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Biomedical subjects

C Y Lu

Publications and source records attributed to C Y Lu.

At least 37 records · Page 2Linked to original sources

Immunogenicity and fecal poliovirus excretion in sequential use of inactivated and oral poliovirus vaccines.

BACKGROUND AND PURPOSE: Though inoculation with inactivated poliovirus vaccine (IPV) is advocated, sequential use of IPV and live oral poliovirus vaccines (OPV) has many advantages. This study aimed to define the immunogenicities of IPV and OPV in Taiwanese children after the use of a sequential schedule of IPV-OPV and also to determine whether prior IPV inoculation hampers the fecal passage of OPV. METHODS: Fifty-nine infants were recruited to receive IPV-OPV sequential vaccinations consisting of IPV given at the ages of 2 and 4 months and OPV given at the ages of 6 and 18 months. Blood samples were taken at ages 2, 6, 18, and 19 months for antibody determination, and stool samples were collected to isolate vaccine strains of poliovirus after the second dose of OPV, at the age of 18 months. RESULTS: None of the children had severe systemic or local reactions. Protective antibodies were detected in all infants at the age of 6 months, 2 months after the second IPV dose. The antibody titers were augmented at the age of 19 months, 1 month after the booster dose of OPV. Stool samples collected 7 days after the second dose of OPV yielded at least one type of poliovirus in 9 of 18 children. Analysis of stool samples revealed that poliovirus was excreted by the 28th day in only two of the children. CONCLUSIONS: Our study showed that both IPV and OPV exhibit immunogenicity in Taiwanese children. Side effects of an IPV-OPV sequential schedule were mild and infrequent. Viral shedding in stools after OPV vaccination was preserved in a substantial proportion of subjects. These findings suggest that this sequential vaccination schedule can maintain herd immunity.

Antibodies, Viral↗

Hepatitis A virus infection in Taipei in 1999.

BACKGROUND AND PURPOSE: Hepatitis A is a disease that is heavily affected by sanitation status. Hepatitis A is much less prevalent compared with decades ago in Taiwan, as in many rapidly developing regions. Hepatitis A vaccine is still self-paid under the National Health Insurance program and is still not widely utilized by the general public in Taiwan. This seroepidemiologic study evaluated the prevalence of antihepatitis A virus (anti-HAV) seropositivity in Taipei in 1999. METHODS: A total of 1017 serum samples from healthy inhabitants in Taipei were examined for anti-HAV antibody by qualitative enzyme immunoassay. RESULTS: The overall seroprevalence rate was 25.2% (255/1013) in the nonvaccinated population. The seropositivity rate for anti-HAV antibody among children younger than 12 months old was 23.3%. The rates dropped to between 1% and 4.8% among subjects between 1 and 20 years of age. A markedly higher rate of 40% was observed in subjects aged between 20 and 30 years. The seropositivity rate in subjects aged 31 to 50 was 80%. More than 90% of subjects older than 50 years were seropositive. The vaccination rate was low (0.5%). CONCLUSION: Our findings indicate that Taipei is an area of intermediate endemicity for hepatitis A virus. To achieve better herd immunity, a more active approach to the adoption of hepatitis A vaccine is warranted.

Adolescent↗

Empirical monotherapy with meropenem in serious bacterial infections in children.

The efficacy and safety profile of meropenem were analyzed according to data collected from hospitalized pediatric patients aged 4 days to 20 years who had serious bacterial infections and were treated in a major teaching hospital in Taipei. Of the 53 patients enrolled, 47 were analyzed for clinical efficacy and 53 for safety. The satisfactory clinical response rate was 57% in lower respiratory tract infection, 58% in septicemia, 100% in complicated urinary tract infection, osteomyelitis, and central nervous system infection, 83% in skin and soft tissue infection, and 93% in intra-abdominal infection. Eleven (21%) patients experienced adverse events related to meropenem. The most commonly observed adverse reactions were elevated hepatic enzymes (7.5%), increased alkaline phosphatase (3.8%), and thrombocytosis (3.8%). There was no meropenem-related seizure, withdrawal, or death. The results of this study suggested that meropenem is well tolerated even in young infants, and is effective in treating serious childhood bacterial infection. However, this study also identified a proportion of hospitalized pediatric patients with isolates that were resistant to meropenem. The trends in meropenem resistance among nosocomially acquired bacteria should be monitored closely.

