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Biomedical subjects

K H Hsieh

Publications and source records attributed to K H Hsieh.

At least 73 records · Page 4Linked to original sources
PubMed1993

Increased plasma platelet-activating factor in children with acute asthmatic attacks and decreased in vivo and in vitro production of platelet-activating factor after immunotherapy.

BACKGROUND: To explore the possible role of platelet-activating factor (PAF) in the pathogenesis of bronchial asthma, circulating PAF and in vitro production of PAF were studied. METHODS: Radioimmunoassay kits were used in 15 children with acute asthmatic attacks, in 25 newly diagnosed asthmatic children, in 25 good and 18 poor responders to immunotherapy, and in 18 healthy controls. RESULTS: The results demonstrated the following: (1) PAF was present in the blood of healthy controls. (2) New patients had much higher circulating PAF than did healthy controls (p < 0.005), and the circulating PAF decreased after immunotherapy in good (p < 0.005) but not in poor responders. (3) The circulating PAF increased up to 20 times that of healthy controls during acute asthmatic attacks. (4) The spontaneous and allergen-stimulated secretion of PAF were markedly increased in new patients and decreased to normal after successful immunotherapy (p < 0.005). (5) No increased spontaneous and allergen-stimulated production of PAF was found during acute attacks, but granulocytes from those patients still produced the greatest amount of PAF when stimulated with calcium ionophore A23187. (6) Although a major portion of allergen-induced PAF was secreted, less than 10% of ionophore-induced PAF was secreted. CONCLUSION: The findings that the circulating PAF increased markedly during acute asthmatic attacks and the enhanced in vivo and in vitro productions of PAF decreased to normal after successful immunotherapy strongly suggest that PAF may be involved in the pathogenesis of bronchial asthma.

Acute Disease↗
PubMed1993

Association of HLA-DR14-DR52 with low responsiveness to hepatitis B vaccine in Chinese residents in Taiwan.

To determine the HLA-linked immune response gene that controls low responsiveness to hepatitis B surface antigen (HBsAg), HLA typing was performed in 33 initial non-responders (male:female = 23:10, age 1.5-46 years) who had poor antibody response (anti-HBs < 10 mIU ml-1) after four doses of plasma-derived hepatitis B vaccine. Of 33 initial non-responders, 26 received two additional doses of either the same vaccine (n = 18) or recombinant hepatitis B vaccine (n = 8) and returned for anti-HBs measurement. At 1 month after the sixth dose, anti-HBs was still < 10 mIU ml-1 in 20 cases and 10-20 mIU ml-1 in three cases. Analysis of HLA antigen frequencies in these 23 ultimate low responders revealed that nine (39%) were positive for DR14, a statistically significant association of low responsiveness to hepatitis B vaccine with HLA-DR14. In addition, 26% of the ultimate low-responders were positive for DQ3, a frequency significantly lower than the expected rate in the general population. Among the nine ultimate low-responders with DR14, seven were heterozygous for this allele, while the other two cases had a single isolated DR14; and all nine were in association with DR52. These results suggest that a DR14-DR52 association, probably dominantly expressed, may be involved in the low immune responsiveness to hepatitis B vaccine of the Chinese population in Taiwan.

Adolescent↗
PubMed1993

Lupus patients with peripheral vascular thrombosis: the significance of measuring anticardiolipin antibody.

The purpose of this study was to determine the significance of measuring anticardiolipin (ACL) antibodies in Chinese lupus patients with peripheral vascular thrombosis. A total of 252 lupus patients were evaluated prospectively for the presence of peripheral vascular thrombosis in a 3-year period. Tests of ACL antibodies with three isotypes were done serially during follow-up. There were 10 lupus patients with five episodes of arterial thrombosis and seven episodes of venous thrombosis by the evidence of angiographical and/or pathological findings. The ACL antibody status was negative (< 2 standard deviation [SD]), low (2 to 5 SD) and high (> 5 SD) for 43.3%, 22.6%, and 34.1% patients, respectively. Patients with high levels (> 5 SD) of ACL antibodies had a high frequency of peripheral vascular thrombosis than patients with negative levels (> 2 SD) of ACL antibodies (P < .05). It is concluded that serial measurement of ACL antibodies in lupus patients is useful in predicting the occurrence of peripheral vascular thrombosis. Clinicians should be alert to the possibility of such complication in lupus patients with high ACL antibodies levels when visiting the emergency service.

