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Biomedical subjects

F C Chang

Publications and source records attributed to F C Chang.

At least 19 recordsLinked to original sources

Modification of medullary respiratory-related discharge patterns by behaviors and states of arousal.

The modulatory influences of behaviors and states of arousal on bulbar respiratory-related unit (RRU) discharge patterns were studied in an unanesthetized, freely behaving guinea pig respiratory model system. When fully instrumented, this model system permits concurrent monitoring and recording of (i) single units from either Bötzinger complex or nucleus para-ambiguus; (ii) electrocorticogram; and, (iii) diaphragmatic EMG. In addition to being used in surveys of RRU discharge patterns in freely behaving states, the model system also offered a unique opportunity in investigating the effects of pentobarbital on RRU discharge patterns before, throughout the course of, and during recovery from anesthesia. In anesthetized preparations, a particular RRU discharge pattern (such as tonic, incrementing or decrementing) typically displayed little, if any notable variation. The most striking development following pentobarbital was a state of progressive bradypnea attributable to a significantly augmented RRU cycle duration, burst duration and an increase in the RRU spike frequencies during anesthesia. In freely behaving states, medullary RRU activities rarely adhered to a fixed, immutable discharge pattern. More specifically, the temporal organization (such as burst duration, cycle duration, and the extent of modulation of within-burst spike frequencies) of RRU discharge patterns regularly showed complex and striking variations, not only with states of arousal (sleep/wakefulness, anesthesia) but also with discrete alterations in electrocorticogram (ECoG) activities and a multitude of on-going behavioral repertoires such as volitional movement, postural modification, phonation, mastication, deglutition, sniffing/exploratory behavior, alerting/startle reflexes. Only during sleep, and on occasions when the animal assumed a motionless, resting posture, could burst patterns of relatively invariable periodicity and uniform temporal attributes be observed. RRU activities during sniffing reflex is worthy of further note in that, based on power spectrum analyses of concurrently recorded ECoG activities, this particular discharge pattern was clearly associated with the activation of a 6-10 Hz theta rhythm. These findings indicated that bulbar RRU activity patterns are subject to change by not only behaviors and sleep/wakefulness cycles, but also a variety of modulatory influences and feedback/feedforward biases from other central and peripheral physiological control mechanisms.

Animals

Pharmacological characterization of excitatory synaptic potentials in rat basolateral amygdaloid neurons.

The pharmacological properties of synaptic responses in rat basolateral amygdaloid (BLA) neurons were studied using intracellular recording techniques. Three distinct types of synaptic potential were evoked by stimulation of the adjacent ventral endopyriform nucleus: 1) a fast excitatory postsynaptic potential (f-EPSP); 2) a late EPSP (1-EPSP) following the f-EPSP; and 3) a multiphasic hyperpolarization following the initial depolarizing potential. Superfusion of 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), a selective non-N-methyl-D-aspartate (non-NMDA) receptor antagonist, blocked the f-EPSP in a concentration-dependent manner. The ED50 for this effect was around 4 microM. In the presence of CNQX, however, a small depolarizing potential remained. This residual depolarizing component was markedly enhanced on removing Mg++ from the perfusing medium and could subsequently be abolished by DL-2-amino-5-phosphonovaleate (DL-APV, 50 microM) indicating its mediation via NMDA receptor-coupled ionophore. The l-EPSP was reversibly blocked by DL-APV. These results suggest that the pyriform cortex-amygdala pathway is mediated through excitatory amino acids acting on non-NMDA as well as NMDA receptors located on the BLA neurons.

2-Amino-5-phosphonovalerate

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

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

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

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

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

Intravenous cholangiography in the diagnosis of acute cholecystitis.

