Biomedical subjects

Bor-Luen Chiang

Publications and source records attributed to Bor-Luen Chiang.

At least 19 recordsLinked to original sources

PubMed2004

Risk of infection in hospitalised children with systemic lupus erythematosus: a 10-year follow-up.

The objective of this study was to investigate infection and sepsis in hospitalised children with systemic lupus erythematosus (SLE). Between 1991 and 2000 we reviewed 72 episodes of suspected infection in 42 children with SLE from all hospitalised children with SLE at a medical center in Taiwan. Data comprised clinical and laboratory characteristics of SLE at the time of infection. Infections were identified and categorised as minor or major. A total of 125 patients (110 girls, 15 boys) were admitted 557 times. Forty-two patients had infections, giving an infection rate of 33.6%. There were a total of 72 infections including 20 proven infections; 61 cases of these were minor infections and 11 cases of these were major infections (10 cases were sepsis). Four patients died because of sepsis. By univariate analysis, major infection (sepsis) was significantly associated with a high SLE disease activity index score, lower complement levels and higher anti-DNA titres. In conclusion, our data confirm that infection is common in hospitalised children with SLE. Sepsis, most frequent in major infections, is associated with disease activity and causes significant mortality. These facts should be borne in mind when children with SLE are hospitalised.

Adolescent↗

PubMed2004

Patient data, early SARS epidemic, Taiwan.

Of the first 10 patients in the epidemic of severe acute respiratory syndrome (SARS) in Taiwan, 4 were closely associated with a SARS patient in an airplane. Loose stools or diarrhea, hemophagocytosis syndrome, and high serum levels of interleukin (IL)-6, IL-8, and tumor necrosis factor-a associated with lung lesions were found in all 10 patients.

Adult↗

PubMed2003

Morin sulfates/glucuronides exert anti-inflammatory activity on activated macrophages and decreased the incidence of septic shock.

Morin is a flavonoid present in fruits and Chinese herbs. Based on in vitro studies, morin has been reported to show various beneficial biological activities. However, there is growing evidence that conjugative metabolism is central to the biological fate of flavonoids. Therefore, the biological effects of morin could be primarily determined by its conjugated metabolites. In this study, the effects of morin and its sulfates/glucuronides on the production of nitric oxide (NO) and cytokines from lipopolysaccharide (LPS)-activated macrophages were individually investigated and compared. The results indicated that the 50% NO production was inhibited from LPS-activated RAW 264.7 cells by 1.25 mM morin and 1.25 microM morin sulfates/glucuronides. Meanwhile, the 50% inhibition concentration (IC50) values of morin and morin sulfates/glucuronides in activated peritoneal macrophages were 1.5 mM morin and 1.5 microM morin sulfates/glucuronides, respectively. In addition, 30% of the tumor necrosis factor-alpha (TNF-alpha) and 35% of the interleukin (IL)-12 productions from activated macrophages were inhibited by 2-2.5 mM morin and 2-2.5 microM morin sulfates/glucuronides, respectively. Furthermore, phagocyte activities in the peripheral blood of those for mice dosed with morin for two months were about 65-70% of controls. Lower NO production and reduced macrophage phagocytic activities corresponded to LPS-resistant state. These findings indicated that morin may exhibit anti-inflammatory activity and reduced the incidence of experimental septic shock through decreasing the functions of macrophages and may regulate immune response through modulating the cytokine profiles. Therefore, morin could be a promising therapeutic candidate for inflammatory disease due to the strong activity of its metabolites.

Animals↗

PubMed2003

Ribavirin or CpG DNA sequence-modulated dendritic cells decrease the IgE level and airway inflammation.

