Search PubMed⌕ Search

Biomedical subjects

D Wong

Publications and source records attributed to D Wong.

At least 199 records · Page 11Linked to original sources

The effect of pulse repetition rate on the delay sensitivity of neurons in the auditory cortex of the FM bat, Myotis lucifugus.

1. Echo delay is the primary cue used by echolocating bats to determine target range. During target-directed flight, the repetition rate of pulse emission increases systematically as range decreases. Thus, we examined the delay tuning of 120 neurons in the auditory cortex of the bat, Myotis lucifugus, as repetition rate was varied. 2. Delay sensitivity was exhibited in 77% of the neurons over different ranges of pulse repetition rates (PRRs). Delay tuning typically narrowed and eventually disappeared at higher PRRs. 3. Two major types of delay-sensitive neurons were found: i) delay-tuned neurons (59%) had a single fixed best delay, while ii) tracking neurons (22%) changed their best delay with PRR. 4. PRRs from 1-100/s were represented by the population of delay-sensitive neurons, with the majority of neurons delay-sensitive at PRRs of at least 10-20/s. Thus, delay-dependent neurons in Myotis are most active during the search phase of echolocation. 5. Delay-sensitive neurons that also responded to single sounds were common. At PRRs where delay sensitivity was found, the responses to single sounds were reduced and the responses to pulse-echo pairs at particular delays were greater than the single-sound responses. In facilitated neurons (53%), the maximal delay-dependent response was always larger than the best single-sound responses, whereas in enhanced neurons (47%), these responses were comparable. The presence of neurons that respond maximally to single sounds at one PRR and to pulse-echo pairs with particular echo delays at other PRRs suggests that these neurons perform echo-ranging in conjunction with other biosonar functions during target pursuit.

Acoustic Stimulation↗

Spectral selectivity of FM-FM neurons in the auditory cortex of the echolocating bat, Myotis lucifugus.

1. Spectral sensitivity was examined in delay-sensitive neurons in the auditory cortex of the awake FM bat, Myotis lucifugus. FM stimuli sweeping 60 kHz downward in 4 ms were used as simulated pulse-echo pairs to measure delay-dependent responses. At each neuron's best delay, the pulse and/or echo were divided into 4 FM quarters (Ist, IInd, IIIrd, and IVth), each sweeping 15 kHz in 1 ms, and quarters essential for delay sensitivity were determined for both pulse and echo. 2. For the pulse, the IVth quarter was essential for delay sensitivity in the majority of neurons. For the echo, the essential quarter for most neurons was the IInd, IIIrd, or IVth. 3. Different quarters of the pulse and echo were essential for delay sensitivity in 68% of the neurons examined. 4. This study provides neurophysiological evidence linking both spectral and temporal processing in delay-sensitive neurons of Myotis. Since spectral cues can provide target-shape information, sensitivity to both spectral and temporal parameters in single neurons may endow these neurons in FM bats with the potential for target analysis other than echo-ranging.

Acoustic Stimulation↗

The influence of stimulus duration on the delay tuning of cortical neurons in the FM bat, Myotis lucifugus.

1. Echolocating bats use echo delay as the primary cue to determine target distance. During target-directed flight, the emitted pulses increase in repetition rate and shorten in duration as distance decreases. To determine how these parameters affect the delay tuning of neurons in the auditory cortex of the awake bat, Myotis lucifugus, we examined the responses of 104 delay-sensitive neurons as the pulse repetition rate (PRR) and duration were independently varied. Stimulus duration of 4, 2 and 1 ms and PRR of 5-100/s were used for both the pulse and echo to determine delay sensitivity. These parameter ranges span those used during the search, approach, and the initial terminal phases of echolocation. 2. As the stimulus duration was shortened, the range of PRRs for delay sensitivity was extended to higher rates in 41% of the neurons, narrowed or disappeared in 40%, and remained unchanged in 4%. The remaining 15% were not categorized since it was not possible to determine a trend in which the range of delay-sensitive PRRs changed with stimulus duration. 3. Three types of tracking neurons (i.e., neurons that change their best delay during target-directed flight) were found. For the first type, the best delay (BD) shortened with shorter stimulus duration, for the second type, BD shortened with both shorter stimulus durations and higher PRRs, and for the third type, BD shortened with higher PRRs. 4. These results suggest that the stimulus parameters of sonar emission influence delay tuning and hence processing by cortical neurons in FM bats.

