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Biomedical subjects

H M Kim

Publications and source records attributed to H M Kim.

At least 199 records · Page 11Linked to original sources

Effect of Kumhwang-San on anaphylactic reaction in a murine model.

We investigated the effect of Kumhwang-San on anaphylactic reaction. Kumhwang-San dose-dependently inhibited mast cell-mediated systemic anaphylactic reaction induced by compound 48/80. Kumhwang-San significantly inhibited plasma histamine levels induced by compound 48/80. Kumhwang-San dose-dependently inhibited histamine release from the rat peritoneal mast cells activated by compound 48/80 or substance P. The level of cAMP in rat peritoneal mast cells, when Kumhwang-San was added, transiently and significantly increased about 3-fold compared with that of basal cells. These results suggest that Kumhwang-San will be beneficial in the treatment of anaphylactic reaction.

Anaphylaxis↗

The nitric oxide-producing properties of Ulmi radicis cortex extract.

We investigated the effect of Ulmi radicis cortex extract (UrCE) on the production of nitric oxide (NO). Stimulation of mouse peritoneal macrophages with UrCE after the treatment of recombinant interferon-gamma (rIFN-gamma) resulted in the increased NO synthesis. UrCE had no effect on NO synthesis by itself. When UrCE was used in combination with rIFN-gamma, there was a marked cooperative induction of NO synthesis in a dose-dependent manner. The optimal effect of UrCE on NO synthesis was shown 6 h after treatment with rIFN-gamma. NO production was inhibited by NG-monomethyl-L-arginine. The increased production of NO from rIFN-gamma plus UrCE-stimulated cells was decreased by the treatment of protein kinase C inhibitor such as staurosporin. In addition, synergy between rIFN-gamma and UrCE was mainly dependent on UrCE-induced tumor necrosis factor-alpha (TNF-alpha) secretion. All the preparations of UrCE were endotoxin free. These results suggest that the capacity or UrCE to increase NO production from rIFN-gamma-primed mouse peritoneal macrophages is the result of UrCE-induced TNF-alpha secretion.

Animals↗

A case of primary bilateral adrenal lymphoma with partial adrenal insufficiency.

Unilateral or bilateral non-Hodgkin's lymphomas arising primarily in the adrenal glands are extremely rare. These lymphomas are usually present with large, bilateral adrenal masses with or without lymphadenopathy, and may be accompanied by adrenal insufficiency in some cases. A review of the literature indicates that patients with primary lymphoma of the adrenal glands usually do not have disease elsewhere, and if present, it is frequently extranodal. We report here an unusual case of primary bilateral adrenal lymphoma with partial adrenal insufficiency.

Adrenal Gland Neoplasms↗

Conformal and intensity modulated irradiation of head and neck cancer: the potential for improved target irradiation, salivary gland function, and quality of life.

PURPOSE: To develop techniques which facilitate sparing of the major salivary glands while adequately treating the targets in patients requiring comprehensive bilateral neck irradiation (RT). PATIENTS AND METHODS: Conformal and static, multisegmental intensity modulated (IMRT) techniques have been developed. The salivary flow rates before and periodically after RT have been measured selectively from each major salivary gland and the residual flows correlated with glands' dose volume histograms. Subjective xerostomia questionnaires have been developed and validated. The pattern of local-regional recurrences has been examined using CT scans at the time of recurrence, transferring the recurrence volumes to the planning CT scans and regenerating the dose distributions at the recurrence sites. RESULTS: Target coverage and dose homogeneity in IMRT treatment plans were found to be significantly better than standard RT plans. Significant parotid gland sparing was achieved. The relationships among dose, irradiated volume and saliva flow rates from the parotid glands were characterized by dose and volume thresholds. A mean dose of 26 Gy was found to be the threshold for stimulated saliva. Subjective xerostomia was significantly reduced in patients irradiated with parotid sparing techniques, compared to patients with similar tumors treated with standard RT. The large majority of recurrences occurred inside high-risk targets. CONCLUSIONS: Tangible gains in salivary gland sparing and target coverage are being achieved and an improvement in some measures of quality of life is suggested by our findings. A mean parotid gland dose of < or = 26 Gy should be a planning objective if significant parotid function preservation is desired. The pattern of recurrence suggests that careful escalation of the dose to targets judged to be at highest risk may improve tumor control.

Dose-Response Relationship, Radiation↗

Synthesis and antitumor activity of 4-phenyl-1-arylsulfonyl imidazolidinones.

