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Biomedical subjects

K H Hsieh

Publications and source records attributed to K H Hsieh.

At least 55 records · Page 3Linked to original sources
PubMed1996

Evaluation of efficacy of traditional Chinese medicines in the treatment of childhood bronchial asthma: clinical trial, immunological tests and animal study. Taiwan Asthma Study Group.

Traditional Chinese medicines (TCM) have been used to treat bronchial asthma for several centuries and a certain degree of clinical benefit has been observed; however, scientific substantiation is lacking. A multicenter, double-blind and placebo-controlled study was therefore conducted to evaluate the clinical efficacy in terms of symptom score, medication score, morning and evening PEFRs, and changes of immunoregulatory function, such as distribution of lymphocyte subsets and in vivo and in vitro production of lymphokines (IFN-gamma and IL-4) and inflammatory mediators (histamine, PGE2 and LTC4). Furthermore, the protective effect of TCM on the late asthmatic reaction (LAR) was evaluated by using asthmatic guinea pigs. Three hundred and three asthmatic children were classified by Chinese doctors, according to a standardized questionnaire designed on the basis of basic logic of Chinese medicine, into three groups of specific constitution (group A, B and C). Group A consisted of 32 herb A-treated patients and 34 placebo-treated; group B, 74 herb B-treated and 64 placebo-treated; and group C, 55 herb C-treated and 44 placebo-treated. The study period was six months. The results were: 1) Both treatment group and placebo group showed an improvement in all clinical parameters, thus demonstrating a placebo effect. However, the improvement was usually greater in the former than the latter, although only the difference in PEFR was significant; 2) Herb A could increase total T cell and decrease B cell; 3) Herb A and B enhanced production of PGE2 but not LTC4, IFN-gamma and IL-4; 4) There was a general tendency for in vivo and in vitro production of histamine to decrease at the end of study in both treatment group and placebo group; however, the decrease was significantly greater in the former than the latter; 5) In asthmatic guinea pigs, 10-day's pretreatment with Chinese herbs could reverse the decrease of sGaw, suppress eosinophilia in bronchoalveolar lavage fluid (BALF), prevent the eosinophil infiltration of airways, increase PGE2 production and decrease LTC4 production in serum and BALF. Thus, traditional Chinese medicines did show a certain degree of clinical efficacy. The decreased production of histamine and LTC4, increased production of PGE2 that were found in both asthmatic children and asthmatic guinea pigs, and prevention of occurrence of LAR by suppressing eosinophil infiltration of airways and preserving airway conductance that were observed in asthmatic guinea pigs after allergen challenge might be used to account partly for the effectiveness.

Adolescent↗
PubMed1996

Isolation of type 1 and type 2 cloned mite allergen-specific T cells from an asthmatic child.

Allergen-specific T cells have been thought to play a central role in the pathogenesis of asthma. It has been well documented that allergen-specific T cells derived from atopic patients are predominantly of type 2 T helper cell pattern. However, allergen-specific T cells derived in nonatopic normals are of type 1 in contrast to atopic patients. The purpose of the study was to develop and characterize both mite allergen-specific TH1 and TH2 clones from the same asthmatic child. With exogenous supplemental cytokine, both TH1 and TH2 clones from the same patient have been developed and maintained in this laboratory for more than one year. All these T cell clones showed dose dependent allergen-specific proliferative response and expressed with CD4+, CD45RA- markers. Elucidation of the origin and interaction between these two different types of T helper cells might shed light on understanding the pathogenesis of atopic diseases and the mechanisms of hyposensitization in atopic patients.

Allergens↗
PubMed1996

Different kinds of antigen-presenting cells exert different effects on T-helper cells development.

