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Biomedical subjects

Wei-Kung Wang

Publications and source records attributed to Wei-Kung Wang.

At least 19 recordsLinked to original sources
PubMed2006

Slower rates of clearance of viral load and virus-containing immune complexes in patients with dengue hemorrhagic fever.

BACKGROUND: Although previous studies have revealed the contribution of an initial high level of dengue virus replication to the severe and potentially life-threatening diseases dengue hemorrhagic fever (DHF) and dengue shock syndrome, the involvement of dengue virus in the immunopathological processes during the transition from fever to defervescence, which is a critical stage in determining the progression to DHF, has not been appreciated. Previously, we reported that dengue virus can be detected in the immune complexes of patients with DHF during this period. METHODS: We investigated plasma dengue viral load, virus in immune complexes, antibody response, complements, and cytokines for 54 patients with dengue fever (a relatively mild form of disease) and 49 patients with DHF. The patients had confirmed secondary infection with dengue virus type 2 from a large outbreak in southern Taiwan in 2002. RESULTS: Patients with DHF had a significantly higher viral load and a slower rate of clearance than patients with dengue fever. For viral loads >5.7 log RNA copies/mL on the day of defervescence, the positive and negative predictive values for DHF are 0.88 and 0.95, respectively. A higher level and slower decline of dengue virus-containing immune complexes (and a subsequently higher elevation of C5a and soluble interleukin 2 receptor) were found in patients with DHF, compared with patients with dengue fever. CONCLUSIONS: These findings indicate that slower rates of clearance of viral load and virus-containing immune complexes are associated with subsequent immune activation and contribute to the progression of DHF at this critical stage. Moreover, viral load on the day of defervescence can predict cases of DHF.

Adolescent↗
PubMed2005

Strategically examining the full-genome of dengue virus type 3 in clinical isolates reveals its mutation spectra.

BACKGROUND: Previous studies presented the quasispecies spectrum of the envelope region of dengue virus type 3 (DENV-3) from either clinical specimens or field-caught mosquitoes. However, the extent of sequence variation among full genomic sequences of DENV within infected individuals remains largely unknown. RESULTS: Instead of arbitrarily choosing one genomic region in this study, the full genomic consensus sequences of six DENV-3 isolates were used to locate four genomic regions that had a higher potential of sequence heterogeneity at capsid-premembrane (C-prM), envelope (E), nonstructural protein 3 (NS3), and NS5. The extent of sequence heterogeneity revealed by clonal sequencing was genomic region-dependent, whereas the NS3 and NS5 had lower sequence heterogeneity than C-prM and E. Interestingly, the Phylogenetic Analysis by Maximum Likelihood program (PAML) analysis supported that the domain III of E region, the most heterogeneous region analyzed, was under the influence of positive selection. CONCLUSION: This study confirmed previous reports that the most heterogeneous region of the dengue viral genome resided at the envelope region, of which the domain III was under positive selection pressure. Further studies will need to address the influence of these mutations on the overall fitness in different hosts (i.e., mosquito and human) during dengue viral transmission.

Adult↗
PubMed2005

The eccentric position of the heart in the mammalian body and optimal energy transfer in single tube models.

Many phenomena cannot be explained by traditional haemodynamics models. For example, the hearts of all mammals are neither at one end of the circulatory system nor at the geometric centre. Based on a new circulation model, we report that if the heart is located at either of these two positions, the energy saving rule will be violated. We assume that the main arterial system is under a steady, distributed transverse vibration with the heart as the input power source. The equation of motion of the artery is governed by a new pressure wave equation with total energy. We analyse the effects of the heart position on the pressure pulse shape and the spectrum. By a simplifying T-tube model, we find that there are many harmonic oscillating modes for the overall arterial system. The position of the heart affects the weights of different modes. If the heart is at the midpoint or at one end of the body, none of the even harmonic modes can be excited. If the heart is at a third along the whole system, the third oscillation mode in the system is missing. Thus, from an efficiency point of view, this model gives a strong reason for all mammals' hearts being at an eccentric position. Tube simulations were carried out to confirm the theoretical prediction. A new standing wave model to analyse the variation of the pressure pulse shape along the artery is discussed. The interesting result indicates that our new pressure wave equation possesses a high problem solving potential. It provides a new tool for studying arterial dynamics.

Animals↗
PubMed2005

Detection of severe acute respiratory syndrome coronavirus RNA in plasma during the course of infection.

