Biomedical subjects

C L Huang

Publications and source records attributed to C L Huang.

At least 19 recordsLinked to original sources

PubMed2005

Botulinum toxins inhibit the antidiuretic hormone (ADH)-stimulated increase in rabbit cortical collecting-tubule water Permeability.

The mammalian renal collecting duct increases its water permeability in response to antidiuretic hormone (ADH). ADH causes cytoplasmic endosomes containing the water channel, aquaporin 2 (AQP 2), to fuse with the apical membrane so that the water permeability of the tubule increases many times above baseline. SNARE proteins are involved in the docking and fusion of vesicles with the cell membrane in neuron synapses. Whether these proteins are involved in the fusion of vesicles to the cell membrane in other tissues is not entirely clear. In the present study, we examined the role of SNARE proteins in the insertion of water channels in the collecting-duct response to ADH by using botulinum toxins A, B and C. Toxins isolated from clostridium botulinum are specific proteases that cleave different SNARE proteins and inactivate them. Tubules were perfused in vitro with botulinum toxin in the perfusate (50 nM for A and B and 15 nM for C). ADH (200 pM) was then added to the bath after baseline measurements of osmotic water permeability (P(f)) and the change in P(f) was followed for one hour. Botulinum toxins significantly inhibited the maximum P(f) by approximately 50%. Botulinum toxins A and C also decreased the rate of rise of P(f). Thus, SNARE proteins are involved in the insertion of the water channels in the collecting duct.

Animals↗

PubMed2004

Factors associated with women's and children's body mass indices by income status.

OBJECTIVE: To describe associations between eating behaviors, dietary intake, physical activity, attitudes toward diet and health, sociodemographic variables and body mass index (BMI) among women and children, and differences by household income. DESIGN: Data from the 1994-1996 Continuing Survey of Food Intakes by Individuals (CSFII) and the Diet and Health Knowledge Survey (DHKS) were examined using multivariate regression to estimate the associations between BMI and behavioral and environmental variables among women and children. SUBJECTS: CSFII 1994-1996 is representative of the US population. DHKS surveyed CSFII respondents 20 y of age and over. Our samples consisted of 2419 adult women and 1651 school-age children. MEASUREMENTS: CSFII respondents reported 24 h recalls of all food intakes on 2 nonconsecutive days and their personal and household characteristics, including self-reported height and weight. DHKS collected data on knowledge and attitudes toward dietary guidance and health from CSFII adult respondents. RESULTS: Significant correlations between women's BMI and age, race, dietary patterns, TV watching, and smoking was observed among women from both low- and high-income households. Beverage consumption, eating out, the importance of maintaining healthy weight, and exercise were correlated with BMI only among women from high-income households. Among children, age, race, income, and mother's BMI were significantly correlated with child BMI. CONCLUSIONS: Among women, the associations between some behavioral and environmental factors and BMI differ by household income. Intervention programs need to target specific eating and physical activity behaviors to promote a healthy body weight.

Adult↗

PubMed2001

Effects of premature stimulation on HERG K(+) channels.

1. The unusual kinetics of human ether-à-go-go-related gene (HERG) K(+) channels are consistent with a role in the suppression of arrhythmias initiated by premature beats. Action potential clamp protocols were used to investigate the effect of premature stimulation on HERG K(+) channels, transfected in Chinese hamster ovary cells, at 37 degrees C. 2. HERG K(+) channel currents peaked during the terminal repolarization phase of normally paced action potential waveforms. However, the magnitude of the current and the time point at which conductance was maximal depended on the type of action potential waveform used (epicardial, endocardial, Purkinje fibre or atrial). 3. HERG K(+) channel currents recorded during premature action potentials consisted of an early transient outward current followed by a sustained outward current. The magnitude of the transient current component showed a biphasic dependence on the coupling interval between the normally paced and premature action potentials and was maximal at a coupling interval equivalent to 90 % repolarization (APD(90)) for ventricular action potentials. The largest transient current response occurred at shorter coupling intervals for Purkinje fibre (APD(90) - 20 ms) and atrial (APD(90) - 30 ms) action potentials. 4. The magnitude of the sustained current response following premature stimulation was similar to that recorded during the first action potential for ventricular action potential waveforms. However, for Purkinje and atrial action potentials the sustained current response was significantly larger during the premature action potential than during the normally paced action potential. 5. A Markov model that included three closed states, one open and one inactivated state with transitions permitted between the pre-open closed state and the inactivated state, successfully reproduced our results for the effects of premature stimuli, both during square pulse and action potential clamp waveforms. 6. These properties of HERG K(+) channels may help to suppress arrhythmias initiated by early afterdepolarizations and premature beats in the ventricles, Purkinje fibres or atria.

