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Biomedical subjects

K C Luk

Publications and source records attributed to K C Luk.

At least 19 recordsLinked to original sources
PubMed2006

Predator-labeling effect on byssus production in marine mussels Perna viridis (L.) and Brachidontes variabilis (Krauss).

Mussels Perna viridis and Brachidontes variabilis were exposed to chemical cues from the predatory crab Thalamita danae maintained on different diets, and byssal thread production of the mussels was studied. P. viridis produced the highest number as well as the thickest and longest byssal threads when they were exposed to crabs maintained on a diet of P. viridis as compared with those exposed to crabs maintained on a diet of the top shell Monodonta labio, the rock oyster Saccostrea cucullata, or crabs that were starved. For B. variabilis, results were similar, in that a diet containing B. variabilis elicited the greatest response as compared with other treatments. This indicates that the mussels were able to discriminate chemical cues released from predators maintained on different diets, and respond accordingly to the level of predation risk. By increasing the strength of byssal attachment as a defensive trait, the chance of being dislodged and consumed by crabs is reduced. As energy cost involved in the induction of an antipredatory response is considerable, this defensive trait seems to be an advantage to the mussels in enhancing efficiency. The short response time in byssal thread production allows the mussels to increase resistance against predation by crabs at the time when predation pressure is the highest in a tidal cycle.

Animals↗
PubMed2005

Netrin receptor deficient mice exhibit functional reorganization of dopaminergic systems and do not sensitize to amphetamine.

Netrins are guidance cues that play a fundamental role in organizing the developing brain. The netrin receptor, DCC (deleted in colorectal cancer), is highly expressed by dopaminergic (DA) neurons. DCC may therefore participate in the organization of DA circuitry during development and also influence DA function in the adult. Here we show that adult dcc heterozygous mice exhibit a blunted behavioral response to the indirect DA agonist amphetamine and do not develop sensitization to its effects when treated repeatedly. These behavioral alterations are associated with profound changes in DA function. In the medial prefrontal cortex, dcc heterozygotes exhibit increased tyrosine hydroxylase (TH) protein levels and dramatic increases in basal concentrations of DA and DA metabolites. In contrast, in the nucleus accumbens, dcc heterozygotes show no changes in either TH or DA levels, but exhibit decreased concentrations of DA metabolites, suggesting reduced DA activity. In addition, dcc heterozygous mice exhibit a small, but significant reduction in total number of TH-positive neurons in midbrain DA cell body regions. These results demonstrate for the first time that alterations in dcc expression lead to selective changes in DA function and, in turn, to differences in DA-related behaviors in adulthood. These findings raise the possibility that changes in dcc function early in life are implicated in the development of DA dysregulation observed in certain psychiatric disorders, such as schizophrenia, or following chronic use of drugs of abuse.

Animals↗
PubMed2001

Naturally occurring sequence polymorphisms within HIV type 1 group O protease.

Mutations within the protease gene associated with reduced susceptibility to protease inhibitors have been well documented for HIV-1 group M subtype B strains. In contrast, limited genotypic and phenotypic information is available for the genetically diverse HIV-1 group O strains. Preexisting resistance-associated polymorphisms have the potential to contribute to a poor virological response to antiviral drug treatment in group O-infected patients. In the present study, the protease genes of 28 protease inhibitor-naive HIV-1 group O-infected patients were analyzed to identify any naturally occurring amino acid polymorphisms associated with drug resistance. Comparison of the consensus group O protease sequence with subtype B of group M indicated that both groups have almost identical sequences in the protease active site, the flap and the substrate-binding site. Analysis of the 28 individual protease sequences revealed polymorphisms at 34% of the positions within the protease gene, but no primary mutations associated with protease inhibitor resistance. In contrast, each of the strains harbored multiple secondary or accessory mutations associated with resistance to protease inhibitors in group M viruses. Residues 10I, 15V, 36I, 41K, 62V, 63T/A/K/I, 64V, 71V, and 93L were identified in most strains. The presence of multiple natural sequence polymorphisms associated with drug resistance in the protease gene of group O viruses may contribute to a more rapid emergence of drug resistance phenotype and treatment failure in group O-infected patients.