Adolescent↗
PubMed1993

Molecular cloning of a house dust mite allergen with common antibody binding specificities with multiple components in mite extracts.

Plaque radio-immuno assay has been used to isolate an IgE-binding clone from a lambda gt11 library of Dermatophagoides pteronyssinus cDNA. The clone HD6 contained DNA encoding a 215 residue protein which contained a predicted 17 amino acid residue leader sequence, no cysteines and a single N-glycosylation site. The 198 residue mature protein would have a predicted MW of 22,177 D. No homologues were found in searches of the data banks. Sera from 14/38 allergic children reacted strongly with the polypeptide produced by the clone (37%). Skin tests showed reactivity in 16/30 (53%) allergic patients and 0/10 of controls. Affinity purification of rabbit antibodies with the clone showed that antibodies to the polypeptide had specificities to multiple products in mite extracts corresponding to components of Mr 29, 27 and 24 K by Western blotting. Absorption studies of IgE in allergic serum indicated further entities at 13 and 11.5 kD. It is proposed to name this allergen Der p VII.

Allergens↗
PubMed1993

Effect of inhaled beclomethasone dipropionate in the treatment of recurrent wheezing in infancy and early childhood.

Forty-one children, aged six to 36 months (mean, 23.3 months), with a past history of acute bronchiolitis with or without recurrent wheezing episodes were treated with either a beclomethasone dipropionate metered dose inhaler 150 microgram twice daily, or a placebo for 12 weeks. Aerosols were inhaled through an AeroChamber (Trudell, Canada) using a mask. The patients were followed up biweekly. The two groups were well matched in anthropometric data and frequency of wheezing prior to the study being undertaken. At the end of four to six weeks, the beclomethasone dipropionate treatment group showed a significant improvement in both wheezing and sleep patterns, and systemic steroid therapy was able to be tapered. No significant side effect could be ascribed to this treatment.

Acute Disease↗
PubMed1992

Cellular immune response to HBcAg in mother-to-infant transmission of hepatitis B virus.

Cellular immunity to HBcAg was studied in hepatitis B virus carrier children and neonates born to hepatitis B virus carrier mothers. A significant proliferative response of peripheral blood mononuclear cells to HBcAg was found in 5 of 10 children with elevated ALT levels but in none of the nine HBeAg-positive children with normal ALT levels. HBeAg but not HBsAg was detected in cord blood of 9 of 10 neonates born to HBeAg-positive carrier mothers, suggesting exposure of these neonates to HBeAg in utero. However, cord mononuclear cells from neonates born to HBeAg-positive carrier mothers did not show a significant change in the proportion of suppressor and helper T-cell subsets or proliferative response to HBcAg. Nor did they produce interleukin-2 receptor after being cocultured with HBcAg. The unresponsiveness of peripheral-blood mononuclear cells or cord mononuclear cells to HBcAg was not reversed by CD8+ cell depletion. Although cord blood mononuclear cells from neonates born to carrier mothers positive for antibody to HBeAg also did not respond to HBcAg, we encountered an infant, born to a carrier mother positive for antibody to HBeAg, who contracted acute hepatitis B at 2.5 mo of age. The baby's peripheral-blood mononuclear cells showed a significant proliferative response to HBcAg. These results support the view that transplacental maternal HBeAg probably induces a specific unresponsiveness of helper T cells to HBcAg and HBeAg in the neonates born to HBeAg-positive carrier mothers. This specific helper T cell tolerance could be maintained throughout the early replicative phase of carrier state but might break someday with the appearance of raised ALT level.

Adolescent↗
PubMed1992

Characterization of histamine-releasing activity: role of cytokines and IgE heterogeneity.