It has been well documented that environmental factors such as antigen-presenting cells and related cytokines can affect the development of T-helper cells. The purpose of this study was to investigate the role of different antigen-presenting cells on T-cell development. Ovalbumin (OVA) combined with complete Freud's adjuvant (CFA) was used to sensitize mice subcutaneously or intraperitoneally, and then to follow-up production of IgG and IgE anti-OVA antibodies. In addition, semiquantitative PCR was used to determine the level of cytokine mRNA of different antigen-presenting cells. Resulting data showed that antigen-presenting cells expressed with different characteristics: (1) IgG2a anti-OVA antibody was higher in mice sensitized subcutaneously compared to those sensitized intraperitoneally. (2) The levels of cytokine mRNA were higher in antigen-stimulated spleen cells of mice immunized subcutaneously compared to those of mice immunized intraperitoneally. (3) Langerhans cells expressed a high level of IL-12; in contrast, peritoneal B cells expressed a high level of IL-10, but not IL-12. In summary, cytokine levels such as IL-10 and IL-12 were different among different kinds of APC, and their role in production of different isotypes of antibodies needs further elucidation.

Animals↗
PubMed1996

IgE and monoclonal antibody binding by the mite allergen Der p 7.

BACKGROUND: The recently characterized group 7 house dust mite allergens give positive skin-test reactions in 53% of allergic patients. OBJECTIVE: This study was performed to compare the IgE binding activity of natural and recombinant Der p 7, to measure the binding in allergic sera in comparison to major allergen Der p 2 and characterize the response by competitive inhibition with monoclonal antibodies. METHODS: IgE anti Der p 2 and Der p 7 antibodies against the recombinant allergens and monoclonal binding activities were measured by a solid phase radioimmune assay. RESULTS: A competitive binding assay showed that rDer p 7 inhibited 91% of IgE-binding to natural Der p 7 in 2 sera and 73% in a further two. The IgE binding of rDer p 2 and Der p 7 from 41 sera was then compared. Of the sera 88% and 46% respectively showed positive binding. All of the 19 sera which bound Der p 7 also bound Der p 2 but 11 (58%) had bound IgE to Der p 7 as high or higher than the binding to Der p 2. These sera were mostly high responders to both allergens. A panel of six monoclonal antibodies produced against either rDer p 7 or rDer f7 was used for epitope analysis. All of these reacted with each allergen by enzyme linked immunosorbent assay (ELISA) and immunoblotting. Two patterns of cross inhibition of monoclonal antibody binding were observed and of five monoclonal antibodies tested, four could inhibit the binding of IgE (WH9, WH22, WP8 and HD19) while one (WH14) could not. CONCLUSIONS: Although Der p 7 only reacts with 50% of allergic sera it often has a high IgE binding activity and may be more important than the major Der p 2 allergen in a high percentage of subjects. The combined competitive inhibition experiments show the IgE response is directed at several specificities.

Antibodies, Monoclonal↗
PubMed1996

Decreased production of IFN gamma and increased production of IL-6 by cord blood mononuclear cells of newborns with a high risk of allergy.

BACKGROUND: The underlying mechanisms of elevated IgE level in atopic patients are still obscure, however, extensive efforts have been tried to identify an immunological parameter as a predictor of atopy. OBJECTIVE: This study compared the difference in cytokine production by cord blood mononuclear cells between new borns with high-risk of allergy (family allergy score, FAS > or = 3) and those with low-risk (FAS = 0). METHODS: Following stimulation with PHA (100 micrograms/mL) and PMA (1 ng/mL), the cytokines produced by cord blood CD4+ T cells in the presence of monocytes were measured by ELISA kits and the mRNA was detected by reverse transcription-polymerase chain reaction (RT-PCR) technique. RESULTS: Our results showed: CD4+ T cells in the presence of monocytes and isolated monocytes from the high-risk group produced a much greater amount of IL-6, either spontaneously or after stimulation, than did those of the low-risk group; CD4+ T cells of low-risk group produced a significantly greater amount of interferon gamma (IFN gamma) than did those from the high-risk group; IL-4 cannot be detected by ELISA kit, and only a trace amount of IL-4 mRNA was detected by RT-PCR technique; cord blood basophils stimulated with PHA and PMA could produce a significant amount of IL-4; there was an inverse correlation between the production of IFN gamma and cord blood IgE level (high-risk group, r = 0.647, n = 17) and the number of natural killer (NK) cells (CD3- CD16+ CD56+) was significantly lower in high-risk group than for low-risk group. CONCLUSION: Our data suggested increased production of IL-6 and decreased production of IFN gamma of cord blood mononuclear cells appear to be the hallmark of newborns from the high-risk population.