Amino Acid Sequence↗
PubMed2001

GABA promotes survival but not proliferation of parvalbumin-immunoreactive interneurons in rodent neostriatum: an in vivo study with stereology.

Amino-acid neurotransmitters regulate a wide variety of developmental processes in the mammalian CNS including neurogenesis, cell migration, and apoptosis. In order to investigate the role of GABA in early development of forebrain interneurons, we determined the survival of parvalbumin-immunoreactive GABAergic interneurons in the adult rat striatum following prenatal exposure to either GABA(A) receptor agonist or antagonist. Unbiased stereology was used to quantify parvalbumin-immunoreactive neuron number in the neostriatum of adult rats exposed to the drugs in utero, and the results were compared to pair-fed or vehicle controls. Embryos were exposed to the GABA(A) antagonist (bicuculline) or agonist (muscimol) during previously defined proliferative or post-proliferative periods for parvalbumin-immunoreactive interneurons. Unbiased stereology using the optical fractionator was used to estimate the total number of parvalbumin-immunoreactive neurons in neostriatum of experimental and control rats. No significant alteration in parvalbumin-immunoreactive neuron number was observed in rats treated with either bicuculline (1 or 2mg/kg/day) or muscimol (1mg/kg/day) during the proliferative phase. Administration of bicuculline during the post-proliferative phase significantly reduced parvalbumin-immunoreactive neuron number in the neostriatum. A concomitant decrease in neostriatal volume was also observed, suggesting that the effect is not restricted to parvalbumin-immunoreactive interneurons. Positional analysis revealed loss of normal regional distribution gradients for parvalbumin-immunoreactive neurons in neostriatum of rats exposed to bicuculline in the embryonic post-proliferative phase. This data collectively suggests that GABA promotes survival but not proliferation of parvalbumin-immunoreactive progenitors. GABA may also promote migration of subpopulations of interneurons that ultimately populate the ventral telencephalon.

Animals↗
PubMed1993

High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR.

Quantitative competitive polymerase chain reaction (QC-PCR) methods were used to quantify virion-associated human immunodeficiency virus type-1 (HIV-1) RNA in plasma from 66 patients with Centers for Disease Control stage I to IVC1 infection. HIV-1 RNA, ranging from 100 to nearly 22,000,000 copies per milliliter of plasma (corresponding to 50 to 11,000,000 virions per milliliter), was readily quantified in all subjects, was significantly associated with disease stage and CD4+ T cell counts, and decreased by as much as 235-fold with resolution of primary infection or institution of antiretroviral therapy. Plasma virus levels determined by QC-PCR correlated with, but exceeded by an average of 60,000-fold, virus titers measured by endpoint dilution culture. Quantitation of HIV-1 in plasma by QC-PCR may be useful in assessing the efficacy of antiretroviral agents, especially in early stage disease when conventional viral markers are often negative.

Acquired Immunodeficiency Syndrome↗
PubMed1993

A new device for blockout procedures in rotational path removable partial dentures.

The rationale of a rotation axis is discussed and on this basis a blockout device is designed for rotational path removable partial dentures. This device has three basic components, which are (1) the acrylic resin block, (2) the rotation axis, and (3) the functional part. In the blockout procedures for removable partial dentures with tilted mandibular molars, the rotation axis of the prosthesis is first localized by the blockout device. A knife edge, made of Duralay resin that corresponds to the survey lines of teeth to be used as supports, is constructed and is joined to the functional part of the blockout device. Blockout regions are determined by the rotational movement of the Duralay resin knife edge along the rotation axis of the blockout device. In addition to the function of blockout, the device can also be used to analyze diagnostic casts for critical undercuts. Internal and external types of blockout devices are also discussed.

Acrylic Resins↗
PubMed1993

(2,3)-alpha-Methylenepenams: synthesis and in vitro activity.

