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Biomedical subjects

T Chang

Publications and source records attributed to T Chang.

At least 19 recordsLinked to original sources

Inactivation of histone H1 kinase by Ca2+ in rabbit oocytes.

The present study investigated the role of intracellular Ca2+ (Ca2+i) elevation on the inactivation of maturation promoting factor (MPF) in rabbit oocytes. The effects of the number of Ca2+ stimulations and of the amplitude of Ca2+i elevation on the profile of histone H1 kinase activity were determined. A Ca2+ stimulation consisted of transferring mature oocytes from culture medium to 0.3 M mannitol containing 0.1-1.0 mM CaCl2, and pulsing them at 1.25 kV/cm for 10 microseconds, or microinjecting 2-8 mM CaCl2 into the oocyte cytoplasm. The number of electrically-induced Ca2+ stimulations was varied, and amplitude of the Ca2+i rise was controlled by altering Ca2+ concentration in the pulsing medium or the injection pipette. Ca2+i concentration was determined with fura-2 dextran; oocytes were snap-frozen at indicated time points and assayed for H1 kinase activity. The activity was quantified by densitometry and expressed as a fraction of activity in nonstimulated oocytes. Electrically-mediated Ca2+i rises inactivated H1 kinase in a manner dependent on the number of Ca2+ stimulations. A single Ca2+ stimulation inactivated H1 kinase to 30-40% of its initial activity. However, H1 kinase inactivation was only transient, regardless of the amplitude of the electrically- or injection-mediated Ca2+i elevation. Increasing the number of Ca2+ stimulations helped to maintain H1 kinase activity at basal (pronuclear) levels. The results show the necessity of a threshold of Ca2+i concentration to trigger MPF inactivation, and suggest a role for the extended period of time over which Ca2+i oscillates at fertilization.

Animals

Factors involved in nuclear reprogramming during early development in the rabbit.

Mechanisms of nuclear reprogramming and assessment of potential malfunctions that could be deleterious for development were evaluated in rabbit zygotes, parthenotes, and nuclear transfer embryos by analysis of DNA replication, nucleolar fibrillarin label, and localization of nuclear material reactive to the MPM-2 antibody. Nuclear transfer embryos were derived from G1/early S-phase donor nuclei and MII oocytes. In nuclear transfer embryos, DNA rereplication was likely to have occurred because label was incorporated, possibly in the centromeric regions of the chromosomes, prior to premature chromosome condensation and again following pronuclear formation. In parthenotes, DNA replication began very late in the cell cycle, which may be due to deficiencies in the artificial activation stimulus. The presence of fibrillarin label in the nucleolus was used as an indication of nucleolar transcriptional activity. Fibrillarin label was absent in embryos of all types up to the 16-32-cell stage. Although fibrillarin reappeared in nuclear transfer and parthenote embryos at the appropriate stage, not all blastomeres showed label indicating impaired development in these embryos. Labelling of phosphorylated epitopes by MPM-2 antibody showed a change in pattern of labelling during early development. Early cleavage stage embryos did not exhibit labelling over the spindle poles as did blastomeres from 32-cell embryos and tissue culture cells. All cell types exhibited labelling during interphase as dots located primarily over the nucleus in blastomeres from 32-cell embryos and in tissue culture cells, together with cytoplasmic label in embryos at early cleavage stages. Nuclear transplant embryos had a normal pattern of MPM-2 label. In contrast, the appearance of MPM-2 label in parthenotes depended on the type of calcium stimulation. These results demonstrate defects in DNA synthesis, nucleolar activity, and specific phosphorylation events, likely resulting from an improper activation stimulus and chromosome condensation in the transplanted nucleus.

Animals

Granular cell tumour of the neurohypophysis.

Granular cell tumours of the neurohypophysis are very rare. Their aetiology and nature are uncertain. Most investigators consider them to arise from pituicytes or Schwann cells of the posterior lobe of the hypophysis. They are found most commonly in older people. A surgically proven symptomatic case is reported.

Adult

Embolization of carotid cavernous fistula by means of direct puncture through the superior orbital fissure.

