Biomedical subjects

W Kang

Publications and source records attributed to W Kang.

At least 37 records · Page 2Linked to original sources

PubMed2001

Influence of P-glycoprotein modulators on cardiac uptake, metabolism, and effects of idarubicin.

PURPOSE: The clinical utility of anthracyclines like idarubicin (IDA) is limited by the occurrence of multidrug resistance and cardiotoxicity. Previous studies have demonstrated that the multidrug transporter P-glycoprotein (P-gp) is present in the heart and have suggested that it exerts a protective function. We sought to determine the influence of P-gp inhibitors verapamil and PSC 833 on myocardial uptake, metabolism, and actions of IDA. METHODS: In Langendorff-perfused rat hearts, the outflow concentration-time curve and the residual amount in cardiac tissue of IDA and its active metabolite idarubicinol (IDOL) were measured after 0.5 mg dose of IDA in the absence and presence of the P-gp inhibitors verapamil and PSC 833. RESULTS: During perfusion (80 min), 2% of the IDA dose was converted to IDOL in the heart. Myocardial uptake of IDA was significantly increased by verapamil but not by PSC 833, which increased the recovery of IDA and IDOL. IDA significantly decreased left ventricular developed pressure to approximately 40% and increased coronary vascular resistance to 140% of baseline level, respectively. The vasoconstrictive effect was markedly potentiated by PSC 833. CONCLUSIONS: The enhancement of myocardial IDA uptake by verapamil could be due to a decrease in P-gp-mediated efflux. PSC 833 inhibits cardiac metabolism (non-IDOL pathways) and increases the acute cardiotoxicity of IDA.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

PubMed2001

Potential sources of the 1995 Venezuelan equine encephalitis subtype IC epidemic.

Venezuelan equine encephalitis viruses (VEEV) belonging to subtype IC have caused three (1962-1964, 1992-1993 and 1995) major equine epizootics and epidemics. Previous sequence analyses of a portion of the envelope glycoprotein gene demonstrated a high degree of conservation among isolates from the 1962-1964 and the 1995 outbreaks, as well as a 1983 interepizootic mosquito isolate from Panaquire, Venezuela. However, unlike subtype IAB VEEV that were used to prepare inactivated vaccines that probably initiated several outbreaks, subtype IC viruses have not been used for vaccine production and their conservation cannot be explained in this way. To characterize further subtype IC VEEV conservation and to evaluate potential sources of the 1995 outbreak, we sequenced the complete genomes of three isolates from the 1962-1964 outbreak, the 1983 Panaquire interepizootic isolate, and two isolates from 1995. The sequence of the Panaquire isolate, and that of virus isolated from a mouse brain antigen prepared from subtype IC strain P676 and used in the same laboratory, suggested that the Panaquire isolate represents a laboratory contaminant. Some authentic epizootic IC strains isolated 32 years apart showed a greater degree of sequence identity than did isolates from the same (1962-1964 or 1995) outbreak. If these viruses were circulating and replicating between 1964 and 1995, their rate of sequence evolution was at least 10-fold lower than that estimated during outbreaks or that of closely related enzootic VEEV strains that circulate continuously. Current understanding of alphavirus evolution is inconsistent with this conservation. This subtype IC VEEV conservation, combined with phylogenetic relationships, suggests the possibility that the 1995 outbreak was initiated by a laboratory strain.

Amino Acid Sequence↗

PubMed2001

Evolutionary relationships and systematics of the alphaviruses.

Partial E1 envelope glycoprotein gene sequences and complete structural polyprotein sequences were used to compare divergence and construct phylogenetic trees for the genus Alphavirus. Tree topologies indicated that the mosquito-borne alphaviruses could have arisen in either the Old or the New World, with at least two transoceanic introductions to account for their current distribution. The time frame for alphavirus diversification could not be estimated because maximum-likelihood analyses indicated that the nucleotide substitution rate varies considerably across sites within the genome. While most trees showed evolutionary relationships consistent with current antigenic complexes and species, several changes to the current classification are proposed. The recently identified fish alphaviruses salmon pancreas disease virus and sleeping disease virus appear to be variants or subtypes of a new alphavirus species. Southern elephant seal virus is also a new alphavirus distantly related to all of the others analyzed. Tonate virus and Venezuelan equine encephalitis virus strain 78V3531 also appear to be distinct alphavirus species based on genetic, antigenic, and ecological criteria. Trocara virus, isolated from mosquitoes in Brazil and Peru, also represents a new species and probably a new alphavirus complex.