A series of alpha-methylene penicillins was synthesized and SAR were studied. The alpha-isomers were found to be chemically reactive and biologically active in contrast to the beta-isomers. In addition, the alpha-isomers have broader spectrum of in vitro activity than the corresponding penicillins. Generally, the alpha-isomers are more active against gram-negative bacteria than the corresponding penicillins, but slightly weaker in potency towards gram-positive organisms.

Anti-Bacterial Agents↗
PubMed1993

Determination of plasma viral load in HIV-1 infection by quantitative competitive polymerase chain reaction.

OBJECTIVES: To better characterize viral load profiles through the course of HIV-1 disease and in response to treatment, and to further evaluate quantitative competitive polymerase chain reaction for measurement of viral load, we extended our comparative evaluation of this and other viral load measurements to a total of 118 patients, representing all stages of HIV-1 disease. DESIGN: For cross-sectional analysis across the spectrum of HIV-1 disease, plasma viral load was evaluated in 112 HIV-1-infected patients by quantitative competitive polymerase chain reaction analysis, plasma p24 antigen assay, plasma immune complex-dissociated p24 antigen assay and an endpoint dilution viral culture. Longitudinal specimens from six additional patients were analyzed, extending from the time of presentation with symptomatic acute HIV-1 infection through up to more than 2 years of follow-up. Longitudinal specimens were also studied for three patients over the period of initiation of zidovudine treatment, for 6 weeks of treatment and following temporary withdrawal of the treatment. METHODS: All measurement techniques were assessed in replicate aliquots of plasma. RESULTS: Quantitative competitive polymerase chain reaction was the most sensitive measure of viral load, and was best correlated with CD4+ T-cell counts. In longitudinally studied patients, this technique also allowed measurement of plasma virus levels throughout the period of follow-up, even when culture and p24 assays became negative following resolution of acute HIV-1 infection. The quantitative competitive polymerase chain reaction was also able to detect rapid and substantial changes in viral load associated with initiation and temporary withdrawal of antiviral treatment. CONCLUSIONS: The quantitative competitive polymerase chain reaction is promising as a sensitive and accurate method for measuring plasma viral load in HIV-1-infected patients, and is useful for following changes in viral load over the natural history of infection and following treatment intervention. The technique is particularly useful for patients with > 200 x 10(6) CD4+ T cells/l, in whom other viral markers are typically negative.

Biomarkers↗
PubMed1993

Quantitative competitive polymerase chain reaction for accurate quantitation of HIV DNA and RNA species.

Inherent features of the PCR make this procedure suboptimal for quantitative applications. For typical clinical specimens, the absolute amount of product derived from PCR does not always bear a consistent relationship to the amount of target sequence present at the start of the reaction. Competitive PCR approaches to quantitation of nucleic acid sequences overcome the limitations of basic PCR methods for quantitation. We have developed a competitive PCR method known as quantitative competitive PCR for quantitation of HIV DNA and RNA sequences. Key features of the technique include quantitation, based on the relative amounts of products produced from the target sequence and a competitive template introduced into test specimens, and stringent internal control of all reactions, including the reverse transcription step in RNA PCR. The method is suitable for analysis of clinical specimens and may be particularly valuable for accurate quantitation of viral load in patients undergoing treatment with experimental therapies.

Base Sequence↗
PubMed1992

Hepatitis E virus (HEV): strain variation in the nonstructural gene region encoding consensus motifs for an RNA-dependent RNA polymerase and an ATP/GTP binding site.

