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Biomedical subjects

J R Wang

Publications and source records attributed to J R Wang.

At least 19 recordsLinked to original sources

Complete genome analysis of enterovirus 71 isolated from an outbreak in Taiwan and rapid identification of enterovirus 71 and coxsackievirus A16 by RT-PCR.

Hand, foot, and mouth disease (HFMD) and encephalomyelitis were two major clinical manifestations during the 1998 enterovirus 71 (EV71) epidemic in Taiwan. To investigate whether different clinical patterns were caused by alterations in EV71 genomes, the complete nucleotide sequences of four EV71 strains associated with HFMD or encephalomyelitis were compared. Among these viral strains, two or three nucleotide differences were found within the 5'-noncoding region, and two or four amino acid differences were found within the regions encoding viral polyproteins; however, none of these differences were correlated with either clinical manifestation. Because coxsackievirus A16 was another major causative agent of HFMD, a reverse transcription-polymerase chain reaction assay, with high sensitivity and specificity for identification of EV71 (both 100%) and coxsackievirus A16 (100 and 98.8%), was developed for the rapid differential identification of these two viruses in HFMD patients.

5' Untranslated Regions↗

Molecular epidemiology of enterovirus 71 in Taiwan.

Taiwan suffered a severe and widespread outbreak of enterovirus infection in 1998. More than 400 children were hospitalized, with seventy-eight fatalities due to central nerve system (CNS) involvement and cardiopulmonary collapse. Enterovirus 71 (EV71) was incriminated as the causative agent for the fatal cases. To understand the viral molecular epidemiology in this outbreak, fragments of 207-bp length of the VP4 region in 23 Taiwanese EV 71 isolates were sequenced. Pair-wise comparison revealed a 17.5-24.4% difference between the isolates and the prototype BrCr. However, all the changes in the VP4 region of the isolated strains were synonymous substitutions. Phylogenetic analysis was performed on these 23 isolates and 21 others deposited in GenBank. In this study, forty-four EV71 isolates from the world were separated into three distinct genotypes: A, B and C. The EV71 prototype strain, BrCr/70, is the only strain of genotype A. Group B included strains from the United States, Japan and Taiwan. Most strains in genotype B were isolated prior to 1990. Group C consisted of strains from Japan and Taiwan. Most strains of genotype C were isolated after 1990, they were further divided into 3 clusters: i.e. C-1, C-2 and C-3. In Taiwan, two genotypes, B and C-3, were co-circulating during the outbreak in 1998, although a minor group of genotype B may have appeared in Taiwan before 1986. The majority of the isolates clustered in genotype C-3. Genotype C showed a higher evolutionary rate than genotype B (3.9 x 10(-3) vs. 1.4 x 10(-3)) in the VP4 region. There seems to be a worldwide trend with strains of genotype B appearing earlier than strains of genotype C which took over later in the dominance.

Base Sequence↗

The thermal environment of arboreal pools and its effects on the metabolism of the arboreal, oophagous tadpoles of a Taiwanese tree frog, Chirixalus eiffingeri (Anura: Rhacophoridae).

We have studied seasonal and diurnal fluctuations of water temperature in bamboo stumps and the effect of temperature on the energy metabolism of arboreal, oophagous tadpoles of Chirixalus eiffingeri. We collected tadpoles (Gosner stage 28-29) in February and August from Chitou, Taiwan and acclimated them to 12 and 22 degrees C. Using a closed system, we measured tadpole oxygen consumption (V.O(2)) at 12, 17 and 22 degrees C. The water temperature was lowest in February (11-13 degrees C), increased rapidly during March and April and was highest from May to August (20-24 degrees C). Diel fluctuations in the temperature of the pools of water in bamboo stumps mirrored fluctuations in air temperature. Tadpoles collected in February and August exhibited metabolic compensation in that tadpoles acclimated at 12 degrees C had significantly higher V.O(2) than those acclimated at 22 degrees C. There are at least two possible explanations for the presence of metabolic compensation in C. eiffingeri tadpoles. Firstly, the larval period of C. eiffingeri ranges from 40 to 78 days, a tadpole could experience relatively large fluctuations in body temperature (up to 10 degrees C) during the development. As a result, C. eiffingeri tadpoles most likely evolved metabolic compensation to maintain activity levels under different thermal environments. Secondly, because arboreal pools are small, thermally unstratified, aquatic microhabitats, tadpoles are unable to behaviorally select preferred temperatures. As a result, metabolic compensation allows tadpoles to regulate their physiological functions.

