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Biomedical subjects

H L Ng

Publications and source records attributed to H L Ng.

10 recordsLinked to original sources

Treatment of vancomycin-intermediate Staphylcoccus aureus endocarditis with linezolid.

We report a case of infective endocarditis due to vancomycin-intermediate Staphylococcus aureus that developed after repeated courses of vancomycin. The patient had underlying end stage renal disease and dissecting aortic aneurysm with aortic graft and prosthetic aortic valve replacement. He responded to prolonged combination therapy with linezolid and amikacin without undergoing surgical intervention.

Acetamides↗

The first patient with locally acquired dengue fever in Hong Kong.

This report is of the first locally acquired case of dengue fever. The diagnosis was made even in the absence of a history of travel outside Hong Kong. The patient was a 21-year-old man, who presented with high fever, leukopenia, thrombocytopenia, and elevated liver enzymes. His haematocrit revealed mild haemoconcentration but the albumin was normal throughout the course of the illness. His blood pressure remained low with no tachycardia or overt shock syndrome. The pyrexia subsided 4 days after admission to hospital and all haematological and biochemical abnormalities eventually normalised. The pathogenesis, diagnostic criteria of dengue haemorrhagic fever and dengue shock syndrome, and control of dengue infection are discussed.

Adult↗

The rotary pursuit test is not an index of normal psychomotor function in humans.

OBJECTIVE: This study sought to assess whether the rotary pursuit test is a good indication of the psychomotor performance of human subjects during normal working hours. Circadian hormonal profiles of salivary melatonin and cortisol were also established for correlation with performance. METHODS: Ten healthy individuals working in the Department of Obstetrics and Gynecology laboratory participated in this study. The experiment was conducted during a normal 8.5-hour working day in which routine laboratory tasks such as running radioimmunoassays were performed. Saliva samples were collected every 2 hours starting at 8:00 a.m. Simultaneously, self-rated questionnaires on mood states, sleepiness, stress, and types of food and drinks consumed were also recorded. At 10:00 a.m., 12:00 noon, 2:00 p.m., and 4:00 p.m., the subjects' were tested on the rotary pursuit machine, on which their ability to track a rotating target with a stylus was tested by means of measuring the time the stylus stays on target. RESULTS: The circadian profiles of salivary melatonin and cortisol were similar to what previous studies have shown. Increases in cortisol levels were associated with food intake, work stress, or spontaneous awakening. Tracking performance (time on target) improved significantly from 10:00 a.m. to 2:00 p.m. and then decreased nonsignificantly at 4:00 p.m. only at the speed setting of 60 rpm. There was no correlation between the three parameters measured. SUMMARY: Variation of psychomotor performance during a normal working day and in noncircadian disrupted individuals cannot be measured by the rotary pursuit test. Furthermore, a learning effect could mask any variation in performance.

Adult↗

Local conformational variations observed in B-DNA crystals do not improve base stacking: computational analysis of base stacking in a d(CATGGGCCCATG)(2) B<-->A intermediate crystal structure.

The crystal structure of d(CATGGGCCCATG)(2) shows unique stacking patterns of a stable B<-->A-DNA intermediate. We evaluated intrinsic base stacking energies in this crystal structure using an ab initio quantum mechanical method. We found that all crystal base pair steps have stacking energies close to their values in the standard and crystal B-DNA geometries. Thus, naturally occurring stacking geometries were essentially isoenergetic while individual base pair steps differed substantially in the balance of intra-strand and inter-strand stacking terms. Also, relative dispersion, electrostatic and polarization contributions to the stability of different base pair steps were very sensitive to base composition and sequence context. A large stacking flexibility is most apparent for the CpA step, while the GpG step is characterized by weak intra-strand stacking. Hydration effects were estimated using the Langevin dipoles solvation model. These calculations showed that an aqueous environment efficiently compensates for electrostatic stacking contributions. Finally, we have carried out explicit solvent molecular dynamics simulation of the d(CATGGGCCCATG)(2) duplex in water. Here the DNA conformation did not retain the initial crystal geometry, but moved from the B<-->A intermediate towards the B-DNA structure. The base stacking energy improved in the course of this simulation. Our findings indicate that intrinsic base stacking interactions are not sufficient to stabilize the local conformational variations in crystals.

Base Composition↗

The structure of a stable intermediate in the A <--> B DNA helix transition.