Acoustic Stimulation↗

Long-term drift and timolol therapy: possible role for pulsed therapy.

Eyes treated with a topical betablocker may exhibit the phenomenon of longterm drift, leading to loss of intraocular pressure control. It has been suggested that discontinuation of the betablocker may restore sensitivity to betablocker therapy, and that this phenomenon might be enhanced by the administration of an adrenergic agonist during this holiday period. This study was set up to examine further this hypothesis. Nine patients with ocular hypertension receiving treatment with timolol were entered into the study. Timolol was discontinued then re-started after four weeks of treatment with dipivefrin. This treatment cycle was repeated after a further four weeks. IOP was measured every two weeks. Re-introduction of timolol was associated with a significant lowering of IOP at two weeks (3.2 mmHg in the first cycle, p < 0.01, 3.4 mmHg in the second cycle, p < 0.01). Discontinuation of timolol and treatment with dipivefrin was not associated with a significant change in IOP.

Aged↗

Upregulation of intercellular adhesion molecule-1 (ICAM-1) expression in primary cultures of human brain microvessel endothelial cells by cytokines and lipopolysaccharide.

The expression of intercellular adhesion molecule-1 (ICAM-1) by human cerebral endothelium was studied in primary cultures of human brain microvessel endothelial cells following treatment with bacterial lipopolysaccharide (LPS), tumor necrosis factor-alpha (TNF-alpha), interleukin-1 beta (IL-1 beta) and interferon-gamma (IFN-gamma). Surface expression of ICAM-1 was examined with the immunogold silver staining technique. Intact cerebral endothelial cells constitutively express low levels of ICAM-1. Stimulation with LPS and cytokines induces upregulation of ICAM-1 which is minimal with IFN-gamma and maximal with LPS or a combination of IFN-gamma and TNF-alpha. Upregulation of ICAM-1 expression is concentration- and time-dependent, is observed as early as 4 h following incubation and persists for up to 72 h in the continuous presence of LPS or cytokines. The ICAM-1 expression is not reversed by 3 days after removal of the LPS or cytokines. These findings may be relevant to the interactions between leukocytes and brain microvessel endothelial cells in inflammatory and demyelinating diseases of the CNS.

Brain↗

Processing of pure-tone and FM stimuli in the auditory cortex of the FM bat, Myotis lucifugus.

FM bats perceive their surroundings during echolocation by analyzing frequency-modulated (FM) acoustic signals. Results from this study indicate a cortical organization in Myotis lucifugus which is largely made up of neurons sensitive to FM sounds (FM-sensitive neurons). Three types of neurons were distinguished by their responses to pure-tone and FM stimuli: (1) Type I FM-sensitive units (83%), Type II FM-sensitive units (13%) and pure-tone sensitive units (4%). Type I FM-sensitive units responded to pure tones, but exhibited greater response magnitudes to FM stimuli when the best FM swept through the BF. An orderly frequency representation was found when the frequencies of pure tones essential for response (EPTs) in Type I units were mapped along the cortical surface. The EPTs for Type I neurons were usually found within the last millisecond of a downward FM sweep. As outlined by two neuronal network models, both the responses of Type I and II units could likely result from the convergence of excitatory and inhibitory lower level neurons with slightly differing BFs. Type II units were selective for an FM sweep and showed negligible to no response to pure-tone stimuli. Pure-tone sensitive units exhibited weak or no responses to FM stimuli. These neurons were clustered in a small area located rostrodorsal to the tonotopic zone and had significantly lower best frequencies than adjacent EPT frequencies of Type I FM-sensitive neurons.