3' Untranslated Regions↗

PubMed2001

Study of retinal nerve fibre layer thickness in eyes with high tension glaucoma and hemifield defect.

AIM: To quantitatively evaluate retinal nerve fibre layer (RNFL) difference in areas of apparently normal appearing visual field in eyes with high tension glaucoma (HTG) and hemifield defects using scanning laser polarimetry. METHODS: 40 eyes from 40 patients with HTG with superior or inferior hemifield defects based on the Humphrey field analyser (HFA) underwent RNFL thickness measurements. 20 normal eyes from 20 subjects matched in age and refractive error were selected as a control group. The RNFL thickness was measured with a scanning laser polarimeter. Mean RNFL thickness was evaluated in four quadrants (superior, inferior, nasal, and temporal). A superior or inferior quadrant in the defined ring of scanning laser polarimetry corresponds to inferior or superior hemifield in HFA. RESULTS: The mean RNFL thickness in the unaffected quadrant (the quadrant corresponding to the hemifield with apparently normal visual field based on HFA) of the HTG group was significantly thinner than the average RNFL thickness of the corresponding quadrant of the control eyes. The RNFL thickness of the unaffected quadrant in the eyes with HTG was reduced and statistically similar to that of the affected quadrant. Symmetry, calculated as the ratio of superior to inferior RNFL thickness, showed no statistical difference between the study and control group. CONCLUSION: Changes in RNFL are present in the apparently normal hemifield in the eyes with HTG. The thickness of the RNFL is reduced symmetrically in both superior and inferior quadrants based on the GDx parameters.

Adult↗

PubMed2001

Virulence and viremia characteristics of 1992 epizootic subtype IC Venezuelan equine encephalitis viruses and closely related enzootic subtype ID strains.

Following a 19-year hiatus, Venezuelan equine encephalitis (VEE) reemerged in western Venezuela in December 1992. This outbreak is important in understanding VEE emergence because phylogenetic studies imply that sympatric, enzootic, subtype ID VEE viruses mutated to generate the epizootic/epidemic. Although the 1992-1993 strains belong to subtype IC, a serotype implicated in extensive outbreaks during the 1960s and in 1995, relatively small numbers of human and equine cases occurred in 1992-1993. We, therefore, evaluated the pathogenicity of these Venezuelan enzootic ID and epizootic IC viruses to determine 1) if they exhibit phenotypes like those described previously for more distantly related enzootic and epizootic strains, and 2) if the 1992-1993 outbreak was limited by the inability of these IC viruses to exploit equines as amplification hosts. All strains were virulent in mice and guinea pigs, but were benign for cotton rats, natural hosts of enzootic viruses. However, only the IC strains produced equine disease, with mean peak viremias of 10(5) suckling mouse 50% lethal doses per mL serum, and some titers exceeding 10(7). These viremias approximate those observed previously with VEE strains isolated during more extensive epizootics, suggesting that efficient equine amplification did not limit the scope and duration of the 1992-1993 outbreak. Enzootic ID virus infection protected all horses from challenge with epizootic strain P676, supporting the hypothesis that epizootics bypass regions of enzootic transmission due to natural immunization of equines by enzootic VEE viruses.

Animals↗

PubMed2000

Ethnic differences in the age-related distribution of serum prostate-specific antigen values: a study in a healthy Korean male population.

