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Biomedical subjects

K H Hsieh

Publications and source records attributed to K H Hsieh.

At least 127 records · Page 7Linked to original sources

Interleukin 2 and lymphokine-activated killer cells in the treatment of childhood primary hepatocellular carcinoma--a preliminary report.

Recombinant interleukin-2 (RIL-2) and lymphokine-activated killer (LAK) cells were administered to 2 boys with the end-stage of primary hepatocellular carcinoma (HCC); the efficacy and toxicity were evaluated. Immunologically, the natural killer and LAK activities were enhanced. Clinically, the side effects were similar to those reported for adults but milder. This kind of treatment may be considered for children with the early stages of hepatocellular carcinoma.

Carcinoma, Hepatocellular↗

Elevated serum interleukin-2 receptor; increased in vitro immunoglobulin synthesis and lack of response to testosterone-enhanced in vitro interleukin-2 production in ankylosing spondylitis.

The pathogenesis of ankylosing spondylitis (AS) remains unknown, although previous studies have strongly suggested that it may result from immunological aberration. To further explore the pathogenetic mechanisms, in vitro syntheses of immunoglobulins and interleukin-2 (IL-2) by peripheral blood mononuclear cells (MNC), and the serum level of the interleukin-2 receptor (IL-2R) were studied in 35 patients with definite AS and in 28 healthy controls. MNC were cultivated in the presence of pokeweed mitogen (PWM) for seven days. Immunoglobulins in the supernatants were measured by rate nephelometer (Immunochemistry System Analyser II, Beckman.) In vitro synthesis of IL-2 was carried out by cultivating MNC in medium only; in medium containing physiological concentration of the male sex hormone i.e., testosterone 500 ng/dl and estradiol 2 ng/dl; and in medium containing physiological concentration of female sex hormone, i.e., testosterone 50 ng/dl and estradiol 20 ng/dl. IL-2 was quantitated using an IL-2-dependent cytotoxic T lymphoid cell line (CTLL). Serum IL-2R was measured using an IL-2R test kit (CELLFREE, T Cell Sciences, Cambridge, MA). The results showed: In vitro synthesis of IgG, IgA and IgM was significantly higher in AS than in controls; In vitro synthesis of IL-2 was significantly enhanced by testosterone in normal control, but not in AS; and Serum IL-2R was significantly elevated in patients with AS. These findings, viewed in conjunction with previous results here, lead to postulation that an inflammatory process, elicited in HLA-B27-positive males and caused by an infectious agent invading via the mucosa may both cause immunological abnormalities and provoke various symptoms and signs of AS.

Adolescent↗

Decreased expression of high affinity interleukin 2 receptors after hyposensitization to house dust.

The lymphoproliferative response to allergen usually decreases after long-term hyposensitization (immunotherapy). In order to delineate the working mechanism of this kind of treatment, expression of interleukin 2 receptors (IL-2 R) on house dust and phytohemagglutinin-activated lymphocytes was compared in 15 normals, 18 newly diagnosed and 28 hyposensitized asthmatic children. Interleukin 2 receptors were analyzed by fluorescent-activated cell sorter (FACS), uptake of 125I-labelled anti-human IL-2R monoclonal antibody (anti-Tac), and proliferative response to recombinant IL-2 (rIL-2). The results showed that there was no difference in the expression of IL-2R among three studied groups, if IL-2R were detected by anti-Tac. When compared to the other two groups, house dust-activated lymphoblasts from new patients proliferated vigorously in the presence of very low rIL-2 (0.02 to 1.0 nM), suggesting the presence of much higher numbers of high affinity IL-2R. Decreased high affinity IL-2R may partly explain the diminished lymphoproliferation to allergen after long-term hyposensitization.

Adolescent↗

Rheumatic fever recurrences: controlled study of 3-week versus 4-week benzathine penicillin prevention programs.

