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Biomedical subjects

Li-Min Huang

Publications and source records attributed to Li-Min Huang.

At least 19 recordsLinked to original sources

Differences in replication capacity between enterovirus 71 isolates obtained from patients with encephalitis and those obtained from patients with herpangina in Taiwan.

The cellular-tropism and biological characteristics of enterovirus 71 (EV71) isolates in Taiwan (TW) were studied. Growth curve experiments were conducted using cell lines that were possibly exhibited pathogenesis, and RT-PCR and sequencing tests were undertaken to amplify the 5' non-coding region (5'-NCR). The encephalitis isolate EV71 TW98NTU2078 was PBMC-tropic, temperature-resistant (Tr) at 40 degrees C, and easier to replicate in HTB-14 (astrocytoma) than the herpangina isolate EV71 TW98NTU1186 (The viral yields were 100-fold higher than those of the herpangina isolate EV71 TW98NTU1186 at 96 hr post infection.). The herpangina isolate EV71 TW98NTU1186 was non-PBMC-tropic, and temperature-sensitive (Ts) at 40 degrees C. The replication of EV71 TW98NTU1186 in HTB-14 was lower. No EV71 isolate infected HTB-37 (human colon adenocarcinoma cells). The encephalitis EV71 isolate exhibited better replication and transmission in PBMCs and astrocytes than did the EV71 isolate without CNS involvement.

Animals↗

Disease burden and related medical costs of rotavirus infections in Taiwan.

BACKGROUND: The disease burden and associated medical costs of rotavirus infections in inpatient and outpatient sectors in Taiwan were examined in anticipation of the availability of new rotavirus vaccines. METHODS: The yearly national case number and medical costs for all for inpatients and outpatients with acute gastroenteritis (AGE) were extracted from the Bureau of National Health Insurance database in Taiwan according to ICD-9-CM codes. A retrospective study was also performed using records of children with AGE seen at three hospitals in Taiwan in 2001 to identify laboratory confirmed rotavirus infection cases. The annual incidence and related medical costs of AGE due to rotavirus infection were then estimated. RESULTS: Children <5 years old comprised 83.6% of inpatient and 62.0% of outpatient pediatric AGE cases in Taiwan in 2001. Rotavirus was the most common agent detected among AGE patients in this age group in the three hospitals, and was detected in 32.9% (221/672) of inpatient and 24% (23/96) of outpatient stool specimens tested for microbial etiologies. An estimated 277,400 to 624,892 cases of rotavirus infections sought medical care in Taiwan in 2001, equaling one in 2 to 5 children <5 years old required medical care due to rotavirus infection. The incidence of hospitalization due to rotavirus infections was 1,528-1,997/100,000 for children <5 years old. The total associated medical costs due to rotavirus infection were estimated at US $10-16 millions in Taiwan in 2001. Although the per-capita medical cost of rotavirus infection was lower in Taiwan than in the United States or Hong Kong, the personal economic burden was similar among the three places when normalized for gross national incomes per capita. CONCLUSION: Infections caused by rotavirus constitute an important human and economic burden among young children in Taiwan. A safe and effective vaccine is urgently needed.

Adolescent↗

Status of cellular rather than humoral immunity is correlated with clinical outcome of enterovirus 71.

We valuated specific cellular and humoral immune response of cases of enterovirus 71 (EV71) infection and correlated immune response with clinical outcome. After obtaining informed consent, we enrolled 30 EV71 cases including 7 cases with brainstem encephalitis plus pulmonary edema, 12 cases of CNS (CNS) involvement and 11 uncomplicated cases. We measured antibodies specific to EV71, lymphocyte proliferation response and EV71-stimulated cellular response of Th1/Th2 cytokines and chemokines. The 7 EV71 cases involving brainstem encephalitis plus pulmonary edema had a significantly lower phytohemagglutinin stimulation index than other cases (p = 0.04). After EV71 stimulation of peripheral mononuclear cells, there was a significant increase in cellular Th1 cytokine (gamma-interferon) and proinflammatroy cytokines. However, cases with pulmonary edema had significantly lower cellular gamma-interferon (p = 0.04), lower cellular IL-1beta (p = 0.04), lower cellular IL-6 (p = 0.04), lower cellular tumor necrosis factor-alpha response (p = 0.04), and lower cellular macrophage inflammatory protein-1alpha (p = 0.04) response compared with other cases. Their titers of EV71 neutralizing antibodies demonstrated no difference among cases. These results suggest lower EV71-specific cellular response may be associated with immunopathogenesis of EV71-related pulmonary edema.