PURPOSE: To embolize carotid cavernous fistulas (CCFs) by means of transorbital puncture of the cavernous sinus (CS) and the cavernous segment of the internal carotid artery (ICA) through the superior orbital fissure. MATERIALS AND METHODS: Five patients with CCF were treated with embolization of the CS, and six were treated with embolization of both the CS and the cavernous portion of the ICA after transorbital puncture. All except one had previously undergone occlusion of the ipsilateral proximal ICA before direct transorbital puncture. RESULTS: The fistulas in these cases were all obliterated completely. Only two patients had temporary ptosis. No other remarkable complications were noted. The patent ICA on the side of the fistula in one patient remained patent after embolization. CONCLUSION: Direct transorbital puncture through the superior orbital fissure is an alternate treatment for CCF, especially when the ipsilateral ICA has been occluded.

Adult

Chronically stressed wrists in adolescent gymnasts: MR imaging appearance.

PURPOSE: To investigate the magnetic resonance (MR) imaging appearance of a chronically stressed wrist and to assess the utility of MR imaging for evaluation of injuries to the growth plate. MATERIALS AND METHODS: Coronal T1-weighted spin-echo and gradient-echo MR images were obtained of 93 wrists in 47 high-risk gymnasts of a Chinese opera school. MR imaging and radiographic findings were correlated in 93 wrists. RESULTS: The major MR imaging abnormalities of 47 radii with abnormal radiographic findings were horizontal fractures (n = 23), physeal cartilage extension to metaphysis (n = 17), and physeal widening (n = 17). The major MR abnormalities of 46 radii with normal radiographs included physeal cartilage extension (n = 12), metaphyseal bone bruise (n = 8), and vertical fractures (n = 4). CONCLUSION: Physeal cartilage extension into the metaphysis represents a healing sign in chronically stressed adolescent wrists. MR imaging findings including horizontal fracture and physeal cartilage extension to the metaphysis suggest that physeal widening occurred secondary to metaphyseal injury.

Adolescent

Wrist injuries in adolescent gymnasts of a Chinese opera school: radiographic survey.

PURPOSE: To determine the prevalence of chronic wrist injuries among adolescent gymnasts and the consequences of repetitive stress. MATERIALS AND METHODS: Students of a Chinese opera school underwent radiography of both wrists and answered a questionnaire. They were separated into study (n = 261) and control (n = 63) groups according to participation in or abstinence from exercise training, respectively. They were further separated into fused and unfused physis subgroups. The ulnar variance was measured on posteroanterior radiographs. Abnormalities of distal radii were investigated. RESULTS: An increase in both mean ulnar variance and frequency of ulnar-plus variance was noted in the study subgroups. Fourteen (8.2%) of 170 wrists of the fused physis study subgroup had an exceedingly large ulnar-plus variance. Sixty-one (17.3%) of 352 wrists had abnormal morphology of the distal radii in the unfused physis study subgroup. Widening of the physis was the most common finding. CONCLUSION: Chronic, repetitive stress in the wrists of adolescent gymnasts results in a localized growth disturbance of the distal radius with resultant ulnar-plus variance. Stress injuries of the physis may lead to permanent sequelae, even in asymptomatic individuals.

Adolescent

Disposition of gabapentin (neurontin) in mice, rats, dogs, and monkeys.

Gabapentin, an analog of gamma-aminobutyric acid, exhibits anticonvulsant properties in both animal models and humans. Gabapentin pharmacokinetics was studied in laboratory animals using HPLC and radiometry. Oral bioavailability was 40% in monkeys administered 25 mg/kg, 79% in mice and rats receiving 50 mg/kg, and 80% in dogs administered 50 mg/kg. Binding to plasma proteins was < 3%. Maximum blood or plasma concentrations generally occurred within 2 hr of an oral dose. In rats and monkeys, increases in maximum plasma concentrations and/or areas under the curve were less than dose-proportional following oral administration, most likely because of saturable absorption. However, intravenous pharmacokinetics in rats were linear over the dosage range of 4-500 mg/kg. Mean intravenous elimination half-life was 1.7 hr in rats, 2.9 hr (14C only) in dogs, and 3.0 hr in monkeys. In rats and dogs, repeated administration did not alter gabapentin or 14C pharmacokinetics. Additionally, gabapentin did not induce hepatic cytochrome P450 monooxygenases in rats. There were no age- (rats only) or gender-associated changes in pharmacokinetic parameters. [14C]Gabapentin was extensively distributed to tissues. In the dog, gabapentin was metabolized to N-methylgabapentin (approximately 34% of dose); whereas metabolism in mouse, rat, and monkey was minimal (< 5%). The principal route of excretion was via urine. In summary, as an antiepileptic drug, gabapentin exhibited desirable pharmacokinetic properties, such as linear elimination kinetics, not highly bound to plasma proteins, not extensively metabolized, and not an inducer of hepatic cytochrome P450.