Histamine-releasing factors (HRFs) are a group of cytokines that cause histamine release (HR) from basophils and mast cells. The concept of the priming effect of cytokines and the heterogeneity of IgE involved in the HRF-induced HR have been emphasized in recent years. In this study, we performed a series of experiments to elucidate the above-mentioned hypotheses. The stock HRF were obtained by stimulating mononuclear cells (MNC) with phytohemagglutinin (PHA). Maximal activity was observed 36 hr after culture. By gel filtration, HRF was eluted with a peak activity ranging from 12 to 18 KD. A large portion (75%) of HRF activity could be neutralized by a combination of antibodies against interleukin 1 (IL-1), IL-3, IL-8, granulocyte-macrophage colony-stimulating factor (GM-CSF), and tumor necrosis factor-alpha (TNF-alpha). The stimulation of basophils with 100 ng/ml each of IL-3, IL-6, IL-7, GM-CSF, or TNF-alpha alone caused 10% HR; however, when the cells were pretreated with 10 ng/ml of either IL-3, IL-6, IL-7, IL-8, TNF-alpha, or GM-CSF and then stimulated with anti-IgE, a marked increase in HR was regularly observed. The combination of 100 ng/ml each of IL-1, IL-3, IL-8, GM-CSF, and TNF-alpha could induce only about 20% HR; furthermore, such combinations did not have an additive or synergistic priming effect on anti-IgE-induced HR compared to the effect of single cytokines. Stripping of surface-bound IgE with lactic acid markedly reduced the capacity of basophils to release histamine in response to MNC-HRF and anti-IgE. Passive sensitization of IgE-stripped basophils with high-HRF responders' serum could restore their responsiveness to both MNC-HRF and anti-IgE, but passive sensitization with low-HRF responders' serum could restore responsiveness to anti-IgE only. Moreover, passage of MNC-HRF through high-, but not low-HRF, responders' IgE-Sepharose columns significantly reduced the HR activity of MNC-HRF. Finally, although the eluant could induce only 10% HR, the majority of its HR activity could be restored by the addition of effluent but not by the mixture of IL-1, IL-3, IL-8, GM-CSF, and TNF-alpha, suggesting the presence of a complex interaction among those cytokines. In summary, MNC-HRF contained at least two types of HRF activity; one was IgE dependent and the other was IgE independent.(ABSTRACT TRUNCATED AT 400 WORDS)

Basophils↗
PubMed1992

Major histocompatibility complex (MHC) class II restriction, lymphokine production, and IgE regulation of house dust mite-specific T-cell clones.

To elucidate the regulatory mechanism of human IgE synthesis, we have cloned house dust mite (Dermatophagoides pteronyssinus; Dp)-specific T-cell clones from three asthmatic children and three healthy individuals. Twelve clones were cloned from each group. All of these clones were CD3+, CD4+, CD8-, and HLA-DR+. After stimulation with allergen in the presence of antigen presenting cells (APCs), half of the T-cell clones from asthmatic children and one-third of those from normals produced interleukin 4 (IL-4). None of the patients' clones produced interferon gamma (IFN-gamma), while 10 of 12 normals' clones did. After stimulation with calcium ionophore A23187 and phorbol myristic acetate (PMA), the production of IL-4 was markedly increased in both patients and normals. However, only 3 of the 12 patients' clones produced IFN-gamma, while all of the normals' clones did. The T-cell clones of both patients and normals produced comparable IL-2. To study the kinetics of lymphokine productions, a HLA-DRw12-restricted T-cell clone (FYD 3.1) was stimulated, respectively, with a combination of A23187 and PMA, phytohemagglutinin (PHA), or Dp antigen in the presence of APCs. Maximal IL-2 and IL-4 productions were detected 12 hr after A23187 and PMA stimulation, whereas IFN-gamma could not be detected even 36 hr after stimulation. When stimulated with PHA, the production of IFN-gamma peaked on the fourth day, but IL-4 was not detected. After stimulation with Dp antigen and APCs, IL-4 and IL-2 were detected on the second and third days, but IFN-gamma was not detected. The IgE production by autologous purified B cells in the presence of allergen or IL-4 was found to be augmented by the FYD 3.1 T-cell clones. IFN-gamma was observed to counteract the effects of the T-cell clones and IL-4. Thus, the secretory patterns of lymphokine and kinetics of lymphokine production of allergen-specific T-cell clones can be used to explore the regulatory mechanism of human IgE synthesis [corrected].

Adult↗
PubMed1992

Thymopentin treatment in severe atopic dermatitis--clinical and immunological evaluations.