Antibodies, Viral↗

Caspase-8 acts as a key upstream executor of mitochondria during justicidin A-induced apoptosis in human hepatoma cells.

Justicia procumbens is a traditional Taiwanese herbal remedy used to treat fever, pain, and cancer. Justicidin A, isolated from Justicia procumbens, has been reported to suppress in vitro growth of several tumor cell lines as well as hepatoma cells. In this study, justicidin A activated caspase-8 to increase tBid, disrupted mitochondrial membrane potential (Delta psi(m)), and caused the release of cytochrome c and Smac/DIABLO in Hep 3B and Hep G2 cells. Justicidin A also reduced Bcl-x(L) and increased Bax and Bak in mitochondria. Caspase-8 inhibitor (Z-IETD) attenuated the justicidin A-induced disruption of Delta psi(m). Growth of Hep 3B implanted in NOD-SCID mice was suppressed significantly by oral justicidin A (20 mg/kg/day). These results indicate that justicidin A-induced apoptosis in these cells proceeds via caspase-8 and is followed by mitochondrial disruption.

Animals↗

Necrotizing pneumococcal pneumonia in children: the role of pulmonary gangrene.

Little is known about the mechanism of necrotizing pneumonia caused by Streptococcus pneumoniae in children. Pulmonary gangrene secondary to vascular thrombosis was reported in adults with necrotizing pneumococcal pneumonia. We conducted a retrospective study of 15 children with a diagnosis of necrotizing pneumococcal pneumonia at National Taiwan University Hospital to explore its association with pulmonary gangrene, based on evidence from chest computed tomography, serial chest radiographic patterns, and pathologic results. S. pneumoniae serotype 14 was the prevalent pneumococcal serotype. Overall, 63.6% of isolates were not susceptible to penicillin. One child with pneumonia caused by S. pneumoniae serotype 3 complicated by hemolytic uremic syndrome had a rapidly fatal course. An autopsy in this patient documented lung necrosis and pulmonary gangrene. Radiographic follow-up was performed during the clinical course in 9 patients, and showed no evidence of pulmonary gangrene. Four children had no radiographic follow-up. The relationship between pulmonary gangrene and necrotizing pneumonia was unclear in the remaining one. In conclusion, necrotizing pneumococcal pneumonia may be infrequently associated with pulmonary gangrene in children.

Child↗

Influenza pandemics: past, present and future.

