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Biomedical subjects

K H Hsieh

Publications and source records attributed to K H Hsieh.

At least 91 records · Page 5Linked to original sources
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 +/- 15.5 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 stopping 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 metastasis also increased in size and number in 4 patients. Transient decrease in serum alpha-fetoprotein was found in 6 patients. These results suggest that systemic IL-2 immunotherapy, even in combination with chemotherapy, is not effective for the treatment of far advanced hepatocellular carcinoma. However, in view 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

Tumoricidal activity of interferon-r activated peripheral monocytes in colorectal cancer patients.

Peripheral blood monocytes obtained from 8 colorectal cancer patients and 6 normal controls were incubated in vitro with interferon-r (IFN-r) in the presence of bacterial lipopolysaccharide (LPS). The cytotoxic properties of the monocyte were determined subsequent to the interaction with radiolabeled autologous, allogeneic, as well as cultured colorectal cancer cells. Monocytes from normal controls and all colorectal cancer patients were activated in vitro to become tumoricidal; monocytes lysed tumorigenic cells but not nontumorigenic cells. Activators of protein kinase C (e.g. phorbol esters, PMA) and Ca2+ ionophores (A23187) when added alone did not effect the activation state of the monocyte. Whereas, PMA and A23187 cooperatively reproduced the ability of IFN-r to prime monocytes for tumoricidal activity. In the presence of PMA, A23187, and EGTA, the addition of excessive Ca2+ was sufficient for priming, whereas the addition of excessive Mg2+ was much less efficient. Priming by IFN-r, however, was not blocked by EGTA. An efflux of Ca2+ from preloaded monocytes was significantly increased by A23187 and by IFN-r. Quin-2/AM, an intracellular chelator of Ca2+, blocked priming by IFN-r. The results suggest that priming of monocytes for tumoricidal function by IFN-r may be involved in the activation of protein kinase C and mobilization of intracellular Ca2+.

Aged↗
PubMed1991

Mouse dander-allergic bronchial asthma--a case report.

A case of mouse dander-allergic bronchial asthma is reported. A 47-year-old female professor of pharmacy has experienced severe chest discomfort, dyspnea and wheezing, and itching nose and eyes each time when she contacted with mice in recent months although she has done animal (mouse) experiments for many years without any difficulty. Those symptoms usually recovered spontaneously after removing the mice or using bronchodilator. The causal relationship between mouse dander and bronchial asthma was established, in addition to history of exposure, by a positive skin test, a strong RAST and overwhelming bronchial provocation test. The allergen was identified, by SDS-PAGE and immunoblotting to be a 21 Kd molecule.

Allergens↗
PubMed1991

Analysis of house dust mite-specific IgE, IgG4, and IgG antibodies during immunotherapy in asthmatic children.

House dust mite (Dermatophagoides pteronyssinus, DP) specific IgE, IgG4, and IgG antibodies were analyzed by Western blotting in 18 asthmatic children during the course of 2-years' allergen-specific immunotherapy. Although more than 50 protein bands could be identified in the crude mite extracts by SDS-PAGE, only eight of them elicited both IgE and IgG4 antibodies in most patients. The molecular weights were 110, 60, 55, 43, 33, 27, 16, and 14 kD, respectively. No antibodies against new antigens were induced after immunotherapy. There was a significant correlation between the intensity of reactive bands of Western blotting and RAST. IgG4 antibody was increased in 72% (13/18) of patients, but the simultaneous change in IgE varied. Analysis of allergen-specific IgE and IgG4 antibodies by Western blotting may provide a useful tool for evaluation of clinical response to immunotherapy.

Adolescent↗
PubMed1990

Altered production of histamine-releasing factor (HRF) activity and responsiveness to HRF after immunotherapy in children with asthma.

To delineate the working mechanisms of immunotherapy (IT) (hyposensitization), the production of, and responsiveness to, histamine-releasing factor (HRF) was studied in four groups. These groups consisted of 32 newly diagnosed children with asthma, 40 good responders and 18 poor responders to IT (older than 2 years), and 15 healthy subjects. The results demonstrated (1) peripheral blood mononuclear cells of new patients produced a much greater HRF activity, either spontaneously or after stimulation, than did those of normal subjects, (2) the spontaneous HRF activity decreased significantly in good responders, whereas that of poor responders increased, (3) both the allergen (mite)- and mitogen (phytohemagglutinin [PHA])-stimulated HRF activity was decreased, although decrease was not significant, in good responders, but the activity was not changed in poor responders, (4) the granulocytes of new patients responded to HRF much more vigorously than did granulocytes of normal subjects. The responsiveness diminished significantly in both good and poor responders, although the magnitude of decrease was slightly greater in the former, (5) there was a positive correlation between PHA- and mite-stimulated HRF activity, mite-stimulated HRF activity and responsiveness to HRF, and plasma histamine level and responsiveness to HRF in the new patients, and (6) there was an inverse correlation between PHA-stimulated HRF production and responsiveness to HRF in good responders, but the correlation was positive in poor responders. Thus, IT is able to suppress the HRF activity, particularly the type of spontaneous synthesis, and responsiveness to HRF in clinically benefitted children with asthma, and this effect may be used to explain, partly, the efficacy of IT in a proportion of allergic patients.

