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Biomedical subjects

C Y Tang

Publications and source records attributed to C Y Tang.

At least 37 records · Page 2Linked to original sources

Direct interaction of two homeoproteins, homothorax and extradenticle, is essential for EXD nuclear localization and function.

The Drosophila Homothorax (HTH) and Extradenticle (EXD) are two homeoproteins required in a number of developmental processes. EXD can function as a cofactor to Hox proteins. Its nuclear localization is dependent on HTH. In this study we present evidence of in vivo physical interaction between HTH and EXD, mediated primarily through an evolutionarily conserved MH domain in HTH. This interaction is essential for the mutual stabilization of both proteins, for EXD nuclear localization, and for the cooperative DNA binding of the EXD-HTH heterodimer. Some in vivo functions require both EXD and HTH in the nucleus, suggesting that the EXD-HTH complex may function as a transcriptional regulator.

Amino Acid Sequence↗

Alteration of patellofemoral contact during healing of canine patellar tendon after removal of its central third.

Alterations of the patellofemoral (PF) contact pressure and area were assessed using pressure-sensitive film after the removal of the central third of patellar tendon (PT) with healing over time in twelve dogs. The contralateral knee served as control. Histological sections were prepared for descriptive evaluation. No alterations in PT strain, PF contact pressure and area were measured immediately after the removal of the central third of PT compared with that before its removal. Compared with contralateral control, the healing of the donor PF induced a significantly increased PF contact area but not PF contact pressure in the specimens harvested at 6, 12, and 18 months after operation. Increased PF contact area indicated a proximal shift of the PF joint contact during flexion, which was associated with an increased strain of the healing PT under loading. The healing PT became hypertrophic compared with control, but the differences in the cross-sectional area were reduced over time. Histologically, a poorly organized extracellular matrix was observed at 6 months, with a progressive improvement in collagen fiber alignment up to 18 months postoperatively. The results of this study suggest that the removal of the central third of PT does not immediately change PF contact pressure and areas. However, remodeling of the healing tendon may cause an elongated PT, resulting in an increase in PF contact area under a given quadriceps force by knee extension.

Animals↗

Removal of the lateral or medial third of patellar tendon alters the patellofemoral contact pressure and area: an in vitro experimental study in dogs.

OBJECTIVES: To compare patellofemoral contact pressure and areas after immediate removal of the lateral, central, or medial third of patellar tendon. DESIGN: In vitro experiment in 12 dogs. BACKGROUND: Alteration of the vector sum of the quadriceps muscle contraction after removal of partial patellar tendon might result in changes of patellar tracking in the trochlea. METHODS: Patellofemoral contact pressure and areas were recorded using Fuji pressure-sensitive film at 45 degrees, 60 degrees, and 90 degrees of knee flexion under an isometric quadriceps force of 100% body weight. The patellofemoral contact imprint from the intact knees were obtained as control, and the lateral (n=4), central (n=4), and medial (n=4) third of the patellar tendon were subsequently removed and the patellofemoral contact imprint was recorded. RESULTS: The patellofemoral contact area was found to increase with increasing knee flexion angles. No change in patellofemoral contact pressure and areas was found after removal of the central third patellar tendon. However, after removal of either lateral or medial third of patellar tendon, the patellofemoral contact was rotated with increasing knee flexion angles. This was due to the altered vector sum of the quadriceps force, resulting in significantly decreased patellofemoral contact areas and simultaneously a significantly increased contact pressure, characterized with concentration of patellofemoral contact pressure on both lateral and medial facets of the patellofemoral joint. CONCLUSIONS: The results suggest that removal of the central third of patellar tendon may not alter the patellofemoral contact pressure and areas as compared with removal of either lateral or medial third of patellar tendon that may result in an altered postoperative tracking mechanism of the patellofemoral joint immediately after operation. RELEVANCE: Findings of this in vitro animal study supports the use of central third of patellar tendon as autograft for anterior cruciate ligament reconstruction. However, further experimental studies are needed to investigate how the postoperative healing of the host patellar tendon will influence the findings obtained from this in vitro study.

Animals↗

Clinical trials of pacing mode selection.