To compare the merits of 3-week versus 4-week injections of benzathine penicillin G in preventing recurrence of rheumatic fever, 179 patients aged 4 to 19 years were assigned to one of the two programs. Age, weight, cardiac status, and streptococcal infections among the patients and their family members studied in each program were comparable. Eight-two patients and their family members were monitored for streptococcal infections. Compliance in the two programs was comparable. Of the 63 patients who stayed in the 4-week program, RF recurred in six, as a result of prophylaxis failure in five and associated with partial compliance in one. Of the 90 patients in the 3-week program, RF recurred in one, associated with partial compliance; no failures occurred (P = 0.01). We recommended that for RF chemoprophylaxis in individuals at great risk, regardless of age, benzathine penicillin injections should be administered every 3 rather than every 4 weeks.

Adolescent↗

Role of the C-terminal carboxylate in angiotensin II activity: alcohol, ketone, and ester analogues of angiotensin II.

[Ac-Asn1, Val5]angiotensin II analogues containing a C-terminal alcohol (Phe-ol), methyl ketone (Pmk), methyl ester (Phe-OMe), or alpha-methyl methyl ester (Phe(alpha Me)-OMe) were prepared in order to examine the relative importance of COOH-mediated ionic vs. hydrogen bonding interactions in angiotensin activities. Based on the observation that only [Ac-Asn1,Phe-OMe8]AII (AII, angiotensin II) had significant activities (20% oxytocic and 13% pressor) in the rat, with all other analogues having negligible agonistic and antagonistic effects, it is concluded that ionic interaction of the C-terminal carboxylate with the receptor is necessary for angiotensin binding and that hydrogen bonding has little effect. Thus, the different potencies observed for the AII methyl ester and for various C-terminal analogues previously reported may simply reflect their relative abilities to generate the active carboxylate species in situ.

Alcohols↗

Immunological defects in allergic asthmatic children and working mechanisms of hyposensitization--a review.

Patients with allergic diseases are characterized by the presence of elevated serum IgE and specific IgE antibodies against a variety of environmental allergens, especially house dust, mites and molds in Taiwan. A series of studies on allergic asthmatic children have been conducted to explore the non-immunological and immunological causes for their augmented production of IgE antibody and to explore the working mechanisms of hyposensitization. The results showed that the patients had multiple defects in their defects in their defense mechanisms, including hyper-permeability of mucosae, hyperreactivity of target organs, defective phagocyte functions, and deficient helper and suppressor T-cell functions. Hyposensitization was able to partially correct the immunological aberrations. More over, a newly found lymphokine termed "T-cell growth factor" or "interleukin 2" may be used not only as an indicator for the initiation and termination of hyposensitization, but may also provide a promising tool for the treatment of allergic diseases in the future because of its capability of enhancing and expanding allergen-specific suppressor T cells.

Allergens↗

Abnormal in vitro immunoglobulin synthesis of lymphocytes and increased circulating immune complex in patients with ankylosing spondylitis.

To explore the immunopathogenetic mechanisms of hypergammaglobulinemia in ankylosing spondylitis (AS), the functions of B cell, helper T (OKT4) cell and suppressor T (OKT8) cell were examined, by using the co-cultivation technique for in vitro immunoglobulin biosynthesis, in 7 patients with active AS, 7 with inactive AS and 14 normal controls. Circulating immune complexes (CIC) in those subjects were also measured by a solid phase C1q binding assay. After B, OKT4 and OKT8 cells were separated from the heparinized peripheral blood, coculture of these cells which were either from the same patient, the same normal control, or their combination was carried out. The in vitro synthesized immunoglobulins were measured by a rate nephelometer (Immuno-chemistry system, analyzer II). The results were: In patients with active AS, the amounts of IgG and IgA synthesized by co-cultured B and T4 cells from patients (p) and T8 from the normal (n) were significantly higher than those of the normal controls; In patients with inactive AS, the amounts of IgG and IgA produced by co-cultured Bp + T4p + T8n, Bp + T4n + T8n, Bn + T4n + T8p, and Bn + T4p + T8p were significantly higher than those for the respective normal controls; The CIC in active AS was elevated significantly over that in the normal controls. These results suggest that in patients of AS, B cells and helper T cells are hyperactive, while suppressor T cells are depressed. The abnormal function of lymphocytes may cause elevated concentrations of immunoglobulins and CIC in the serum.