Action Potentials↗

PubMed2001

Detection of pharmacologically mediated changes in cerebral activity by functional magnetic resonance imaging: the effects of sulpiride in the brain of the anaesthetised rat.

Blood oxygenation level dependent (BOLD) contrast functional magnetic resonance imaging (fMRI) was used to study the effects of the D(2)-like receptor selective antagonist, sulpiride, at 2 Tesla in the brain of the alpha-chloralose anaesthetised rat. Region of interest (ROI) analysis indicated significant (P<0.05) bilateral increases in BOLD signal intensity in the frontal cortex following a single administration of sulpiride (10 mg/kg i.v.). BOLD signal changes were slow in onset and increased gradually during the experiment, reaching 8.0+/-0.5% (mean+/-S.E.M.) above pre-injection control values 165 min after drug administration. Signal increases remained high at the experiment end (3 h post sulpiride administration). Sulpiride (30 mg/kg i.v.) had a similar effect in the frontal cortex, increasing signal 5.2+/-1.8% above control values by 174 min; its effects were, however, more variable between rats, and were not statistically significant. Sulpiride (3 mg/kg i.v.) had no significant effect upon BOLD signal intensity in any brain region. No dose of sulpiride resulted in any significant BOLD signal changes in the striatum or cerebellum. These data are supportive of the notion that sulpiride causes an increase in frontal dopaminergic function by antagonism of presynaptically located dopamine D(2) receptors in this brain region, consistent with its therapeutic action. Furthermore, the utility of BOLD contrast fMRI as a means of detecting changes in neuronal activity contingent upon the administration of a psychoactive pharmacological agent has been demonstrated.

Animals↗

PubMed2001

Calcium waves induced by hypertonic solutions in intact frog skeletal muscle fibres.

1. Regenerative Ca2+ waves and oscillations indicative of calcium-induced calcium release (CICR) activity were induced in fully polarized, fluo-3-loaded, intact frog skeletal muscle fibres by exposure to hypertonic Ringer solutions. 2. The calcium waves persisted in fibres exposed to EGTA-containing solutions, during sustained depolarization of the membrane potential or following treatment with the dihydropyridine receptor (DHPR)-blocker nifedipine. 3. The waves were blocked by the ryanodine receptor (RyR)-specific agents ryanodine and tetracaine, and potentiated by caffeine. 4. In addition to these pharmacological properties, the amplitudes, frequency and velocity of such hypertonicity-induced waves closely resembled those of Ca2+ waves previously described in dyspedic skeletal myocytes expressing the cardiac RyR-2. 5. Quantitative transmission and freeze-fracture electronmicroscopy demonstrated a reversible cell shrinkage, transverse (T)-tubular luminal swelling and decreased T-sarcoplasmic reticular (SR) junctional gaps in fibres maintained in and then fixed using hypertonic solutions. 6. The findings are consistent with a hypothesis in which RyR-Ca2+ release channels can be partially liberated from their normal control by T-tubular DHPR-voltage sensors in hypertonic solutions, thereby permitting CICR to operate even in such fully polarized skeletal muscle fibres.

Anesthetics, Local↗

PubMed2001

Normal conduction of surface action potentials in detubulated amphibian skeletal muscle fibres.