Acoustic Stimulation↗

Peribulbar anaesthesia: failure to abolish the oculocardiac reflex.

Peribulbar anaesthesia is a form of regional anaesthesia which has been used with increasing popularity in cataract surgery. Recently indications for its use have been extended to include surgery for vitreo-retinal disease and strabismus. This study shows that in nine of 11 patients in whom the oculocardiac reflex was stimulated by traction on an extra-ocular muscle, peribulbar anaesthesia failed to abolish the reflex. In each of these patients, the reflex manifested as a bradycardia. In one subject, the bradycardia was profound, showing no QRS complex for five seconds. We recommend that cardiac rhythm be monitored throughout procedures performed under peribulbar anaesthesia, and that a vagolytic agent be available for immediate use.

Anesthesia, Conduction↗

Dorsal penile nerve block in neonatal circumcision: chloroprocaine versus lidocaine.

Dorsal penile nerve blocking (DPNB) has been used with success in decreasing neonatal stress during circumcision. This study was designed to confirm the effectiveness of lidocaine in DPNB and to demonstrate that chloroprocaine, a shorter acting anesthetic, is as effective in blocking circumcision stress as lidocaine, but, because of its shorter plasma elimination half-life and time of onset of action, is safer. Five groups of 15 neonates were matched for weight, age, and Apgar scores and randomly assigned to a control group, one lidocaine group and three chloroprocaine groups with 2-, 3- and 5-minute postinjection waiting periods. Each neonate was subjected to six events during circumcision for which heart rate, tissue oxygenation, and cry duration were recorded. We found that, as in previous investigations, DPNB with lidocaine was effective in reducing neonatal stress, as was evident from decreased excursion from baseline heart rate, tissue oxygenation, and cry duration when compared with the control group (nonblocked). Furthermore, chloroprocaine DPNB approximates the effectiveness of lidocaine, as was evident from decreased change from baseline cry duration, tissue oxygenation, and heart rate during the most stressful events, particularly in the 3-minute wait chloroprocaine group. This more rapid onset of regional anesthesia decreases DPNB circumcision time and benefits patients, parents, and physicians.

Anesthetics, Local↗

Trunk kinematics during locomotor activities.

We investigated upper-body (ie, trunk) angular kinematics (motions) during gait, stair climbing and descending, and rising from a chair in two reference frames--relative to the pelvis and to room coordinates. Bilateral kinematic data were collected from 11 healthy subjects (6 female, 5 male), who were 27 to 88 years of age (mean = 58.9, SD = 17.9). During stair climbing, maximum trunk flexion relative to the room was at least double that during stair descending and gait. Arising from a chair required the most trunk flexion/extension range of motion (ROM) but the least abduction/adduction and medial/lateral (internal/external) rotation. Trunk ROM during gait was small (mean less than or equal to 12 degrees) and consistent with previous literature. Trunk range of motion relative to the room during stair climbing and descending was greater than trunk ROM during gait in all planes. The pelvis and trunk rotate in the transverse plane in greater synchrony during stair descending (mean = 8.1 degrees, SD = 5.6 degrees) than during gait (mean = 12.0 degrees, SD = 4.2 degrees). For all activities, trunk frontal and sagittal ROM relative to the pelvis was greater than that relative to the room coordinates. This finding suggests that trunk/pelvis coordination may be used to reduce potentially destabilizing anti-gravity trunk motions during daily activities. We conclude that upper-body kinematics relative to both pelvis and gravity during daily activities are important to locomotor control and should be considered in future studies of patients with locomotor disabilities.

Activities of Daily Living↗

HIV infected patients: correlation of cutaneous disease with degree of immunosuppression.

The AIDS epidemic has become a world-wide health problem since the disease was identified ten years ago. An HIV-dermatology outpatient clinic was established at the Albion Street Centre in Sydney to manage patients with cutaneous manifestations of AIDS. This study reviews the spectrum of skin disorders seen, and attempts to correlate skin disease with the degree of immunosuppression as reflected by CD4 or T helper lymphocyte counts, whereas previous reports have attempted to correlate skin disease with clinical signs and symptoms. Brief summaries of HIV disease and the cutaneous manifestations of AIDS are given.