We examined severe acute respiratory syndrome-associated coronavirus (SARS-CoV) RNA in plasma of 32 patients (probable SARS cases) by a quantitative real-time reverse transcription-PCR assay and reported that the highest detection rate, 75%, was found between day 5 and day 7 of illness, followed by rates of 64, 50, and 38% found between day 8 and day 11, day 2 and day 4, and day 12 and day 16, respectively. Analysis of sequential SARS-CoV load in plasma from six cases revealed different patterns of viremia, with the peak between day 4 and day 8. Our findings of the high detection rate of SARS-CoV RNA in plasma before day 11, together with the relative convenience of collecting and handling plasma, suggest that plasma can be used for early diagnosis of SARS.

Adult↗
PubMed2005

Immunofluorescence assay for detection of the nucleocapsid antigen of the severe acute respiratory syndrome (SARS)-associated coronavirus in cells derived from throat wash samples of patients with SARS.

An antigen detection assay for severe acute respiratory syndrome (SARS) coronavirus was established in this study by an indirect immunofluorescence test, which utilized cells derived from throat wash samples of patients with SARS and a rabbit serum that recognized the nucleocapsid protein of SARS-associated coronavirus (SARS-CoV) but not that of other human coronavirus tested. It detected SARS-CoV in 11 of 17 (65%) samples from SARS patients as early as day 2 of illness but in none of the 10 samples from healthy controls. Compared with other diagnostic modalities for detecting SARS-CoV, this assay is simpler, more convenient, and economical. It could be an alternative for early and rapid diagnosis, should SARS return in the future.

Antigens, Viral↗
PubMed2004

Temporal relationship of viral load, ribavirin, interleukin (IL)-6, IL-8, and clinical progression in patients with severe acute respiratory syndrome.

Although viral replication and overwhelming immune responses are believed to contribute to the progression of severe acute respiratory syndrome (SARS), little is known about the temporal relationship between viral load, ribavirin, proinflammatory cytokines, and clinical progression. We report that ribavirin was not effective in reducing the SARS coronavirus load in 3 of 8 probable cases studied and that elevated levels of interleukin (IL)-6 and IL-8 subsequent to the peak viral load were found in 8 and 6 cases, respectively. The nadir lymphocyte count during lymphopenia, the peak level of lactate dehydrogenase, and the peak density of pulmonary infiltrates lag further behind the peak viral load by a median of 4, 5, and 3.5 days, respectively. These findings provide important information for therapeutic strategies to treat SARS.

Adult↗
PubMed2004

Preparation and anti-HIV activities of retrojusticidin B analogs and azalignans.

Ten lignans (2-11) and a series of azalignans including 1-aryl-pyrronaphthalenes 20-24 and 3-N-alkylaminomethyl-1-arylnaphthalenes 25-28, structurally related to two HIV reverse transcriptase inhibitors, retrojusticidin B and phyllamyricin A, were prepared from phyllanthin (1) for evaluation of anti-HIV activities. Anti-HIV activity of these compounds on a R5 pseudotype virus, ConB/pNL43E-L+, in the U87-CD4-CCR5 cells has been measured. Compounds 5, 22, 23, and 28 showed good anti-HIV activity with IC(50) value of 0.25, 1.07, 0.01, 0.32 microg/mL, respectively.

Anti-HIV Agents↗
PubMed2004

Lymphocyte activation and hepatic cellular infiltration in immunocompetent mice infected by dengue virus.

Activation and expansion of dengue virus-specific T cells and abnormal liver functions in dengue patients have been documented. However, it remains to be determined whether T cells are involved in the pathogenic mechanism of dengue virus infection. In this study, immunocompetent C57BL/6 mice were employed to study dengue virus-induced T cell activation. Mice were inoculated with 10(8) PFU dengue virus serotype 2 strain 16681 by the intravenous route. Dengue viral core RNA was detected by RT-PCR in mouse serum, liver, spleen, and brain at different time points after infection. Splenic T cells were activated as evidenced by their expression of CD69 and O-glycosylated CD43 at as early as day 3 after infection. Splenic T cell expression of O-glycosylated CD43 and IFN-gamma production coordinately peaked at day 5. Coincided with the peak of splenic T cell activation was hepatic lymphocyte infiltration and elevation of liver enzymes. Flow cytometric analysis revealed the infiltrating CD8(+) T cell to CD4(+) T cell ratio was 5/3. After a second inoculation of dengue virus, hepatic T cell infiltration and liver enzyme levels increased sharply. The infiltrating hepatic CD8(+) T cell to CD4(+) T cell ratio increased to 5.8/1. A strong correlation was found between T cell activation and hepatic cellular infiltration in immunocompetent mice infected with dengue virus. The kinetics of liver enzyme elevation also correlated with that of T cell activation. These data suggest a relationship between T cell infiltration and elevation of liver enzymes.