Basophils↗
PubMed1996

Glutathione-S-transferase induces murine dermatitis that resembles human atopic dermatitis.

BACKGROUND: The molecular and functional basis of allergen-induced inflammation seen in atopic dermatitis (AD) remains undefined. OBJECTIVE: The objective of this study is to establish a murine model to dissect the pathological mechanisms of inflammatory reactions leading to the development of AD. METHODS: An inbred strain of mice, BALB/c, when injected peritoneally with 30 micrograms of recombinant Sj26 protein (rSj26), a glutathione-S-transferase of Schistosoma japonicum worm, developed systematic dermatitis 21 days after immunization. The pathology of the dermatitis was examined by histological evaluation and immunostaining. The immediate skin hypersensitivity was demonstrated by serum transfer and skin test. Epicutaneous patch test was used to demonstrate the antigen-specific late phase response. RESULTS: Significant responses of rSj26-specific IgE were detected 2 weeks after immunization, and such changes paralleled formation of skin lesions. The diseased skin pathology showed inflammatory changes such as infiltration of mononuclear cells and eosinophils in the dermis and mild spongiosis in the epidermis. Numerous IgE bearing cells were also detected in the dermis. Peripheral blood showed eosinophilia at the same time. In addition, rSj26-specific positive skin test and epicutaneous patch test could be demonstrated in rSj26-sensitized mice. CONCLUSIONS: These results suggest that rSj26 is capable of eliciting atopic dermatitis-like lesions in BALB/c mice. This can be a useful animal model for elucidating allergen-induced immune responses and the development of various therapeutic interventions of atopic dermatitis in humans.

Animals↗
PubMed1996

Successful bone marrow transplantation in a Chinese boy with Wiskott-Aldrich syndrome.

We describe the successful use of HLA-compatible sibling bone marrow transplantation (BMT) in a 17-month-old Chinese boy in whom Wiskott-Aldrich syndrome (WAS) was diagnosed on the basis of eczema, thrombocytopenia, recurrent otitis media and abnormal immunological tests. The conditioning chemotherapy included 2 days' oral busulfan, 40 mg/m2/6 hours, and 2 days' intravenous cyclophosphamide, 60 mg/kg/day (BU2CY2). Complete hematological chimerism was achieved 3 weeks after transplantation. Eight months after his BMT the eczema has resolved, platelet count is normal, and he no longer has frequent infections. BU2CY2 as a preconditioning regimen gave complete lymphohematopoietic engraftment in this WAS patient with no evidence of graft-versus-host disease. The excellent clinical response of this patient and the inevitable fatal outcome of WAS support the opinion that where a histocompatible donor is available, BMT at the earliest opportunity is the best option. We believe this is the first case of successful BMT in a Chinese patient with WAS.

Asian People↗
PubMed1995

Establishment of human IgE system in severe combined immunodeficient mice with peripheral blood mononuclear cells from asthmatic children.

The frequency of allergic diseases, such as asthma, has increased rapidly during the past decade; however, the exact mechanisms have not been established. In this study we tried to establish an in vivo system to investigate immune regulation of allergic diseases by using severe combined immunodeficient (SCID) mice. Peripheral blood mononuclear cells isolated from asthmatic children or normal adults were injected into peritoneal cavities of SCID mice. Human IgG, IgA, IgM, and IgE could be detected in SCID mice reconstituted with human PBMCs (SCID-PBL-hu mice) 3 weeks later. Moreover, the mice injected with peripheral blood mononuclear cells from asthmatic children had much higher IgE levels than mice reconstituted with cells from normal adults. Phenotypic analysis of spleen cells and peritoneal exudate cells from SCID-PBL-hu mice demonstrated that human lymphocytes could survive in the peritoneal cavity and spleen for several months. After intraperitoneal immunization, mite-specific IgE antibodies could also be detected in SCID-PBL-hu mice. This study indicates that the human IgE system can be established in SCID mice and that this model can be used to study the regulation of IgE production and the immunopathogenesis of human allergic disease.