Adult↗

Increase of mitochondria and mitochondrial DNA in response to oxidative stress in human cells.

Mitochondrial respiratory function is impaired in the target tissues of patients with mitochondrial diseases and declines with age in various human tissues. It is generally accepted that respiratory-chain defects result in enhanced production of reactive oxygen species and free radicals in mitochondria. Recently, we have demonstrated that the copy number of mitochondrial DNA (mtDNA) is increased in the lung tissues of elderly human subjects. The mtDNA copy number was suggested to be increased by a feedback mechanism that compensates for defects in mitochondria harbouring mutated mtDNA and a defective respiratory system. However, the detailed mechanism remains unclear. In this study, we treated a human lung fibroblast cell line, MRC-5, with H(2)O(2) at concentrations of 90-360 microM. After the treatment for 24-72 h, we found that cells were arrested at G(0) and G(1) phases but that mitochondrial mass and mtDNA content were significantly increased in a concentration- and time-dependent manner. Moreover, the oxidative stress induced by buthionine sulphoximine was also found to cause an increase in mitochondrial mass of the treated cells. Increased uptake of a vital mitochondrial dye Rhodamine 123 and enhanced tetrazolium [MTT, 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide] reduction revealed that the mitochondria increased by H(2)O(2) treatment were functional. In addition, the increase in the mitochondrial mass was also observed in cell-cycle-arrested cells induced by mimosine, lovastatin and genistein. Taken together, these findings suggest that the increase in mitochondrial mass and mtDNA content are the early molecular events of human cells in response to endogenous or exogenous oxidative stress through cell-cycle arrest.

Cell Cycle↗

Docosahexaenoic acid decreases IRF-1 mRNA and thus inhibits activation of both the IRF-E and NFkappa d response elements of the iNOS promoter.

BACKGROUND: Nitric oxide produced by inducible nitric oxide synthase (iNOS) may be cytotoxic during cardiac, hepatic, and renal acute allograft rejection. Because the incidence of rejection is decreased by fish oils that contain docosahexaenoic acid (DHA), we investigated the effects of DHA on iNOS. Using nuclear run-on assays and iNOS-promoter constructs, we previously showed that docosahexaenoic acid (DHA) inhibits activation of the iNOS gene by murine macrophages that had been stimulated in vitro by IFNgamma plus lipopolysaccharide. METHODS: In our current investigation, our purpose has been to determine how DHA inhibits iNOS gene activation in murine macrophages, by using gel retardation and Northern blotting techniques. We studied the effects of DHA on the formation nuclear protein complexes that interact with the critical iNOS promoter's response elements for IRF-1 (IRF-E -923 to -913 bp) and NF-kappaB (NFkappa d -85 to -75 bp). RESULTS: We now show that DHA inhibited increases of IRF-1 mRNA abundance in response to IFNgamma plus lipopolysaccharide. As expected, we found that this prevented formation of the nuclear protein complex that binds to the IRF-E DNA response element. We also found that inhibition of IRF-1 inhibited formation of the nuclear protein complex that binds to the NFkappa d DNA response element. CONCLUSIONS: DHA decreases the abundance of IRF-1 mRNA in stimulated cells. That, in turn, results in the decreased nuclear protein binding to the major iNOS promoter response elements (IRF-E and NF-kappaB). We found that this occurred because IRF-1 is a component of both the nuclear protein complex that binds to IRF-E and the nuclear protein complex that binds to NFkappa d.

Animals↗

Spectrum of beta thalassemia mutations and their linkage to beta-globin gene haplotypes in the Indo-Mauritians.

