PubMed Health⌕ Search

Biomedical subjects

M Chun

Publications and source records attributed to M Chun.

54 records · Page 3Linked to original sources
PubMed1988

Bidirectionality of mixed lymphocyte stimulation (Mls) response. Effects of Mlsb stimulator cells on Mlsa helper cells.

The activation of BALB/c lymphocytes in the mixed lymphocyte reaction to Mls-disparate APC has been shown to encompass up to 20% of the mature resting helper T lymphocyte population. In addition to these overtly Mls-responsive cells, our studies have revealed a second population that respond to the Mls difference of DBA/2 spleen cells in conjunction with the mitogen Con A. This part of the Mls response is therefore latent. As mitogen and Mls-stimulating effect act in synergy, it is likely that both stimuli act on the same cell, and hence the Mls effect can be regarded as a regulatory interaction between APC and Th cell. By use of congenic BALB.Mlsa mice, the regulatory effect has been mapped to the Mls locus. The regulatory influence has also been demonstrated in DBA/2 Th cells (Mlsa) stimulated simultaneously with mitogen and Mls-disparate (Mlsb) APC, consistently causing inhibition of mitogen-induced proliferation in this reverse Mls direction. This antagonistic effect has also been linked to the Mls locus. We conclude that the Mls reaction governed by the a and b alleles is bidirectional, producing synergy with class II-dependent activation signals in the direction of Mlsa----Mlsb, and antagonism in the direction Mlsb----Mlsa. Both the classical Mls and the reverse Mls effects have been demonstrated at the clonal level. These results are in accord with the previously proposed hypothesis that the Mls molecule serves as a down-regulatory stimulus in the activation of Th cells. Mls responses of Mlsb T cells are explained as the consequence of a diminished down-regulation by Mlsa APC. Conversely, the reverse Mls response described here can be considered a consequence of inordinately high down-regulation of the Mlsa T cell responses by Mlsb APC.

Animals↗
PubMed1988

Radiotherapy in the treatment of pituitary adenomas.

Between 1970 and 1985, 145 patients were treated for pituitary adenomas and 126 patients were available for analysis. Sixty patients were treated with surgery alone (Group I), 54 were treated with surgery and radiation therapy (Group II), and 12 received irradiation only without tissue diagnosis (Group III). Extent of tumor was evaluated by CT scan, PEG, and surgical reports. There were 22 microadenomas in Group I and only 1 microadenoma in Group II. The mean follow-up was 6.4 years, 85% (51/60) of patients in Group I, 93% of patients in Group II, and only 50% of those treated with irradiation alone achieved tumor control. With subsequent salvage treatment, overall tumor control in Group I was 97%. The mean time to recurrence was 3.7 years (Group I), 4.5 years (Group II), and 4 years (Group III). In summary, combined treatment is effective to decrease the chance of local recurrence of pituitary adenomas. Nevertheless, because of successful salvage treatment after surgical failure, overall outcome is similar. Without persistent symptom after surgery or large residual tumor in or near the critical structures, postoperative irradiation can be deferred until tumor regrowth.

Adenoma↗
PubMed1988

Ifm(2)2 is a myosin heavy chain allele that disrupts myofibrillar assembly only in the indirect flight muscle of Drosophila melanogaster.

Using a combination of molecular and genetic techniques we demonstrate that Ifm(2)2 is an allele of the single-copy sarcomeric myosin heavy chain gene. Flies homozygous for this allele accumulate wild-type levels of mRNA and protein in tubular muscle of adults, but fail to accumulate detectable amounts of myosin heavy chain mRNA or protein in the indirect flight muscle. We propose that the mutation interferes with either transcription of the gene or splicing of the primary transcript in the indirect flight muscle and not in other muscle tissues. Biochemical and electron microscopic analysis of flies homozygous for this mutation has revealed that thick filament assembly is abolished in the indirect flight muscle resulting in the instability of wild-type thick filament proteins. In contrast, thin filament and Z disc assembly are marginally affected. We discuss a working hypothesis for sarcomere assembly and define and experimental approach to test the predictions of this proposed pathway for sarcomere assembly.

Alleles↗
PubMed1988

Brachytherapy in the treatment of recurrent solitary brain metastases.