Adult↗

Altered interleukin-2 (IL-2) production and responsiveness after hyposensitization to house dust.

Interleukin-2 (IL-2 or T cell growth factor, TCGF) is a lymphokine absolutely required for clonal expansion of activated T-lymphocytes with specific cytotoxic, helper, and suppressor functions. The capability of production of and responsiveness to IL-2 in 15 normal children, 28 newly diagnosed, and 22 hyposensitized (greater than 1 yr) children with asthma was studied. The results demonstrated (1) The lymphocytes from newly diagnosed patients produced a much greater amount of IL-2 when they were stimulated with specific allergen (house dust) but not with phytohemagglutinin (PHA) than did those from both hyposensitized patients and normal subjects. (2) The responsiveness to IL-2 of activated lymphocytes from hyposensitized patients was much more vigorous than those from both new patients and normal subjects, whether the responder lymphocytes were pretreated with PHA or house dust. Thus, hyposensitization is able to modulate the immunobiologic functions of T cells with respect to production of and responsiveness to IL-2, and such alterations may contribute to the immunologic changes occurring in patients receiving long-term hyposensitization.

Adolescent↗

Changes of lymphoproliferative responses of T cell subsets to allergen and mitogen after hyposensitization in asthmatic children.

The cellular basis for the mechanism of hyposensitization was studied by examining the changes in the numbers and proliferative responses to house dust and phytohemagglutinin (PHA) of T cell subsets of 25 house dust-sensitive asthmatic children before and 1 yr after hyposensitization. The results demonstrated (1) No difference was observed in the mean percentages of OKT3+ cells and OKT8+ cells between normal subjects and patients both before and after hyposensitization, but the absolute numbers of both types of cells in untreated patients were much higher than in the normal subjects or treated patients because of relative lymphocytosis in the untreated patients, (2) While the mean percentage of OKT4+ cells of the untreated patients was lower than that of the normal subjects (40.8 +/- 4.7% vs 44.8 +/- 4.5%, p less than 0.007), the absolute number was higher in the former than that in the latter because of the same reason. After hyposensitization, the mean percentage of the OKT4+ cells was slightly increased, and (3) Hyposensitization was able to restore the proliferative capability to PHA and depress the sensitivity to specific allergen of OKT4+ cells on the one hand and augment the proliferative responses to both PHA and allergen of OKT8+ cells on the other. Taken together, these immunologic changes may explain partly the suppressed IgE-antibody production and decreased lymphoproliferative response to specific allergen after hyposensitization.

Adolescent↗

Different immunoregulatory functions of T lymphocytes responding in autologous mixed lymphocyte reaction between allergic patients and normals.

In order to clarify the self-regulatory functions of T lymphocytes in allergic patients, the autologous mixed lymphocyte reaction (AMLR) was studied in 35 asthmatic children with elevated serum IgE. Twelve normals were included as control. The mononuclear cells (MNC's) of allergic patients produced much larger amount of IgE than did the MNC's of normals, but the capability of IgG production and blastogenic response to phytohemagglutinin (PHA) was similar between these two groups. There was no difference in the proliferative response of T lymphocytes to autologous non-T-cells between patients and normals, but the autoreactive T lymphocytes from normals were able to suppress the in vitro IgE biosynthesis and blastogenic response to PHA of fresh autologous MNC's, whereas those from allergic patients enhanced, rather than suppressed, both immunologic phenomena. It is therefore concluded that the apparent difference in the immunoregulatory properties of T lymphocytes responding in AMLR between allergic patients and normals may be used to partly explain the augmented IgE production in atopic individuals.

Adolescent↗