Novel 1-(1-benzoylindoline-5-sulfonyl)-4-phenyl-4,5-dihydroimidazolon es 3 synthesized show highly potent and broad cytotoxicities. Among them compound 3b (DW2143) exhibits much more potent cytotoxicities than doxorubicin and highly effective antitumor activities against murine (3LL, Colon 26) and human xenograft (NCI-H23, SW620) tumor models.

Animals↗

Involvement of CYP3A1, 2B1, and 2E1 in C-8 hydroxylation and CYP 1A2 and flavin-containing monooxygenase in N-demethylation of caffeine; identified by using inducer treated rat liver microsomes that are characterized with testosterone metabolic patterns.

Caffeine (CA) is oxidized by rat liver microsomal enzymes to theobromine (TB), paraxanthine (PX), and theophylline (TP) by N-demethylation and to trimethylurate (TMU) by C-8 hydroxylation, In order to identify the specific enzymes responsible for productions of these primary CA metabolites, liver microsomes enriched with various isoforms of cytochrome P450 (CYP) and flavin-containing monooxygenase (FMO) are prepared by pretreatment of rats with several inducers. The specific increases in various CYP or FMO activities are identified with the diagnostic testosterone metabolic patterns or the thiobenzamide S-oxidation assay. They are then employed to metabolize the CA. Liver microsomes isolated from rats pretreated with phenobarbital (PB-microsomes) did not have increased FMO activity but had increased activities for hydroxylating the testosterone at 6 beta-(CYP3A1), 16 beta-(CYP2B1), and 2 beta-(CYP3A1) positions. This PB-microsomes had increased activity for TMU production from CA (result of C-8 hydroxylation). Liver microsomes isolated from rats pretreated with acetone (AC-microsomes) had a normal level of FMO activity but had enhanced rates of 6 beta-(CYP3A1) and 2 beta-(CYP3A1) hydroxylations of testosterone. The AC-microsomes again had increased activity for production of TMU. Similarly, the liver microsomes isolated from rats pretreated with dexamethasone (DEX-microsomes) had a normal level of FMO activity but had enhanced rates of forming 6 beta-and 2 beta-hydroxytestosterone (Cyp3A1) as well as androstenedione (CYP3A1). The DEX-microsomes again had increased activity for production of TMU only. Liver microsomes isolated from rats pretreated with 3-methylcholanthrene (MC-microsomes), however, had increased FMO activity and also enhanced rates of forming the 7 alpha-(CYP1A1/2, and 2A1), 6 beta-(CYP3A1), and 2 beta-(CYP3A1) hydroxytestosterone. The MC-microsomes had increased activity for producing all of the four primary metabolites of CA, i.e. the N-demethylation metabolites like TB, PX. and TP, as well as the C-8 hydroxylation metabolite TMU. By the process of association of the obtained results, liver microsomes with increased contents of CYP2B1, 3A1, and 2E1 could catalyze the C-8 hydroxylation at an increased rate producing increased amount of TMU. Increased productions of CA N-demethylation metabolites (TB, PX, and TP) are, however, catalyzed by the increased activities of CYP1A2 and FMO which are associated uniquely with the MC-microsomes.

Animals↗

Inhibitory effect of mast cell-mediated immediate-type allergic reactions in rats by spirulina.

We investigated the effect of spirulina on mast cell-mediated immediate-type allergic reactions. Spirulina dose-dependently inhibited the systemic allergic reaction induced by compound 48/80 in rats. Spirulina inhibited compound 48/80-induced allergic reaction 100% with doses of 100-1000 microg/g body weight, i.p. Spirulina (10-1000 microg/g body weight, i.p.) also significantly inhibited local allergic reaction activated by anti-dinitrophenyl (DNP) IgE. When rats were pretreated with spirulina at a concentration ranging from 0.01 to 1000 microg/g body weight, i.p., the serum histamine levels were reduced in a dose-dependent manner. Spirulina (0.001 to 10 microg/mL) dose-dependently inhibited histamine release from rat peritoneal mast cells (RPMC) activated by compound 48/80 or anti-DNP IgE. The level of cyclic AMP in RPMC, when spirulina (10 microg/mL) was added, transiently and significantly increased about 70-fold at 10 sec compared with that of control cells. Moreover, spirulina (10 microg/mL) had a significant inhibitory effect on anti-DNP IgE-induced tumor necrosis factor-alpha production. These results indicate that spirulina inhibits mast cell-mediated immediate-type allergic reactions in vivo and in vitro.

Animals↗

Inhibition of wound-induced expression of transforming growth factor-beta 1 mRNA by its antisense oligonucleotides.