Conventional therapy for solitary brain metastases includes radiotherapy and surgical resection in selected cases. Often, however, the metastasis recurs and limits the quality of life and survival of the patient. Once the metastasis recurs, therapeutic options are limited. Brachytherapy delivers a high total dose of radiation to a localized area, allowing reirradiation at the time of recurrence. Three patients with recurrent brain metastases treated with iridium-192 implants are presented; two of these patients had breast carcinoma and one had malignant melanoma. The implants allowed long term survival in the two patients with recurrent metastatic breast carcinoma. Unfortunately, the patient with melanoma did not respond to the brachytherapy and died within 7 months of implantation. The approaches to treatment to metastatic brain tumors and the rationale for using brachytherapy are discussed.

Brachytherapy↗
PubMed1987

Combination immunotherapy of cancer in a mouse model: synergism between tumor necrosis factor and other defense systems.

Bacterial lipopolysaccharide (LPS) induces the release of factors into the serum which enable mice to reject experimental tumors. One such factor is tumor necrosis factor which causes acute necrosis of syngeneic sarcoma transplants in mice. Effective therapeutic use of tumor necrosis factor is limited, however, by its toxicity. We show here that the efficacy of tumor necrosis factor can be substantially increased by combining its application with low doses of LPS. Our data suggest that LPS exerts its antitumor effects by engaging more than one defense mechanism. Characteristic for the activation of a biological system is a concomitant induction of negative feedback mechanisms which antagonize the initial stimulus. Interference with the negative feedback response may substantially increase biological reactions. We show here that the blocking of two negative feedback responses occurring as a consequence of treatment with LPS, namely the production of prostaglandin E and the generation of suppressor T-lymphocytes, increases dramatically the ability of mice to reject tumor transplants. Thus, through appropriate combination of different factors one may reduce the dose of each below toxic levels and through interference with negative feedback responses increase the efficacy of antitumor reagents. We consider our findings in the context of formulating an effective immunotherapy of malignancies and as a promising step toward it.

Animals↗
PubMed1987

Intracellular cAMP regulates the cytotoxicity of recombinant tumor necrosis factor for L cells in vitro.

Tumor necrosis factor (TNF) destroys certain tumor cells in vitro. Using the classical TNF-sensitive cell line L929 and its resistant derivative, we show here that the sensitivity of cells to TNF depends in large measure on the intracellular cAMP concentration. An experimental increase of the intra-cellular cAMP concentration can substantially enhance the sensitivity of L-cells to TNF. This increase in TNF sensitivity is seen only in TNF-sensitive cells but not in TNF-resistant cells. An increase in intracellular cAMP levels has been obtained by adding cell permeable dibutyryl cAMP to the culture medium or by culturing L929 cells in the presence of reagents which cause the elevation of intracellular cAMP concentrations.

Animals↗
PubMed1986

Conditional requirement for accessory cells in the response of T cells to Con A.

The response to Concanavalin A (Con A) of unseparated lymph node cells and of T cells isolated from them has been studied over a mitogen dose range of 0.2 microgram to 16 micrograms/ml. Accessory cell depleted T cells respond only to high doses of Con A and then only weakly. The magnitude (proliferative activity) of the response as well as the sensitivity to the mitogen can be modified by accessory cells (AC), lymphokines and by chemical modification of cell surface glycoproteins. Accessory cell function can be inhibited by antibodies directed against cell surface molecules on accessory cells (Ia) or on T cells (L3T4). Changes in the mitogen sensitivity of the response are not necessarily associated with changes in the magnitude of the response. The mitogen sensitivity can be decreased with anti-Ia antibody and can be increased by treatment with IL-l and/or interferon gamma (IFN-). We postulate that the increase in sensitivity to Con A is a function of the density of cell surface molecules with which T and AC cells interact. The magnitude of the response is primarily determined by the frequency of AC in culture; it decreases as the number of AC is reduced and increases as AC are added to the cultures. Mitogen sensitivity is a new tool for the analysis of nonspecific T cell activation. Our data bring the accessory cell requirement for mitogen activation of T cells into a new perspective: AC--or factors produced by them--are essential when low (1-2 micrograms/ml Con A) doses are used and are less or not at all necessary when high doses (6-10 micrograms/ml) of mitogen are applied.