The beta thalassemia alleles in 53 thalassemic Indo-Mauritian patients and their families consisting of 23 homozygous beta-thalassemia, 9 HbE/beta-thalassemia, 18 HbS/beta-thalassemia, 1 HbD/beta-thalassemia, 1 deltabeta/beta-thalassemia and 1 HbH/beta-thalassemia from the island of Mauritius were studied. Characterization by polymerase chain reaction-based reverse dot blot hybridization technique revealed that the IVS1-5 (G-->C) mutation accounted for 74% of the beta thalassemic alleles, while six other mutations occurred at much lower frequencies: HbE codon 26 (G-->A); 10.4%, codon 8/9 (+G); 3.5%, codon 30 (AGG-->ACG) also called IVSI (-1).G-->C; 3.5%, codon 15 (G-->A); 3.5%, codon 41/42 (-CTTT); 2.4% and -28 (A-->G); 2.4%. Association of these mutations to specific beta globin gene sequence framework and haplotype allowed to trace their ancestral link. These data are useful in future molecular screening of the population in view of implementing a thalassemia prevention and control program in Mauritius.

Alleles↗

Nitric oxide inhibits INFgamma-induced increases in CIITA mRNA abundance and activation of CIITA dependent genes--class II MHC, Ii and H-2M. Class II TransActivator.

BACKGROUND: Nitric oxide (NO) has been recently implicated as a powerful inhibitor of immune responses during allograft rejection, and some autoimmune and infectious diseases. We previously showed that one potential regulatory effect of NO is inhibition of IFNgamma-stimulated expression of Class II MHC on macrophages. Activation of this gene is mediated by the "Class II TransActivator" (CIITA). We now ask whether NO inhibits CIITA and thus the family of genes regulated by CIITA--Class II MHC, Ii, and H-2M. The latter two genes participate in antigen processing and formation of the cell-surface peptide-Class II MHC complex. METHODS: Murine macrophages--both peritoneal macrophages and the RAW264.7 macrophage line--were stimulated in vitro with IFNgamma. NO production was measured by the Greiss reagent. Transcription of Class II MHC was measured by nuclear run-on assay. mRNA abundance of Class II MHC, Ii, H-2M, and CIITA was measured by Northern blotting and RT-PCR. RESULTS: NO inhibits IFNgamma-induced increases in the abundance and transcription of the Class II MHC Ab gene. The increases in mRNA abundance of CIITA, Ii, and H-2M are also inhibited. As a control, we found that NO did not inhibit LPS-induce increases in TNFalpha mRNA abundance. CONCLUSIONS: NO inhibits IFNgamma-induced increases in CIITA, and thus inhibits the CIITA-regulated genes: Class II MHC, Ii, and H-2M. Early during rejection, NO production by macrophages may result after stimulation by IFNgamma produced by CD4+ T cells, and be an effector of allograft damage. High concentrations of NO may then act as a feedback inhibitor which decreases antigen presentation by macrophages and thus decreases CD4 T cell activation.

Animals↗

Human genetic factors related to susceptibility to mild malaria in Gabon.

Several human genetic factors, including red blood cell polymorphisms (ABO blood group, sickle-cell trait, G6PD deficiency) as well as point mutations in the mannose binding protein (MBP) and in the promoter regions of both the TNF-alpha and NOS2 genes, influence the severity of disease due to infection with Plasmodium falciparum. We assessed their impact on mild P. falciparum malaria, as part of a longitudinal investigation of clinical, parasitological and immunological parameters in a cohort of 300 Gabonese schoolchildren. We found the following frequencies: blood group O (0.54), sickle-cell trait (0.23), G6PD deficiency (0.09), MBP gene mutations (0.34), TNF-alpha promoter mutations (at positions -238: 0.17 and -308: 0.22) and NOS2 promoter mutation (0.18). Blood group O or hemoglobin AA were associated with protection against higher parasitemia. Girls with normal G6PD enzyme activity were protected against clinical malaria attacks. In addition, we demonstrated for the first time that the mutation at position -238 of the gene coding for the promoter region of TNF-alpha was positively correlated with the level of the antibody response specific for epitopes of the antigens MSA-2 and RAP-1 of P. falciparum.

