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K H Mok

Publications and source records attributed to K H Mok.

11 recordsLinked to original sources
PubMed2000

Local structural elements in the mostly unstructured transcriptional activation domain of human p53.

DNA transcription is initiated by a small regulatory region of transactivators known as the transactivation domain. In contrast to the rapid progress made on the functional aspect of this promiscuous domain, its structural feature is still poorly characterized. Here, our multidimensional NMR study reveals that an unbound full-length p53 transactivation domain, although similar to the recently discovered group of loosely folded proteins in that it does not have tertiary structure, is nevertheless populated by an amphipathic helix and two nascent turns. The helix is formed by residues Thr(18)-Leu(26) (Thr-Phe-Ser-Asp-Leu-Trp-Lys-Leu-Leu), whereas the two turns are formed by residues Met(40)-Met(44) and Asp(48)-Trp(53), respectively. It is remarkable that these local secondary structures are selectively formed by functionally critical and positionally conserved hydrophobic residues present in several acidic transactivation domains. This observation suggests that such local structures are general features of acidic transactivation domains and may represent "specificity determinants" (Ptashne, M., and Gann, A. A. F. (1997), Nature 386, 569-577) that are important for transcriptional activity.

Amino Acid Sequence↗
PubMed2000

Nuclear magnetic resonance solution conformation of alpha-conotoxin AuIB, an alpha(3)beta(4) subtype-selective neuronal nicotinic acetylcholine receptor antagonist.

The neuronal nicotinic acetylcholine receptors constitute a highly diverse group, with subtypes consisting of pentameric combinations of alpha and beta subunits. alpha-Conotoxins are a homologous series of small peptides that antagonize these receptors. We present the three-dimensional solution structure of alpha-conotoxin AuIB, the first 15-residue alpha-conotoxin known to selectively block the alpha(3)beta(4) nicotinic acetylcholine receptor subtype. The pairwise backbone and heavy-atom root mean square deviation for an ensemble of 20 structures are 0.269 and 0.720 A, respectively. The overall fold of alpha-conotoxin AuIB closely resembles that of the alpha4/7 subfamily alpha-conotoxins. However, the absence of Tyr(15), normally present in other alpha4/7 members, results in tight bending of the backbone at the C terminus and effectively renders Asp(14) to assume the spatial location of Tyr(15) present in other neuronal alpha4/7 alpha-conotoxins. Structural comparison of alpha-conotoxin AuIB with the alpha(3)beta(2) subtype-specific alpha-conotoxin MII shows different electrostatic surface charge distributions, which may be important in differential receptor subtype recognition.

Amino Acid Sequence↗
PubMed2000

Nerve fiber analyzer and short-wavelength automated perimetry in glaucoma suspects: a pilot study.

PURPOSE: To test the relationship between the results of short-wavelength automatic perimetry (SWAP) and retinal nerve fiber layer (RNFL) measurements with scanning laser polarimetry (Nerve Fiber Analyzer, NFA) in age-matched normal subjects, glaucoma suspects, and early glaucoma patients. DESIGN: Case-control study. PARTICIPANTS AND METHODS: Thirty-eight normal subjects, 32 glaucoma suspects, and 14 early glaucoma patients were recruited. All subjects underwent RNFL assessment by NFA, achromatic visual field testing (24-2 threshold), and repeated SWAP (24-2 threshold blue-on-yellow). MAIN OUTCOME MEASURES: Mean deviation (MD) of visual field testing and RNFL values were obtained. RESULTS: Glaucoma suspects were divided into two groups according to their SWAP results: high risk (with SWAP abnormalities) and low risk (with normal SWAP result). No statistically significant difference in SWAP MD and RNFL values were observed between normal and low-risk groups (P > 0.05), but these values were found to be significantly lower in high-risk and early glaucoma groups (P < 0.01). CONCLUSIONS: This study suggests that RNFL examination by NFA may be a useful test for the early detection of glaucomatous damage of glaucoma suspects. It appears to provide agreement with SWAP abnormalities and is more sensitive than conventional standard automated perimetry.

Case-Control Studies↗
PubMed2000

Nerve fibre layer measurement of the Hong Kong Chinese population by scanning laser polarimetry.

PURPOSE: To obtain normal retinal nerve fibre layer (RNFL) measurements by scanning laser polarimetry in a local Hong Kong Chinese population and to identify the correlation of the measurements with age. METHODS: One hundred and fifty-nine normal Hong Kong Chinese volunteers of different ages were recruited for this study. RNFL values were measured using a Nerve Fibre Analyzer GDx (Laser Diagnostic Technologies, CA). RESULTS: Mean peripapillary RNFL measurements at the superior, inferior, temporal and nasal regions were 95.0 +/- 15.6, 97.0 +/- 16.3, 47.0 +/- 9.0 and 43.9 +/- 15.1 microns respectively (mean +/- SD). There was a highly significant negative correlation in average RNFL values with increasing age (approximately 1.9 microns per decade, p = 0.001). A significant negative correlation with increasing age was also identified in the RNFL values in all four regions and they decreased by similar amounts (p < 0.05). No correlation with age was observed for relative ratio parameters such as superior/nasal ratio, inferior/nasal ratio and max. modulation (p > 0.05). CONCLUSION: RNFL values of the Hong Kong Chinese population appeared to decrease over time cross-sectionally. Since they decreased by similar amounts at four regions, use of relative ratio parameters for analysis has an advantage over absolute values, as they were not affected by age.