Animals↗
PubMed1985

Enhancement of cytotoxic activity of natural killer cells by interleukin 2, and antagonism between interleukin 2 and adenosine cyclic monophosphate.

Two cytokines, interferon (IFN) and interleukin 2 (IL-2), activate murine natural killer (NK) cells in vitro. Together both factors synergize considerably. Antibody against IFN eliminates the response of NK cells to IFN as well as to IL-2, whereas antibody against IL-2 blocks the effect of IL-2 but not of IFN. These findings as well as previous observations imply that both factors act on the same cell but have different roles. We suggest that IFN induces NK cell activation and IL-2 enhances this effect. Further studies revealed that besides inducing cytotoxicity in NK cells IFN induces the production of prostaglandin E (PGE) which inhibits NK cell activation. We propose therefore that IFN has a dual effect on NK cells: it induces NK cells to become cytotoxic and initiates a negative feedback by increasing the production of PGE. IL-2, which synergizes with IFN in the activation of NK cells, ceases to do so when the negative feedback (PGE-mediated) is blocked with indomethacin. We infer that IL-2 enhances NK cell activity by interfering with the negative feedback rather than by aiding NK cell activation.

Animals↗
PubMed1982

Modulation of interferon-induced NK cells by interleukin 2 and cAMP.

The mechanism by which interferon (IFN) and interleukin 2 (IL-2) activate NK cells has been examined. Added alone, either lymphokine activates NK cells; together they synergize. NK cells generated by IFN, IL-2 or IFN plus IL-2 are indistinguishable on the basis of their cell surface phenotype. Precursor NK cells are Qa5+, MK 2.2-, Ly-6- and effector NK cells are Qa5+, MK 2.2+, Ly-6+. Sequential factor addition showed that IFN must be present at the start of culture, whereas IL-2 could be added later with no loss of effect. Antibody to IFN was shown to block not only the action of IFN but also to prevent NK cell activation by IL-2. These results are taken to suggest that IFN initiates NK cell activation and IL-2 controls later stages. The synergistic effect of IL-2 is counteracted by cAMP. Considering the variety of systems in which IL-2 is active and the diversity of its effects, it is proposed that its antagonism with cAMP may be a basis for the biologic activity of IL-2.

Animals↗
PubMed1981

Mechanism of NK cell activation: relationship between Qa5+ NK cells and lymphocytes.

Interferon (IF) induces within 20 hr of incubation Qa5+Thy-1- NK cells but Qa5-Thy-1+ cytotoxic cells in cultures of murine splenocytes. The mechanism of Qa5+ NK cell activation has been studied by using tumor necrosis serum (TNS), concanavalin A (Con A), and lipolysaccharide (LPS) as additional NK cell-inducing reagents. It was found that IF and TNS activate precursor NK cells directly without the involvement of accessory cells. The T cell mitogen Con A and the B cell mitogen LPS, on the other hand, induced Qa5+ NK cells only in the presence of lymphocytes. Con A-stimulated T cells and LPS-stimulated B cells release factors into the culture medium that activate Qa5+ NK cells. Since Con A and LPS are known to be interferon inducers, it is inferred that Con A-induced and LPS-induced activation of NK cells is mediated by IF. The data demonstrate that NK cells become activated as a consequence of lymphocyte activation and thus suggest a relationship between lymphocyte dependent- and NK cell-dependent defense systems. This relationship is also implied by observations made with NZB mice. NZB mice lose NK cell activity at the time when they develop autoimmune diseases.

Animals↗
PubMed1980

Immobilization of beta-galactosidase, albumin, and gamma-globulin on epoxy-activated acrylic beads.