Asthma is an allergic disease that is characterized by the imbalance between Th1 and Th2 cells and by the predominant Th2-type immune response. In this study, we investigated the application of dendritic cell (DCs)-based immunotherapy in modulating the immune response of allergic diseases. DCs incubated with ovalbumin (OVA), OVA plus ribavirin, OVA plus CpG-oligodeoxynucleotides (ODN 1826), or OVA plus non-CpG-ODN (ODN 1745) for 48 hours were injected intravenously into four corresponding groups of BALB/c mice. All of the mice were then immunized with OVA intraperitoneally 7 days later to establish an animal model of asthma. Serum levels of OVA antibody, airway hyperresponsivness, cell composition and cytokine levels in the bronchoalveolar lavage fluid, and cytokine profiles of spleen cells were analyzed. The data showed that ribavirin and ODN 1826 increased interleukin-12 synthesis and inhibited interleukin-10 production. ODN 1826 could also enhance the expression of B7.1, B7.2, major histocompatibility complex I, and major histocompatibility complex II molecules. Furthermore, the DCs modulated by ribavirin and ODN 1826 could downregulate the Th2-type immune response in vivo and could alleviate airway inflammation. This study elucidated the effect of ribavirin and CpG-ODN on DCs and demonstrated that in vitro modulated DCs might be a potential therapeutic approach for asthma.

Adjuvants, Immunologic↗

PubMed2003

Differential susceptibility to staphylococcal superantigen (SsAg)-induced apoptosis of CD4+ T cells from atopic dermatitis patients and healthy subjects: the inhibitory effect of IL-4 on SsAg-induced apoptosis.

This study had two aims: 1) to determine whether there are differences between atopic dermatitis (AD) patients and healthy subjects in staphylococcal superantigen (SsAg)-induced CD4(+) T cell activation, cytokine production, chemokine receptor expression, and apoptosis; and 2) to investigate the effect of IL-4 on SsAg-induced apoptosis. By using immunofluorescence and annexin V staining, we analyzed PBMC with or without staphylococcal enterotoxin B (SEB) stimulation in the presence or absence of rIL-4 or anti-IL-4-neutralizing Abs in 15 healthy subjects and 27 AD patients. We found that SEB preferentially induced production of Th1 cytokine in SEB-reactive (TCRVbeta3(+) or Vbeta12(+) or Vbeta17(+)) CD4(+) T cells from healthy subjects and Th2 cytokine in those from AD patients. SEB induced up-regulation of CXCR3(+) cells in SEB-reactive CD4(+) T cells from healthy subjects and CCR4(+) cells in those from AD patients. SEB-reactive CD4(+) T cells from AD patients were more resistant to SEB-induced apoptosis than those from healthy subjects. There was no significant difference between AD and healthy subjects in SEB-induced activation of CD4(+) T cells. CXCR3(+) CD4(+) T cells were more susceptible to SEB-induced apoptosis than CCR4(+) CD4(+) T cells in healthy subjects. Exogenously added IL-4 inhibited SEB-induced apoptosis of SEB-reactive CD4(+) and CXCR3(+) CD4(+) T cells but not of CCR4(+) CD4(+) T cells in healthy subjects. Inhibition of endogenous IL-4 increased SEB-induced apoptosis of SEB-reactive CD4(+) T cells from AD patients. These results might provide new clues to the mechanism that SsAgs contribute to the persistence and exacerbation of allergic skin inflammation in AD.

Adolescent↗

PubMed2003

Antitumor and antimetastatic activity of IL-23.

The structure and T cell stimulatory effects of the recently discovered cytokine IL-23 are similar to, but distinct from, those of IL-12. Although the antitumor activities of IL-12 are well characterized, the effect of IL-23 on tumor growth is not known. In this study, murine CT26 colon adenocarcinoma and B16F1 melanoma cells were engineered using retroviral vectors to release single-chain IL-23 (scIL-23) to evaluate its antitumor activity. In BALB/c mice, scIL-23-transduced CT26 cells grew progressively until day 26 to an average size of 521 +/- 333 mm(3), then the tumors started to regress in most animals, resulting in a final 70% rate of complete tumor rejection. scIL-23 transduction also significantly suppressed lung metastases of CT26 and B16F1 tumor cells. In addition, mice that rejected scIL-23-transduced tumors developed a memory response against subsequent wild-type tumor challenge. Compared with scIL-12-expressing CT26 cells, scIL-23-transduced tumors lacked the early response, but achieved comparable antitumor and antimetastatic activity. These results demonstrated that IL-23, like IL-12, provided effective protection against malignant diseases, but it probably acted by different antitumor mechanisms. As a first step in identifying these antitumor mechanisms, tumor challenge studies were performed in immunocompromised hosts and in animals selectively depleted of various lymphocyte populations. The results showed that CD8(+) T cells, but not CD4(+) T cells or NK cells, were crucial for the antitumor activity of IL-23.

