activity. When cardiac membranes were photolabeled with either the dihydropyridine [3H]azidopine or the PAA [3H]azidopamil prior to purification, a single, specifically labeled component of 185,000-190,000 daltons was present in the purified fractions. The properties of this 185-kDa cardiac DHP/PAA receptor were compared to the smaller 165-kDa DHP/PAA receptor previously purified from skeletal muscle. Antibodies raised against the 165-kDa skeletal muscle DHP/PAA receptor reacted with both rabbit and chick skeletal muscle receptors, but only poorly recognized, if at all, the cardiac 185-190 kDa component. The 185-kDa peptide present in the purified fractions obtained from cardiac muscle did not undergo substantial phosphorylation by cAMP-dependent protein kinase, while the purified 165-kDa peptide from rabbit and chick skeletal muscle was a good substrate for this kinase. The results show that the DHP and PAA receptors in cardiac muscle are contained in a 185-190-kDa peptide that is significantly larger than, and structurally and immunologically different from, it skeletal muscle counterpart.

Affinity Labels↗