Alanine Transaminase↗
PubMed2004

Pressure pulse velocity is related to the longitudinal elastic properties of the artery.

It is known that arteries in their natural position are always subject to a longitudinal stress. However, the effect of this strong longitudinal tension has seldom been addressed. In this paper, we point out that the traditional pulse wave velocity formulae considering only the circumferential elasticity fail to include all the important energies. We present a vigorous derivation of a pressure wave equation, the pressure wave equation with total energy, which considers all the important energies of the whole arterial system by treating the arterial wall and the blood as one system. Our model proposes that the energy transport in the main arterial system is primarily via the transverse vibration motion of the elastic wall. The final equation indicates that the longitudinal stress is essential and the high frequency phase velocity is related to the longitudinal tension along the arterial wall and its Young's shearing modulus. By applying this equation, we suggest that longitudinal elastic property is an important factor in hemodynamics and in the treatment of cardiovascular diseases.

Animals↗
PubMed2004

Losing harmonic stability of arterial pulse in terminally ill patients.

OBJECTIVE: To measure the coefficient of variation of the harmonic magnitude (HCV) of the radial arterial pulse before death of cancer patients. METHODS: We non-invasively recorded the radical arterial pulse of 21 end-stage cancer patients, 31 healthy subjects, and 47 outpatient department (OPD) patients. During the 2-week study, eight cancer patients expired. RESULTS: There were no considerable differences in diastolic or systolic blood pressure between cancer patients and other subjects; however, all six HCVs were significantly higher in the cancer patients (P<0.05). Within the cancer patient group, the first and second HCV were notably higher in the patients that expired (P<0.05), and the first to fourth HCVs were significantly increased on their last day (P<0.05). In the control healthy subjects and the OPD group, the HCVs were below 5 and 8%, respectively. In the cancer patients, the third to sixth HCVs were higher than 15%. On the last day of the cancer patients that expired, even the first and second HCVs were higher than 15%. CONCLUSIONS: During the dying process, the traditional diastolic and systolic blood pressure did not show significant changes; however, all the harmonic components gradually lost their stability. The HCVs, which increased first for the high-frequency components and then the low-frequency components, could quantitatively reflect the severity of different stages of illness.

Aged↗
PubMed2004

The natural frequencies of the arterial system and their relation to the heart rate.

We assume the major function of the arterial system is transporting energy via its transverse vibration to facilitate the blood flowing all the way down to the microcirculation. A highly efficient system is related to maintaining a large pressure pulse along the artery for a given ventricular power. The arterial system is described as a composition of many infinitesimal Windkessels. The strong tethering in the longitudinal direction connects all the Windkessels together and makes them vibrate in coupled modes. It was assumed that at rest condition, the arterial system is in a steady distributed oscillatory state, which is the superposition of many harmonic modes of the transverse vibration in the arterial wall and the adherent blood. Every vibration mode has its own characteristic frequency, which depends on the geometry, the mass density, the elasticity, and the tethering of the arterial system. If the heart rate is near the fundamental natural frequency, the system is in a good resonance condition, we call this "frequency matching." In this condition, the pulsatile pressure wave is maximized. A pressure wave equation derived previously was used to predict this fundamental frequency. The theoretical result gave that heart rate is proportional to the average high-frequency phase velocity of the pressure wave and the inverse of the animal body length dimension. The area compliance related to the efficiency of the circulatory system is also mentioned.

Animals↗
PubMed2004

Study of sequence variation of dengue type 3 virus in naturally infected mosquitoes and human hosts: implications for transmission and evolution.

Dengue virus is an arbovirus that replicates alternately in the mosquito vector and human host. We investigated sequences of dengue type 3 virus in naturally infected Aedes aegypti mosquitoes and in eight patients from the same outbreak and reported that the extent of sequence variation seen with the mosquitoes was generally lower than that seen with the patients (mean diversity, 0.21 versus 0.38% and 0.09 versus 0.23% for the envelope [E] and capsid [C] genes, respectively). This was further verified with five experimentally infected mosquitoes (mean diversity, 0.09 and 0.10% for the E and C genes, respectively). Examination of the quasispecies structures of the E sequences of the mosquitoes and of the patients revealed that the sequences of the major variants were the same, suggesting that the major variant was transmitted. These findings support our hypothesis that mosquitoes contribute to the evolutionary conservation of dengue virus by maintaining a more homogenous viral population and a dominant variant during transmission.

Aedes↗
PubMed2004

Detection of SARS-associated coronavirus in throat wash and saliva in early diagnosis.