OBJECTIVES: To further improve the use of prostate-specific antigen (PSA) as a screening test for prostate cancer in Asian countries, we sought to establish the normal distribution of serum PSA values in Korean men, because, until recently, studies conducted to establish normal serum PSA values have involved few Asian populations. METHODS: Between May 1995 and June 1997, 5805 healthy Korean men 30 to 79 years old who visited our hospital for a routine health checkup were entered into a prospective study of early screening for prostate cancer. All men underwent detailed clinical examinations, including a digital rectal examination and serum PSA determination. All men who were more than 50 years old with abnormal digital rectal examination findings and/or an elevated serum PSA level (greater than 4.0 ng/mL) also underwent transrectal ultrasound-guided sextant biopsy. Four were found to have cancer and were excluded from the analysis. RESULTS: The median serum PSA concentration (5th to 95th percentile range) was 0.8 ng/mL (0.2 to 1.8) for patients 30 to 39 years old (n = 1382); 0.8 ng/mL (0.2 to 2.0) for patients 40 to 49 years old (n = 1776); 0.9 ng/mL (0.2 to 2.4) for those 50 to 59 years old (n = 1775); 1.0 ng/mL (0.2 to 3.9) for men 60 to 69 years old (n = 746); and 1.3 ng/mL (0.5 to 6.3) for patients 70 to 79 years old (n = 122). The serum PSA concentration correlated with age (P <0.001), with an increase by approximately 1.2% annually, although the statistical correlation was weak (r = 0.16). Almost no change occurred in the median serum PSA value in patients 50 years old or younger; a gradual increase was observed in patients older than 50. In those 50 years old or older, the median and 95th percentile serum PSA values for Korean men were lower than those for white men. CONCLUSIONS: Contrary to earlier observations that the serum PSA level strongly correlates with age, the influence of age on serum PSA was found to be weaker in this study. Moreover, the results also demonstrated that the distribution of the serum PSA level differs along ethnic lines. The cutoff value for serum PSA in mass screening for prostate cancer should be adjusted in nonwhite races.

Adult↗

PubMed2000

Quantum hall ferromagnetism in a two-dimensional electron system

Experiments on a nearly spin degenerate two-dimensional electron system reveals unusual hysteretic and relaxational transport in the fractional quantum Hall effect regime. The transition between the spin-polarized (with fill fraction nu = 1/3) and spin-unpolarized (nu = 2/5) states is accompanied by a complicated series of hysteresis loops reminiscent of a classical ferromagnet. In correlation with the hysteresis, magnetoresistance can either grow or decay logarithmically in time with remarkable persistence and does not saturate. In contrast to the established models of relaxation, the relaxation rate exhibits an anomalous divergence as temperature is reduced. These results indicate the presence of novel two-dimensional ferromagnetism with a complicated magnetic domain dynamic.

Journal Article↗

PubMed2000

Tunnelling between the edges of two lateral quantum Hall systems

The edge of a two-dimensional electron system in a magnetic field consists of one-dimensional channels that arise from the confining electric field at the edge of the system. The crossed electric and magnetic fields cause electrons to drift parallel to the sample boundary, creating a chiral current that travels along the edge in only one direction. In an ideal two-dimensional electron system in the quantum Hall regime, all the current flows along the edge. Quantization of the Hall resistance arises from occupation of N one-dimensional edge channels, each contributing a conductance of e2/h. Here we report differential conductance measurements, in the integer quantum Hall regime, of tunnelling between the edges of a pair of two-dimensional electron systems that are separated by an atomically precise, high-quality, tunnel barrier. The resultant interaction between the edge states leads to the formation of new energy gaps and an intriguing dispersion relation for electrons travelling along the barrier: for example, we see a persistent conductance peak at zero bias voltage and an absence of tunnelling features due to electron spin. These features are unexpected and are not consistent with a model of weakly interacting edge states. Remnant disorder along the barrier and charge screening may each play a role, although detailed numerical studies will be required to elucidate these effects.

Journal Article↗

PubMed2000

Significantly increased expression of beta-glucuronidase in the central nervous system of mucopolysaccharidosis type VII mice from the latency-associated transcript promoter in a nonpathogenic herpes simplex virus type 1 vector.