Transforming growth factor-beta 1 (TGF-beta 1) is a member of a gene superfamily that regulates proliferation, differentiation and other functions in many cell types. To gain insight into the role of TGF-beta 1 in wound repair, we have analysed the ability of an antisense TGF-beta 1 oligodeoxynucleotides (ODN) to specifically inhibit wound-induced expression of TGF-beta 1 mRNA in the mouse skin. Although injury induced the expression of TGF-beta 1 mRNA at the wound sites, expression of TGF-beta 2-or TGF-beta 3-mRNA was not detected. In comparison to the 24 h following injury, higher levels of TGF-beta 1 mRNA expression were observed in the wound sites after 72 h. Northern blotting and in situ hybridisation analysis showed that wound sites treated with antisense TGF-beta 1 ODN exhibited no detectable levels of TGF-beta 1 mRNA after injury, whereas the sites treated with sense TGF-beta 1 ODN possessed significant amounts of its mRNA. Our results demonstrated that antisense TGF-beta 1 ODN inhibited the wound-induced expression of TGF-beta 1 mRNA in vivo.

Animals↗

The effect of combined epidural and light general anesthesia on stress hormones in open heart surgery patients.

This study was designed to evaluate the potential advantages of combined epidural and light general anesthesia over the commonly employed general anesthesia during open heart surgery. Twenty-four patients undergoing mitral valve replacement were thus studied. General anesthesia was maintained with an isoflurane-nitrous oxide-oxygen was mixture and morphine sulfate (0.4 mg/kg i.v. initially) followed by postoperative pain control with morphine in 12 patients (group GA). The remaining 12 patients (group EAA) received continuous epidural bupivacaine (0.125%)-morphine (50 micrograms/ml) supplemented with the same gas mixture as group GA. Epidural infusion was continued until the third postoperative day. Changes in the serum cortisol and beta-endorphin levels together with postoperative pain relief defined as good (scale 0-2), fair (3-4), or poor (5-10) were observed serially. Lower cortisol levels were observed in group EAA than in group GA (P < 0.05) just before skin closure, on the second and the third postoperative day. The beta-endorphin levels were substantially lower in group EAA than in group GA throughout the observation. The pain scores were good in 2 patients (17%), fair in 6 (50%), and poor in 4 (33%) for group GA, and good in 8 (67%), fair in 3 (25%), and poor in 1 (8%) for group EAA. We thus conclude that a combined epidural and light general anesthesia is considered to attenuate the stress response and thereby provides a better quality of postoperative pain control.

Adult↗

Immunogenicity of synthetic conjugates of Lewis(y) oligosaccharide with proteins in mice: towards the design of anticancer vaccines.

Many human carcinomas overexpress the Lewis(y) (Le[y]) blood-group epitope [Fucalpha1-->2Galbeta1-->4 (Fucalpha1-->3)GlcNAcbeta1-->3Gal-]. With a view to developing Le(y) based vaccines we have examined the immunogenicity of Le(y)-protein conjugates in mice. Le(y) pentasaccharide was synthesized as its allyl glycoside and coupled to keyhole limpet hemocyanin (KLH) by reductive amination or by a novel method utilizing a maleido-derivitized alkyl carboxyhydrazide as a bridging group to 2-iminothiolane-derivitized KLH. Le(y) oligosaccharide was also coupled to bovine serum albumin by reductive amination. Immunization of groups of mice with the three conjugates, together with the immunological adjuvant QS21, showed that Le(y) oligosaccharide directly coupled to KLH was the most efficient conjugate for eliciting IgG and IgM antibody responses to naturally occurring forms of Le(y) epitopes carried on mucins and glycolipids. These antibodies were also reactive with and cytotoxic to a human breast cancer cell line expressing Le(y) (MCF-7). These experiments suggest that Le(y)-KLH antigen and QS21 adjuvant could be considered as an immunogenic therapeutic vaccine in carcinoma patients.

Animals↗

Alteration of protease expression phenotype of mouse peritoneal mast cells by changing the microenvironment as demonstrated by in situ hybridization histochemistry.