The severe acute respiratory syndrome-associated coronavirus (SARS-CoV) is thought to be transmitted primarily through dispersal of droplets, but little is known about the load of SARS-CoV in oral droplets. We examined oral specimens, including throat wash and saliva, and found large amounts of SARS-CoV RNA in both throat wash (9.58 x 10(2) to 5.93 x 10(6) copies/mL) and saliva (7.08 x 10(3) to 6.38 x 10(8) copies/mL) from all specimens of 17 consecutive probable SARS case-patients, supporting the possibility of transmission through oral droplets. Immunofluorescence study showed replication of SARS-CoV in the cells derived from throat wash, demonstrating the possibility of developing a convenient antigen detection assay. This finding, with the high detection rate a median of 4 days after disease onset and before the development of lung lesions in four patients, suggests that throat wash and saliva should be included in sample collection guidelines for SARS diagnosis.

Adult↗
PubMed2003

High levels of plasma dengue viral load during defervescence in patients with dengue hemorrhagic fever: implications for pathogenesis.

Studies of the pathogenesis of dengue hemorrhagic fever (DHF), a potentially life-threatening disease, have revealed the importance of initial high levels of virus replication. However, the possible involvement of virus during the transition from fever to defervescence, a critical stage in determining the severity of disease, has not been appreciated. Using quantitative reverse transcription-polymerase chain reaction, we examined the levels of plasma dengue viral load during both fever and defervescence periods in patients from a DEN-3 outbreak in southern Taiwan in 1998. Higher levels of plasma dengue viral RNA were found in DHF patients than in DF patients. During defervescence, while the level of plasma dengue viral RNA was undetectable in most DF patients, it remains high in all DHF patients. Using a modified immunoprecipitation assay, we demonstrated for the first time that the plasma dengue viruses persisting during defervescence were in the immune complexes for most DHF patients. These findings suggest that continued active viral replication or delay in the clearance of viremia contributes to the pathogenesis of DHF. Moreover, high levels of plasma dengue viral RNA during defervescence may serve as a disease marker for DHF.

Adult↗
PubMed2003

Microbiologic characteristics, serologic responses, and clinical manifestations in severe acute respiratory syndrome, Taiwan.

The genome of one Taiwanese severe acute respiratory syndrome-associated coronavirus (SARS-CoV) strain (TW1) was 29,729 nt in length. Viral RNA may persist for some time in patients who seroconvert, and some patients may lack an antibody response (immunoglobulin G) to SARS-CoV <21 days after illness onset. An upsurge of antibody response was associated with the aggravation of respiratory failure.

Adult↗
PubMed2003

Evaluation of herbal formulas by pulse analysis method.

AIM: To distinguish the component difference between two similar herbal formulas by pulse analysis method. Many Chinese herbs were found to have specific effects on the Fourier components of the blood pressure pulse; it might infer a specific blood redistribution process on the body and reflect the health conditions of specific organs or tissues. The pulse effect of an herbal formula was similar to the linear combination of all its herbal compositions. METHODS: Two different versions of the herbal formula Liu-Wei-Dihuang were fed to the Wistar rats as a single blind test. The blood pressure pulses on the rat tail artery were recorded and then transformed to the frequency domain by Fourier analyzer. RESULTS: Formula A, Bai-Wei-Dihuang, with two more herbs Cortex Cinnamomi and Radix Aconiti added to Liu-Wei-Dihuang, increased the harmonic proportion of the 1st harmonic (C1) but decreased C4, C5. Formula B is composed in the same way but without Rhizoma Batatatis and Poria cocos; it increased the DC of the pulse spectrum (C0), but decreased C2, C3, C4, C5, C6. CONCLUSION: The component adjustment of an herbal formula could be distinctly and quantitatively detected by pulse analysis method.

Animals↗
PubMed2003

Concurrent infections by two dengue virus serotypes among dengue patients in Taiwan.

The co-circulation of multiple dengue virus serotypes in the same region has been reported in several countries in Southeast Asia as well as in Central and South America for decades. Although outbreaks involving more than one serotype of dengue virus have been reported in Taiwan since 1987, concurrent infection in the same individual by multiple serotypes of dengue virus have never been identified. Using a modified multiplex reverse transcription-polymerase chain reaction assay, we detected and determined the serotypes of 21 dengue patients during an outbreak in southern Taiwan in 2000. While either dengue type 2 or type 3 virus was found in most cases, 2 of the 21 cases were concurrent infections by both dengue type 2 and dengue type 3 viruses. This was further confirmed by sequence analysis of the amplified products. This study reports for the first time that concurrent infections occur in Taiwan, and suggests that future virologic surveillance of dengue outbreak in Taiwan should take this into consideration.

Base Sequence↗