Influenza A virus is well known for its capability for genetic changes either through antigen drift or antigen shift. Antigen shift is derived from reassortment of gene segments between viruses, and may result in an antigenically novel virus that is capable of causing a worldwide pandemic. As we trace backwards through the history of influenza pandemics, a repeating pattern can be observed, namely, a limited wave in the first year followed by global spread in the following year. In the 20th century alone, there were three overwhelming pandemics, in 1918, 1957 and 1968, caused by H1N1 (Spanish flu), H2N2 (Asian flu) and H3N2 (Hong Kong flu), respectively. In 1957 and 1968, excess mortality was noted in infants, the elderly and persons with chronic diseases, similar to what occurred during interpandemic periods. In 1918, there was one distinct peak of excess death in young adults aged between 20 and 40 years old; leukopenia and hemorrhage were prominent features. Acute pulmonary edema and hemorrhagic pneumonia contributed to rapidly lethal outcome in young adults. Autopsies disclosed multiple-organ involvement, including pericarditis, myocarditis, hepatitis and splenomegaly. These findings are, in part, consistent with clinical manifestations of human infection with avian influenza A H5N1 virus, in which reactive hemophagocytic syndrome was a characteristic pathologic finding that accounted for pancytopenia, abnormal liver function and multiple organ failure. All the elements of an impending pandemic are in place. Unless effective measures are implemented, we will likely observe a pandemic in the coming seasons. Host immune response plays a crucial role in disease caused by newly emerged influenza virus, such as the 1918 pandemic strain and the recent avian H5N1 strain. Sustained activation of lymphocytes and macrophages after infection results in massive cytokine response, thus leading to severe systemic inflammation. Further investigations into how the virus interacts with the host's immune system will be helpful in guiding future therapeutic strategies in facing influenza pandemics.

Disease Outbreaks↗

Safety and immunogenicity of heptavalent pneumococcal conjugate vaccine booster in taiwanese toddlers.

BACKGROUND/PURPOSE: Pneumococcal infection causes high morbidity and mortality in children. Prevention of pneumococcal diseases by effective vaccination is an urgent need. This study evaluated the safety and immunogenicity of heptavalent pneumococcal conjugate (7VPnC) vaccine (serotypes 4, 6B, 9V, 14, 18C, 19F, 23F) booster dose administered at 15-20 months of age in Taiwanese toddlers. METHODS: Fifty-eight healthy Taiwanese toddlers who were primed with three doses of the 7VPnC vaccine in infancy received a booster dose in an open-label, noncomparative trial. Routine oral polio vaccine and diphtheria toxoid, tetanus toxoid, and pertussis vaccine were administered concomitantly. Surveillance for safety was conducted after vaccination. Antibody concentration to each of the seven pneumococcal serotypes was measured before and 1 month after the booster dose. RESULTS: Mild to moderate local reactions were common (45-50%). Fever, fussiness, restlessness, and loss of appetite were the most frequent systemic reactions (31-50%). Before the booster dose of vaccine, 68% (for serotype 18C) to 100% (for serotype 14) of subjects had antibody concentrations >or= 0.2 microg/mL to different pneumococcal serotypes. After the booster dose, the geometric mean concentration of IgG increased significantly (p < 0.001) for all seven serotypes indicating the induction of immunologic memories. Ninety-eight percent of the toddlers had antibody concentration >or= 0.2 microg/mL against all serotypes after the booster. CONCLUSION: The 7VPnC vaccine containing the prevalent serotypes in Taiwan is safe and effective in boosting immunity against pneumococcal disease in Taiwanese children.

Antibodies, Bacterial↗

Molecular epidemiology of G9 rotaviruses in Taiwan between 2000 and 2002.

Since the mid-1990s, novel G9 rotaviruses have been detected in many countries, suggesting that G9 is a globally important serotype. The molecular epidemiology of G9 rotaviruses in Taiwan from 2000 to 2002 was investigated in this study. G9 rotavirus first appeared in 2000 with 4 cases and constituted 33.8% and 54.8% of the rotavirus-positive samples in 2001 and 2002, respectively. These G9 strains belonged to P[8]G9, subgroup II, and long electropherotype, except one belonged to P[4]G9, subgroup II, and short electropherotype. Nucleotide sequencing and phylogenetic analysis of 52 Taiwanese G9 rotaviruses showed that the VP7 genes shared a high degree of identity to overseas G9 rotaviruses detected after 1993 and that the VP8* portions of the VP4 genes were more closely related to those of local rotaviruses of other G types. The two P[8]G9 strains with high nucleotide identities in the VP7 and the partial VP4 genes, 01TW591 of Taiwan from 2001 and 95H115 of Japan from 1995, varied in four genes, genes 2, 3, 7, and 8, which was revealed by RNA-RNA hybridization. Representative strains for different RNA patterns were also analyzed in the partial VP2 and VP3 genes; the nucleotide identities were high between Taiwanese G9 strains and local G3 or G2 strains. These results suggested that Taiwanese G9 rotaviruses possibly had evolved through reassortment between overseas G9 strains and circulating rotaviruses of other G types.