An open clinical trial of thymopentin was conducted on 16 children with severe atopic dermatitis. The patients were treated with injections three times a week of 50 mg thymopentin for six weeks. They were then divided randomly into two groups: group A continued thymopentin for an additional six weeks, and group B were treated with normal saline. Clinical parameters and immunological function were evaluated serially. The total severity score started to decline from baseline significantly three weeks after treatment, and continued throughout the study period in group A but began to flare up in group B two weeks after stopping thymopentin. All the eight patients in group A completed the trial but three out of eight in group B dropped out because of flaring up of skin lesion. In vitro production of interleukin-4 tended to decrease and that of interferon gamma tended to increase, but total serum IgE, in vitro IgE synthesis, and abnormally low CD8+ CD11b+ suppressor T cells remained unchanged. Histamine releasing factor (HRF), plasma histamine, and respiratory burst activities of polymorphonuclear leucocytes were appreciably decreased after thymopentin treatment. It is concluded that the clinical efficacy of short term thymopentin treatment very possibly results from the decreased production of HRF and decreased release of polymorphonuclear leucocyte derived inflammatory mediators and may have no relation with antigen-IgE immune reaction.

Adolescent↗
PubMed1992

A long-term immunological study of childhood onset systemic lupus erythematosus.

Immunological dysregulation is an important cause of the development of systemic lupus erythematosus (SLE). Serological evaluation has been useful in the clinical management of patients and as a prognostic indicator. Sixteen patients who developed SLE as children were followed up for more than three years and immunological data collected. The results showed that (a) complement C3 concentration was lower in the active stage of SLE, especially during a major clinical exacerbation, but rarely preceded a major flare up. The concentration was often normal during the mildly to moderately active stage. In contrast, a low complement C4 concentration often preceded a major clinical exacerbation and could be of longer duration, sometimes persisting regardless of disease activity. (b) A T cell subset distribution study showed persistently low CD4 positive T cells in the peripheral blood of patients with SLE during the long term follow up, strongly suggesting that the intrinsic defect is mainly localised in T helper/inducer cells. These abnormal cellular defects did not tend to return to normal even in long term remission. (c) The persistently higher serum interleukin 2 and interleukin 2 receptor concentrations in SLE strongly suggested that the T cells were preactivated in vivo and that these phenomena might persist even in remission. (d) The best single parameter for predicting active SLE was anti-dsDNA. It was highly correlated with disease activity in most patients, and the asymptomatic increase of anti-dsDNA (greater than or equal to 60 U/ml, radioimmunoassay) was often followed by a major clinical exacerbation, especially in patients with a simultaneously low complement C4 concentration, suggesting that it might be an important warning sign of a major flare up. High dose steroids are indicated in this group of patients.

Adolescent↗
PubMed1992

The effect of immunotherapy on interleukin-1 and tumor necrosis factor production of monocytes in asthmatic children.

A longitudinal study was conducted to determine the pathogenesis and effect of immunotherapy (IT) on monocyte function. Production of interleukin-1 (IL-1) and tumor necrosis factor (TNF) by peripheral blood monocytes in 31 asthmatic children before and one year after IT was compared. Twenty-two children completed the treatment course, and 13 age-matched healthy children served as controls. Adherent monocytes were isolated and stimulated with either crude mite extract of Dermatophagoid farinae (Df) for 7 days or lipopolysaccharide (LPS) for 3 days. The amount of TNF and IL-1 in culture supernatant was quantified by TNF and IL-1 enzyme-linked immunosorbent assay (ELISA) kits, respectively. The LPS-stimulated TNF production in patients was not different before or after IT (245.8 +/- 110.9 vs. 213.3 +/- 161.6 pg/0.1 ml, p +/- 0.202), but was significantly higher than the control (66.7 +/- 42.7 pg/0.1 ml; p less than 0.0001). The LPS-stimulated IL-1 production was similar among the three groups. When stimulated with Df antigen, monocytes from asthmatic patients produced a greater amount of TNF and IL-1 than did those from the control (p less than 0.001). Furthermore, although the production of TNF decreased after successful IT (360.2 +/- 181.6 vs 243.9 +/- 189.1 pg/0.1 ml, p less than 0.05), the production of IL-1 did not change (679.9 +/- 254.1 vs. 534.8 +/- 257.6 pg/0.1 ml, p greater than 0.05). Thus, repeated long-term administration of allergen (IT) was able to suppress specifically the TNF, but not IL-1 production of monocytes.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

The change of allergen-specific IgG subclass antibodies during immunotherapy in mite-sensitive asthmatic children.