Adolescent↗
PubMed1999

NMR solution conformation of an antitoxic analogue of alpha-conotoxin GI: identification of a common nicotinic acetylcholine receptor alpha 1-subunit binding surface for small ligands and alpha-conotoxins.

The three-dimensional solution conformation of an 11-residue antitoxic analogue of alpha-conotoxin GI, des-Glu1-[Cys3Ala]-des-Cys13-conotoxin GI (CANPACGRHYS-NH(2), designated "GI-15" henceforth), has been determined using two-dimensional (1)H NMR spectroscopy. The disulfide loop region (1C-6C) and the C-terminal tail (8R-11S) are connected by a flexible hinge formed near 7G, and the pairwise backbone rmsds for the former and the latter are 0.58 and 0.65 A, respectively. Superpositioning GI-15 with the structure of alpha-conotoxin GI shows that the two share an essentially identical fold in the common first disulfide loop region (1C-6C). However, the absence of the second disulfide loop in GI-15 results in segmental motion of the C-terminal half, causing the key receptor subtype selectivity residue 8R (Arg9 in alpha-conotoxin GI) to lose its native spatial orientation. The combined features of structural equivalence in the disulfide loop and a mobile C-terminal tail appear to be responsible for the activity of GI-15 as a competitive antagonist against native toxin. Electrostatic surface potential comparisons of the first disulfide region of GI-15 with other alpha-conotoxins or receptor-bound states of acetylcholine and d-tubocurarine show a common protruding surface that may serve as the minimal binding determinant for the neuromuscular acetylcholine receptor alpha 1-subunit. On the basis of the original "Conus toxin macrosite model" [Olivera, B. M., Rivier, J., Scott, J. K., Hillyard, D. R., and Cruz, L. J. (1991) J. Biol. Chem. 266, 1923-1936], we propose a revised binding model which incorporates these results.

Amino Acid Sequence↗
PubMed1999

Retinal nerve fiber layer measurement by nerve fiber analyzer in normal subjects and patients with glaucoma.

OBJECTIVE: To identify the pattern of retinal nerve fiber layer (RNFL) loss in glaucoma using the Nerve Fiber Analyzer (NFA). DESIGN: Case-control study. PARTICIPANTS: A total of 80 normal and 75 age- and race-matched chronic open-angle glaucoma subjects were recruited. INTERVENTION: The RNFL thickness was assessed with a scanning laser polarimeter (Nerve Fiber Analyzer GDX, Laser Diagnostic Technologies Inc., San Diego, CA). Analysis of variance was used to compare the corresponding RNFL measurement indices of the different groups. MAIN OUTCOME MEASURES: Superior/nasal (S/N) and inferior/nasal (I/N) ratios of NFA are sensitive parameters to differentiate between glaucoma and nonglaucoma subjects. RESULTS: Peripapillary RNFL measurements at the superior and inferior regions were significantly lower in the glaucoma group (P<0.001) but were similar in temporal and nasal regions (P>0.05). Using nasal value as reference, S/N and I/N ratios were significantly lower in the glaucoma groups (P<0.001) and also decreased with increasing severity of glaucoma. CONCLUSIONS: In glaucoma, RNFL was more susceptible to loss in the superior and inferior regions than in the nasal and temporal regions. The S/N and I/N ratio parameters provided by the NFA appeared to give further discriminating ability in early glaucoma.

Adult↗
PubMed1999

Tono-Pen tonometer and corneal thickness.

PURPOSE: To compare the intraocular pressure (IOP) measurements taken at the central cornea with those taken at the mid-peripheral cornea using the Tono-Pen tonometer. METHODS: Forty-eight normal human subjects had their IOP measurements taken (i) with the Goldmann tonometer, (ii) with the Tono-Pen at the central cornea and (iii) with the Tono-Pen at the mid-peripheral cornea. The central and mid-peripheral corneal thickness at the site of IOP measurements were then determined by ultrasonic pachymetry. RESULTS: The mean IOP with the Goldmann tonometer was 15.7 +/- 3.1 mmHg. The mean Tono-Pen IOPs at the central and midperipheral cornea were 15.2 +/- 3.2 mmHg and 15.7 +/- 3.3 mmHg respectively. The mean midperipheral corneal thickness (578 microns) was significantly higher than the mean central thickness (538 microns) (p < 0.001). CONCLUSION: There was no significant difference between the IOP taken with the Tono-Pen and with the Goldmann tonometer. In addition, no clinically significant difference was observed between the IOP readings of central and mid-peripheral cornea measured by the Tono-Pen.