Hepatitis is transmitted by a number of infectious agents. The epidemiological characterization of waterborne or enterically transmitted non-A, non-B hepatitis (ET-NANBH) is unique when compared with other known hepatitides. We have reported on the molecular cloning of a cDNA clone derived from the etiologic agent associated with ET-NANBH, the hepatitis E virus (HEV). The complete sequence of these first molecular clones, isolated from an HEV-infected human after passage in Macaca fascicularis (cynomolgus macaques), illustrates a distant relationship to other known positive-strand RNA viruses of plants and animals. The translated major open reading frame (ORF-1) from these clones indicates that this portion of the genome encodes a polyprotein with consensus sequences found in RNA-dependent RNA polymerase and ATP/GTP binding domains. The latter activity has been associated with putative helicases of positive-strand RNA viruses. These viral-encoded enzymatic activities identify this region and ORF-1 as containing at least two different nonstructural genes involved in HEV replication. Molecular clones obtained from two other geographically distinct HEV isolates demonstrated sequence heterogeneity in this nonstructural gene region. Further study will be required to elucidate the pathogenic significance (if any) of this observed divergence in the nonstructural region.

Adenosine Triphosphate↗
PubMed1991

[A new blockout instrument for the construction of rotational path removable partial dentures. A case report].

This article introduces a new blockout device for rotational path removable partial dentures. The concept of rotation axis is discussed, from which a more convenient tool for clinical use is derived. The blockout instrument can be divided into three parts: the acrylic block, the rotation axis and the functional part. In the case of tilted mandibular molars, distal and lingual surfaces of anterior abutments should be blocked out according to the rotational path of insertion. In the blockout procedures, the blockout instrument is mounted between the two rotation centers on the two distal abutments with dental stone, so as to coincide the rotation axis of the instrument and that of the denture to be constructed. After the areas below the survey line of the anterior abutments are aproned with wax, Duralay resin is applied onto the areas above the survey line, and extended to join the functional parts of the blockout instrument. After setting, Duralay resin is removed and the portion above the survey line is trimmed to form a knife edge which corresponds to the survey line. Thereafter, the blockout areas are determined by the rotation movement of the knife-edge shaped Duralay resin along the rotation axis of the blockout instrument. This blockout method is more easily performed compared to the method mentioned by Firtell and Jacobson. In addition to the function of blockout, it can also be assisted in analyzing undercut and diagnosis.

Denture, Partial, Removable↗
PubMed1990

Isolation of a cDNA from the virus responsible for enterically transmitted non-A, non-B hepatitis.

Major epidemic outbreaks of viral hepatitis in underdeveloped countries result from a type of non-A, non-B hepatitis distinct from the parenterally transmitted form. The viral agent responsible for this form of epidemic, or enterically transmitted non-A, non-B hepatitis (ET-NANBH), has been serially transmitted in cynomolgus macaques (cynos) and has resulted in typical elevation in liver enzymes and the detection of characteristic virus-like particles (VLPs) in both feces and bile. Infectious bile was used for the construction of recombinant complementary DNA libraries. One clone, ET1.1, was exogenous to uninfected human and cyno genomic liver DNA, as well as to genomic DNA from infected cyno liver. ET1.1 did however, hybridize to an approximately 7.6-kilobase RNA species present only in infected cyno liver. The translated nucleic acid sequence of a portion of ET1.1 had a consensus amino acid motif consistent with an RNA-directed RNA polymerase; this enzyme is present in all positive strand RNA viruses. Furthermore, ET1.1 specifically identified similar sequences in complementary DNA prepared from infected human fecal samples collected from five geographically distinct ET-NANBH outbreaks. Therefore, ET1.1 represents a portion of the genome of the principal viral agent, to be named hepatitis E virus, which is responsible for epidemic outbreaks of ET-NANBH.

Amino Acid Sequence↗
PubMed1989

GLQ223: an inhibitor of human immunodeficiency virus replication in acutely and chronically infected cells of lymphocyte and mononuclear phagocyte lineage.