Animals↗
PubMed1995

Precore mutant of hepatitis B virus in childhood fulminant hepatitis B: an infrequent association.

Serum HBV DNA from infants and children with fulminant hepatitis B (FHB) or acute self-limiting hepatitis B (AHB) and patients believed to be contamination sources was amplified by polymerase chain reaction (PCR) followed by direct sequencing of the precore region. A precore mutation from G to A at nucleotide 1896 was found in 5 of 14 FHB patients and in 3 of 10 AHB patients. Among the 10 infants who developed hepatitis during the first 6 months of age, the precore mutation was detected in only 2 of 7 with FHB and in 1 of 3 with AHB. In 1 infant with FHB, a shift from wild type to precore mutant predominance occurred in the serum virus population during the incubation period. Thus, the precore mutation is neither necessary nor sufficient to cause FHB in childhood, although its contributory role cannot be excluded. Factors other than precore mutations may be important in the pathogenesis of FHB.

Acute Disease↗
PubMed1995

Molecular cloning and immunological characterization of the house dust mite allergen Der f 7.

BACKGROUND: The allergen Der p 7 from Dermatophagoides pteronyssinus has been defined by molecular cloning and shown to be an important specificity in 50% of mite-allergic patients. OBJECTIVE: This study compares the cDNA sequence and serological reactivity of Der f 7 from D. farinae with Der p 7. METHOD: cDNA encoding Der f 7 was amplified by polymerase chain reaction, sequenced and expressed as a fusion with glutathione-S-transferase for IgE and monoclonal antibody binding studies. RESULTS: Der f 7 cDNA encoded a 213 polypeptide containing a predicted 17 amino acid leader sequence, no cysteines and a single N-glycosylation site similar to Der p 7. The predicted 196 residue mature polypeptide had 86% identity to Der p 7 and a calculated molecular weight of 22,348Da. No homologues were found in searches of the data banks. The Der f 7 fusion protein showed a single band of 46 kDa by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and reacted with IgE antibodies in 19/41 (46%) of sera from asthmatic children. The degree of binding was usually 30% of that to Der p 7 consistent with the exposure of the patients to D. pteronyssinus. Monoclonal antibodies (WH9 and WH22) against Der p 7 reacted with Der f 7 but inhibition studies showed a 10-fold difference in reactivity. CONCLUSION: Der f 7 has a predicted 213 residue polypeptide with 86% homology and serological crossreactivity to Der p 7.

Allergens↗
PubMed1995

Characterization of the house dust mite allergen Der p 7 by monoclonal antibodies.

The house dust mite allergen Der p 7, which was defined by cDNA cloning, has been shown to react with about 50% of allergic sera and corresponds to or is antigenically related to at least three different sized components in mite extracts. To characterize these entities, monoclonal antibodies (MoAbs) were generated by immunizing BALB/c mice affinity-purified Der p 7-GST (glutathione S-transferase) fusion protein. MoAbs WH9 and WH22 showed positive reactivity to recombinant Der p 7 negative reactivity to GST and the Der p 5-GST fusion protein in ELISA and immunoblotting. The specificity of both MoAbs was confirmed by inhibition of the ELISA activity by recombinant Der p 7 but not by the recombinant Der p 5. Immunoblot analysis demonstrated that both MoAbs showed reactivities to components with molecular weights (mol. wt.) of 31, 30 and 26 kDa reactive to both MoAbs. At least six major forms with different pI or size were indicated by 2-D gel analysis. In addition to characterization of Der p 7, both MoAbs may also be considered for use in the standardization of Der p 7 in mite extracts.