Fifty-six Dermatophagoid farinae (D.f)-sensitive asthmatic children were hyposensitized by D.f-crude extract for two years. Serum total IgG subclass antibodies and D.f-specific IgE and IgG subclass antibodies were measured by ELISA before and after 2 years of treatment. The results showed that 1) After two years of treatment, there were significantly higher levels of total serum IgG1 in both responder and non-responder groups than those before treatment (p less than 0.01). The responder group also had significantly higher values of total IgG2 and IgG4 after immunotherapy (IT) (p less than 0.05), but not in the non-responder group. 2) The serum levels of D.f-specific IgG3 and IgG4 antibodies in responder group increased significantly after IT (p less than 0.05). On the contrary, the D.f-specific IgE and IgG1 IgG1 in the responder group were significantly lower than those before IT. No signi- in the responder group were significantly lower than those before IT. No signi-body titres before and after IT was found in non-responder group. 3) There was a significant correlation between the total IgG4 and D.f-specific IgG4 antibody (r = 0.634, p less than 0.01). The correlation coefficient was 0.634. No correlation was found between the other IgG subclass antibodies and D.f-specific IgG subclass antibodies. 4) Correlations between the levels of D.f-specific IgE and IgG subclass antibodies were highly significant both in IT-responder and non-responder groups. There was a significant correlation between the levels of D.f-specific IgG1 and IgG4 in non-responders, while no relationship was observed in the responder group.(ABSTRACT TRUNCATED AT 250 WORDS)

Allergens↗
PubMed1991

Interleukin 2 therapy in severe atopic dermatitis.

Interleukin 2 (IL-2) at a dose of 10,000 to 20,000 U/kg/q 8 hr was given for 9-12 days to six patients with cases of severe atopic dermatitis (AD) which were refractory to conventional therapy. After IL-2 therapy, the clinical symptoms and signs of eczema including pruritus, scratching, papulovesicles, and lichenification were much improved, but all of them recurred 2-6 weeks after stopping treatment. Adverse reactions were similar to those reported previously, but all of them subsided after discontinuation of therapy. Laboratory findings showed decreased T-cell subsets, especially CD4+ cells, and increased IL-2R+ (CD25) cells, but there was no significant change in serum IL-2, serum IgE, or in vitro IgE production. Immunopathological studies of the skin biopsies showed decreased mononuclear-cell infiltration, depletion of CD4+ cells, and enhanced expression of CD25 and HLA-DR antigens. As lymphokine-activated killer (LAK)-cell activity against cultured fibroblasts was similar in patients with AD and in normals and CD1+ Langerhans cells were not decreased after IL-2 therapy, we speculate that the depletion of helper/inducer CD4+ cells and hence abrogation of the exaggerated antigen processing and cellular activation in diseased skin are the explanation for the transient efficacy of IL-2 in the treatment of atopic dermatitis.

CD4-Positive T-Lymphocytes↗
PubMed1991

Immunologic study of the asplenia syndrome.

Asplenia syndrome is usually associated with complex congenital cardiovascular defects. These patients often succumb to overwhelming infections. A complete immunological evaluation was therefore conducted on 13 consecutive patients with asplenia syndrome and 12 age-matched patients with congenital heart disease but without evident splenic problems. IgG, IgA, IgM and C3 and C4 values were normal for age in all subjects studied. T cell subsets, including the percentage of CD3, and CD4 cells and the CD4/CD8 ratio were significantly different in patients and controls (P less than 0.01, respectively). Lymphoproliferative responses to mitogens (ConA, concanavalin A, phytohemagglutinin and pokeweed mitogen) were also decreased in patients. Fc-mediated clearance of sensitized autologous erythrocytes was significantly impaired in patients (n = 13) when compared with age-matched controls (n = 5) (clearance t1/2 59.0 +/- 9.6 minutes vs. 12.5 +/- 1.6 minutes, P less than 0.001). Thus profoundly impaired reticuloendothelial clearance and decreased T cell function might account for the life-threatening infections frequently seen in patients with congenital asplenia syndrome.

Abnormalities, Multiple↗
PubMed1991

Effects of PAF antagonist, BN52021, on the PAF-, methacholine-, and allergen-induced bronchoconstriction in asthmatic children.