Adaptation, Physiological↗

Proteomic detection of changes in protein synthesis induced by NGX6 transfected in human nasopharyngeal carcinoma cells.

In the previous study, we cloned a new gene, named NGX6, related to nasopharyngeal carcinoma (NPC) at 9p. To study its function in the pathogenesis of NPC, we have investigated changes in protein synthesis between NPC cell line HNE1 and that transfected with the gene. Using high-resolution two-dimensional electrophoresis, we found that 22 protein spots showed variations that were significant and reproducible. Analysis of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and database searches identified seven proteins that were upregulated and seven proteins that were downregulated. These proteins included Fas, zinc-finger protein (ZNF), RAB, and Ah receptor-interacting protein (AIP). The functional implications of the identified proteins are discussed.

Down-Regulation↗

Detection rate of Actinobacillus actinomycetemcomitans on the permanent 1st molars of primary school children in Taiwan by polymerase chain reaction.

BACKGROUND, AIMS: Actinobacillus actinomycetemcomitans (Aa) has been implicated as the putative micro-organism for localized juvenile periodontitis (LJP). The most distinct clinical features of LJP include severe angular bony defects of the mesial sides of permanent first molars and the onset of disease during puberty. Currently, no large-scale studies have been performed which address the change in detection rates of Aa on the mesial sides of permanent 1st molars following eruption and up to puberty. METHOD: In this study, subgingival plaque samples were taken from the mesial pockets of 2 randomly selected permanent 1st molars from 328 primary school children and 50 adult staff, and analyzed by polymerase chain reaction (PCR) to detect Aa. RESULTS: The results showed a 5.5% prevalence rate of Aa which increased after the eruption of 1st molars and peaked near puberty. There were no significant differences in the detection rates of Aa among different groups in terms of gender, plaque index (PII), and gingival index (GI); however, the higher detection rates of Aa were significantly associated with increased probing depths at p<0.05. CONCLUSION: PCR analysis of the subgingival plaques demonstrated a prevalence of Aa which peaked near puberty, suggesting that Aa may be important for LJP in Taiwan.

Adult↗

Detection of putative periodontal pathogens in non-insulin-dependent diabetes mellitus and non-diabetes mellitus by polymerase chain reaction.

It has been assumed that there is a relationship between periodontal diseases and diabetes mellitus, however the putative periodontal microorganisms in non-diabetes mellitus (non-DM) individuals and non-insulin-dependent diabetes mellitus (NIDDM) patients have not been well studied. In this study, the detection rates of 5 putative periodontal pathogens: Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Eikenella corrodens, Treponema denticola, and Candida albicans by polymerase chain reaction (PCR) between NIDDM and non-DM adults were compared. A total of 246 adults were randomly recruited and periodontal parameters including: plaque index (P1I), gingival index (GI), probing depth (PD) and attachment level (AL) were recorded. Subgingival plaque samples were collected by sterile curettes from the most diseased and healthy sites based on PD and AL. The differences in periodontal parameters and microbiological data in healthy and diseased sites between non-DM and NIDDM patients were compared by chi-square analysis. The results showed no significant differences in age, gender, GI, P1I, PD, and prevalence of the 5 microorganisms between the NIDDM and the non-diabetic groups. However, except for A. actinomycetemcomitans, the prevalence of the periodontal microorganisms tested was significantly higher (p <0.001) in diseased sites than in the healthy sites in both groups. The P1I, GI, PD and AL were significantly higher in T. denticola positive sites than in negative sites. The results suggested that P. gingivalis, T. denticola, E. corrodens and C. albicans may play important roles in the periodontitis of both NIDDM and non-DM individuals, however the etiology of periodontitis in both groups may not be different from each other.