Herpes simplex virus (HSV) has the ability to establish life-long latent infections in postmitotic neurons and to remain transcriptionally active, continuously expressing latency-associated transcripts (LAT) while producing minimal disease. These properties have made HSV an excellent candidate for neuronal gene transfer. Previously, we have shown that in mucopolysaccharidosis type VII mice (MPS VII, beta-glucuronidase deficiency) the LAT promoter is capable of expressing beta-glucuronidase (GUSB) in the trigeminal ganglion and the brainstem after latency is established. However, the number of neurons expressing GUSB is much lower than the number expressing 2-kb LAT following a wild-type virus infection. In this study, we have evaluated the effect of the position of the coding sequence relative to the LAT promoter on beta-glucuronidase gene expression in the central nervous system (CNS). Non-neurovirulent (ICP-34.5-deleted HSV-1) vectors were used, allowing direct intracranial injection. Significantly more GUSB activity was detected in brains of MPS VII mice inoculated with a recombinant virus (HSV-LAT-GUSB-JS) in which the GUSB cDNA was inserted near the LAT promoter, compared to viruses where it was inserted farther downstream in either the LAT exon 1 or overlapping exon 1 and the 2-kb LAT intron. This vector produced more than 100 times the number of positive cells than the other constructs. During acute infection, the distribution of viral replication differed from the distribution of GUSB enzyme expression. Viral antigen was predominately present in cells around the site of injection in the caudate putamen and in ependymal cells lining the ventricles. In contrast, GUSB expression was present mainly in cells of the thalamus and hypothalamus, which did not exhibit viral antigen, suggesting that GUSB enzyme activity was expressed from latently but not acutely infected neuronal cells. This vector design should be useful for high-level expression of various genes in the CNS.

Animals↗

PubMed2000

Overexpression of proenkephalin in the amygdala potentiates the anxiolytic effects of benzodiazepines.

To elucidate the role of opioid peptides in control of the anxiety-like behavior and anxiety-reducing actions of benzodiazepines, a recombinant, replication-defective herpes virus (SHPE) carrying human preproenkephalin cDNA was delivered to rat amygdala. Viral infection resulted in a strong, localized transgene expression after 2-4 days which diminished after one week. Anxiety-like behavior and the anxiolytic effect of diazepam were assessed three days after gene delivery using the elevated plus maze test. While SHPE infection alone did not reduce anxiety-like behavior, rats infected with SHPE exhibited a greater response to the anxiolytic effect of diazepam when compared to rats infected with a control virus (SHZ.1) containing the lacZ gene. The enhancement of diazepam action by SHPE was naloxone reversible, region-specific, and correlated with the time course of preproenkephalin expression. The findings implicate amygdalar opioid peptides in regulating the anxiolytic effects of benzodiazepines. This study also demonstrates the usefulness of recombinant herpes virus in evaluating the role of single gene products within specific brain sites in pharmacological responses and complex behaviors.

Amygdala↗

PubMed2000

Evidence for nucleic acid binding ability and nucleosome association of Bombyx mori nucleopolyhedrovirus BRO proteins.

The Bombyx mori nucleopolyhedrovirus (BmNPV) genome contains five related members of the bro gene family, all of which are actively expressed in infected BmN cells. Although their functions are unknown, their amino acid sequences contain a motif found in all known viral and prokaryotic single-stranded DNA binding proteins. To determine if they bind to nucleic acids, we fractionated the nuclei of BmNPV-infected BmN cells using a histone extraction protocol. We detected BRO-A, BRO-C, and BRO-D in the histone H1 fraction using anti-BRO antibodies. Micrococcal nuclease treatment released these BRO proteins from the chromatin fraction, suggesting their involvement in nucleosome structures. Chromatographic fractionation showed that BRO-A and/or BRO-C interacted with core histones. Expression of partial sequences of BRO-A proved that the N-terminal 80 amino acid residues were required for DNA binding activity. We also demonstrated that BmNPV BRO proteins underwent phosphorylation and ubiquitination followed by proteasome degradation, which may explain their distribution in the cytoplasm as well as the nucleus. We propose that BRO-A and BRO-C may function as DNA binding proteins that influence host DNA replication and/or transcription.

Animals↗

PubMed2000

[Effect of radiotherapy on penetration of 5-FU in blood-pancreatic barrier in rats].