Adult↗

hsp80 of Neurospora crassa: cDNA cloning, gene mapping, and studies of mRNA accumulation under stress.

Using mRNA isolated from Neurospora crassa mycelium, grown for 14 h at normal growth temperature of 28 degrees C, and heat shocked for 1 h at 48 degrees C, a cDNA library was prepared in the expression vector lambda gt11. Following immunoscreening of this library with a polyclonal antiserum raised against a 80-kilodalton heat-shock protein (HSP80), cDNA clones containing 1.1- and 1.4-kilobase inserts were selected. Analysis of the partial nucleotide sequence and the deduced amino acid sequence of the cDNA clones revealed a remarkable extent of homology with other eukaryotic stress-90 family proteins; 85% identity of the amino acid sequence with that of yeast HSP90(82) was seen. The C-terminal end of the sequence contained the MEEVD motif, characteristic of eukaryotic stress proteins with a predominantly cytosolic localization. The gene for N. crassa HSP80 was mapped to the right arm of linkage group V, using restriction fragment length polymorphism mapping. Its expression during heat shock and recovery was monitored by probing Northern blots of RNA isolated from mycelium grown under various stress conditions.

Amino Acid Sequence↗

Calcium oscillations in parotid acinar cells induced by microsomal Ca(2+)-ATPase inhibition.

Previous studies have demonstrated in single rat parotid acinar cells that the microsomal Ca(2+)-ATPase inhibitor thapsigargin mobilizes Ca2+ specifically from the inositol 1,4,5-trisphosphate (IP3)-sensitive Ca2+ store, activates plasma membrane Ca2+ permeability, and induces intracellular Ca2+ concentration ([Ca2+]i) oscillations that are quite similar to those activated by carbachol. Nevertheless, the IP3-sensitive Ca2+ store remains continuously depleted during thapsigargin-induced oscillations, indicating that this pool is not involved in the oscillation mechanism. To determine the specificity of thapsigargin's effects, in the present study we have examined the effects on [Ca2+]i in single rat parotid acinar cells of two other microsomal Ca(2+)-ATPase inhibitors, cyclopiazonic acid (CPA) and 2,5-di-tert-butyl-1,4-benzohydroquinone (BHQ), and compared them with the effects of thapsigargin in the same cells. Our results demonstrate that thapsigargin, CPA, and BHQ all similarly deplete the IP3-sensitive Ca2+ store specifically, activate plasma membrane Ca2+ influx, and induce [Ca2+]i oscillations, strongly suggesting that these agents have a specific inhibitory action on microsomal Ca(2+)-ATPase activity. BHQ, in addition, inhibits plasma membrane Ca2+ influx. The data lend strong support to a model in which the state of Ca2+ filling of the IP3-sensitive store regulates plasma membrane Ca2+ influx. These results suggest either that a Ca2+ pump is involved which is insensitive to structurally dissimilar inhibitors or that a Ca2+ pump is not involved in refilling of the Ca2+ pool involved in [Ca2+]i oscillations in these cells.

Animals↗

Histochemical and immunohistochemical characteristics of mast cells in nasal polyps.

In surgically excised nasal polyps, most epithelial mast cells were formalin sensitive, chloroacetate esterase (CAE) negative, and chymase negative. Thus, this represents a population of mast cells not identified by staining for CAE. On the other hand, most stromal mast cells were formalin resistant and CAE positive, and although there was some polyp-to-polyp variability in their content of neutral protease, most of these cells were positive for both tryptase and chymase. The percentage of metachromatic cells in the epithelium and the number of metachromatic cells per unit area of polyp tissue did not correlate with an index of allergy skin test reactivity or the serum IgE concentration. The percentage of mast cells surrounded by pericellular tryptase, suggesting activation/degranulation, was significantly higher in the stroma than in the epithelium. The findings demonstrate differences between the stroma and the epithelium in phenotype and state of activation of mast cells; these are postulated to be due to distinct microenvironmental factors that affect mast cells at these sites.