ABO Blood-Group System↗

Identification of a locus for disseminated superficial actinic porokeratosis at chromosome 12q23.2-24.1.

Disseminated superficial actinic porokeratosis is an autosomal dominant cutaneous disorder characterized by many uniformly small, minimal, annular, anhidrotic, and keratotic lesions. The genetic basis for this disease is unknown. Using a genomewide search in a large Chinese family, we identified a locus at chromosome 12q23.2-24. 1 responsible for disseminated superficial actinic porokeratosis. The fine mapping study indicates that the disseminated superficial actinic porokeratosis gene is located within a 9.6 cM region between markers D12S1727 and D12S1605, with a maximum two-point LOD score of 20.53 (theta = 0.00) at D12S78. This is the first locus identified for a genetic disease where the major phenotype is porokeratosis. The study provides a map location for isolation of a gene causing disseminated superficial actinic porokeratosis.

China↗

Long-term outcomes of renal transplantation: a result of the original endowment of the donor kidney and the inflammatory response to both alloantigens and injury.

Recent data suggest that long-term allograft survival might be affected by two factors. The first is the endowment of the allograft, which consists of two elements: the nephron mass and the ability of these nephrons to repair injuries sustained during the transplant process. The second factor is renal inflammation. Although inflammation is traditionally ascribed to alloreactivity, recent data have shown that there is also a renal inflammatory response to early injury after transplantation, to brain death in the donor, and as part of the maladaptive response to nephron loss. These two factors contribute to the detrimental effects of delayed graft function or acute rejection on the long-term survival seen in most studies, and the beneficial effects of anti-inflammatory agents on the maladaptive response to nephron loss.

Animals↗

Geographical differences in human herpesvirus 8 seroepidemiology: a survey of 1,201 individuals in Asia.

Since the discovery of human herpesvirus 8 (HHV8) as a contributory cause of Kaposis sarcoma, the clinical role of this virus has been actively investigated. An understanding of HHV8 seroepidemiology is critical for the study of its pathogenesis within a specific environment. A sero-survey is described in Taiwan of 1,201 individuals ranging in age from under 1 year to over 70. Indirect immunofluorescence assay was used to determine antibody titers against both latent and lytic antigens of HHV8. The results indicate that very few individuals (3-4%) were exposed to HHV8 before 10 years of age. Infection rate peaked (19.2%) between the ages of 21 to 40. Females showed a slightly higher seroprevalence for HHV8 than males, but the difference was not statistically significant. Pregnancy did not correlate with increased HHV8 infection rate nor with augmented HHV8 antibody titers. It is concluded that HHV8 in Taiwan is predominantly an infectious agent for adults. In this geographical locale, HHV8 is similar to herpes simplex virus type 2 in its likely transmission occurring presumptively through sexual routes. However, the study also indicates that a smaller portion of HHV8-transmission could occur through nonsexual contacts.

Adolescent↗

Diagnosis of Ebola haemorrhagic fever by RT-PCR in an epidemic setting.