Adult↗

Respiratory viral infections among pediatric inpatients and outpatients in Taiwan from 1997 to 1999.

The present study examined the association of specific virus infections with acute respiratory tract conditions among hospitalized and outpatient children in a subtropical country. A total of 2,295 virus infections were detected in 6,986 patients between 1997 and 1999, including infections caused by respiratory syncytial virus (RSV) (1.7%), parainfluenza virus (2.0%), influenza B virus (2.6%), adenovirus (4.0%), herpes simplex virus type 1 (4. 4%), influenza A virus (5.5%), and enterovirus (12.7%). There were 61 mixed infections, and no consistent seasonal variation was found. One or more viruses were detected among 24.8% of hospitalized patients and 35.0% of outpatients. The frequencies and profiles of detection of various viruses among in- and outpatients were different. The occurrence of enterovirus infections exceeded that of other viral infections detected in 1998 and 1999 due to outbreaks of enterovirus 71 and coxsackievirus A10. RSV was the most prevalent virus detected among hospitalized children, whereas influenza virus was the most frequently isolated virus in the outpatient group. Most respiratory viral infections (39.3%) occurred in children between 1 and 3 years old. RSV (P < 0.025) and influenza A virus (P < 0.05) infections were dominant in the male inpatient group. In addition, most pneumonia and bronchiolitis (48.4%) was caused by RSV among hospitalized children less than 6 months old. Adenovirus was the most common agent associated with pharyngitis and tonsilitis (45.5%). These data expand our understanding of the etiology of acute respiratory tract viral infections among in- and outpatients in a subtropical country and may contribute to the prevention and control of viral respiratory tract infections.

Adolescent↗

Cleaning method of the oil field wastewater treatment by UF process.

This article introduces experiments and researches of polysulphone ultrafiltration membrane's effect on oil field polluted water and approaches renewing oil field polluted water and approaches renewing of membrane's flux by different detergents and cleaning method. Good result has been achieved by doing experiments and the renewal rate of membrane is over 90%.

Detergents↗

[Experimental study of protective effect of tongxinluo capsule on isoproterenol induced myocardial injury in rats].

OBJECTIVE: To study the protective effect of Tongxinluo capsule (TXLC) on myocardial injury induced by isoproternol. METHODS: Myocardial injury was induced in 34 rats by subcutaneous injection of isoproterenol (85 mg/kg). The experimental animals were randomly divided into the control group, isoproterenol group and TXLC group. The histopathological change of myocardia was investigated by HE staining, the myocardial cell apoptosis were observed by TUNEL method and the ultrastructure of myocardial cell examined by electron microscope. RESULTS: No cell degeneration and necrosis, only very few cells of apoptosis positive were found in the control group. While in the isoproterenol group, marked necrosis of myocardial tissue and increase of apoptosis cells were found, and characteristic changes of cell apoptosis were observed under electron microscope. After TXLC treatment, the myocardial necrosis and cell apoptosis were markedly alleviated. CONCLUSION: Isoproterenol could induce myocardial necrosis and apoptosis, TXLC could alleviate the myocardial injury through preventing myocardial cell necrosis and apoptosis.

Animals↗

An outbreak of enterovirus 71 infection in Taiwan 1998: a comprehensive pathological, virological, and molecular study on a case of fulminant encephalitis.