3T3 Cells↗

PubMed2003

Roles of keratinocyte inflammation in oral cancer: regulating the prostaglandin E2, interleukin-6 and TNF-alpha production of oral epithelial cells by areca nut extract and arecoline.

Betel quid (BQ) chewing is an etiologic factor of oral cancer and submucus fibrosis (OSF). Keratinocyte inflammation is crucial for the pathogenesis of cancer and tissue fibrosis. We found that areca nut (AN) extract (100-400 micro g/ml) induced PGE2 production by KB cells by 2.34- to 23.1-fold and also TNF-alpha production by gingival keratinocytes (GK). Arecoline (0.2-1.2 mM) elevated PGE2 production by KB cells by 2.5- to 6.1-fold. AN extract (200-400 micro g/ml) also induced IL-6 production by GK (7.5- to 8.4-fold) and KB cells. In contrast, arecoline (0.1-1.2 mM) suppressed IL-6 production by GK and KB cells, with 42-81 and 41-63% inhibition, respectively. A 48 h exposure of GK to 800-1200 micro g/ml AN extract led to 37-69% cell death. Arecoline cytotoxicity to GK was noted at concentrations of 0.8-1.2 mM, which led to 28-38% cell death. AN extract (400-800 micro g/ml) induced Cox-2 and IL-6 mRNA expression and also COX-2 protein production by KB cells. IL-6 (5-100 ng/ml) suppressed GK growth by 20-33%, but enhanced oral fibroblast (OMF) and KB cell growth. PGE2 (0.05-5 micro g/ml) and anti-IL-6 antibody (ab) (50-1000 ng/ml) showed little effect on GK and KB cell growth. Incubation of GK and KB cells with aspirin, anti-IL-6 ab and anti-TNF-alpha ab showed little effect on arecoline- and AN-induced cytotoxicity, cell cycle arrest and apoptosis. Exposure to anti-TNF-alpha ab slightly affected arecoline- and AN-modulated PGE2 and IL-6 production by GK and KB cells. Arecoline- and AN-conditioned medium decreased phytohemagglutinin-mediated CD4+ and CD8+ T cell activation. These results indicate that BQ chewing contributes to the pathogenesis of cancer and OSF by impairing T cell activation and by induction of PGE2, TNF-alpha and IL-6 production, which affect oral mucosal inflammation and growth of OMF and oral epithelial cells.

Areca↗

PubMed2003

Proteomics and immunological analysis of a novel shrimp allergen, Pen m 2.

Shellfish are a common cause of adverse food reactions in hypersensitive individuals and shrimp is one of the most frequently reported causes of allergic reactions. A novel allergen from Penaeus monodon, designated Pen m 2, was identified by two-dimensional immunoblotting using sera from subjects with shrimp allergy, followed by matrix-assisted laser desorption ionization time-of-flight mass spectrometry analysis of the peptide digest. This novel allergen was then cloned and the amino acid sequence deduced from the cDNA sequence. The cloned cDNA encoded a 356-aa protein with an acetylated N terminus at Ala2, identified by postsource decay analysis. Comparison of the Pen m 2 sequence with known protein sequences revealed extensive similarity with arginine kinase (EC 2.7.3.3) from crustaceans. Pen m 2 was purified by anion exchange chromatography and shown to have arginine kinase activity and to react with serum IgE from shrimp allergic patients and induce immediate type skin reactions in sensitized patients. Using Pen m 2-specific antisera and polyclonal sera from shrimp-sensitive subjects in a competitive ELISA inhibition assay, Pen m 2 was identified as a novel cross-reactive Crustacea allergen. This novel allergen could be useful in allergy diagnosis and in the treatment of Crustacea-derived allergic disorders.