Acetates

Controlling chaos in the brain.

In a spontaneously bursting neuronal network in vitro, chaos can be demonstrated by the presence of unstable fixed-point behaviour. Chaos control techniques can increase the periodicity of such neuronal population bursting behaviour. Periodic pacing is also effective in entraining such systems, although in a qualitatively different fashion. Using a strategy of anticontrol such systems can be made less periodic. These techniques may be applicable to in vivo epileptic foci.

Action Potentials

Dephosphorylation of sperm midpiece antigens initiates aster formation in rabbit oocytes.

During fertilization in most mammals, the penetrating sperm organizes an aster of microtubules. We have investigated the mechanisms underlying this function of the sperm by a series of experiments based on microinjection of isolated sperm midpieces into unfertilized oocytes. These midpieces contain antigens recognized by the MPM-2 antibody. These antigens, which are absent from the rest of the tail fraction, correspond to three phosphorylated polypeptides of 77, 81, and 85 kDa. Dephosphorylation with alkaline phosphatase abolishes antigenicity on blots and in whole sperm. Reactivity to the antibody disappears between 1 and 3 hr after calcium stimulation of oocytes, following the decline in H1 kinase activity and coincident with aster formation. In unactivated oocytes, no aster forms and the antigen remains unchanged. MPM-2 treatment of midpieces prior to injection blocks their ability to form asters in oocytes activated by calcium stimulation. The epitope also disappears in 6-methyl-aminopurine-treated oocytes, implying that maintenance of the phosphorylated state requires kinase activity. A result that confirms this view is that sperm midpieces dephosphorylated by alkaline phosphatase can be rephosphorylated after injection into oocytes or by exposure in vitro to a Xenopus oocyte cytoplasmic fraction high in H1 kinase activity. We suggest that the microtubule nucleation activity of sperm midpieces after fertilization is triggered by the calcium-induced decrease in maturation promoting factor, which results in dephosphorylation of specific sperm centrosomal proteins.

Animals

Determination of 2,2-dimethyl-N-(2,4,6-trimethoxyphenyl) dodecanamide, CI-976, in rat plasma by reversed-phase high-performance liquid chromatography.

A quantitative reversed-phase high-performance liquid chromatographic procedure was developed to facilitate the preclinical development of a new Acyl-CoA:cholesterol acyltransferase inhibitor, CI-976 (I). This procedure has a lower quantitation limit of 0.06 micrograms/ml and a quantitation range of 0.06 to 8.0 micrograms/ml of I in rat plasma. The method was applied to pharmacokinetic and toxicokinetic studies of I in rat. With minor modifications, it has also been employed for analysis of I in human, monkey, and rabbit plasma.

Anilides

N-butyl-2-cyanoacrylate for embolisation of carotid aneurysm.

We report the use of an N-butyl-2-cyanoacrylate (NBCA) mixture for embolisation of six cases of carotid aneurysm after detachable balloons, and/or microcoils had been placed in the aneurysm. The mixture was injected into the aneurysm to prevent delayed bleeding or distal migration of the balloons, or microcoils. No subarachnoid haemorrhage or distal migration of the balloons or microcoils occurred up to 4.5 years after embolisation. Reflux of the NBCA mixture into the parent artery occurred in one patient, who had a neurological deficit which recovered in a month. NBCA mixture may be useful in embolisation of intracranial or skull base arterial aneurysms, for reducing the size of remaining lumen in an aneurysm at high risk of rebleeding which accommodate no more balloons or microcoils, or preventing possible delayed migration of balloons or microcoils. However, prevention of leakage of the mixture into the parent artery remains a problem.