1. The influence of the transverse (T) tubules on surface action potential conduction was investigated by comparing electrophysiological and confocal microscopic assessments of tubular changes in osmotically shocked and control fibres from frog sartorius muscle. 2. The membrane-impermeant fluorescent dye, di-8-ANEPPs spread readily from the bathing extracellular solution into the tubular membranes in control, intact fibres. Prior exposure of muscles to a hypertonic glycerol-Ringer solution, its replacement by an isotonic Ca(2+)-Mg(2+) Ringer solution and cooling sharply reduced such access. In contrast, dye application in the course of this osmotic shock procedure stained the large tubular vacuoles hitherto associated with successful muscle detubulation. 3. Conduction velocities in intact, control fibres (1.91 +/- 0.048 m s(-1), mean +/- S.E.M., n = 32 fibres) agreed with earlier values reported at room temperature (18-21 degrees C) and were unaffected by prior episodes of steady cooling to 8-10 degrees C (1.91 +/- 0.043 m s(-1), n = 30). 4. Cooling to 11.5 degrees C reduced these velocities (1.47 +/- 0.081 m s(-1), n = 25) but action potential waveforms still included early overshoots and the delayed after-depolarizations associated with tubular electrical activity. 5. In contrast, action potentials from cooled, superficial fibres in osmotically shocked muscles lacked after-depolarization phases implying tubular detachment. Their mean conduction velocities (1.62 +/- 0.169 m s(-1), n = 25) were not significantly altered from values obtained in untreated controls or in intact fibres in muscle similarly treated with glycerol, in direct contrast to earlier results. 6. Cooling produced similar reductions in maximum rates of voltage change dV/dt in action potentials from all fibre groups with lower rates of change shown by detubulated fibres. 7. Use of an antibody to a conserved epitope of the alpha-subunit of voltage-gated sodium channels suggested a concentration of sodium channels close to the mouths of the T tubules. 8. These electrophysiological and anatomical findings are consistent with a partial independence of electrical events in the transverse tubules from those responsible for the rapid conduction of surface regenerative activity. 9. The findings are discussed in terms of a partial separation of the electrical activity propagated over the surface membrane, from the initiation of propagated activity within the T tubules, by the triggering of the sodium channels clustered selectively around the mouths of the T tubules.

Action Potentials↗

PubMed2001

The association of K-ras gene mutation and vascular endothelial growth factor gene expression in pancreatic carcinoma.

BACKGROUND: Previously, the authors reported the role of the vascular endothelial growth factor (VEGF) as an angiogenic factor in 40 patients with pancreatic carcinoma. In this study, they investigated the mechanism underlying the regulation of VEGF gene expression and evaluated VEGF expression and K-ras gene status in 48 patients with pancreatic carcinoma. METHODS: The authors used quantitative reverse transcriptase-polymerase chain reaction analysis and direct sequencing techniques for a retrospective study of VEGF gene expression and K-ras gene status in tumor tissue samples from 48 patients with pancreatic carcinoma. Immunohistochemistry also was used to investigate VEGF protein expression. RESULTS: Thirty-one tumors (64.6%) were evaluated with high VEGF expression, and 17 tumors (35.4%) were evaluated with low VEGF expression. Of the 48 primary pancreatic tumors studied, 33 tumors (68.8%) contained mutations of the K-ras gene. There was a significant correlation between VEGF expression and K-ras status. Twenty-five of 33 tumors (75.8%) with mutant K-ras genes showed high VEGF expression, whereas only 6 of 15 tumors with the wild type K-ras (40.0%) showed high VEGF expression (P = 0.038). The mean (+/- standard error) VEGF conservation rate for the 33 tumors with mutant K-ras was 1.839 +/- 1.241, and that for the 15 tumors with wild type K-ras was 1.057 +/- 0.983 (P = 0.037). Furthermore, the median survival for patients with mutant K-ras was shorter than for those with wild type K-ras (10.6 months vs. 27.6 months, respectively; P = 0.026), whereas the median survival for patients with high VEGF expression was shorter compared with that for patients with low VEGF expression (9.5 months vs. 26.4 months, respectively; P = 0.002). Cox regression model analysis indicated that only the VEGF status was a significant factor for prognosis (P = 0.024). Other variables, i.e., K-ras status, histopathologic tumor grade, tumor status, lymph node status, metastatic status, gender, and age at surgery, were not significant. CONCLUSIONS: The results of this study suggest that K-ras oncogene mutation may be associated with VEGF expression and that patients with pancreatic carcinoma who have high VEGF expression are associated with a poor prognosis.