BACKGROUND: In a recent enterovirus outbreak in Taiwan, serotype 71 was the culprit of encephalitis causing rapid clinical deterioration and death among young children. OBJECTIVES: Since knowledge of enterovirus 71 (EV71) infection in the central nervous system is still limited, the purpose of the present case study was attempted to uncover the pathogenesis of the virus. STUDY DESIGN: We performed a detailed pathological examination, virological and molecular studies on a case of EV71 infection with a rapidly fatal outcome. In addition, the whole genome of the virus was sequenced to determine the genetic relationships to other enteroviruses and two other EV71 strains (a prototype BrCr and a neurovirulent MS strain), and to provide the genetic basis of its neurovirulence of the new isolate, NCKU9822 strain. RESULTS: Characteristic features of acute encephalomyelitis were observed, with most prominent lesions in the spinal cord and brain stem. Mild myocarditis and pancreatitis were also noticed. EV71 antigen was localized to neurons on immunohistochemical staining. EV71 was recovered from all organs with inflammatory reaction. Sequence analysis showed that overall NCKU9822 and the two EV71 strains shared 80% nucleotide identity and 95% amino acid identity. It had only 45% amino acid and 52% nucleotide identities with polioviral P1 capsid region. CONCLUSION: The spinal cord and brain stem were the main targets of EV71 in the fatal cases in this outbreak, however, heart and pancreas might also be involved. Since the amino acid sequences in the P1 region are conserved (97% identity) among the three EV71 strains as compared to other enteroviruses and polioviruses, these EV71 neurovirulent strains might share the same mechanisms of neurovirulence, and the mechanisms might be different from those in polioviruses.

Brain↗

An outbreak of enterovirus 71 infection in Taiwan, 1998: epidemiologic and clinical manifestations.

BACKGROUND: An outbreak of enterovirus infections occurred throughout Taiwan in 1998. The diseases were manifectated with hand, foot, and mouth disease (HFMD), some associated with meningitis, encephalitis, or acute flaccid paralysis (AFP). OBJECTIVES: This study is aimed to characterize and analyze the epidermologic and clinical features during the outbreak. STUDY DESIGN: The epidemiologic information was collected from the Ministry of Health on passive surveillance; clinical and virological investigations were carried out at National Cheng Kung University Medical Center. RESULTS: Between April and December 1998, 405 children were hospitalized, and 78 patients died during this outbreak in Taiwan. There were 119 cases identified to be EV71 infection in Tainan and Chiayi areas; 105 cases by virus isolation and 14 by serological assay. The outbreak had a biphasic curve with peak in June and October, especially in the southern Taiwan. Seventy-two percent of patients were below 3 years of age. The spectrum of disease included HFMD in 54, HFMD with central nerve system (CNS) involvement in 37, herpangina in 12, aseptic meningitis in three, encephalitis/ meningoencephalitis in ten, acute flaccid paralysis in three. There was nine fatal cases complicated with neurogenic pulmonary edema. Myoclonus with sleep disturbance was the most important early sign of EV71 infection with CNS involvement. CONCLUSION: Our experience demonstrated that the EV71 isolated in Taiwan had strong dermatotropic as well as neurotropic tendencies. Early detecting CNS involvement and commencing aggressive therapy may reduce the mortality.

Adolescent↗

An outbreak of enterovirus 71 infection in Taiwan, 1998. II. Laboratory diagnosis and genetic analysis.