Allergens↗

PubMed2003

Both allergen-specific CD4 and CD8 Type 2 T cells decreased in asthmatic children with immunotherapy.

Allergen-specific immunotherapy (IT) has been used for the treatment of atopic diseases since the turn of this century. The precise working mechanisms, however, remain to be clarified. The aim of this study was to investigate the role of particular subsets of allergen-specific T cells in the non-atopic individuals, untreated asthmatic children and the asthmatic children receiving immunotherapy. We collected peripheral blood from 16 untreated asthmatic children and 17 asthmatic children receiving immunotherapy over one and half years. All the patients were sensitive to mite allergen. Peripheral blood mononuclear cells (PBMC) were isolated and, in vitro, stimulated with crude mite extract to enrich the mite-specific T-cell population. After 14 days, the enriched mite-specific T cells were stimulated with phorbol-12-myristate-13-acetate (PMA) and ionomycin for intracellular detection of cytokines such as IFN-gamma, IL-4 in CD4+ and CD8+ T lymphocytes. The data here demonstrated that the levels of mite-specific IgG4 and IgA increased significantly in asthmatic children after immunotherapy. In addition, both IL-4 expressing CD4+ and CD8+ T cells were significantly lower in asthmatic children after immunotherapy compared with those of before treatment and the normal control (p < 0.05). In contrast, the frequency of IFN-gamma expressing CD4+ and CD8+ T cells did not significantly differ between untreated and SIT-treated groups. All these data suggested that decreased Type 2 CD4+ and CD8+ T cells might be closely correlated with the regulatory mechanisms of immunotherapy.

Adolescent↗

PubMed2003

Cyclosporin A therapy for steroid-dependent Henoch-Schönlein purpura.

Henoch-Schönlein purpura is one of the most common types of systemic vasculitis in children. Although recurrence is frequent, most cases are benign and self-limited. Standard treatment consists of supportive care and nonsteroid antiinflammatory drugs and/or steroid. Here we report 2 cases of Henoch-Schönlein purpura, both of which had a prolonged and corticosteroid-dependent disease course. After treatment with cyclosporin A, the symptoms and signs subsided gradually in both cases with no recurrence after tapering of corticosteroid and cyclosporin A.

Child, Preschool↗

PubMed2003

Common variable immunodeficiency with hypoglycemia, Kikuchi lymphadenitis, and hemiparesis in two siblings.

Common variable immunodeficiency is a heterogeneous group of disorders with arthritis and/or arthralgia as its most commonly associated autoimmune manifestation. We report 2 cases of common variable immunodeficiency in siblings who also had other unusual signs and symptoms. A 10-year-old boy suffered from bradycardia, hypothermia, hypoglycemia, and chronic eczema. His 13-year-old sister suffered from Kikuchi lymphadenitis, hypoperfusion and atrophy of the left cerebral hemisphere, and hemiparesis. They both showed classical laboratory findings of common variable immunodeficiency and the boy's associated symptoms responded to intravenous immunoglobulin therapy. The findings from these cases suggest that a defect in the neuro-endocrine-immune axis may be one of the genetic bases of common variable immunodeficiency.

Adolescent↗

PubMed2003

Association between levels of TNF-alpha and TNF-alpha promoter -308 A/A polymorphism in children with Kawasaki disease.