The DNA dodecamer CATGGGCCCATG in a crystal structure of resolution 1.3 A has a conformation intermediate between A and B DNA. This trapping of a stable intermediate suggests that the A and B DNA families are not discrete, as previously believed. The structure supports a base-centered rather than a backbone-centered mechanism for the A <--> B transition mediated by guanine tracts. Interconversion between A and B DNA provides another means for regulating protein-DNA recognition.

Amino Acid Sequence↗

Detecting protein function and protein-protein interactions from genome sequences.

A computational method is proposed for inferring protein interactions from genome sequences on the basis of the observation that some pairs of interacting proteins have homologs in another organism fused into a single protein chain. Searching sequences from many genomes revealed 6809 such putative protein-protein interactions in Escherichia coli and 45,502 in yeast. Many members of these pairs were confirmed as functionally related; computational filtering further enriches for interactions. Some proteins have links to several other proteins; these coupled links appear to represent functional interactions such as complexes or pathways. Experimentally confirmed interacting pairs are documented in a Database of Interacting Proteins.

Amino Acid Sequence↗

Structure of a dicationic monoimidazole lexitropsin bound to DNA.

An X-ray crystal structure has been solved of the complex of a dicationic lexitropsin with a B-DNA duplex of sequence CGCGAATTCGCG. The lexitropsin is identical to netropsin except for replacement of the first methylpyrrole ring by methylimidazole, converting a =CH- to =N-. Crystals are isomorphous with those of the DNA dodecamer in the absence of drug. Although the =N- for =CH- substitution was intended to make that locus on the drug molecule compatible with a G.C base pair, electrostatic attraction for the two cationic ends of the drug predominates, and this lexitropsin binds to the same central AATT site as does the parent netropsin. But unlike netropsin, this lexitropsin exhibits end-for-end disorder in the crystal. Both orientations were refined separately to completion. Final residual errors at 2.25 A resolution for the 2358 reflections above 2 sigma in F are R = 0.165 for one orientation (LexA) with 37 water molecules and 0.164 for the inverted drug orientation (LexB) with 40 water molecules. This molecular disorder is probably attributable to a weakening of binding to the AATT site occasioned by the imidazole-for-pyrrole substitution.

Antibiotics, Antineoplastic↗

Inhibitors of protein and RNA synthesis block the cytotoxic effects of non-steroidal antiestrogens.

Non-steroidal antiestrogens such as tamoxifen are known to exert cytotoxic effects against various cell lines in culture. When the antiestrogens are present at sufficiently high concentrations, their cytotoxicity cannot be reversed by estrogens and is demonstrable even with cell lines which lack the estrogen receptor. The mechanism of this cytotoxicity, which is clearly independent of estrogen antagonism, remains unknown. Using two murine cancer cell lines (the K36 leukemia and the EL4 lymphoma cell line), the human breast cancer cell line MCF7, and two non-steroidal antiestrogens (tamoxifen and clomiphene), our laboratory attempted to determine whether the cytotoxic action of non-steroidal antiestrogens was mediated by a mechanism requiring protein or RNA synthesis. In the case of K36 and EL4 cells, inclusion of tamoxifen or clomiphene in the culture medium regularly caused the viable call count to fall below 20-30% of control in 36-48 h. Under these conditions, the addition of inhibitors of protein or RNA synthesis consistently increased viable cell count in a dose-dependent manner. With cultures of K36 cells grown in the presence of 10 microM tamoxifen, for example, the addition of appropriate concentrations of emetine, cycloheximide, puromycin, or actinomycin D increased the percentage of viable cells to 5.0, 2.4, 4.0, and 4.0 times that of control, respectively. Additional experiments revealed that the macromolecular synthesis inhibitors, while effective in inhibiting protein or RNA synthesis to varying degrees, did not affect the cellular uptake of [3H]tamoxifen, suggesting that their ability to protect cells against antiestrogen-induced cell death was not due to an inhibition of cellular uptake of antiestrogens. In the case of MCF7 cells, however, inhibition of protein synthesis did not protect the cells against the cytotoxic effect of tamoxifen. These observations suggest that non-steroidal antiestrogens may exert their cytotoxic effect by at least two different mechanisms; only one of these require de novo protein synthesis. The effect of antiestrogens on K36 and EL4 cells may provide a useful system for the identification of proteins involved in cell death.

Animals↗