Current recommendations in favor of dual-chamber over single-chamber ventricular pacing for patients with sinus node dysfunction or AV conduction disorders were made largely based on observational data and expert opinions. The first randomized pacing mode selection study was relatively small and suggested survival advantage with physiologic pacing only after an extended follow-up duration of 5.5 years. Preliminary results of the first large-scale multicenter randomized pacing mode selection trial revealed only modest reduction in atrial fibrillation without survival advantage after 3 years of physiologic pacing. Two other large-scale multicenter randomized trials comparing physiologic versus ventricular pacing are currently ongoing. They may provide further scientific evidence based on which more objective recommendations can be made with respect to pacing mode selection.

Cardiac Pacing, Artificial↗

Visual target detection paradigm for the study of selective attention.

The current protocol can be used to examine selective attention. It has been used to acquire behavioral performance data in neurologically healthy normal control subjects and schizophrenic patients. A modified version, also described here, has been used to acquire functional neuroimaging data in normal subjects using positron emission tomography. Subject response accuracy and reaction times are recorded while subjects detect visual stimuli in either hemifield (left vs. right of a fixation point) or along the vertical meridian (above or below fixation). The lateralized presentation of stimuli permits the study of hemispheric specialization for selective attentional processes. Attentional load is manipulated by presenting larger-sized target stimuli alone (i.e., the letter 'O') or smaller-sized target stimuli surrounded by flanking letters. This protocol report includes a description of subject exclusion criteria, procedural details, relevant experimental conditions and variables, suggestions for data analysis, expected results, and a discussion of the protocol's significance for attentional research along with suggestions for future research.

Attention↗

Extracellular Mg(2+) modulates slow gating transitions and the opening of Drosophila ether-à-Go-Go potassium channels.

We have characterized the effects of prepulse hyperpolarization and extracellular Mg(2+) on the ionic and gating currents of the Drosophila ether-à-go-go K(+) channel (eag). Hyperpolarizing prepulses significantly slowed channel opening elicited by a subsequent depolarization, revealing rate-limiting transitions for activation of the ionic currents. Extracellular Mg(2+) dramatically slowed activation of eag ionic currents evoked with or without prepulse hyperpolarization and regulated the kinetics of channel opening from a nearby closed state(s). These results suggest that Mg(2+) modulates voltage-dependent gating and pore opening in eag channels. To investigate the mechanism of this modulation, eag gating currents were recorded using the cut-open oocyte voltage clamp. Prepulse hyperpolarization and extracellular Mg(2+) slowed the time course of ON gating currents. These kinetic changes resembled the results at the ionic current level, but were much smaller in magnitude, suggesting that prepulse hyperpolarization and Mg(2+) modulate gating transitions that occur slowly and/or move relatively little gating charge. To determine whether quantitatively different effects on ionic and gating currents could be obtained from a sequential activation pathway, computer simulations were performed. Simulations using a sequential model for activation reproduced the key features of eag ionic and gating currents and their modulation by prepulse hyperpolarization and extracellular Mg(2+). We have also identified mutations in the S3-S4 loop that modify or eliminate the regulation of eag gating by prepulse hyperpolarization and Mg(2+), indicating an important role for this region in the voltage-dependent activation of eag.

Animals↗

Mg(2+) modulates voltage-dependent activation in ether-à-go-go potassium channels by binding between transmembrane segments S2 and S3.