BACKGROUND AND PURPOSE: Tumor necrosis factor-alpha (TNF-alpha) has been shown to play a central role in the pathogenesis of vasculitis in Kawasaki disease (KD). We investigated the serum levels of TNF-alpha and soluble TNF receptor 1 (STNFR1) levels, and genetic polymorphisms of the TNF-alpha promoter gene in children with KD to delineate the genetic basis of KD. METHODS: A total of 18 children (12 boys and 6 girls) with KD were studied, 9 of whom had the complication of coronary artery lesion (CAL) within 30 days after the onset of symptoms. Serum levels of TNF-alpha and STNFR1 were assayed by enzyme-linked immnosorbent assay, and DNA polymorphisms of the 5' flanking region of TNF-alpha promoter gene at position -308 [guanine (G) to adenine (A)] and -238 (G to A) were studied by direct nucleotide sequencing. RESULTS: The serum TNF-alpha level in KD patients was 113 +/- 209.9 pg/mL (range, 2.0 to 756.9 pg/mL; median, 24.7 pg/mL; normal, < 10 pg/mL). The serum levels of STNFR1 in KD (4255 +/- 2425 pg/mL) were higher than those of the control group (160 +/- 116 pg/mL). Allele frequencies of -308A and -238A were 11.1% and 0% in the KD patients, and 0% and 3.1% in the control group. Neither TNF-alpha promoter polymorphism nor any significant risk factor for CAL was identified in KD patients. One patient, who was homozygous for -308A, showed the highest TNF-alpha level and elevated STNFR1 level but had no evidence of CAL. Positive correlations were found between serum levels of STNFR1 and C-reactive protein (r = 0.731, p = 0.007), and between STNFR1 and leukocyte counts at admission (r = 0.620, p = 0.008). CONCLUSIONS: Increased serum levels of TNF-alpha and STNFR1 were found in KD patients but there was no correlation between these levels. The relationship between the pathogenesis of KD and TNF-alpha gene promoter -308G to A mutation towards cytokine production remains to be clarified.

Case-Control Studies↗

PubMed2003

Therapeutic effect of interferon-gamma for prevention of severe infection in X-linked chronic granulomatous disease.

Chronic granulomatous disease (CGD) is an inherited phagocytic disorder caused by defective oxidative burst activity of neutrophils and monocytes. Patients with CGD may present with recurrent, life-threatening bacterial or fungal infections and often need repeated hospitalization as early as infancy. We report a case of a boy aged 3 years and 1 month with a history of oral thrush, chronic diarrhea, skin abscesses, multiple small joints osteomyelitis, and multiple liver abscesses since 2 months of age. X-linked chronic granulomatous disease was diagnosed by nitroblue tetrazolium test and further confirmed by genetic study using single strand conformation polymorphism (SSCP) analysis and genomic DNA sequencing. Two episodes of aspergillosis with severe aspergillus lung empyema and life-threatening Klebsiella pneumoniae infections were noted in the first 2 years of life despite long-term prophylaxis with trimethoprim-sulfamethoxazole and itraconazole. Recombinant human interferon-gamma (rINF-gamma) 50 microg/m(2) subcutaneous injection 3 times per week was added after his last episode of severe infection. Thereafter, the boy had normal growth and development with no evidence of severe infection during 18 months of follow-up at our outpatient clinic.

Antiviral Agents↗

PubMed2003

Retrospective analysis of mortality and morbidity of pediatric systemic lupus erythematosus in the past two decades.

A total of 153 pediatric systemic lupus erythematosus patients (131 girls and 22 boys) under 18 years of age who were newly diagnosed between 1980 and 2001 were retrospectively analyzed. All patients were followed up until death, loss of follow-up, or December 31, 2002. The mean follow-up duration was 6.11 +/- 9.02 years. There were no differences in sex and family history between the 1980-to-1990 cohort and the 1991-to-2001 cohort. The rate of complications of infection, skeletal manifestation, and end-stage renal disease were significantly higher in the 1980-to-1990 cohort (p=0.007, 0.001, and 0.000, respectively). Infection was the leading cause of death, and there were no differences in the cause of death between the 2 cohorts except end-stage renal disease (p=0.005). The survival rate was significantly worse in the 1980-to-1990 cohort than in the 1991-to-2001 cohort (p=0.0012). The 2 significant poor prognostic factors were being female and the development of end-stage renal disease. We conclude that the mortality and morbidity of SLE has improved over the past 2 decades. It may be associated with newer treatment modalities and better supportive care available recently.

Adolescent↗

PubMed2003

Hyper-IgM syndrome: a case report.