Antigens, Viral↗

Stenotrophomonas maltophilia bacteremia in pediatric patients-- a 10-year analysis.

BACKGROUND AND PURPOSE: Stenotrophomonas maltophilia bacteremia is an important cause of mortality among immunocompromised children. However, there has been little information concerning S. maltophilia bacteremia in the pediatric population. METHODS: We reviewed the drug susceptibility of bloodstream isolates of S. maltophilia and medical charts of S. maltophilia bacteremia patients less than 18 years old at the Department of Pediatrics, National Taiwan University Hospital from January 1993 to June 2003. The risk factors associated with mortality of the patients with S. maltophilia bacteremia were analyzed. RESULTS: In total, 32 episodes (31 patients) of S. maltophilia bacteremia were reviewed. The average rate of nosocomial bloodstream infection was 8.3 episodes per 100,000 patient-days, and an average of 6.4% of them were caused by S. maltophilia. Malignancy was the most common underlying disease (32%). Six episodes of S. maltophilia bacteremia had soft tissue involvement, and only 1 of them underwent surgical intervention and survived. These 32 isolates were most susceptible to trimethoprim-sulfamethoxazole (91%), and no obvious increase in multidrug resistance was noted in the previous 10 years. The crude mortality rate was 40.6%. Malignancy, failure to remove central venous catheter, and ineffective antibiotic treatment were significant risk factors for mortality. CONCLUSIONS: Early and effective antimicrobial therapy and removal of central venous catheter as soon as possible are vital for the successful management of S. maltophilia bacteremia.

Adolescent↗

Lack of association between infection with a novel human coronavirus (HCoV), HCoV-NH, and Kawasaki disease in Taiwan.

We investigated whether infection with a novel human coronavirus (HCoV), called "New Haven coronavirus" (HCoV-NH)--which is similar to and likely represents the same species as another novel HCoV, HCoV-NL63--is associated with Kawasaki disease (KD) in Taiwan. Fifty-three patients with KD were enrolled in our study. Serum, peripheral-blood mononuclear cells, nasopharyngeal aspirates, throat swabs, and rectal swabs from these patients were assayed for HCoV-NL63 by real-time reverse-transcriptase (RT) polymerase chain reaction (PCR), and the throat swabs, nasopharyngeal aspirates, and rectal swabs were also assayed for HCoV-NH by RT-PCR. All PCR results were negative for both HCoV-NL63 and HCoV-NH; therefore, we did not find any association between HCoV-NH infection and KD in Taiwan.

Child, Preschool↗

Development of immunoglobulin G enzyme-linked immunosorbent assay for the serodiagnosis of severe acute respiratory syndrome.

Severe acute respiratory syndrome (SARS) is an emerging infectious disease caused by a novel SARS-associated coronavirus (SARS-CoV). The clinical characteristics are high fever, rapidly progressive diffuse pneumonitis and respiratory distress. It is highly infectious through intimate contact or direct contact with infectious body fluids. Outbreaks within communities and hospitals have been reported. Development of rapid and reliable diagnostic tools is urgently needed. We developed an immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA), using whole virus antigen of SARS-CoV. Eighty-six serum samples collected from patients who were hospitalized for other causes were examined to determine the cut-off O.D. value. The cut-off O.D. value was defined as 0.175 by calculating the mean O.D. value of the 86 sera plus 3 standard deviations. To determine the sensitivity and specificity of the ELISA, 56 positive sera and 204 negative sera were tested. The sensitivity was 96.4% and the specificity was 100%. The results suggest that the IgG ELISA using whole virus antigen of SARS-CoV has a high sensitivity and specificity in detecting SARS IgG antibodies. This IgG ELISA is a powerful tool for serodiagnosis of SARS.