Mouse mast cell protease (MMCP) mRNA expression was examined by in situ hybridization histochemistry. Peritoneal mast cells (PMCs) of WBB6F1-(+/+) mice expressed MMCP-2, MMCP-4, MMCP-5, and MMCP-6 mRNAs, but did not express MMCP-1 mRNA. When proliferation of PMCs was induced by culturing them in methylcellulose with T cell-derived cytokines, cells in mast cell colonies expressed MMCP-1 mRNA. These mast cells were transferred to a suspension culture to induce further proliferation. The phenotype of the resulting PMC-derived cultured mast cells was similar to that of bone marrow-derived cultured mast cells. When 10(5) PMC-derived cultured mast cells or 10(5) bone marrow-derived cultured mast cells were injected into the stomach wall of mast cell-deficient WBB6F1-W/Wv mice, mast cells that appeared in the mucosa and muscularis propria were similar to mast cells in the stomach of intact WBB6F1-(+/+) mice, indicating the injected cells adapted to a new tissue environment. In contrast, when 10(5) PMCs were injected into the stomach wall of WBB6F1-W/Wv mice, the injected PMCs did not adapt to the mucosa. When 20 PMCs were injected, they proliferated and adapted to the mucosal environment. The present results suggest that PMCs adapt to new environments when proliferation occurs before redifferentiation.

Animals↗

Characteristic immunostimulation by angelan isolated from Angelica gigas Nakai.

The immunopharmacological characteristics of angelan, a polysaccharide purified from Angelica gigas Nakai, were investigated in relation to the specificity to immune cells. The treatment of angelan increased the expression of IL-2, IL-4, IL-6, and IFN-gamma. The expression of IL-6 and IFN-gamma was rapidly augmented but that of IL-2 responded later. In the case of IL-4, angelan stimulated at early time after exposure but down-regulated thereafter. These results suggested that macrophages and natural killer cells involved in nonspecific immunity were primarily activated and helper T cells were secondarily affected by angelan. Angelan also had lympho-proliferative potential to B cells, specifically. The specificity of angelan was also elucidated in a cell fractionation experiment. The activated B cells by angelan also increased antibody production. The direct activation of B cells, macrophages, and accessory cells and the indirect activation of helper T cells coordinately increased immune functions such as in vitro and in vivo T-dependent immunization and antibody production. The experiment of host resistance to syngeneic tumors also showed that angelan potentiated the immune functions. In conclusion, angelan, a purified polysaccharide from an oriental herbal drug, showed characteristic immunostimulation, which was different from clinically used polysaccharides such as lentinan and PSK.

Adjuvants, Immunologic↗

Action of Ulmi radicis cortex extract on systemic and local anaphylaxis in rats.

1. To assess the contribution of an aqueous extract of Ulmi radicis cortex (AEURC) in systemic anaphylaxis, compound 48/80 was used as a fatal anaphylaxis inducer in rats. 2. AEURC completely inhibited anaphylactic shock with a dose of 1.0 g/kg body weight (BW) 1 hr before injection of compound 48/80. 3. AEURC significantly inhibited serum histamine levels induced by compound 48/80. 4. AEURC (1.0 g/kg BW) also inhibited by 79.1% passive cutaneous anaphylaxis activated by anti-dinitrophenyl (DNP) IgE. 5. AEURC dose dependently inhibited the histamine release from the rat peritoneal mast cells (RPMCs) by compound 48/80. Moreover, AEURC had a significant inhibitory effect on anti-DNP IgE-induced histamine release and tumor necrosis factor-alpha production from RPMC. 6. The level of cAMP in RPMC, when AEURC was added, significantly increased compared with that of a normal control. 7. These results indicate that AEURC may possess strong antianaphylactic action.

Anaphylaxis↗

Inhibition of mast cell-dependent anaphylactic reactions by the pigment of Polygonum tinctorium (Chung-Dae) in rats.

1. The effect of the pigment obtained from the stem and leaf of Polygonum tinctorium Loar (PtP) on anaphylactic reactions was studied in rats. 2. PtP totally inhibited compound 48/80-induced anaphylactic shock with doses of 10(2) and 10(3) mg/ kg. When PtP was pretreated at concentrations ranging from 10(-2) to 10(3) mg/kg, the serum histamine levels induced by compound 48/80 were reduced in a dose-dependent manner. 3. We also investigated the effect of PtP on mast cell-dependent passive cutaneous anaphylaxis (PCA) activated by anti-dinitrophenyl (DNP) IgE antibody. PtP potently inhibited PCA when administered orally, topically, intraperitoneally and intradermally. However, it did not show inhibitory activity when administered intravenously. 4. PtP inhibited dose dependently histamine release from rat peritoneal mast cells (RPMCs) induced by compound 48/80 and anti-DNP IgE. Moreover, the level of cAMP in RPMC, when PtP was added, significantly increased about 12-fold at 4 min compared with that of basal cells. 5. These results indicate that PtP may possess strong antianaphylactic activity and suggest that differences in bioavailability may cause differential activity following different administration routes.