Biomarkers, Tumor↗

PubMed2001

Identification and characterization of a sodium/calcium exchanger, NCX-1, in osteoclasts and its role in bone resorption.

We provide the first demonstration for a Na+/Ca2+ exchanger, NCX-1, in the osteoclast. We speculate that by using Na+ exchange, NCX-1 couples H+ extrusion with Ca2+ fluxes during bone resorption. Microspectrofluorimetry of fura-2-loaded osteoclasts revealed a rapid and sustained, but reversible, cytosolic Ca2+ elevation upon Na+ withdrawal. This elevation was abolished by the cytosolic introduction (by gentle permeabilization) of a highly specific Na+/Ca2+ exchange inhibitor peptide, XIP, but not its inactive analogue, sXIP. Confocal microscopy revealed intense plasma membrane immunofluorescence with an isoform-specific monoclonal anti-NCX-1 antibody applied to gently permeabilized osteoclasts. Electrophysiological studies using excised outside-in membrane patches showed a low-conductance, Na+-selective, dichlorobenzamil-sensitive, amiloride-insensitive channel that we tentatively assigned as being an NCX. Finally, to examine for physiological relevance, an osteoclast resorption (pit) assay was performed. There was a dramatic reduction of bone resorption following NCX-1 inhibition by dichlorobenzamil and XIP (but not with S-XIP). Together, the results suggest that a functional NCX, likely NCX-1, is involved in the regulation of osteoclast cytosolic Ca2+ and bone resorption.

Animals↗

PubMed2001

Charge movements in intact amphibian skeletal muscle fibres in the presence of cardiac glycosides.

1. Intramembrane charge movements were examined in intact voltage-clamped amphibian muscle fibres following treatment with cardiac glycosides in the hypertonic gluconate-containing solutions hitherto reported to emphasise the features of q(gamma) at the expense of q(beta) charge. 2. The application of chlormadinone acetate (CMA) at concentrations known selectively to block Na(+)-K(+)-ATPase conserved the steady-state voltage dependence of intramembrane charge, contributions from delayed (q(gamma)) charging transients, and their inactivation characteristics brought about by shifts in holding potential. 3. The addition of either ouabain (125, 250 or 500 nM) or digoxin (5 nM) at concentrations previously reported additionally to influence excitation-contraction coupling similarly conserved the steady-state charge-voltage relationships, Q(V), in fully polarised fibres to give values of maximum charge, Q(max), transition voltage, V*, and steepness factor, k, that were consistent with a persistent q component as reported on earlier occasions (Q(max) approximately = 25-27 nC F-1, V* approximately = -45 to -50 mV, k approximately = 7-9 mV). 4. In both cases shifts in holding potential from -90 to -50 mV produced a partial inactivation that separated steeply and more gradually voltage-dependent charge components in agreement with previous characterisations. 5. However, charge movements that were observed in the presence of either digoxin or ouabain were monotonic decays in which delayed (q(gamma)) transients could not be distinguished from the early charging records. These features persisted despite the further addition of chlormadinone acetate over a 10-fold concentration range (5-50 microM) known to displace ouabain from the Na(+)-K(+)-ATPase. 6. Ouabain (500 nM) restored the steady-state charge movement that was previously abolished by the addition of 2.0 mM tetracaine in common with previous results of using ryanodine receptor (RyR)-specific agents. 7. Perchlorate (8.0 mM) restored the delayed 'on' relaxations and increased the prominence of the 'off' decays produced by q(gamma) charge following treatment with cardiac glycosides. This was accompanied by a negative (approximately 10-15 mV) shift in the steady-state charge-voltage relationship but an otherwise conserved maximum charge, Q(max), and steepness factor, k, in parallel with previously reported effects of perchlorate following treatments with RyR-specific agents. 8. The features of cardiac glycoside action thus parallel those of other agents that act on RyR-Ca(2+) release channels yet influence the kinetics but spare the steady-state properties of intramembrane charge.