Extracellular Mg(2+) directly modulates voltage-dependent activation in ether-à-go-go (eag) potassium channels, slowing the kinetics of ionic and gating currents (Tang, C.-Y., F. Bezanilla, and D.M. Papazian. 2000. J. Gen. Physiol. 115:319-337). To exert its effect, Mg(2+) presumably binds to a site in or near the eag voltage sensor. We have tested the hypothesis that acidic residues unique to eag family members, located in transmembrane segments S2 and S3, contribute to the Mg(2+)-binding site. Two eag-specific acidic residues and three acidic residues found in the S2 and S3 segments of all voltage-dependent K(+) channels were individually mutated in Drosophila eag, mutant channels were expressed in Xenopus oocytes, and the effect of Mg(2+) on ionic current kinetics was measured using a two electrode voltage clamp. Neutralization of eag-specific residues D278 in S2 and D327 in S3 eliminated Mg(2+)-sensitivity and mimicked the slowing of activation kinetics caused by Mg(2+) binding to the wild-type channel. These results suggest that Mg(2+) modulates activation kinetics in wild-type eag by screening the negatively charged side chains of D278 and D327. Therefore, these residues are likely to coordinate the bound ion. In contrast, neutralization of the widely conserved residues D284 in S2 and D319 in S3 preserved the fast kinetics seen in wild-type eag in the absence of Mg(2+), indicating that D284 and D319 do not mediate the slowing of activation caused by Mg(2+) binding. Mutations at D284 affected the eag gating pathway, shifting the voltage dependence of Mg(2+)-sensitive, rate limiting transitions in the hyperpolarized direction. Another widely conserved residue, D274 in S2, is not required for Mg(2+) sensitivity but is in the vicinity of the binding site. We conclude that Mg(2+) binds in a water-filled pocket between S2 and S3 and thereby modulates voltage-dependent gating. The identification of this site constrains the packing of transmembrane segments in the voltage sensor of K(+) channels, and suggests a molecular mechanism by which extracellular cations modulate eag activation kinetics.

Amino Acid Sequence↗

Quantitative diffusion measurements in focal multiple sclerosis lesions: correlations with appearance on TI-weighted MR images.

OBJECTIVE: Relative hypointensity on T1-weighted MR imaging has been suggested as a putative disability marker. The purpose of our study was to determine if there are quantifiable diffusion differences among focal multiple sclerosis lesions that appear differently on conventional T1-weighted MR images. We hypothesized that markedly hypointense lesions on unenhanced T1-weighted images would have significantly increased diffusion compared with other lesions, and enhancing portions of lesions would have different diffusion compared with nonenhancing lesions. SUBJECTS AND METHODS: Average apparent diffusion coefficient (ADC) was calculated for 107 lesions identified on T2-weighted images in 16 patients with multiple sclerosis and was compared with the ADC of normal white matter in 16 age- and sex-matched control subjects. Seventy-five nonenhancing lesions (29 isointense, 46 hypointense) and 32 enhancing lesions (6 isointense, 26 hypointense) were categorized on the basis of unenhanced T1-weighted MR imaging. RESULTS: Hypointense and isointense nonenhancing lesions both showed significantly higher ADC than normal white matter (p < 0.0001). Hypointense nonenhancing lesions showed higher ADC values than isointense nonenhancing lesions (p < 0.0001). Diffusion in enhancing portions of enhancing lesions was decreased when compared with nonenhancing portions. CONCLUSION: Quantitative diffusion data from MR imaging differ among multiple sclerosis lesions that appear different from each other on T1-weighted images. These quantitative diffusion differences imply microstructural differences, which may prove useful in documenting irreversible disease.

Adolescent↗

Three-dimensional structure of the Golgi apparatus in mouse spermatids: a scanning electron microscopic study.

In this study, the three-dimensional organization of the Golgi apparatus in mouse spermatids was elucidated by preparing testicular tissue with the osmium-DMSO-osmium method and examining it by stereo-scanning electron microscopy. The cis-most saccule was found to be a regular network of anastomotic membranous tubules covered by a single cisterna of ER. The trans-Golgi network was seen to be composed of irregular saccules perforated by pores at the edge. It appears that the anastomosing trans-Golgi network breaks down into strings of connected vesicles which arise from the edge of the saccules during the cap phase of spermiogenesis. Many apparently individual vesicles seen in thin sections through the trans-Golgi network are actually joined in continuous strings. This was the first time that these structures could be visualized directly without three-dimensional image reconstruction. By correlating the morphology of the Golgi apparatus with the stage of acrosome formation, the Golgi cisternae were found to change dynamically in a cis-trans direction from fenestrated saccules to continuous strings of vesicles, which finally dissipated as transport vesicles at the trans aspect. This suggests that the hypothetical model of cisternal maturation, which dictates that cargo moves through the Golgi apparatus without leaving the cisternal lumen and the secretion occurs by progressive maturation of the Golgi cisternae as they move in the cis-trans direction, may be applicable to acrosome formation.

Acrosome↗

Quality of life of patients with perennial allergic rhinitis: preliminary validation of the Rhinoconjunctivitis Quality of Life Questionnaire in Singapore.