Antigens, Viral↗

Acremonium pyomyositis in a pediatric patient with acute leukemia.

Invasive Acremonium infection in humans is rare. We report a patient with leukemia who developed pyomyositis due to Acremonium species. Painful cutaneous nodules and severe myalgia were the first clinical manifestations during the neutropenic stage after chemotherapy. Magnetic resonance image (MRI) revealed multiple nodular lesions scattered along the intramuscular regions of the lower legs. Culture of an aspiration grew Acremonium species. Surgical drainage was performed. Although all antifungal agents tested showed no in vitro inhibitory activity, we successfully treated this patient with amphotericin B, granulocyte colony-stimulating factor (G-CSF), and surgical drainage.

Acremonium↗

Immunogenicity and reactogenicity of a reduced-antigen-content diphtheria-tetanus-acellular pertussis vaccine in healthy Taiwanese children and adolescents.

PURPOSE: Disease caused by Bordetella pertussis is increasingly being identified among older children and adults in immunized populations, indicating a waning of the vaccine-induced immunity. These findings suggest the need for booster immunization of older children and adults. Modern acellular reduced-antigen-content vaccines have been developed, which can be given as a booster in individuals more than 4 years of age. This study was to assess the immunogenicity and reactogenicity of Boostrix, GlaxoSmithKline Biologicals' reduced-antigen-content diphtheria-tetanus acellular pertussis (dTpa) vaccine, when administered as a booster in healthy subjects previously primed with DTP vaccine. METHODS: Healthy Taiwanese children and adolescents aged 6-8 years and 15-20 years, previously primed with DTP vaccine, were enrolled. All received one dose of Boostrix. Two blood samples were taken from each of them, one before vaccination and one at 1 month after vaccination. Serum antibodies to diphtheria and tetanus toxoids and immunoglobulin G (IgG) antibodies against the pertussis components PT, FHA and PRN were measured by enzyme-linked immunosorbent assay (ELISA) technique. Adverse reactions following vaccination were recorded. RESULTS: A total of 180 subjects were recruited. The vaccine response rates to the pertussis antigens ranged between 89.0-100%. There were no serious adverse events reported during the study period. CONCLUSIONS: The results of this study suggest that Boostrix may be safely and effectively administered as a booster dose to children previously primed with DTP vaccine.

Adolescent↗

Longitudinal analysis of Severe Acute Respiratory Syndrome (SARS) coronavirus-specific antibody in SARS patients.

The serum antibodies to severe acute respiratory syndrome (SARS) coronavirus of 18 SARS patients were checked at 1 month and every 3 months after disease onset. All of them except one, who missed blood sampling at 1 month, tested positive for the immunoglobulin G (IgG) antibody at 1 month. Fifteen out of 17 tested positive for the IgM antibody at 1 month. The serum IgM antibody of most patients became undetectable within 6 months after the onset of SARS. The IgG antibody of all 17 patients, whose serum was checked 1 year after disease onset, remained positive.

Antibodies, Viral↗

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↗

Human immunodeficiency virus type 1 Vpr interacts with antiapoptotic mitochondrial protein HAX-1.

Human immunodeficiency virus type 1 viral protein R (Vpr) is required for viral pathogenesis and has been implicated in T-cell apoptosis through its activation of caspase 3 and caspase 9 and perturbation of mitochondrial membrane potential. To understand better Vpr-mitochondria interaction, we report here the identification of antiapoptotic mitochondrial protein HAX-1 as a novel Vpr target. We show that Vpr and HAX-1 physically associate with each other. Overexpression of Vpr in cells dislocates HAX-1 from its normal residence in mitochondria and creates mitochondrion instability and cell death. Conversely, overexpression of HAX-1 suppressed the proapoptotic activity of Vpr.

Adaptor Proteins, Signal Transducing↗