GLQ223 is a highly purified, formulated preparation of trichosanthin, a 26-kDa plant-derived ribosome-inactivating protein with potent inhibitory activity against human immunodeficiency virus (HIV) in vitro. The compound produced concentration-dependent inhibition of HIV replication in acutely infected cultures of T-lymphoblastoid cells (VB cell line). Treatment with GLQ223 selectively reduced levels of detectable viral proteins compared to total cellular protein synthesis and produced a selective decrease in levels of viral RNA relative to total cellular RNA in acutely infected cells. Substantial inhibition of viral replication was observed at concentrations of GLQ223 that showed little inhibition of parallel uninfected cultures. Selective anti-HIV activity was also observed in cultures of primary monocyte/macrophages chronically infected with HIV in vitro. When freshly drawn blood samples from HIV-infected patients were treated with a single 3-hr exposure to GLQ223. HIV replication was blocked for at least 5 days in subsequently cultured monocyte/macrophages, without further treatment. The anti-HIV activity of GLQ223 in both acutely and chronically infected cells and its activity in cells of both lymphoid and mononuclear phagocytic lineage make it an interesting candidate as a potential therapeutic agent in HIV infection and AIDS.

Antigens, Viral↗
PubMed1988

Isolation of a chicken thioredoxin cDNA clone. Thioredoxin mRNA is differentially expressed in normal and Rous sarcoma virus-transformed chicken embryo fibroblasts.

We have isolated a cDNA clone for chicken thioredoxin by differential screening of a cDNA library. The protein product which this clone encodes is very similar to other thioredoxins, and it displays thioredoxin activity when expressed in Escherichia coli. This clone represents the first metazoan thioredoxin for which the protein or nucleic acid sequence is known. Comparison of the chicken thioredoxin protein sequence with those from bacteria and plants indicates structural features that appear to be essential for activity. Transformation of chicken embryo fibroblasts by Rous sarcoma virus elevates the level of thioredoxin mRNA whereas the level of thioredoxin mRNA in a nonproliferative tissue (brain) is much lower than in chicken embryo fibroblasts.

Amino Acid Sequence↗
PubMed1987

The spleen necrosis virus int gene product expressed in Escherichia coli has DNA binding activity and mediates att and U5-specific DNA multimer formation in vitro.

To facilitate the in vitro study of the spleen necrosis virus (SNV) int gene product, we expressed the viral int locus in an Escherichia coli expression vector. Antiserum made against the protein produced in bacteria precipitated a 44-kDa polypeptide from virus-infected chicken embryo fibroblasts. This result is consistent with the expected size of the SNV int polypeptide. In a protein blotting assay, the expressed protein binds strongly to DNA and was able to complex nonspecifically with both single- and double-stranded DNAs containing or lacking viral sequences. However, under solution conditions favoring transient DNA unwinding, DNA binding was confined to supercoiled molecules containing either the SNV att sequence (the viral cis-acting region required for integration) or the U5 region of the long terminal repeat alone. Under these conditions of specific binding, multimeric DNA species were formed by apparent intermolecular interaction between protein-DNA complexes. These data indicate that retroviral integration may require local DNA unwinding at the att site for complex formation between the int gene product and DNA. This complex may be an intermediate in the viral DNA insertion process.

Amino Acid Sequence↗
PubMed1987

Constitutive expression of a gene encoding a polypeptide homologous to biologically active human platelet protein in Rous sarcoma virus-transformed fibroblasts.

A molecular clone corresponding to a 1.2-kilobase mRNA enriched in Rous sarcoma virus-transformed chicken embryo fibroblasts (CEF) was identified by differential screening of a cDNA library. The induction of the cloned sequence (denoted pCEF-4) in CEF infected by the temperature-sensitive mutant NY72-4 Rous sarcoma virus is rapid and independent of protein synthesis. DNA sequencing of the 1.2-kilobase insert of CEF-4 revealed an open reading frame that predicts an 11-kDa protein. The predicted pCEF-4 gene product is homologous to human connective tissue-activating peptide III (CTAP-III) and platelet factor 4 (PF-4). Serum stimulation of quiescent normal CEF results in a rapid but transient expression of pCEF-4 mRNA. Hence, pCEF-4 mRNA is expressed at the G0-G1 transition and during the first G1 phase of normal CEF reentering the cell cycle. The expression of pCEF-4 mRNA in Rous sarcoma virus-transformed CEF appears to be the result of transcriptional activation and stabilization of the transcript.

Amino Acid Sequence↗