A comparative study was conducted into the immobilization of beta-galactosidase, albumin, and gamma-globulin on an epoxy-activated polyacrylic matrix (oxirane C, Röhm-Pharma GmbH, Darmstadt). The kinetic parameters of the immobilized beta-galactosidase were investigated with three kinds of miniaturized analytical reactors; namely, stirred batch, continuous stirred-tank, and packed-bed reactors. The optimum binding conditions, saturation activity and Michaelis constant of immobilized beta-galactosidase are given, together with determinations of the binding capacity of the oxirane C matrix for the three proteins investigated. For beta-galactosidase a saturation activity of 1300 U/g oxirane C was reached. The maximum binding, achieved by experiment, was 140 mg/g with 0.69 yield for albumin, 120 mg/g with 0.61 yield for gamma-globulin, and 40 mg/g with 0.42 yield for beta-galactosidase. From these data the inner surface of the matrix as a function of the size of the bound proteins was estimated.

Acrylates↗
PubMed1979

Tumor necrosis serum induces a serologically distinct population of NK cells.

Murine spleen cells generate nonspecific cytotoxic cells, referred to as natural killer (NK) cells, within 4 d of incubation in Mishell-Dutton cultures. This NK cell type does not arise in cultures of BALB/c.nu spleen cells or in cultures of T-cell depleted C57BL/6 spleen cells, indicating that its activation depends on T cells. Another type of NK cells is induced by tumor necrosis serum in murine spleen-cell cultures. It arises within 24 h and its activation does not depend on T cells. This cell type (and its precursor) expresses the recently discovered cell-surface marker Qa5 (controlled by the Q region of chromosome 17) that distinguishes this NK cell from the NK cell that depends for its activation on thymic function. Qa5+ NK cells are also induced by interferon.

Animals↗
PubMed1976

Organochlorine pesticides in the Hawaii Kai Marina, 1970-74.

Sediments, water, and oysters from the receiving waters of the Hahaione Valley, a suburban development in south-easter Oahu, Hawaii, were analyzed for organochlorine pesticidal compounds. The insecticides dieldrin, alpha- and gamma- chlordane, and p,p'-DDT were found in the study site environment. Levels were in the low parts per billion range for oysters and sediments and in the low parts per trillion range for water. During the past several years dieldrin residues in the marina study site have increased, even though the only activity known to influence pesticide levels in the valley is the chronic treatment for subterranean and dry wood termites. If present trends continue, dieldrin may pose a threat to biota of the aquatic environment. Findings have shown that residue levels of dieldrin and p,p'-DDT in the sediments are within the LD50 (median lethal dose) range for estuarine fish and thus may have a deleterious effect on bottom-feeding organisms. According to present standards of the Food and Agriculture Organization/World Health Organization, pesticide residue levels within the study site do not appear to constitute a health hazard to humans.

Animals↗
PubMedDate not supplied

Vascular endothelial growth factor in the serum of patients with non-small cell lung cancer: correlation with platelet and leukocyte counts.

BACKGROUND: Vascular endothelial growth factor (VEGF) is a potent angiogenic peptide expressed in a wide variety of tumors, and it stimulates angiogenesis and increases vascular permeability. Increased expression of VEGF may be associated with advanced stage and poor prognosis in patients with non-small cell lung cancer (NSCLC). METHODS: Using enzyme-linked immunosorbent assay, the levels of VEGF were determined in serum from 41 patients with untreated NSCLC (Stage: IIB, 3; IIIA, 6; IIIB, 17; IV, 15; HISTOLOGY: squamous cell carcinoma, 18; adenocarcinoma. 14; undetermined, 9). RESULTS: The median VEGF level was 312 pg/ml, ranging from 70 to 1440 pg/ml. Patients were divided into high VEGF (>312 pg/ml) and low VEGF (< or =312 pg/ml) groups using the median value as a cut-off. There were no significant associations between the serum VEGF levels and various clinicopathologic characteristics including age, gender, histologic type, stage and treatment. A significant positive correlation was found between serum VEGF levels and platelet counts (r=0.495; P=0.001). In addition, serum VEGF levels also correlated with leukocyte counts (r=0.478; P=0.002). In seven patients with measurement of follow-up serum VEGF levels at the end of treatment (chemotherapy and/or radiotherapy), the median serum VEGF level significantly decreased after the treatment (416 pg/ml; range, 96-812 pg/ml vs. 185 pg/ml; range, 49-487 pg/ml; P=0.028). However, the median platelet count (317,000/microl; range, 190,000-395,000/microl vs. 246,000/microl; range, 72,000-271,000/microl; P=0.028) and leukocyte count (10,000/microl; range, 8700-17,200/microl vs. 5100/microl; range, 3900-9500/microl; P=0.018) also decreased after the treatment. There was no statistically significant difference in the median survival of the patients between high VEGF group and low VEGF group (8 months vs. 9 months, P=0.647). CONCLUSIONS: Although serum VEGF level was significantly associated with platelet and leukocyte counts in NSCLC patients, it did not correlate with tumor burden and prognosis of the patients.