Allergens↗
PubMed1995

Dysregulation of T helper cell cytokines in autoimmune prone NZB x NZW F1 mice.

Multifactorial involvement in the pathogenesis of autoimmune NZB/W F1 mice has been well documented. To further elucidate the role of cytokines in the disease development of murine lupus, single spleen cells isolated from NZB/W F1 and non-autoimmune C57BL/6 mice were stimulated with T cell mitogens or anti-CD3 antibody at pre-determined optimal concentration. Supernatants were collected and assayed for production of cytokines including IL-2, gamma-IFN, IL-3, IL-4, IL-5 and IL-10. In both young and old mice, cytokine profiles by mitogen-stimulated T cells showed higher TH2 (type 2 T helper) cell-related cytokine production in NZB/W F1 mice compared to those in non-autoimmune C57BL/6 mice. In contrast, cytokines produced by TH1 (type 1 T helper) cells, such as gamma-IFN and IL-2, were lower in NZB/W F1 mice by stimulation with either mitogen or anti-CD3 antibody. In addition, cytokine production at different time points also demonstrated decreased gamma-IFN and increased IL-4 levels by anti-CD3 stimulated splenic cells in autoimmune NZB/W F1 mice. Furthermore, the IL-10 levels produced by lipopolysaccharide (LPS)-stimulated splenic and peritoneal exudate cells were higher in young NZB/W F1 mice compared to those in C57BL/6 mice. Our data suggest that dysregulation between TH1 and TH2 cells may play an important role in the pathogenesis of autoimmunity in NZB/W F1 mice.

Age Factors↗
PubMed1995

Metered dose inhaler and nebuliser in acute asthma.

One hundred and eleven children with acute asthma were studied to compare delivery of terbutaline by either a metered dose inhaler (MDI) with a valved holding chamber or a nebuliser driven by air. Eligible patients were randomised; the MDI group received three puffs (0.75 mg) of terbutaline and the nebuliser group received 2 ml (5.0 mg) terbutaline solution diluted with 2 ml 0.9% saline for inhalation over 10 minutes. Patients were evaluated by spirometry, pulse oximetry, and clinical severity scoring system at baseline and again 15 minutes after the beginning of treatment. The baseline data of the two groups were not significantly different. All parameters of spirometry, except the peak expiratory flow (PEF) for the nebuliser group, and clinical severity score for both groups significantly improved after terbutaline treatment. Compared with the nebuliser group, the MDI group after treatment had better mean (SD) oxygen saturation (SaO2; 96.82 (1.63)% v 95.44 (1.88)%), frequency of oxygen desaturation (23.2% v 47.3%), absolute increase of PEF (32.6 (37.7) l/min v 10.2 (34.7) l/min), and SaO2 (0.54 (1.64)% v -0.47 (1.84)%). There was also a mean (SD) per cent increase of forced expiratory volume in one second (22.9 (21.0)% v 15.4 (16.1)%), PEF (27.7 (38.4)%) v 7.7 (25.1)%), and SaO2 (0.58 (1.72)% v -0.47 (1.93)%). In conclusion, aerosol treatment by MDI (with a valved holding chamber) in this study proved to be superior to nebuliser treatment in terms of SaO2 and some measurements of spirometry. Respiratory therapists working with children with severe asthma should be aware of the possibility of oxygen desaturation, especially when using room air as the driving gas for nebulisation.

Acute Disease↗
PubMed1995

Detection of Epstein-Barr virus and cytomegalovirus genome in white blood cells from patients with juvenile rheumatoid arthritis and childhood systemic lupus erythematosus.