Adult

Dual inhibitory mechanism of secretin action on acid secretion in totally isolated, vascularly perfused rat stomach.

BACKGROUND/AIMS: Secretin is an inhibitory hormone of gastric acid secretion. However, its inhibitory mechanism has not been well understood. Possible roles of both somatostatin and prostaglandins were investigated. METHODS: Totally isolated rat stomachs were vascularly perfused with Krebs-Ringer buffer containing 50 mumol/L isobutyl methylxanthine at 1.4 mL.min-1. Gastric lumen was perfused with 0.15 mol/L NaCl at 1.0 min.min-1. Effect of secretin in three different doses given intra-arterially on basal acid secretion and acid secretion stimulated by pentagastrin was studied. To determine roles of somatostatin and prostaglandins in the secretin-induced inhibition, an antisomatostatin serum and indomethacin were tested, and both somatostatin and prostaglandin E2 concentrations in portal venous effluent were determined by radioimmunoassay. RESULTS: Both basal- and pentagastrin-stimulated acid secretion were significantly inhibited by secretin. The inhibition was completely reversed by either indomethacin or antisomatostatin serum. Secretin significantly increased concentrations of both somatostatin and prostaglandin E2. Although indomethacin blocked the increase in prostaglandin E2, secretin-induced increase in prostaglandin E2 was not affected by antisomatostatin serum or was indomethacin influenced by somatostatin level. Finally, the inhibition by somatostatin of acid secretion was not affected by indomethacin. CONCLUSIONS: The inhibition of gastric acid secretion by secretin in rats is mediated by simultaneous releases of both somatostatin and prostaglandin E2, which independently inhibit gastric acid secretion.

Animals

Stochastic versus deterministic variability in simple neuronal circuits: I. Monosynaptic spinal cord reflexes.

Long time series of monosynaptic Ia-afferent to alpha-motoneuron reflexes were recorded in the L7 or S1 ventral roots in the cat. Time series were collected before and after spinalization at T13 during constant amplitude stimulations of group Ia muscle afferents in the triceps surae muscle nerves. Using autocorrelation to analyze the linear correlation in the time series demonstrated oscillations in the decerebrate state (4/4) that were eliminated after spinalization (5/5). Three tests for determinism were applied to these series: 1) local flow, 2) local dispersion, and 3) nonlinear prediction. These algorithms were validated with time series generated from known deterministic equations. For each experimental and theoretical time series used, matched time-series of stochastic surrogate data were generated to serve as mathematical and statistical controls. Two of the time series collected in the decerebrate state (2/4) demonstrated evidence for deterministic structure. This structure could not be accounted for by the autocorrelation in the data, and was abolished following spinalization. None of the time series collected in the spinalized state (0/5) demonstrated evidence of determinism. Although monosynaptic reflex variability is generally stochastic in the spinalized state, this simple driven system may display deterministic behavior in the decerebrate state.

Afferent Pathways

Stochastic versus deterministic variability in simple neuronal circuits: II. Hippocampal slice.

Long time series of Schaffer collateral to CA1 pyramidal cell presynaptic volleys (stratum radiatum) and population spikes (stratum pyramidale) were evoked (driven) in rat hippocampal slices. From the driven CA1 region in normal [K+] perfusate, both population spike amplitude and an input-output function consisting of population spike amplitude divided by the presynaptic volley amplitude were analyzed. Raising [K+] in the perfusion medium to 8.5 mM, slices were induced to spontaneously burst fire in CA3 and long time series of inter-burst intervals were recorded. Three tests for determinism were applied to these series: a discrete adaptation of a local flow approach, a local dispersion approach, and nonlinear prediction. Surrogate data were generated to serve as mathematical and statistical controls. All of the population spike (6/6) and input-output (6/6) time series from the normal [K+] driven circuitry were stochastic by all three methods. Although most of the time series (5/6) from the autonomously bursting high [K+] state failed to demonstrate evidence of determinism, one (1/6) of these time series did demonstrate significant determinism. This single instance of predictability could not be accounted for by the linear correlation in these data.