Cornea↗
PubMed1998

Chloride and sodium transport across bovine ciliary body/epithelium (CBE).

PURPOSE: To study the chloride and sodium ion transports across the bovine ciliary body/epithelium (CBE) by a modified Ussing-Zerahn type chamber. METHODS: Isolated bovine CBE preparations were mounted in a modified Ussing-type chamber and the transepithelial electrical parameters were monitored. The inward (stroma to aqueous) and outward (aqueous to stroma) fluxes of 36[Cl] chloride and 22[Na] sodium ions across the CBE were measured under short-circuited conditions. The effect of 0.1 mM of furosemide and bumetanide on the chloride transport were studied. RESULTS: The potential difference (PD), the resistance and the short-circuit current (SCC) across the isolated bovine ciliary body were found to be -0.20+/-0.01 mV (aqueous negative), 75+/-1 omegacm2 and -2.70+/-0.17 microAcm(-2) (mean+/-SEM, n=50) respectively. A statistically significant net inward chloride ion flux of 1.12+/-0.41 microEq h(-1)cm(-2) (p < 0.01) was found (n=15). The net chloride transport was abolished when 0.1 mM furosemide (82% inhibition) and 0.1 mM bumetanide (100% inhibition) were applied bilateral. No significant net sodium ion flux was detected. CONCLUSIONS: Electrolyte and fluid transport across the bovine CBE may be via a bumetanide and furosemide-sensitive chloride transport mechanism. The Na-K-2Cl cotransporter plays a significant role in the trans-CBE chloride transport. The net chloride flux/current was about 12 times higher than the measured SCC, suggesting that the chloride ion transport may be coupled to other ion species.

Animals↗
PubMed1998

Space analysis: a comparison between sonic digitization (DigiGraph Workstation) and the digital caliper.

The introduction of the DigiGraph Workstation permits the use of sonic digitization to measure lateral cephalometric values, mesiodistal tooth size and arch perimeter discrepancy as a one-stop diagnostic record taking set-up. This study compared the reproducibility of mesiodistal total tooth widths and arch perimeter values, on plaster casts, given by the DigiGraph Workstation and by digital calipers. Forty-seven sets of plaster casts of Southern Chinese children (mean age 12.5 years) comprised the sample. Arch perimeter was measured using calipers in six segments from the distal of the first permanent molar to its antimere in each arch. The total mesiodistal widths of all teeth, excluding second and third molars, were also measured. The difference between the available arch perimeter and the total tooth widths was taken as the arch perimeter discrepancy. Sonic digitization of the study casts was completed according to instructions of the DigiGraph software. Paired t-tests and F-tests were used to compare the two methods. Compared with manual measurement, there was an over-estimation of the total tooth widths by 1 mm in the mandible and 0.5 mm in the maxilla, and an arch perimeter discrepancy of 1.6 mm in the mandible and 0.4 mm in the maxilla when using the sonic method. The sonic digitization was not as reproducible as the digital caliper and its clinical usefulness in evaluating the space problem of an individual malocclusion should be interpreted with caution.

Calibration↗
PubMed1998

In vitro bovine ciliary body/epithelium in a small continuously perfused Ussing type chamber.

Our goal is to assess the viability of an in vitro preparation of bovine ciliary body/epithelium (CBE) in a small volume Ussing-type chamber. A new small volume Ussing-type chamber with continuous perfusion was developed for bovine CBE. The trans-CBE electrical parameters were monitored and the electrical responses of the CBE to ouabain (1 and 0.01 mM) were recorded. The trans-CBE fluxes of [14C]-L-ascorbate and [3H]-L-glucose were also studied. The bovine CBE preparation was stable inside the chamber in terms of its potential difference (PD), short circuit current (SCC) and trans-CBE resistance. They were -0.51+/-0.05 mV (aqueous side negative), -5.43+/-0.04 microAcm-2 and 94+/-2 Q.cm2 (mean s.e.m., n=35), respectively. The preparation hyperpolarised when 0.01 mM ouabain was administered to the aqueous side, depolarised when ouabain was applied to the stromal side. [3H]-L-glucose diffusion was about 74 nEq h(-1)cm(-2) in either direction (n=12). Taking the area magnification factor of the CBE into consideration, the diffusional L-glucose flux across the bovine CBE was comparable to other tight epithelia. A significant net ascorbate flux (0.26+/-0.05 nEq h(-1)cm(-2), n=4, p<0.01) was found in the stroma to aqueous direction. We have developed a viable in vitro bovine CBE preparation which was (1) electrically stable, (2) responsive to ouabain, (3) tight to L-glucose diffusion, and (4) capable of actively secreting ascorbate. A net trans-CBE chloride transport (0.81+/-0.30 microEq h(-1)cm(-2), n=12, p=0.01) from stromal to aqueous side was found in the present in vitro model under short-circuited conditions.

Animals↗