Hyperimmunoglobulin M syndrome is a rare primary immunodeficiency disorder. We report a case of a 6-month-old boy who suffered from developmental delays, frequent respiratory tract infection, and unusual fungal and bacterial infection. X-linked hyperimmunoglobulin M syndrome was ultimately diagnosed with decreasing immunoglobulin-G, A, and E (immunoglobulin G = 51.3 mg/dL, immunoglobulin A = 8.32 mg/dL, immunoglobulin E <17.5 mg/dL), elevating immunoglobulin M (immunoglobulin M = 140 mg/dL), and decreasing T-cell expression of the CD40 ligand over flow cytometry. Seizure episodes and hypotonia developed with greater signal intensity at the putamen in a brain magnetic resonance imaging, which is compatible with hypoxic ischemic encephalopathy. This is the youngest proven case of hyper-IgM syndrome in Taiwan ever reported.

CD4-Positive T-Lymphocytes↗

PubMed2003

Clinical observation between chronic sustained cough with asthma and childhood inguinal hernia.

Inguinal hernias are common and cause problems for the health services. Several factors are thought to influence their development. Patients under 16 years old who had received hernioplasty at National Taiwan University Hospital were enrolled in a study to analyze the correlation between preceding recurrent cough with asthma and later hernia development. Patients aged 5 and 6 years old (when admitted for hernioplasty in 2000) were particularly focused. This entailed further analysis of their birth history, family atopic history, specific allergic diseases (allergic rhinitis, atopic dermatitis, asthma), hernia type (direct or indirect), the onset of chronic cough and asthma. One hundred and sixty three patients (2.66%) from a total hernioplasty population of 6130 were found to have had preceding asthma with recurrent cough before having the hernioplasty intervention. One hundred twenty-five patients were aged 5 to 6 years old, among whom 8 (6.4%) patients were found to have asthma, and 20 (16%) patients were noted to have recurrent sustained cough. All the hernia types were indirect and were received with high suture ligation. In conclusion, the incidence of asthma was not significantly higher in the group of individuals receiving hernioplasty. However, a higher incidence of recurrent sustained cough was noted, which could be a relatively important factor for the hernia development. Further reliable cough measurements would be needed to evaluate the severity of recurrent sustained cough as the potential risk for the hernia development.

Asthma↗

PubMed2003

Methimazole-induced lupus erythematosus: a case report.

A 15-year-old girl had a history of diffuse goiter and received methimazole treatment 2 months before admission to the hospital. She developed bilateral lower leg edema 5 days before admission and the laboratory examinations revealed leukopenia, anemia, proteinuria, and granular cast. Positive antinuclear antibodies and anti-double strand (anti-ds) DNA antibodies were noted, although complement levels were not reduced. Myeloperoxidase antineutrophil cytoplasmic antibody was positive. A renal biopsy disclosed that there was focal segmental glomerulosclerosis. Methimazole was discontinued, and she was treated with prednisolone and Plaquenil, after which the symptoms and laboratory tests became normal within 40 days. The prednisolone was discontinued after treatment for seven months. Currently, the anti-dsDNA, C3, C4, CBC, urinalysis, and thyroid function tests are within normal limits. With hydroxychloroquine and levothyroxine, she was free of symptoms after discontinuation of methimazole until now (about 21 months).

Adolescent↗

PubMed2003

The role of food allergens in childhood asthma.

Eighty-eight patients' sera with allergen-specific IgE levels elevated only to food allergens were collected between October 1997 and March 2002 at the National Taiwan University Hospital. Thirty-three of the patients fulfilled the diagnostic criteria of asthma and were included. Most (72.7%) patients had elevated serum allergen-specific IgE levels only to one food allergen. The most common food allergens were milk and egg white. The patients with elevated soy bean-specific IgE levels had significantly higher levels of serum food allergen-specific IgE than those with either elevated milk or egg white-specific IgE levels. This study investigated some food allergen responses of asthmatic patients whose serum allergen-specific IgE levels were elevated only to food allergens. The results suggested that the allergic asthmatic response in our patients was most likely related to food rather than aeroallergens or fungal allergens.

Age Factors↗