Platelet-activating factor (PAF) is an inflammatory mediator capable of inducing protracted inflammation of the airways and bronchial hyperreactivity. Twenty-one asthmatic children were evenly divided into three groups and each group performed a double-blind, placebo-controlled and crossover study on the effect of aerosolized BN52021, a PAF antagonist, on the bronchoconstriction induced by PAF, methacholine, or specific allergen, respectively. One group of healthy children was included for comparison. Total WBC, neutrophils, and eosinophils were counted before and after PAF challenge. The results showed the following: (1) six of seven asthmatics and one of seven normal subjects gave a positive bronchial provocation with PAF; (2) in asthmatics, prior inhalation of BN52021 could inhibit the bronchoconstriction induced by PAF (6/6) and allergen (3/7), but not by methacholine; and (3) 5 min after inhalation of PAF, there was a marked decrease of peripheral blood eosinophils and neutrophils that could be inhibited by prior inhalation of BN52021 in normal subjects but not in asthmatics. These findings support the idea that PAF may be involved in the pathogenesis of bronchial asthma and PAF antagonist may have a role in the prevention and treatment of this disease.

Allergens↗
PubMed1991

Immunochemotherapy with recombinant interleukin-2 and adriamycin in primary hepatocellular carcinoma.

Recombinant interleukin-2 (rIL-2) and adriamycin were administered systemically to treat nine patients (age 15.5-68 years, mean 48.9 years) with far advanced primary hepatocellular carcinoma. Three patients were newly diagnosed, and the remaining patients had received surgery, transcatheter arterial embolization, chemotherapy and other treatments but without improvement. RIL-2 was given at a dose of 10,000 to 30,000 units/kg every 8 hours for consecutive 9 days, and on the fifth day, a single dose of adriamycin 30 to 60 mg/M2 was administered. Four patients interrupted the immunotherapy because of severe intolerable side effects, 4 patients completed one course and the remaining one received 2 courses of treatment. Various adverse reactions were encountered, however, they subsided promptly after stop of therapy. All patients failed to respond to the regimen. Primary hepatic tumors continued to enlarge in 8 patients and remained unchanged in one, and pulmonary metastases also increased in size and number in 4 patients. Transient decrease in serum alpha-fetoprotein was found in 6 patients. These results suggests that systemic IL-2 immunotherapy, even in combination with chemotherapy, is not effective for the treatment of far advanced hepatocellular carcinoma. However, in viewing of its immune amplifying effect, rIL-2 in combination with other treatment modalities may still be worth trying in early stages of hepatocellular carcinoma.

Adolescent↗
PubMed1991

Lysis of herpes simplex virus-infected cells by lymphokine-activated killer cells.

Activation of human peripheral blood mononuclear cells (PBMC) or murine splenocytes with recombinant interleukin-2 (rIL-2) has been found to be able to generate cells which are lytic in vitro for a variety of cells infected by herpes simplex virus (HSV). Lymphokine-activated killer (LAK) cells were generated by the incubation of human PBMC or murine splenocytes with 500 u/ml of rIL-2 for 3 to 4 days in a CO2 incubator at 37 degrees C. These cells were lytic to cultured tumor cell lines, yet sparing normal primary cell cultures as has been reported. Human PBMC infected with HSV, however, were susceptible to the lytic effect of these LAK cells. From 30 to 50 percent lysis of HSV-infected human PBMC was observed when the effector-to-target ratios were 40:1 and 100:1 respectively by four hr 51Cr-release assays. Similar cytolytic effect was observed when mouse embryonic fibroblasts (MEF) were infected with HSV and used as targets when rIL-2-activated mouse splenocytes were used as effectors. The cytolytic effects of LAK cells on the HSV-infected cells can be demonstrated even after lowering of NK activities by the treatment of effector cells with anti-NK antibody Leu-11b plus complement. Cytolytic effects were not restricted to the autologous system, and could be demonstrated in the heterologous system as well. Human LAK cells killed not only HSV-infected autologous PBMC but also infected mouse embryonic fibroblasts. However, mouse LAK cells exhibit species-specific cytotoxicity. In conclusion, it was demonstrated that LAK cells are cytolytic to HSV-infected cells in both human and murine systems.

Animals↗