Acetates↗

Hepatotoxicity of amiodarone.

Amiodarone, a commonly used antiarrhythmic agent, has numerous adverse effects. The purpose of this case report is to highlight its hepatotoxicity, an unusual complication of long term amiodarone therapy. Our patient is a 76-year-old man with underlying ischaemic heart disease and recurrent ventricular tachycardia. Eleven months after commencing amiodarone, he developed asymptomatic raised aminotransferases which resolved following drug withdrawal. Amiodarone was then reintroduced and four years later, the patient developed hepatomegaly, worsening liver biochemistry and histopathological changes consistent with early cirrhosis. His symptoms improved following discontinuation of amiodarone. However, hepatomegaly and a low serum albumin still persist four years later.

Aged↗

Free cytoplasmic Ca2+ concentration oscillations in thapsigargin-treated parotid acinar cells are caffeine- and ryanodine-sensitive.

The microsomal Ca-ATPase inhibitor thapsigargin induces in rat salivary acinar cells [Ca2+]i oscillations which, though similar to those activated by agonists, are independent of inositol phosphates or inositol 1,4,5-trisphosphate (IP3)-sensitive intracellular Ca2+ stores (Foskett, J. K., Roifman, C., and Wong, D. (1991) J. Biol. Chem. 266, 2778-2782). To examine whether the oscillation mechanism resides in another, thapsigargin- and IP3-insensitive intracellular store, we examined the effects of caffeine and ryanodine, known modulators of Ca2+ release from sarcoplasmic reticulum in excitable cells. Oscillations were induced by caffeine (1-20 mM) in nonoscillating thapsigargin-treated acinar cells, which required the continued presence of caffeine, whereas caffeine was without effect or reduced oscillation amplitude in oscillating cells. Ryanodine (10-50 microM) inhibited oscillations in most of the cells. These results suggest that Ca2+ oscillations in parotid acinar cells are driven by periodic Ca2+ release from an IP3-insensitive Ca2+ store with properties similar to sarcoplasmic reticulum of excitable cells.

Animals↗

A long-term study of hepatitis C virus replication in non-A, non-B hepatitis.

BACKGROUND: Although antibodies to the hepatitis C virus (HCV) are known to be associated with non-A, non-B hepatitis, little is known about the pattern of HCV replication, its relation to antibody levels, and the clinical course of non-A, non-B hepatitis. METHODS: We measured HCV RNA in serial serum samples from five patients with post-transfusion non-A, non-B hepatitis who were followed for 10 to 14 years after transfusion. We also studied four chimpanzees that were experimentally infected with serum from four of these patients. Serum HCV RNA was detected by a "nested" polymerase-chain-reaction (PCR) assay that used two sets of primers derived from the third (NS3) and fourth (NS4) non-structural gene regions of the HCV genome. RESULTS: HCV sequences were detected by PCR in only two of the five patients and two of the four chimpanzees with the set of primers corresponding to the NS3 region, but in all five patients (and in all four chimpanzees) with the primers from the NS4 region. Serum HCV RNA was first detected within three weeks of transfusion in all five patients and within one week in three patients. The viremia lasted less than 4 months in the patient (and two chimpanzees) with acute, self-limited hepatitis, whereas it persisted for 10 to 14 years in the four patients (and for 1 and 3 years in two chimpanzees) with chronic non-A, non-B hepatitis. Antibodies to HCV were first detected at week 12 to 14; they disappeared after nine years in the patient with self-limited disease and became borderline after five years in one of the patients with chronic disease. CONCLUSIONS: During the early phase of primary HCV infection, there is a period of several months of sero-negativity during which HCV RNA is the only diagnostic marker of infection. The disappearance of HCV RNA from serum appears to correlate with the resolution of non-A, non-B hepatitis, whereas viremia persists in patients whose disease progresses to chronic hepatitis. In contrast, antibody levels do not necessarily remain elevated in patients with chronic disease.