BACKGROUND: An epidemic of enterovirus 71 (EV71) occurred in Taiwan from April to December of 1998, with two peaks, one in June and the other in October. Many enteroviruses were isolated in our laboratory from 258 cases during this outbreak. Approximately half of the enteroviruses isolated were EV71 and one fifth were coxsackievirus A16. OBJECTIVES: To analyze laboratory findings in the EV71 epidemic of 1998 in Taiwan, various EV71 specimens in different cell lines were examined. In addition, genetic analysis of 5' non-coding region (NCR) was performed to analyze the strain variation in this outbreak. RESULTS: The cytopathic effect induced by EV71 was observed 2-13 (mean of 4.5) days post-inoculation in Vero cells and 4-15 (mean of 6.6) days in green monkey kidney (GMK) cells inoculated with throat swabs. Of the total positive EV71 cases, virus was most frequently obtained from throat swabs (91.7%), less from stools (64.8%), and none from cerebral spinal fluid (CSF). Molecular analyses of EV71 by sequencing the 5' NCR of 34 strains obtained from different clinical categories and various geographic areas showed that their sequences differed (0-13 bp in 681 bp sequenced) by approximately 0-2%. The sequences of these isolates differed from EV71 prototype BrCr or MS strain by 17.5-19%, with the exception of two samples which exhibited nucleotide variation by only 8.9 and 8.2%, when compared to the MS strain. CONCLUSION: EV71 was most frequently isolated from throat swab specimens in Vero cells. The molecular analyses of the 5' NCR of EV71 revealed that most isolates from this epidemic belonged to a group of closely related clones and only two were in a different group which was clustered with the EV71 MS strain.

Adolescent↗

Enterovirus infections with special reference to enterovirus 71.

The enteroviruses comprise a large group of immunologically distinct serotypes of viruses belonging to the family of Picornaviridae. Many enteroviruses cause diseases in human, but the infections are generally mild as asymptomatic, therefore, enteroviruses are considered to be unimportant as human pathogens. However, enteroviruses may also result in serious or even fatal disease (as shown in the enterovirus 71 (EV71) epidemic in Taiwan in 1998). There are three types of polioviruses, Coxsackievirus group A and group B viruses, and echoviruses group. All together a total of 67 types are available. Starting from enterovirus type 68 to 71, they are named as enterovirus types. Enterovirus type 72 is hepatitis A virus. Paralytic disease of poliomyelitis was recorded in ancient time but characterization of poliovirus was not reported until the turn of the 19th century that poliomyelitis was a viral disease. The major breakthrough for diagnosing and controlling of poliomyelitis was the discovery that poliovirus can be propagated in human embryonic tissues in cultures. As soon as cultures of human and monkey cells began to use for isolating polioviruses in stool specimen of patients, more unknown viruses were isolated which unlike polioviruses nor Coxsackie viruses; they were called "orphan" viruses or human enteric viruses, name later simplified to "echoviruses". Morphologically all enteroviruses are alike. They are small, ether insensitive viruses with an RNA genome. Their nucleic acid is single stranded, and the nucleocapsid has a cubic (icosahedral) symmetry, and is naked. The host ranges of enteroviruses vary greatly from one type to the next and even among strains of the same type. Polioviruses have a very restricted host range among laboratory animals. Virus isolation is the best method for diagnosis of enterovirus infection, but infection in the central nervous system (CNS) may be detected by polymerase chain reaction (PCR). Currently final identification and serotyping of enteroviruses are by indirect immunofluorescent tests using monoclonal antibody or by neutralization test using antiserum pools described by Lim and Benyesh-Melnick. The incidence and prevalence of diseases associated with the enterovirus infections are varied. The circulation of enteroviruses recently in Tainan and the epidemic of EV71 in Taiwan in 1998 are described in this review. Although poliovirus infection may be eradicated from the world due to the efficient vaccination program, there is no specific antiviral agents for either treatment or prevention for other enterovirus infections. In 1991, a new antiviral "pleconaril" which is a novel orally bioavailable and systematically acting small molecule inhibitor for picornaviruses. "Pleconaril" is currently in clinical trials for treatment of enterovirus meningitis and respiratory infections.

Animals↗

An epidemic of enterovirus 71 infection in Taiwan. Taiwan Enterovirus Epidemic Working Group.