Animals↗

PubMed2001

Proteolytic activation of ETK/Bmx tyrosine kinase by caspases.

Etk/Bmx is a member of the Btk/Tec family of kinases, which are characterized by having a pleckstrin homology domain at the N terminus, in addition to the Src homology 3 (SH3), SH2, and the catalytic domains, shared with the Src family kinases. Etk, or Btk kinases in general, has been implicated in the regulation of apoptosis. To test whether Etk is the substrate for caspases during apoptosis, in vitro translated [(35)S]methionine-labeled Etk was incubated with different apoptotic extracts and recombinant caspases, respectively. Results showed that Etk was proteolyzed in all conditions tested with identical cleavage patterns. Caspase-mediated cleavage of Etk generated a C-terminal fragment, containing the complete SH2 and tyrosine kinase domains, but without intact pleckstrin homology and SH3 domains. This fragment has 4-fold higher kinase activity than that of the full-length Etk. Ectopic expression of the C-terminal fragment of Etk sensitized the PC3 prostate cancer cells to apoptosis in response to apoptosis-inducing stimuli. The finding, together with an earlier report that Etk is potentially antiapoptotic, suggests that Etk may serve as an apoptotic switch, depending on the forms of Etk existing inside the cells. To our knowledge, this is the first case where the activity of a tyrosine kinase is induced by caspase cleavage.

Apoptosis↗

PubMed2001

Activation of protein kinase A and atypical protein kinase C by A(2A) adenosine receptors antagonizes apoptosis due to serum deprivation in PC12 cells.

We found in the present study that stimulation of A(2A) adenosine receptors (A(2A)-R) prevents apoptosis in PC12 cells. This A(2A)-protective effect was blocked by protein kinase A (PKA) inhibitors and was not observed in a PKA-deficient PC12 variant. Stimulation of PKA also prevented apoptosis, suggesting that PKA is required for the protective effect of A(2A)-R. A general PKC inhibitor, but not down-regulation of conventional and novel PKCs, readily blocked the protective effect of A(2A)-R stimulation and PKA activation, suggesting that atypical PKCs (aPKCs) serve a critical role downstream of PKA. Consistent with this hypothesis, stimulation of A(2A)-R or PKA enhanced nuclear aPKC activity. In addition, the A(2A)-protective effect was blocked by a specific inhibitor of one aPKC, PKCzeta, whereas overexpression of a dominant-positive PKCzeta enhanced survival. In contrast, inhibitors of MAP kinase and phosphatidylinositol 3-kinase did not modulate the A(2A)-protective effect. Dominant-negative Akt also did not alter the A(2A)-protective effect, whereas it significantly reduced the protective action of nerve growth factor. Collectively, these data suggest that aPKCs can function downstream of PKA to mediate the A(2A)-R-promoted survival of PC12 cells. Furthermore, the results indicate that different extracellular stimuli can employ distinct signaling pathways to protect against apoptosis induced by the same insult.

Adenosine↗

PubMed2001

Diffusion-weighted MRI used to detect in vivo modulation of cortical spreading depression: comparison of sumatriptan and tonabersat.