Asthma↗
PubMed1990

Proliferation, interleukin-2 production and receptor expression in peripheral blood mononuclear cells from colorectal cancer patients.

Peripheral blood mononuclear cells (PBMC) were cultured with phytohemagglutinin (PHA) in 46 colorectal cancer patients and 27 normal controls. By collectively comparing the cancer patients with the normal controls, the cancer patients had: (1) decreased interleukin-2 (IL-2) secretion, (2) fewer interleukin-2 receptor (IL-2R) expression on cell surface, and (3) less 3H thymidine incorporation. The ability of the phorbol ester, phorbol 12-myristate 13-acetate (PMA), and the calcium ionophore, A23187, in co-stimulation with PHA, to enhance the IL-2 secretion, IL-2R expression and 3H thymidine incorporation were studied in the PBMC of colorectal cancer patients. By adding A23187 into the PHA-stimulated PBMC from colorectal cancer patients, IL-2 production and IL-2R expression were increased up to levels equal to that obtained in PHA-stimulated PBMC from normal controls. Whereas there was no significant increase in proliferative response. However, PMA has no effect on all three parameters. A23187 is known to be effective in elevating cytosolic free Ca2+ and PMA is regarded as an activator of protein kinase C. Therefore, we may conclude that the impairment of IL-2 production and IL-2R expression in PHA-stimulated cultures is mainly due to failure of the free Ca2+ release which can be repaired by A23187. While protein kinase C activation may not be impaired since its deficit in IL-2 production and IL-2R expression can not be corrected by PMA.

Aged↗
PubMed1990

Enhanced natural killer cell activity in patients with cervical carcinoma by postoperative PS-K immunotherapy.

The cell-mediated immunity in 19 patients with stage I and II cervical carcinoma was evaluated before and after postoperative PS-K immunotherapy. Lymphocyte subpopulations were enumerated using specific monoclonal antibodies (moAbs) of the Leu series (Leu2, Leullb, Leu15, and Leu19) and the OKT series (OKT3, and OKT4). A 4-hour 51Cr-release assay was used to measure natural killer (NK) cell activity. Serum levels of interleukin-2 (IL-2), soluble interleukin-2 receptor (IL-2R), and tumor necrosis factor (TNF) were also determined before and after postoperative PS-K immunotherapy. The results showed that the number of cells carrying the marker of a non-major histocompatibility complex (MHC), restricted cytotoxic lymphocytes in the peripheral blood and NK activity at three different effector/target ratios increased significantly after postoperative PS-K immunotherapy. It is therefore concluded that postoperative PS-K immunotherapy enhanced the NK activity in patients with cervical carcinoma, in which NK activity tended to be lower. Further clinical investigation to assess the effectiveness of PS-K immunotherapy in improving the overall survival is in progress.

Adjuvants, Immunologic↗
PubMed1990

Immunologic and virologic status of multitransfused thalassemic patients.

Viral markers of hepatitis B virus (HBV), cytomegalovirus (CMV) and human immunodeficiency virus (HIV), immunoglobulins and complements, T-cell subpopulation antibodies (OKT series) and mitogen responses have been investigated in 68 multitransfused thalassemic patients and in 46 age-matched children. Results showed (1) 56 patients (82.4%) had been exposed to HBV; 29 patients (42.6%) had been exposed to CMV and none were HIV infection. (2) Increased IgG, IgA, OKIal, and decreased C3, OKT3, OKT4, OKT4/OTK8 ratio showed in patients as compared to controls. (3) An apparent increase in lymphocyte proliferation was seen in patients' cultures with or without mitogen (PHA and ConA) stimulation. (4) No definite factors such as sex, age at first transfusion, number of transfusions or HBsAg carrier status correlated with the abnormal change of immunological tests. (5) Immunological investigation, done on 2 occasions six months apart, revealed no significant modifications except that 13 patients (19%) who were initially seronegative for CMV converted to seropositive. These investigations suggest that, although saline-washed RBC was used for the transfused patients, there was high prevalence of HBV and CMV infection. Further studies of lymphocyte function (i.e. lymphokines) are needed to understand the increased spontaneous proliferation in culture and PHA, ConA mitogen responses.