This study reports the first field evaluation of a new diagnostic technique for Ebola virus disease with sensitivity and specificity. Ebola virus causes rare but fulminating outbreaks in Equatorial Africa. Rapid differentiation from other infections is critical for timely implementation of public health measures. Patients usually die before developing antibodies, necessitating rapid virus detection. A reverse transcriptase-polymerase chain reaction (RT-PCR) assay was developed, implemented and evaluated at Centre International de Recherches Médicales de Franceville (CIRMF) in Gabon, to detect Ebola viral RNA in peripheral blood mononuclear cells (PBMC). Twenty-six laboratory-confirmed patients during and 5 after the acute phase of Ebola haemorrhagic fever, 15 healthy controls and 20 febrile patients not infected with Ebola virus were studied. RT-PCR results were compared with ELISA antigen capture, and Ebola specific IgM and IgG antibody detection. Ebola virus RNA was amplified from 26/26 specimens from the acute phase, 3/5 during recovery, 0/20 febrile patients and 1/15 negative controls. Sensitivity of RT-PCR in identifying acute infection and early convalescence compared with antigen or IgM detection was 100% and 91% respectively, and specificity compared with antigen detection and IgM assay combined was 97%. Antigen capture detected only 83% of those identified by PCR, and IgM only 67%. Ebola virus RNA was detected in all 13 fatalities, only 5 of whom had IgM and none IgG. RT-PCR detected Ebola RNA in PBMC one to three weeks after disappearance of symptoms when antigen was undetectable. RT-PCR was the most sensitive method and able to detect virus from early acute disease throughout early recovery.

Disease Outbreaks↗

Pertussis seroepidemiology in Taipei.

PURPOSE: We evaluated the seroprevalence of pertussis among apparently healthy Taipei residents. METHODS: From January 1992 through December 1994, we recruited subjects from a well baby clinic (children < 3 years), kindergartens, primary, and secondary schools and colleges (3-20 years), a health exam clinic (> 20 years), and obstetric clinics (pregnant women). Subjects were stratified into 12 groups according to age and pregnant women were considered separately. The serum antibody titers against filamentous hemagglutinin (FHA) and pertussis toxin (PT) were measured by enzyme-linked immunosorbent assay. RESULTS: The anti-PT and anti-FHA titers were elevated in the 4 to 6-month and 19 to 20-month age groups, coinciding with regular pertussis vaccinations. The anti-PT titers rose again in the 3 to 4-year age group, reflecting a higher prevalence of natural pertussis infection. The anti-PT titers gradually decreased among older age groups, although a peak occurred in the 11 to 15-year age group. The sequential changes in anti-FHA titers followed those of anti-Pt titers in the younger age groups, but the anti-FHA titers were persistently elevated beyond 15 years of age. The antibody levels were similar in the two sexes, except that anti-PT titers were higher in males of 19 to 20 months and 21 to 30 years of age. Anti-PT titers were equivalent between neonates (0-2 months) and pregnant women, but anti-FHA titers were much lower in neonates. CONCLUSIONS: The seroprevalence patterns in this study indicate that young children, adolescents, and even adults remain at risk of pertussis, despite the current immunization program. Booster vaccinations after completion of the current four-dose immunization schedule, possibly continuing into adolescence, should be considered to block the transmission of infection.

Adhesins, Bacterial↗

Enteric adenovirus infection in children in Taipei.

Enteric adenoviruses (EAds), including type 40 (Ad40) and 41 (Ad41), can cause acute and severe diarrhea in young children. To delineate the epidemiological features of pediatric EAds infection in Taiwan, we conducted a retrospective study of all cases of EAds gastroenteritis in children treated at National Taiwan University Hospital for the period from July 1993 to December 1997. Stool samples were tested for the presence of Ad40 or Ad41 by enzyme immunoassay (EIA). A total of 64 cases of EAds infection in 63 children aged from 8 days to 81 months old with a median age of 9.5 months treated during the study period were identified. The male-to-female ratio was 1.63 (39/24). No obvious seasonal clustering of EAds cases was noted. Most patients (76.6%) were infected before the age of 2 years. Clinical features included diarrhea (96.9%), fever (54.7%), vomiting (45.3%), mild dehydration (43.8%), symptoms of upper respiratory tract infection (21.9%), and abdominal pain (12.5%). Analysis of fecal samples in patients with diarrhea showed watery diarrhea in 72.2%, diarrhea with mucus in 20%, diarrhea with blood in 3.1% and diarrhea with mucus and blood in 1.6 % of all patients. Nearly one-half (43.5%) of the patients had diarrhea for more than 7 days. Thirty-seven patients (57.8%) were hospitalized due to gastroenteritis or other unrelated diseases, and 11 patients (17.2%) acquired enteric adenovirus infection during hospitalization for other underlying disease. Twelve patients (18.8%) had mixed infections, which included rotavirus, respiratory syncytial virus (RSV) and Salmonella species. There were no deaths in this series. The findings of this study suggest that EAds are important etiologic microbes of pediatric gastroenteritis.