Spreading cortical depolarization and depression of electroencephalographic activity (SD) may underlie the aura and spreading neurovascular events of migraine. Cortical depolarization may also precipitate the progressive development of cerebral pathology following ischemia. However, data on SD in the human brain are sparse, most likely reflecting the technical difficulties involved in performing such clinical studies. We have previously shown that the transient cerebral water disturbances during SD can be quantitatively investigated in the gyrencephalic brain using repetitive diffusion-weighted magnetic resonance imaging (DWI). To investigate whether DWI could detect modulation of the spatiotemporal properties of SD in vivo, the effects of the antimigraine drug sumatriptan (0.3 mg/kg iv) and the novel anticonvulsant tonabersat (10 mg/kg ip) were evaluated in the cat brain. Supporting previous findings, sumatriptan did not affect the numbers of events (range, 4-8), the duration of SD activity (39.8 +/- 4.4 min, mean +/- SEM), and event velocity (2.2 +/- 0.4 mm min(-1)); tonabersat significantly reduced SD event initiation (range, 0-3) and duration (13.2 +/- 5.0 min) and increased primary event velocity (5.4 +/- 0.7 mm min(-1)). However, both drugs significantly decreased, by >50%, the spatial extent of the first KCl-evoked SD event, and sumatriptan significantly increased event propagation across the suprasylvian sulcus (5.5 +/- 0.6 vs 2.4 +/- 0.4 events in controls). These results demonstrate (1) the feasibility of using DWI to evaluate therapeutic effects on SD, and (2) that sumatriptan may directly modulate the spatial distribution of SD activity in the gyrencephalic brain.

Animals↗

PubMed2001

Cortical spreading depression and migraine: new insights from imaging?

The possibility that spreading depression (SD) of cortical activity, a phenomenon observed in all vertebrates, causes the aura of migraine remains an open question in spite of nearly half a century of investigation. SD is also thought to be associated with the progressive neuronal injury observed during cerebral ischaemia. Thus, the ability to detect and investigate SD in humans might prove clinically significant. Animal studies of cortical spreading depression (CSD) have benefited greatly from the advent of relatively non-invasive imaging techniques. The use of these new imaging techniques for clinical studies will accelerate progress in this area of neurobiology.

Animals↗

PubMed2001

Mapping of brain activation in response to pharmacological agents using fMRI in the rat.

Functional MRI (fMRI) was used to investigate the effects of psychotropic compound activity in the rat brain in vivo. The effects of dizocilpine (MK-801) an N-methyl-D-aspartate receptor antagonist and m-chlorophenylpiperazine (mCPP), a 5-HT(2b/2c)-receptor agonist on rat brain activity were investigated over a time interval of about 1 h and the results were compared to published glucose utilisation and cerebral blood flow data. Signal magnitude increases were observed predominantly in limbic regions following MK-801 administration (0.5 mg/kg i.v) whereas signal decreases were restricted to neocortical areas; a characteristic, time dependent pattern of regional changes evolved from the thalamic nuclei to cortical regions. In contrast, mCPP (25 mg/kg i.p) produced gradual signal intensity increases in limbic and motor regions with signal decreases restricted to the visual, parietal and motor cortices. The results from both compounds show remarkable similarity with autoradiographic measurements of cerebral blood flow and glucose uptake. These experiments suggest that the spatio-temporal capabilities of fMRI may be applied to the in vivo investigation of psychoactive compound activity with potential for clinical applications.

Animals↗

PubMed2001

MRI analysis of right ventricular function in normal and spontaneously hypertensive rats.

Right ventricular structure and function were characterized in spontaneously hypertensive rats (SHR) using non-invasive magnetic resonance imaging (MRI) techniques. These studies therefore complement previous reports preoccupied with left ventricular changes associated with this condition. Eight SHR and eight control normotensive Wistar-Kyoto (WKY) rats were each subdivided into equal age-matched groups of 8 and 12 weeks. The right ventricle was imaged through a series of twelve contiguous 1.37-1.75 mm transverse sections at twelve equally spaced time-points that covered both systole and most of diastole thereby completely reconstructing right ventricular anatomy. This gave measurements of right ventricular myocardial mass that were consistent through all twelve time-points in all four experimental groups throughout their cardiac cycles. However, spontaneous hypertension increased this right ventricular myocardial mass, as well as the end-diastolic (EDV) and end-systolic volumes (ESV). Although stroke volume (SV) was conserved, decreases in ejection fraction (EF), a positive shift in the relationship between SV and EDV, and reduced indices of systolic ejection rates in SHR rats compared with the age-matched normal WKY controls indicated significant systolic dysfunction. Additionally, reductions in the rates of diastolic relaxation suggested the onset of diastolic dysfunction. Thus, the non-invasive nature of MRI has made it possible for the first time to demonstrate alterations in structure of the right ventricle and in quantitative indicators of its systolic and diastolic function in the SHR model of hypertension.