Though sufferers of perennial allergic rhinitis do not die from their ailment, they endure years of chronic nose disease that Interferes with many important aspects of their lives. A rhinitis-specific instrument to gauge the quality of life of patients with this disease was published in 1991. Here, we validated the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ) for use in English-speaking patients with perennial allergic rhinitis. We established that the RQLQ distinguishes between patients and control, demonstrates internal consistency and is sensitive to change. This study suggests that the RQLQ can be used to assess the quality of life of patients with perennial allergic rhinitis in Singapore.

Adolescent↗

Healthy adults demonstrate less skin reactivity to commercial extracts of commonly ingested food than to D. farinae.

The aim of this study is to determine the skin reactivity of healthy Oriental adults to commercial extracts of commonly ingested food and the house dust mite D. farinae, a common local aeroallergen. D. farinae and 18 food extracts were skin prick tested on adults without any personal history of atopic diseases and food allergy. The extracts of food not consumed by any subject on religious or personal grounds were not tested for that individual. A total of 103 healthy adults who fulfilled the selection criteria were skin prick tested. There were 35 males and 68 females. Their mean age was 29 years (SD +/- 7.5) with a range of 19 to 49 years. Sixty-eight percent were Chinese, 12.6% Malay, 12.6% Indian and 6.8% other Oriental races. Fifty-four (52.4%) were positive for D. farinae while only 12 (11.7%) were positive for at least one food extract The food extract that gave the most number of positive reactions was shellfish mix (5/102, 4.9%). A family history of atopy did not have any significant correlation with the results of skin test. It was concluded that healthy adults demonstrate less skin reactivity to extracts of commonly ingested food than to D. farinae.

Adolescent↗

MRI white matter diffusion anisotropy and PET metabolic rate in schizophrenia.

A disturbance in the frontal-striatal-thalamic circuitry has been proposed for schizophrenia, but this concept has been based primarily on indirect evidence from psychopharmacology and analogies with animal research. Diffusion tensor imaging, a new MRI technique that permits direct assessment of the large axon masses stretching from the prefrontal cortex to the striatum, was used to study white matter axon bundles. Diffusion tensor images, high-resolution structural MRI and positron emission tomography scans with 18-fluorodexoyglucose were obtained on five patients with schizophrenia and six age- and sex-matched normal controls. Significantly lower diffusion anisotropy in the white matter of the prefrontal cortex in schizophrenic patients than in normal controls was observed in statistical probability maps. Co-registered PET scans revealed significantly lower correlation coefficients between metabolic rates in the prefrontal cortex and striatum in patients than in controls. These twin findings provide convergent evidence for diminished fronto-striatal connectivity in schizophrenia.

Adult↗

Shaker and ether-à-go-go K+ channel subunits fail to coassemble in Xenopus oocytes.

Members of different voltage-gated K+ channel subfamilies usually do not form heteromultimers. However, coassembly between Shaker and ether-à-go-go (eag) subunits, members of two distinct K+ channel subfamilies, was suggested by genetic and functional studies (Zhong and Wu. 1991. Science. 252: 1562-1564; Chen, M.-L., T. Hoshi, and C.-F. Wu. 1996. Neuron. 17:535-542). We investigated whether Shaker and eag form heteromultimers in Xenopus laevis oocytes using electrophysiological and biochemical approaches. Coexpression of Shaker and eag subunits produced K+ currents that were virtually identical to the sum of separate Shaker and eag currents, with no change in the kinetics of Shaker inactivation. According to the results of dominant negative and reciprocal coimmunoprecipitation experiments, the Shaker and eag proteins do not interact. We conclude that Shaker and eag do not coassemble to form heteromultimers in Xenopus oocytes.

Animals↗

Facial measurements for frame design.

Anthropometric data for the purpose of spectacle frame design are scarce in the literature. Definitions of facial features to be measured with existing systems of facial measurement are often not specific enough for frame design and manufacturing. Currently, for individual frame design, experienced personnel collect data with facial rules or instruments. A new measuring system is proposed, making use of a template in the form of a spectacle frame. Upon fitting the template onto a subject, most of the measuring references can be defined. Such a system can be administered by lesser-trained personnel and can be used for researches covering a larger population.

Anthropometry↗

Ophthalmic anthropometry for Hong Kong Chinese adults.