Algorithms

Intestinal schistosomiasis japonica: CT-pathologic correlation.

PURPOSE: To study the pathologic basis of intestinal wall calcification caused by Schistosoma japonicum visualized with computed tomography (CT). MATERIALS AND METHODS: Twelve patients underwent CT of the abdomen to detect what pathologic examination proved to be schistosomiasis japonica. Eight intestinal specimens from five of the patients were subjected to radiography, and the pathologic and radiographic findings were correlated. RESULTS: CT demonstrated curvilinear or nodular calcification in the colon in 11 patients, in the appendix in two, and in the distal ileum in one. In five patients, calcifications resembling tram tracks were found in the sigmoid colon. Pathologic examination of the specimens showed calcified eggs of S japonicum deposited more extensively in the submucosa and subserosa than in the muscularis propria, which led to the tram-track appearance. CONCLUSION: The extensive curvilinear or tram-track calcification found in the colon in patients with schistosomiasis japonica is calcification of deposited eggs.

Aged

Fluctuations of excitability in the monosynaptic reflex pathway to lumbar motoneurons in the cat.

1. It is well known that the amplitude of successive monosynaptic reflexes (MSR), elicited by afferent stimuli of constant strength, fluctuate from trial to trial. Previous evidence suggests that such excitability fluctuations within the motor pool can be introduced either pre- and/or postsynaptically. Using unanesthetized decerebrate or decerebrate/spinal cats, we attempted to evaluate the relative importance of pre- and postsynaptic mechanisms to MSR variability and the potential contribution of changes in the identities of responding motoneurons to such variability. 2. Comparisons between the MSR amplitude, measured in a severed ventral root, and the probability of firing of up to three individual motoneurons in fine filaments teased from the same root, confirmed that both correlated and uncorrelated fluctuations of motoneuron excitability are involved in MSR variability. Linear regression analysis from concurrent intracellular recordings from homonymous motoneurons showed that the MSR fluctuations were correlated with the variations in membrane potential baseline, as well as with the fluctuations in the monosynaptic excitatory postsynaptic potential peak amplitude. In all 11 cases tested, the former correlation was stronger than the latter. 3. Stimulation of the caudal cutaneous sural nerve (CCS) was used to alter the postsynaptic potential background on which triceps surae (GS) MSRs were generated. The interval chosen between CCS conditioning and the GS stimulation excluded the involvement of presynaptic inhibition. When conditioned by preceding CCS stimulation, GS population MSRs generally (8/9 cases tested) increased in amplitude without much change in their overall variance. However, the individual motoneurons that contributed to the population responses did show changes in both relative excitability and in the uncorrelated component of their response variance. About half of the concurrently recorded motoneurons (6/13) showed a decrease in relative excitability after CCS conditioning, 5/13 showed an increase, and 2/13 were unchanged. Comparison of unit and population responses indicated that the identities of the motoneurons that responded at any given level of population response were quite different with and without CCS conditioning. 4. High-frequency stimulation of Ia fibers was used to alter the state of presynaptic Group Ia-afferents that produced population MSRs. Post tetanic potentiation following high-frequency stimulation did not greatly alter the variance of population MSRs or ratio of correlated and uncorrelated fluctuations in MSR responses among individual motoneurons within the responding population. However, intratetanic depression and posttetanic potentiation of population MSRs were accompanied by marked shifts in individual motoneuron excitability relative to the population response, again indicated that changes in the identities of responding motoneurons contributes to population response fluctuations.(ABSTRACT TRUNCATED AT 400 WORDS)

Afferent Pathways

Soft tissue anchor systems.

The concept of soft tissue attachment and reattachment has been addressed over the years through a variety of surgical techniques. This includes tendons and ligaments that have been detached both surgically and traumatically from their osseous origins or insertions. This study is designed to provide the reader with a comprehensive overview of current commercially available devices. Detailed descriptions of the various devices are provided along with a discussion of the advantages and disadvantages of each. Their application and use in reconstructive foot and ankle surgery are also discussed.

Ankle