Adenocarcinoma↗
PubMedDate not supplied

Mls and the helper T-cell repertoire: II. Does the Mls gene product influence the formation of the T-cell repertoire? Studies with Mls tolerance.

In the formation of a repertoire, T cells are selected through a window of autoreactivity which is defined by a low boundary representing the minimal autoreactivity required to enter the T-cell compartment and a high boundary which determines the highest admissible autoreactivity. We propose that the Mls gene product down regulates autoreactivity and thus modifies the formation of the T-cell repertoire. Given the polymorphism of Mls and the assumption that Mlsb is more inhibitory than Mlsd, it is conceivable that Mlsb (responder) mice admit into their T-cell compartment T cells with higher autoreactivity than Mlsd mice. We suggest that it is this highly autoreactive fraction of Mlsb T cells which responds in the overt Mls response. We show that Mls tolerance eliminates T cells responding in the overt Mls response but not T cells responding in the latent Mls response. This is consistent with the finding that T cells responding in the latent Mls response occur in Mlsb as well as in Mlsd mice.

Animals↗
PubMedDate not supplied

The experiences of hilar skeletonization for the treatment of locally advanced proximal bile duct cancer.

BACKGROUND/AIMS: Because proximal bile duct cancer easily involves the surrounding tissue, tumor cells often remain after apparent macroscopically complete radical resection. We evaluated the effect of resective modality of these tumors on prognosis and the effect of postoperative radiotherapy on survival of patients with microscopic residual tumor following local resection in locally advanced proximal bile duct cancer. METHODOLOGY: From November, 1990 to October, 1993, 45 proximal bile duct cancer patients who received local excision were entered onto this prospective, nonrandomized study. The patients were divided into three groups after operation, 16 patients with curative resection; 15 noncurative resection; and 14 nonresection. Patients who had positive lymph nodes or microscopic cancer cells in resection margin or adjacent major vessels, were treated with postoperative external radiotherapy, 5040 cGy for 40 days. RESULTS: The overall 1-, 2-, and 5-year survival of the patients was 62.2%, 24.4%, and 15.6%, respectively. The overall mean and median survival of patients was 24.1 +/- 3.98 (mean +/- SE) months and 13 +/- 0.74 months, respectively. Survival rates between resection and nonresection showed a statistically significant difference (P < 0.05). However, survival rates between curative resection and noncurative resection with postoperative radiotherapy were not statistically significant (P > 0.05). CONCLUSIONS: The resection is the treatment of choice for locally advanced proximal bile duct cancer, if resectable and the noncurative resection followed by postoperative external radiotherapy may be beneficial to the patients with locally advanced proximal bile duct cancer.

Adolescent↗
PubMedDate not supplied

Genetic changes at the beta-2-adrenergic receptor locus on chromosome 5 in human colorectal carcinomas.

Matched normal/tumor DNA pairs from 44 colorectal carcinoma patients were examined for tumor-specific genetic changes using a probe for the beta-2-adrenergic receptor (ADRB2R) gene on chromosome 5. This locus (5q31-q32) maps close to the site of chromosomal deletions recently reported to occur in colorectal carcinomas and distal to the chromosomal location of the familial adenomatous polyposis (FAP) gene (5q21-q22). Our investigation shows tumor-specific allele loss or allelic rearrangement of at least 29% at the AdRb2R locus on chromosome 5 in informative cases. These results suggest that the mechanism by which colorectal carcinomas lose genetic material on chromosome 5 can affect this functional gene located distally to the FAP gene. The possible functional significance that ADRB2R gene changes may have in neoplastic progression is discussed.

Adenomatous Polyposis Coli↗