A database of ophthalmic anthropometry is established which is useful for the design of spectacles for southeast Asian people. Statistical analysis reveals significant variations in the facial dimensions between male and female subjects. Results of the study are given separately for each sex and for the combined population. Hong Kong Chinese are found to have larger frontal angles, bigger angles of splay, and a less prominent bridge in the nose. Spectacle frames should be designed according to the targeted gender population, and to accommodate the characteristics of Asian faces.

Adolescent↗

Gypsy retrotransposon as a tool for the in vivo analysis of the regulatory region of the optomotor-blind gene in Drosophila.

We report here a method for the in vivo dissection of the regulatory region of a gene in the Drosophila genome. Our system includes (i) the reporter genes lacZ and white to detect transcriptional enhancer and silencer activities in a target gene, (ii) an efficient way to induce integration of gypsy elements in the genome, and (iii) unidirectional blocking of regulatory activities by the gypsy element, which is dependent on the su(Hw) protein. The optomotor-blind (omb) gene was analyzed. In the omb(P1) line, a P[lacW] construct is inserted about 1.4 kb upstream of the omb transcription start site. The lacZ reporter gene within P[lacW] exhibits the same expression pattern as omb. The white reporter gene is expressed in a "bipolar" pattern. We induced high frequency gypsy mobilization in omb(P1) and identified two lines (D11 and D13-1) with altered eye pigmentation pattern, which is dependent on su(Hw) activity. A gypsy element was found inserted in the first intron of omb in D13-1 and in P[lacW] in D11. These results indicate that it is the blocking of regulatory activities by gypsy that caused the changes in the white reporter gene expression. The effect of these gypsy insertions on the expression patterns allowed us to predict several aspects of the organization of the regulatory elements in the omb locus.

Animals↗

Transfer of voltage independence from a rat olfactory channel to the Drosophila ether-à-go-go K+ channel.

The S4 segment is an important part of the voltage sensor in voltage-gated ion channels. Cyclic nucleotide-gated channels, which are members of the superfamily of voltage-gated channels, have little inherent sensitivity to voltage despite the presence of an S4 segment. We made chimeras between a voltage-independent rat olfactory channel (rolf) and the voltage-dependent ether-à-go-go K+ channel (eag) to determine the basis of their divergent gating properties. We found that the rolf S4 segment can support a voltage-dependent mechanism of activation in eag, suggesting that rolf has a potentially functional voltage sensor that is silent during gating. In addition, we found that the S3-S4 loop of rolf increases the relative stability of the open conformation of eag, effectively converting eag into a voltage-independent channel. A single charged residue in the loop makes a significant contribution to the relative stabilization of the open stage in eag. Our data suggest that cyclic nucleotide-gated channels such as rolf contain a voltage sensor which, in the physiological voltage range, is stabilized in an activated conformation that is permissive for pore opening.

Amino Acid Sequence↗

Conserved cysteine residues in the shaker K+ channel are not linked by a disulfide bond.

Many voltage-activated K+ channels contain two conserved cysteine residues in putative transmembrane segments S2 and S6. It has been proposed that these cysteines form an intrasubunit disulfide bond [Guy, H.R., & Conti, F. (1990) Trends Neurosci. 13, 201-206]. This proposal was tested using site-directed mutagenesis followed by electrophysiological and biochemical analysis of the Shaker B K+ channel. Each Shaker B subunit contains seven cysteine residues, including the conserved residues C286 and C462 and a less conserved cysteine, C245. Each cysteine in the Shaker B protein can be mutated individually without eliminating functional activity, indicating that the protein does not contain a disulfide bond that is essential for protein folding or the assembly of active channels. To determine whether there is a nonessential disulfide bond, Shaker B protein was subjected to limited proteolysis. Fragments were analyzed by electrophoresis under reducing and nonreducing conditions followed by immunoblotting. The results indicate that the two conserved residues C286 and C462 do not form a disulfide bond with each other or with C245. In addition, the subunits are not linked by disulfide bonds. In HEK293T cells, Shaker B protein is first made as an incompletely glycosylated precursor that is converted to the fully glycosylated mature protein. Glycosylation occurs at two positions in the S1-S2 loop.

Amino Acid Sequence↗