OBJECTIVE: To investigate the effect of radiotherapy dose on penetration of 5-FU (5-fluorouracil) in blood-pancreatic barrier in rats. METHODS: After the pancreatic region of the rats were irradiated by 2, 10, 20, 30 and 40 (Gy) doses of gamma-ray, we investigated the penetration ratio (PR) of 5-FU in the pancreatic tissue with HPLC assay. RESULTS: When treated with low-dose of gamma-ray (2 Gy), the PR of 5-FU increased obviously after 8 hours. But in the high-dose groups (>/= 10 Gy), the PR was less than or had no difference with control group. At the same time, we found that the islets had appeared pathological degeneration, while the pancreatic lobular structure, acini and ducts had no visible changes in 20 Gy group. CONCLUSIONS: After the treatment of low-dose of gamma-ray combined with 5-FU, the effect of chemoradiotherapy may be improved for enhanced PR of 5-FU in pancreatic tissue, and at the same time, chemotherapy and radiotherapy cooperate with each other. But in high dose groups (>/= 10 Gy), radiotherapy may reduce the effect of chemotherapy in acute phase. After high-dose radiotherapy, we should pay attention to the change of glucose-resistance of patient to reduce the incidence of radiotherapy complication.

Animals↗

PubMed2000

[Change of 5-fluorouracil penetration in blood-pancreatic barrier of rats after high-dose radiotherapy].

OBJECTIVE: The high-dose intraoperative radiotherapy has become an important therapy to control local recur of pancreatic carcinoma. But the relevant effect of high-dose radiotherapy on chemotherapy is not clear now. METHODS: We studied the effect of high-dose radiotherapy to the penetration of 5-FU (5-Fluorouracil) in blood-pancreatic barrier of rats after the pancreatic region of the rats had treated with 10(Gy) external beam radiotherapy, the penetration ratio (PR) of 5-FU in the pancreatic tissue was investigated with HPLC assay. RESULTS: We found the PR increased with the time processing. And reached the peak on the 6th day, (PR = 0.8300 +/- 0.1662, P < 0.05). Then, the PR began to descend and was 0.7028 on the 10th day. But it was still significantly higher than control group (P < 0.05). CONCLUSION: After the treatment of high-dose radiotherapy, in addition to chemotherapy on the 4th day, and finished the course on the 10th day, the effect of radiotherapy may improve chemotherapy significantly.

Animals↗

PubMed1999

Identification of a novel 0.7-kb polyadenylated transcript in the LAT promoter region of HSV-1 that is strain specific and may contribute to virulence.

Herpes Simplex virus expresses latency-associated transcripts (LATs) the function of which remains obscure despite increasing knowledge of their structure and expression. Upstream of the LAT coding region is a region of the genome that is poorly characterized although it lies in an area that is responsible for modulation of reactivation efficiency in two different animal models. Transcript mapping with strains 17, McKrae, KOS, and F has revealed strain differences in this region of the viral genome. Strain 17 and McKrae expressed a novel polyadenylated 0.7-kb transcript that is absent from KOS and F. This transcript is expressed in the LAT direction and has the kinetics of a true late gene during the lytic cycle of infection. A deletion mutant, 17DeltaBsa, which does not express the 0.7-kb RNA, is less virulent than the parental strain 17. A rescuant with F sequence (17DeltaBsa/RF) shows virulence similar to F, whereas a rescuant with strain 17 sequence (17DeltaBsa/R17) is similar to strain 17. Virulence is altered by deletion or substitution in the region encoding the 0.7-kb transcript (BsaI-BsaI); however, reactivation in the mouse explant cocultivation assay or the adrenergically induced rabbit reactivation model remained unchanged. The importance of this region for virulence is discussed.

Animals↗

PubMed1999

Changes in nociceptive and anxiolytic responses following herpes virus-mediated preproenkephalin overexpression in rat amygdala are naloxone-reversible and transient.

These results using herpes virus-mediated gene transfer to overexpress enkephalin in the amygdala support the role of amygdalar opioids in the anxiolytic actions of benzodiazepines and supraspinal nociception (see ref. 1). These studies also demonstrate the usefulness of recombinant herpes virus in evaluating the role of single gene products within specific brain sites in pharmacological responses and complex behaviors.