Adolescent↗
PubMed1990

Interleukin-2 immunotherapy in children.

Immunotherapy with interleukin (IL)-2 possesses great potential in the treatment of immune-mediated diseases and cancers. However, only a few reports on a small number of children have appeared in the literature. From March 1988 to March 1989, 11 children and adolescents were treated with IL-2. They included 1 patient with hepatocellular carcinoma, 1 with hepatoblastoma, 6 with childhood atopic dermatitis, and 3 with juvenile rheumatoid arthritis. The dosages ranged from 10,000 to 50,000 U/kg every 8 hours by intravenous drip. The following side effects were observed: anorexia, fever, and chillness (100%), general malaise (82%), irritability (64%), diarrhea (100%), nausea and vomiting (73%), weight gain (82%), edema (82%), abdominal distension (73%), oliguria (82%), cough (91%), dyspnea (27%), pleural effusion (40%), hypotension (82%), skin eruption (82%), oral ulcer (18%), enlarged liver (73%) liver function abnormalities (82%), renal function impairment (36%), electrolyte imbalance (73%), anemia (91%), thrombocytopenia (54%), leukopenia (18%), and eosinophilia (73%). Immunologically, numbers of natural killer cells were increased and natural killer and lymphokine-activated killer cell activities were augmented after IL-2 treatment. There was a tendency for serum levels of IL-2 and receptor IL-2 to decrease, especially in patients with atopic eczema. Ten patients (91%) completed one course (9 to 12 days) of therapy, and the remaining patient interrupted the treatment because of intolerable adverse effects. Clinically, complete remission for 3 months was obtained in 1 juvenile rheumatoid arthritis patient, transient improvement (2 to 6 weeks) in all atopic dermatitis patients, minor response in the hepatoblastoma patient, and no response in the patient with hepatocellular carcinoma.

Adolescent↗
PubMed1990

Rice pollen allergy in Taiwan.

A panel of tests including intracutaneous skin testing (ST), radioallergosorbent test (RAST), immunoblotting and allergen-induced lymphoproliferation was done to study rice pollen allergy in asthmatic children and to characterize the allergens. Of the 312 asthmatic patients skin tested, 29 (9.3%) had positive reactions (wheal greater than or equal to 6 mm) to rice pollen extract at a concentration of 10(-5) g/mL and the remaining 283 (90.7%) were negative. While eight (34.8%) of the 23 ST-positive patients were also RAST-positive, RAST was negative in all 34 ST-negative patients and 20 normals. Immunoblotting revealed three major allergens, with molecular weights of 16 kD, 26 kD, and 32 kD, respectively. Interestingly, RAST-positive patients showed IgE responses to most allergens but only a few of them had IgG antibodies, while normal controls had stronger IgG responses to the same allergens, particularly to 32 kD, but none had IgE antibody. The preliminary results of rice pollen protein induced-lymphoproliferation were not informative; thus, rice pollen proteins do elicit a specific response in asthmatic children and normals, but its pathogenic role in bronchial asthma needs further study.

Adolescent↗
PubMed1990

Association of HLA antigens with myasthenia gravis in Chinese on Taiwan.

HLA phenotypes were studied in 82 Chinese patients with myasthenia gravis (MG) and 202 healthy controls, using standard microcytotoxicity assay. The patients showed significant increase in HLA-Bw46 (46.3% vs 17.3%, chi 2 = 25.7, p less than 0.001), HLA-DR9 (56.1% vs 15%, chi 2 = 35.7, p less than 0.001) and HLA-DQw3 (89% vs 63.6%, chi 2 = 15.9, p less than 0.001). The HLA-DR3 was decreased (2.4% vs 32.7%, chi 2 = 27.0, p less than 0.001). Both HLA-Bw46 and -DR9 were increased in all subgroups except the over 40 at age of onset group. In thymectomised patients, no association with HLA antigen was found in the thymoma group, whereas both involuted and hyperplasic thymus groups had HLA DR9 association and only the hyperplasic thymus group showed HLA Bw46 association. No association with HLA antigens was noted in patients with low antibody titer, however, patients with antibody titers between 0.2 to 2 n mole/1, had an association with HLA Bw46 and DR9. The HLA DQw3 was associated with the group of female MG patients, age onset below 10 and with ocular myasthenia. Finally, the HLA A2, Bw46 and DR9 combination was also significantly increased in patients [24.3% (20/82) vs 7.4% (8/107), chi 2 = 10.5, p less than 0.001], especially in the subgroup of male MG, age onset below 10 and with ocular myasthenia.