Animals↗

PubMed2001

Investigation of feline brain anatomy for the detection of cortical spreading depression with magnetic resonance imaging.

Cortical spreading depression (CSD) and peri-infarct depolarisation (PID) are related phenomena that have been associated with the human clinical syndromes of migraine (CSD), head injury and stroke (PID). Nevertheless the existence of CSD in man remains controversial, despite the detection of this phenomenon in the brains of most, if not all, other animal species investigated. This failure to unambiguously detect CSD clinically may be at least partly due to the anatomically complex, gyrencephalic structure of the human brain. This study was designed to establish conditions for the study of CSD in the brain of a gyrencephalic species using the noninvasive technique of magnetic resonance imaging (MRI). The 3-dimensional (3D) gyrencephalic anatomy of the cat brain was examined to determine the imaging conditions necessary to detect CSD events. Orthogonal transverse, sagittal and horizontal T1-weighted image slices showed that the marginal and suprasylvian gyri were the most appropriate cortical structures to study CSD. This was in view of (1) their simple geometry: (2) their lengthy extent of grey matter orientated rostrocaudally in the cortex: (3) their separation by a sulcus across which CSD spread could be studied and (4) the discontinuity in the grey matter in these regions between the right and left hemispheres dorsal to the corpus callosum. The structure suggested by the T1-weighted images was corroborated by systematic diffusion tensor imaging to map the fractional anisotropy and diffusion trace. Thus a single horizontal image plane could visualise the neighbouring suprasylvian and marginal gyri of both cerebral hemispheres, whereas its complex shape and position ruled out the ectosylvian gyrus for CSD studies. With the horizontal imaging plane, CSD events were reproducibly detected by animating successive diffusion-weighted MR images following local KCl stimulation of the cortical surface. In single image frames, CSD detection and characterisation required image subtraction or statistical mapping methods that, nevertheless, yielded concordant results. In repeat experiments, CSD events were qualitatively similar in appearance whether elicited by sustained or transient KCl applications. Our experimental approach thus successfully describes cat brain anatomy in vivo, and elucidates the necessary conditions for the application of MRI methods to detect CSD propagation.

Animals↗

PubMed2001

Regulation of ROMK trafficking and channel activity.

ROMK potassium channels are present in the thick ascending limbs and cortical collecting ducts of the kidney and are responsible for potassium ion efflux in these segments. ROMK channels are regulated by multiple signalling pathways. This review focuses on recent advances in the regulation of ROMK channels by phosphatidylinositol-4,5-bisphosphate and by membrane trafficking. Relevant publications on the related inward rectifier potassium channels will also be discussed.

Animals↗

PubMed2001

MR diffusion tensor imaging of white matter tract disruption in stroke at 3 T.

Recent advances in MR diffusion weighted imaging (DWI) enable the identification of anisotropic white matter tracts with diffusion tensor imaging (DTI). We aimed to use a novel DTI technique to safely study patients with recent stroke in a high field (3 T) MR machine with its intrinsically higher spatial resolution and signal-to-noise ratio. Of ten patients studied, six had disruption of white matter tracts as determined by DTI. A further patient had distortion of white matter tracts around an infarct rather than actual disruption of the tracts themselves. The lack of tract destruction may imply a beneficial prognosis, information that is not available with conventional DWI.

Adult↗