Amygdala↗

PubMed1999

Characterization of baculovirus repeated open reading frames (bro) in Bombyx mori nucleopolyhedrovirus.

The baculovirus Bombyx mori nucleopolyhedrovirus (BmNPV) contains five related open reading frames (ORFs). Recent sequence analyses of several other baculovirus genomes reveal that these ORFs belong to a unique multigene family called the baculovirus repeated ORFs (bro) family. Here we have characterized these five genes from BmNPV at the transcriptional and translational levels. Reverse transcription-PCR and primer extension analyses indicated that transcription of all bro genes occurs by 2 to 4 h postinfection (p.i.) and reaches maximal levels between at 8 and 12 h p.i. Transcription of all genes is initiated between 50 and 70 nucleotides upstream of the start codon, at a characteristic C(T)AGT motif. Expression of a cat reporter gene under the control of each bro promoter provides evidence that a viral factor(s) is required for the transcription of all bro genes. Immunoblot analysis indicated that a population of BRO proteins is produced vigorously between at 8 and 14 h p.i. Immunohistochemical analysis by confocal microscopy showed that BRO proteins are localized in both the nucleus and the cytoplasm at 8 h p.i. Four BmNPV mutants, in which the bro-a, bro-b, bro-c, and bro-e genes were individually inactivated, were successfully isolated. However, exhaustive efforts failed to isolate a bro-d-deficient mutant. Similarly, it was not possible to isolate a double-deletion bro-a bro-c mutant. The bro-d gene may play an irreplaceable functional role(s) during viral infection, while bro-a and bro-c may functionally complement each other.

Amino Acid Sequence↗

PubMed1999

Genetic and fitness changes accompanying adaptation of an arbovirus to vertebrate and invertebrate cells.

The alternating host cycle and persistent vector infection may constrain the evolution of arboviruses. To test this hypothesis, eastern equine encephalitis virus was passaged in BHK or mosquito cells, as well as in alternating (both) host cell passages. High and low multiplicities were used to examine the effect of defective interfering particles. Clonal BHK and persistent mosquito cell infections were also evaluated. Fitness was measured with one-step growth curves and competition assays, and mutations were evaluated by nucleotide sequencing and RNA fingerprinting. All passages and assays were done at 32 degrees C to eliminate temperature as a selection factor. Viruses passaged in either cell type alone exhibited fitness declines in the bypassed cells, while high-multiplicity and clonal passages caused fitness declines in both types of cells. Bypassed cell fitness losses were mosquito and vertebrate specific and were not restricted to individual cell lines. Fitness increases occurred in the cell line used for single-host-adaptation passages and in both cells for alternately passaged viruses. Surprisingly, single-host-cell passage increased fitness in that cell type no more than alternating passages. However, single-host-cell adaptation resulted in more mutations than alternating cell passages. Mosquito cell adaptation invariably resulted in replacement of the stop codon in nsP3 with arginine or cysteine. In one case, BHK cell adaptation resulted in a 238-nucleotide deletion in the 3' untranslated region. Many nonsynonymous substitutions were shared among more than one BHK or mosquito cell passage series, suggesting positive Darwinian selection. Our results suggest that alternating host transmission cycles constrain the evolutionary rates of arboviruses but not their fitness for either host alone.

Adaptation, Biological↗

PubMed1999

Evaluation of the completeness of cancer case ascertainment in the Seoul male cohort study: application of the capture-recapture method.

Since the completeness of case ascertainment is directly related to the validity of a study, the evaluation of completeness is an essential feature of a cohort study. To estimate the completeness of cancer case ascertainment during a three year period (Jan. 1, 1993, to Dec. 31, 1995) in which the Seoul Male Cohort was followed up, we applied capture-recapture method. Data were obtained from the cancer registries, medical records and death certificates, with cases identified from each source numbering 103, 105, and 38, respectively. After eliminating duplicate cases, the total number was 141, and by using a log-linear model, the number of cases not detected by any of the three data sources was estimated to be 16. For all cancers, the estimated completeness of follow-up was 89.9%.

Adult↗