Acute Disease↗

Synergistic effects of nerve growth factor and granulocyte-macrophage colony-stimulating factor on human basophilic cell differentiation.

We have recently shown that nerve growth factor (NGF) promotes human granulopoiesis, specifically augmenting basophilic cell differentiation observed in methylcellulose hematopoietic colony assays of human peripheral blood. Because the NGF effect was seen in the presence of conditioned medium derived from a human T-cell line (Mo-CM) containing granulocyte-macrophage colony-stimulating factor (GM-CSF), we examined interactions of purified NGF and recombinant human GM-CSF (rhGM-CSF) on granulocyte growth and differentiation. rhGM-CSF stimulated a dose-dependent increase in methylcellulose colony growth at concentrations between 0.1 U/mL and 10 U/mL, and in the presence of NGF at 500 ng/mL this effect was enhanced. The number of basophilic cell colony-forming units (CFU-Baso) and histamine-positive colonies increased synergistically when NGF was added to rhGM-CSF. Furthermore, because Mo-CM acts with sodium butyrate to promote basophilic differentiation of alkaline-passaged myeloid leukemia cells, HL-60, we also examined the interaction of NGF and Mo-CM or rhGM-CSF using this assay. In the presence of NGF, Mo-CM at concentrations of 0.5% to 20% vol/vol, and rhGM-CSF at concentrations of 0.1 U/mL to 100 U/mL synergistically increased histamine production by butyrate-induced, alkaline-passaged HL-60 cells; this was associated with the appearance of metachromatic, tryptase-negative, IgE receptor-positive cells. The effects of rhGM-CSF or Mo-CM were completely abrogated by a specific anti-rhGM-CSF neutralizing antibody in methylcellulose, with or without NGF; the NGF synergy with rhGM-CSF in the HL-60 assay was also inhibited by either anti-rhGM-CSF or anti-NGF antibody. These studies support the notion that differentiation in the basophilic lineage may be enhanced by NGF acting to increase the number of GM-CSF-responsive basophilic cell progenitors.

Basophils↗

Activation of calcium oscillations by thapsigargin in parotid acinar cells.

The tumor promoter thapsigargin releases Ca2+ from intracellular stores by specific inhibition of microsomal Ca-ATPase activity without inositol phosphate formation. Recent studies of the actions of thapsigargin support the concept that the level of Ca2+ within the inositol (1,4,5)-trisphosphate (IP3)-sensitive intracellular pool regulates the Ca2+ permeability of the plasma membrane. We examined the effects of thapsigargin on intracellular Ca2+ concentration ([Ca2+]i) in single rat parotid cells using digital fluorescence microscopy. In the absence of extracellular Ca2+ (Ca2+o), thapsigargin transiently increased [Ca2+]i. Following the thapsigargin-induced [Ca2+]i transient, carbachol in the continued absence of Ca2+o was unable to raise [Ca2+]i, indicating that thapsigargin mobilizes Ca2+ from the IP3-sensitive store. In the converse experiment, carbachol prevented a rise of [Ca2+]i by thapsigargin, suggesting that the IP3- and thapsigargin-sensitive Ca2+ pools are the same. Depletion of Ca2+ from the IP3-sensitive pool by thapsigargin enhanced plasma membrane Ca2+ permeability. Thapsigargin triggered sustained Ca2+ oscillations in Ca2(+)-containing medium which are highly reminiscent of agonist-induced oscillations in these cells. Carbachol addition rapidly raised IP3 levels during oscillations triggered by thapsigargin but did not elevate [Ca2+]i, indicating that the IP3-sensitive pool remains continuously depleted during [Ca2+]i fluctuations. The results from this study rule out the involvement of the IP3-sensitive pool in the mechanisms involved in thapsigargin-induced (and by analogy, agonist-induced) oscillations in parotid cells.

Animals↗