Asian People↗
PubMed1989

Decreased production of CD8 (T8) antigen after immunotherapy.

The working mechanism(s) of immunotherapy still remains ill defined. As T cells bearing CD8 antigen possess suppressor/cytotoxic function, this study was conducted to examine the effect of immunotherapy on the production of CD8 antigen. Peripheral blood mononuclear cells (MNC) were obtained from 21 newly diagnosed and 23 hyposensitized (greater than 1 year) asthmatic children and 13 age-matched normal children. MNC were stimulated with crude mite extract (Dermatophagoides farinae) for 7 days and with phytohemagglutinin and concanavalin A for 3 days. The CD8 antigen and interleukin-2 receptor (IL-2R) in plasmas and culture supernatants were measured by CELLFREE T8 and IL-2R test kits (T Cell Sciences, USA). The results showed the following. (1) Plasma CD8 antigen was markedly increased in new patients compared to normals (536.7 +/- 212.3 vs 222.5 +/- 104.0 units/ml; P less than 0.001) and decreased to normal after immunotherapy (275.7 +/- 98.5 units/ml). (2) When stimulated with mite allergen, MNC from both new and hyposensitized patients produced a much greater amount of CD8 antigen compared to those from normals. However, after immunotherapy MNC tended to produce less CD8 antigen, although not to a significant degree. (3) No difference in CD8 antigen production was seen among three groups when lymphocytes were stimulated with mitogens. (4) Production of CD8 antigen paralleled that of IL-2R. Thus, CD8 production was specifically decreased after immunotherapy and this fact reflects a hyposensitized state of T cells after long-term, repeated injection of allergens.

Adolescent↗
PubMed1989

Topographic probes of angiotensin and receptor: potent angiotensin II agonist containing diphenylalanine and long-acting antagonists containing biphenylalanine and 2-indan amino acid in position 8.

A series of phenylalanine-mimicking amino acids with increasing conformational restraint were prepared and incorporated into angiotensin II, in order to develop topographic probes of angiotensin useful for probing receptor boundaries by molecular graphics analysis and for conformational analysis of the ligand by NMR. In binding studies, all analogues displayed high affinity for rat uterus (Ki of 0.74-6.08 nM) and brain (0.46-1.82 nM) receptors. In smooth muscle (rat uterus) contraction assay, the diphenylalanine-containing [Sar1,Dip8]AII and [Sar1,D-Dip8]AII were potent agonists with respectively 284% and 48% activity of [Asn1]AII. In contrast, the biphenylalanine-containing [Sar1,Bip8]AII, [Sar1,D-Bip8]AII, and the 2-indan amino acid containing [Sar1,2-Ind8]AII were potent inhibitors, approximately 9, 2, and 1.4 times more effective than a standard antagonist, [Sar1,Leu8]AII. Their respective pA10 values in rat uterus assay were 8.87, 8.70, and 8.82. By comparison, the pA10 value for [Sar1,Leu8]AII was 8.35. In rats, a single dose of 10 micrograms of [Sar1,2-Ind8]AII or [Sar1,Bip8]AII produced prolonged blockade of the pressor response toward angiotensin II for over 90 min. The very different pharmacological profiles of these rigid aromatic analogues suggest that the angiotensin receptor activation site consists of a relatively wide and elongated pocket with a narrow opening.

Affinity Labels↗
PubMed1989

The effect of immunotherapy on the in vitro productions of histamine, prostaglandin E2 and leukotriene C4 in asthmatic children.