We reviewed our experience with intravenous cholangiography in the evaluation of 70 patients with suspected acute cholecystitis. Twenty-one of these patients had visualization of the biliary ducts without opacification of the gallbladder, a roentgenographic finding that was considered diagnostic of acute cholecystitis. Twenty of the 21 patients were noted to have acute cholecystitis during exploratory laparotomy. The remaining patient had a normal gallbladder, but was found to have a liver abscess. Opacification of the gallbladder with evidence of gallstones was found in eight patients; all had acute cholecystitis. Visualization of the gallbladder without gallstones was found in 22 patients, revealing no acute cholecystitis in this group. Many of these patients were admitted to the hospital with a primary diagnosis of acute cholecystitis and were spared an unnecessary surgical exploration. Nineteen patients had nonvisualization of the gallbladder and biliary ducts. This roentgenographic finding may be caused by acute intra-abdominal conditions other than cholecystitis and caution is warranted in its interpretation. This test has been found to be a reliable adjunct in the work-up of patients with suspected acute cholecystitis.

Acute Disease

Abdominal aortic aneurysms. A comparative analysis of surgical treatment of symptomatic and asymptomatic patients.

This retrospective study of 120 patients identified three separate variables that influence operative mortality in patients with abdominal aortic aneurysms. These are age, presence or absence of symptoms, and presence of three preoperative risk factors or more. Based on this study and the fact that any aneurysm may rupture without warning, we conclude that observation of good risk asymptomatic patients until symptoms occur is unjustified. Asymptomatic patients less than seventy years old can undergo abdominal aortic aneurysmectomy with minimal mortality. Carefully selected asymptomatic patients more than seventy years old can also under surgical intervention with acceptable results.

Age Factors

Inguinal herniorrhaphy under local anesthesia. A prospective study of 100 consecutive patients with emphasis of perioperative morbidity and patient acceptance.

For various reasons, repair of inguinal hernias under local anesthesia is not well accepted. The purpose of this study is to evaluate the effectiveness of local anesthesia in inguinal hernia repairs. One hundred consecutive inguinal herniorrhaphies are reported. The selection of patients, surgical technique, and incidence of intraoperative and postoperative complications are reported. Patient acceptance and their immediate postoperative course are also described. The study demonstrates that inguinal hernias can be easily repaired under local anesthesia, complications are minimal, and patient acceptance, excellent. We strongly recommend thath this form of anesthesia be used in the "routine" repair of inguinal hernias in cooperative patients.

Adult

Massive upper gastrointestinal hemorrhage in the elderly.

Sixty-six elderly patients with massive upper gastrointestinal bleeding were retrospectively analyzed. This study supports the concept of vigorous resuscitation, early diagnosis with fiberoptic endoscopy, and prompt surgical intervention in patients with continued bleeding. When this approach was utilized in a community hospital, operative mortality was reduced to 5 per cent.

Aged

Burn morbidity: a followup study of physical and psychological disability.

Fifty-one burn patients were studied in a retrospective manner to determine the effects of the burn injury on their ability to return to their pre-burn physical and social status. The results of this study indicate that: 1) 79% of the patients were able to return to work or school, though 45% required a change in work and 25% were not able to continue with their peer groups in school; 2) the average time of disability was 6 months; 3) there was a significant psychological morbidity as demonstrated by self-confessed depression, juvenile delinquency and divorce. There is a need for awareness of these problems so that proper counseling can be offered to the burn patient and his family both during his hospitalization and after discharge.

Absenteeism

Production of antibody against ochratoxin A.

Antibody against ochratoxin A was obtained after repeated injection of different protein-ochratoxin A conjugates to rabbits. Among many protein-ochratoxin conjugates tested, bovine serum albumin-ochratoxin A was found to be the best antigen. The antibody is specific for ochratoxins A, C, and T, but is not specific for ochratoxins B, alpha, and other coumarin derivatives. The sensitivity for ochratoxin A detection using a binding assay is in the range of 0.5 to 10 ng/0.5-ml sample. Detailed methods for the preparation of protein-ochratoxin conjugates, preparation of immune serum, and methods for antibody titers are described.

Animals