BACKGROUND: Enteroviruses can cause outbreaks of hand-foot-and-mouth disease (characterized by vesicular lesions on the hands, feet, and oral mucosa) or herpangina, usually without life-threatening manifestations. In 1998 an epidemic of enterovirus 71 infection caused hand-foot-and-mouth disease and herpangina in thousands of people in Taiwan, some of whom died. METHODS: We assessed the epidemiologic aspects of this outbreak. Cases of hand-foot-and-mouth disease or herpangina in ambulatory patients were reported to the Taiwan Department of Health by a mean of 818 sentinel physicians. Severe cases in hospitalized patients were reported by 40 medical centers and regional hospitals. Viruses were isolated by 10 hospital laboratories and the department of health. RESULTS: The sentinel physicians reported 129,106 cases of hand-foot-and-mouth disease or herpangina in two waves of the epidemic, which probably represents less than 10 percent of the estimated total number of cases. There were 405 patients with severe disease, most of whom were five years old or younger; severe disease was seen in all regions of the island. Complications included encephalitis, aseptic meningitis, pulmonary edema or hemorrhage, acute flaccid paralysis, and myocarditis. Seventy-eight patients died, 71 of whom (91 percent) were five years of age or younger. Of the patients who died, 65 (83 percent) had pulmonary edema or pulmonary hemorrhage. Among patients from whom a virus was isolated, enterovirus 71 was present in 48.7 percent of outpatients with uncomplicated hand-foot-and-mouth disease or herpangina, 75 percent of hospitalized patients who survived, and 92 percent of patients who died. CONCLUSIONS: Although several enteroviruses were circulating in Taiwan during the 1998 epidemic, enterovirus 71 infection was associated with most of the serious clinical manifestations and with nearly all the deaths. Most of those who died were young, and the majority died of pulmonary edema and pulmonary hemorrhage.

Child, Preschool↗

Clinical spectrum of enterovirus 71 infection in children in southern Taiwan, with an emphasis on neurological complications.

An outbreak of enterovirus 71 (EV71) infection occurred in Taiwan in 1998. The clinical spectrums and laboratory findings for 97 patients with virus culture-proven EV71 infections were analyzed. Eighty-seven percent of the patients were younger than age 5 years. Hand-foot-and-mouth syndrome occurred in 79% of the children and central nervous system (CNS) involvement in 35%, including nine fatal cases. The predominant neurological presentations were myoclonus (68%), vomiting (53%), and ataxia (35%). Brain stem encephalitis was the cardinal feature of EV71 CNS involvement during this outbreak. Magnetic resonance imaging and pathological findings illustrated that the midbrain, pons, and medulla were the target areas. EV71 brain stem encephalitis can present either with cerebellar signs and an initially mild, reversible course or with overwhelming neurogenic shock and neurogenic pulmonary edema (NPE) resulting in a fatal outcome. Brain stem encephalitis that progressed abruptly to neurogenic shock and NPE was indicative of poor prognosis in this epidemic. Early aggressive treatment and close monitoring of the neurological signs are mandatory to improve the chance of survival.

Adolescent↗

Fatal coxsackievirus B infection in early infancy characterized by fulminant hepatitis.

OBJECTIVES: to clarify the major features of fatal coxsackievirus B infection characterized by fulminant hepatitis in early infancy. METHODS: clinical manifestations and laboratory investigations concerning five consecutive young infants with overwhelming coxsackievirus B fulminant hepatitis between 1994 and 1997 were retrospectively reviewed. Aetiological diagnosis was made by viral cultures and confirmed by a neutralization test with a type-specific antiserum. RESULTS: all five had a deteriorating clinical course of severe hepatitis complicated by disseminated intravascular coagulopathy (DIC). Coxsackievirus B1 infection was established in four patients and coxsackievirus B3 in one. The pathological findings of the two cases illustrated extensive hepatocellular necrosis. Fulminant hepatitis can occur as a leading presentation of disseminated coxsackievirus B infections and dominant the clinical features in neonates and young infants. CONCLUSIONS: the liver was the target organ of fatal coxsackievirus B infection in our patients. Hepatic involvement progressed rapidly to jaundice and coagulopathy, and was considered to be indicative of poor prognosis. Coxsackievirus B hepatitis may be serious in early infancy.

Coxsackievirus Infections↗