In order to elucidate the working mechanisms of immunotherapy (IT), the in vitro productions of histamine, prostaglandin E2 (PGE2) and leukotriene C4 (LTC4) were studied in 18 newly diagnosed and 20 hyposensitized (greater than 2 yr) asthmatic children. All were sensitive to house dust and dust mites. (D. pteronyssinus). Ten age-matched normal children were included as control. Polymorphonuclear (PMNs) and mononuclear (MNCs) leukocytes were separated by density gradient centrifugation and dextran sedimentation. PMNs (2 x 10(7) cells/ml) and MNCs (2 x 10(7) cells/ml) were stimulated with mite allergen (10 micrograms/ml) and calcium ionophore A23187 (1 microgram/ml) for 15 minutes. The plasma and culture supernatant (sup) histamine levels and sup PGE2 and LTC4 were measured by RIA. The results showed; 1) When compared to new patients, the treated patients had much lower plasma and sup histamine (p less than 0.001), no matter whether PMNs and MNCs were stimulated with allergen or A23187 and the normals had the lowest histamine level among 3 groups; 2) LTC4 in A23187-stimulated sup was lower in treated patients (p less than 0.05); 3) The PGE2 in allergen-stimulated sup was markedly increased in treated patients as compared to new patients (p less than 0.01) and the PGE2 in sup of normals was also much higher than that of new patients. Thus, immunotherapy is able to reverse the abnormal secretory pattern of inflammatory mediators of allergic patients, and this change may account, partly, for its clinical effectiveness.

Animals↗
PubMed1989

Changes of allergen-specific antibodies, circulating immune complexes and restoration of polymorphonuclear leukocyte function after hyposensitization.

To explore the working mechanism(s) and the safety of long-term hyposensitization (HS) with house dust (HD), a series of studies were undertaken on 30 newly diagnosed and 30 hyposensitized asthmatic children. Twenty age- and sex-matched school children were included as control. The results showed: (1) HS was able to decrease the total serum IgE and increase the production of allergen-specific IgG blocking antibody, however, the allergen-specific IgE antibody remained nearly the same after HS for a couple of years, (2) Normal controls had allergen-specific IgG antibody but no IgE antibody, (3) Circulating immune complex concentration in the treated group did not differ significantly from the untreated group, (4) HS was able to suppress in vivo and in vitro histamine production and restore polymorphonuclear leukocyte (PMN) function in terms of Fc gamma R expression. These results suggest that HS is a specific and safe treatment, and provide solid rationale for its use in the treatment of respiratory allergic disease.

Adolescent↗
PubMed1989

Decreased natural killer cell activity in patients with invasive cervical carcinoma.

The cell-mediated immunity in 21,12,14 and 12 patients with preinvasive, stage I and II invasive cervical carcinoma, and in controls respectively, was studied. Lymphocyte subpopulations were enumerated using specific monoclonal antibodies (moAbs) of the Leu series (Leu2, Leu3, Leu4, Leu11b, and Leu15). Double stain using fluorescein-isothiocyanate (FITC) conjugated Leu2 moAb and phycoerythrin (PE) conjugated Leu15 moAb was applied to distinguish cytotoxic T-cells from suppressor T-cells. A 4-hour 51Cr-release assay was used to measure natural killer (NK) cell activity. The results showed that there was no significant difference in lymphocyte subpopulations among these 4 studied groups. However, the NK activity tended to be lower in patients with invasive cervical carcinoma (stage I and II) especially at a high effector/target ratio of 100. It is therefore concluded that functional cytotoxicity assay is more informative in evaluating the status of cell-mediated immunity against tumors than the enumeration of lymphocyte subsets.

Adult↗
PubMed1989

The skin manifestation of acute graft-versus-host disease: clinical and pathological analysis.

We report 11 cases of acute graft-versus-host disease (GVHD); 10 occurred after bone marrow transplantation (BMT) and one following transfusion of nonirradiated whole blood in a patient with severe combined immunodeficiency (SCID). According to the Seattle Classification, 5 cases were of Grade III, 2 Grade II, and 4 Grade I. The skin rash developed between the 6th to 47th day (22 +/- 12 day) after transplantation or transfusion, and was usually manifested initially as erythematous macules or papules in the neck or upper chest. The rash resolved in scaling or became purpuric, pigmented or erythrodermic in severe cases. The grading of skin pathology correlated well with clinical severity of GVHD. Four of the five who had advanced GVHD (Grade III) died. In all 4 cases but one (the SCID case), the skin pathology showed extensive basal vacuolization and multiple dyskeratotic cells. None of the others with mild or focal basal vacuolization and few dyskeratotic cells progressed into advanced GVHD. Three of the 5 cases with advanced GVHD received an underdose of cyclosporin A. These results suggest that severe GVHD carries a poor prognosis and an adequate dose of cyclosporin A is important in alleviating the severity of GVHD and reducing the mortality. The sero-virologic study performed during the skin rash period was negative, suggesting that the skin rash following BMT is mainly caused by GVHD and always precedes intestinal or hepatic manifestations.

Adolescent↗