Adenoviridae Infections↗

Rotavirus gastroenteritis in children: 5-year experience in a medical center.

Rotavirus infection is the leading cause of childhood gastroenteritis. We retrospectively reviewed cases of rotavirus gastroenteritis at National Taiwan University Hospital from January 1993 to December 1997. During the study period there were 429 patients with rotavirus infection with ages ranging from 1 day to 16 years with a median of 13 months. The male-to-female ratio was 1.2:1. Infection occurred before the age of 2 years old in 76% of patients. The seasonal peak occurred in the late winter and early spring during 1993 to 1996, but the case number increased in late spring and summer in 1997. The G serotype of the rotavirus was identified in 302 patients (70%). Vomiting and dehydration developed more frequently following infection with G1 rotaviruses, while an increased frequency of seizures was noted following G2 infection; the differences were not statistically significant. One patient had two episodes of infection; the first one was caused by G1 rotavirus, and the strain causing the second infection could not be typed. In conclusion, the results suggest that there is a strong seasonal variation in the incidence and characteristics of rotavirus infection in Taipei area. The infections caused by G1 and G2 rotaviruses were clinically indistinguishable.

Adolescent↗

Docosahexaenoic acid, a component of fish oil, inhibits nitric oxide production in vitro.

INTRODUCTION: Docosahexaenoic acid (DHA) has been shown to be immunosuppressive in the fetus, and fish oil diets are thought to be beneficial in autoimmune disease and transplantation. This effect may be mediated through nitric oxide (NO). Here, we investigate the effect of DHA on murine macrophages. METHODS: Peritoneal macrophages were subjected to stimulation with various concentrations of interferon gamma-(IFN-gamma) and tumor necrosis factor alpha (TNF-alpha). NO production was assessed by measuring nitrite (Greiss reaction). RESULTS: At all doses of IFN-gamma and TNF-alpha, DHA was found to be inhibitory to NO production. CONCLUSIONS: DHA inhibits macrophage-stimulated NO production in response to IFN-gamma and TNF-alpha. As NO is thought to be important in several disease processes, DHA may be a useful agent in the treatment of conditions such as autoimmune disease.

Animals↗

Concurrent increase of oxidative DNA damage and lipid peroxidation together with mitochondrial DNA mutation in human lung tissues during aging--smoking enhances oxidative stress on the aged tissues.

Although mutation of mitochondrial DNA (mtDNA) in human tissues has been established to associate with intrinsic aging, the impact of environmental factors on the formation and accumulation of mtDNA mutations and oxidative DNA damage in human tissues is poorly understood. We have investigated the levels of mtDNA with the 4977-bp deletion and A3243G point mutation, oxidative DNA damage (indicated by the formation of 8-hydroxy-2'-deoxyguanosine, 8-OH-dG), and lipid peroxides in lung tissues from smokers and nonsmokers of subjects of different ages. The results showed concurrent age-dependent increase of the 4977-bp deleted mtDNA (P < 0.001), 8-OH-dG (P < 0.05), and lipid peroxides (P < 0.05) in the human lung. In the group of subjects above 60 years old, smokers had more extensive DNA damage and lipid peroxidation than did the nonsmokers. However, the levels of mtDNA with the 4977-bp deletion and A3243G point mutation in the lung of smokers were not significantly different from those of the age-matched nonsmokers. Taken together, these results suggest that accumulation of mtDNA with the 4977-bp deletion together with oxidative DNA damage and lipid peroxides is associated with aging and that smoking enhances oxidative damage in human lung tissues.

8-Hydroxy-2'-Deoxyguanosine↗