The role of infectious agents in the pathogenesis of autoimmune diseases has long been a matter of debate. This study investigated the possible role of Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) infections in the pathogenesis of autoimmune diseases by an attempt to demonstrate the presence of the viral genome in the leukocyte of 21 juvenile rheumatoid arthritis (JRA) patients, 20 childhood-onset systemic lupus erythematosus (SLE) patients, and 20 age-matched normals, using polymerase chain reaction (PCR) and DNA probes. The results showed: (1) there was no difference in serum IgG anti-EBV antibody titers among three groups; (2) the EBV PCR-positive rates for JRA and SLE patients and normal controls were 5% (1/21), 10 (2/20), and 0% (0/20), respectively; (3) the HCMV PCR-positive rates for JRA and SLE patients and normal controls were 33% (7/21), 25 (5/20), and 10% (2/20), respectively, and (4) the HCMV-positive rate was 25% for JRA patients with steroid treatment and 33% for those without steroid treatment. It is, therefore, concluded that: (1) the data do not support the participation of EBV and HCMV in the pathogenesis of childhood-onset SLE and JRA; (2) steroid therapy does not increase the frequency of HCMV infection in JRA patients, and (3) immunoincompetence might be one of the major factors contributing to increased susceptibility to HCMV infection in JRA and SLE patients.

Adolescent↗
PubMed1994

Characterization of Der p V allergen, cDNA analysis, and IgE-mediated reactivity to the recombinant protein.

A lambda gt11 library for cDNA from Dermatophagoides pteronyssinus was screened by plaque immunoassay, and a number of related clones that produced IgE-binding proteins were isolated. Their sequences were homologous to that of a cDNA described previously, which contained a reading frame encoding a 17 kd polypeptide and which as determined by serologic analysis corresponded to a protein with relative molecular mass of 14 kd in mite extracts. The cDNA from the lambda gt11 clones was truncated so it was used to obtain longer clones from a lambda gt10 library. Analysis of the sequence of these clones showed that the allergen now designated Der p V is produced from a 132-residue polypeptide, which has a putative 19-residue leader peptide and a 113-residue mature protein. This would have a molecular weight of 14 kd, corresponding to that found in mite extracts. IgE binding studies with the lambda gt11 clone and a fusion of the mature sequence in a pGEX construct showed that it reacted with 50% of allergic sera. Further studies with skin tests indicated that it caused reactions in about 60% of patients with asthma and 29% of those with allergic rhinitis alone.

Allergens↗
PubMed1994

Comparison of three in vitro assays for serum IgE with skin testing in asthmatic children.

The diagnostic performance of three commercial assay kits [Phadezym RAST (PhRAST), Pharmacia CAP system (CAP), and multiple chemiluminescent assay (CLA-MAST)] for measuring serum-specific IgE was evaluated and compared using intradermal skin testing or skin prick testing as reference standards. Serum samples were obtained from allergic patients who were tested with either intradermal skin tests or skin prick tests (96 and 49 subjects, respectively). Six different allergen extracts were tested: Dermatophagoides pteronyssinus, Candida albicans, Aspergillus, short ragweed, Bermuda grass, and cockroach mix. Results showed that when using intradermal skin testing as a reference standard, the CLA-MAST had the lowest sensitivity (75%), specificity (80%), and efficiency (85%) but the Pharmacia CAP system achieved the highest sensitivity, specificity, and efficiency (86%, 94%, and 91%, respectively). When compared with these two relatively new assays, the Phadezym RAST had medium sensitivity (80%), specificity (92%), and efficiency (88%). In contrast, when using skin prick testing as a reference standard, the highest specificity was achieved by Phadezym RAST (95%), followed by Pharmacia CAP system (90%), and MAST (81%). As for the sensitivity of each test, the Phadezym RAST was the lowest (60%) and Pharmacia CAP system reached the highest sensitivity (79%); and for the efficiency test, the score was 87% for CAP, 83% for Phadezym RAST, and 75% for MAST. These results suggest, therefore, that the CAP system is the preferred test and provides a useful guide for prescription of environmental control and immunotherapy in unselected patients.

Adolescent↗