Anaphylaxis↗

Activation of inducible nitric oxide synthase by Yongdam-Sagan-Tang in mouse peritoneal macrophages.

The objective of the current study was to determine the effect of Yongdam-Sagan-Tang (YS-Tang) on the production of nitric oxide (NO). Stimulation of mouse peritoneal macrophages with YS-Tang after the treatment of recombinant interferon-gamma (rIFN-gamma) resulted in increased NO synthesis. YS-Tang had no effect on NO synthesis by itself. When YS-Tang was used in combination with rIFN-gamma, there was a marked co-operative induction of NO synthesis in a dose-dependent manner. The optimal effect of YS-Tang on NO synthesis was shown 6 h after treatment with rIFN-gamma. This increase in NO synthesis was reflected as an increased amount of inducible NO synthase (iNOS) protein. NO production was inhibited by NG-monomethyl-L-arginine. The increased production of NO from rIFN-gamma plus YS-Tang-stimulated cells was decreased by the treatment with staurosporin. In addition, synergy between rIFN-gamma and YS-Tang was mainly dependent on YS-Tang-induced tumor necrosis factor-alpha (TNF-alpha) secretion. All the preparations of YS-Tang were endotoxin free. These results suggest that the capacity of YS-Tang to increase NO production from rIFN-gamma-primed mouse peritoneal macrophages is the result of YS-Tang-induced TNF-alpha secretion.

Animals↗

Effect of Syzygium aromaticum extract on immediate hypersensitivity in rats.

We investigated the effect of aqueous extract of Syzygium aromaticum (L.) Merr. et Perry (Myrtaceae) flower bud (SAFB) on immediate hypersensitivity. SAFB inhibited compound 48/80-induced systemic anaphylaxis in rats (IC50 = 31.25 mg/kg, i.p.). SAFB also inhibited local immunoglobulin E (IgE)-mediated passive cutaneous anaphylactic reaction (IC50 = 17.78 mg/kg, i.v.; IC50 = 19.81 mg/kg, p.o.). When SAFB was pretreated at concentrations ranging from 25 to 1000 mg/kg, the serum histamine levels were reduced in a dose-dependent manner. Moreover, SAFB dose-dependently inhibited histamine release from rat peritoneal mast cells (RPMC) by compound 48/80 or anti-dinitrophenyl IgE. When SAFB was added, the level of cAMP in RPMC transiently and significantly increased about 47-fold at 10 s compared with that of basal cells. These results indicate that SAFB inhibits immediate hypersensitivity by inhibition of histamine release from mast cells in vivo and in vitro.

Animals↗

Suppression of immunoglobulin E-mediated anaphylactic reaction by Hwanglyun-Haedok-Tang water extract.

According to traditional Oriental philosophy, Hwanglyun-Haedok-Tang (HH-Tang) is a prescription for heat clearing of the organism. This prescription has been used against allergic diseases for generations, and still occupies an important place in traditional medicine in Korea. In this study, we investigated the effect of HH-Tang water extract on immunoglobulin E (IgE)-mediated anaphylaxis activated by anti-dinitrophenyl (DNP) IgE antibody. HH-Tang water extract potently suppressed passive cutaneous anaphylaxis (PCA) when intradermally, intraperitoneally, or orally administered. On the other hand, it showed weak suppressive activity when administered intravenously. HH-Tang water extract, dose-dependently suppressed anaphylactic histamine release from rat peritoneal mast cells (RPMC) activated by anti-DNP IgE antibody. Moreover, HH-Tang water extract had a significant suppressive effect on anti-DNP IgE antibody-induced tumor necrosis factor-alpha secretion from RPMC. The level of cAMP in RPMC, when HH-Tang water extract was added, significantly increased compared with that of normal control. These results indicate that HH-Tang water extract may possess strong antianaphylactic action and also suggest that differential activity following administration routes may be caused by difference of bioavailability.

2,4-Dinitrophenol↗

Effect of Polygala tenuifolia root extract on the tumor necrosis factor-alpha secretion from mouse astrocytes.

We investigated whether an aqueous extract of Polygala tenuifolia root (PTAE) inhibits secretion of tumor necrosis factor-alpha (TNF-alpha) from primary cultures of mouse astrocytes. PTAE dose-dependently inhibited the TNF-alpha secretion by astrocytes stimulated with substance P (SP) and lipopolysaccharide (LPS). Interleukin-1 (IL-1) has been shown to elevate TNF-alpha secretion from LPS-stimulated astrocytes while having no effect on astrocytes in the absence of LPS. We therefore also investigated whether IL-1 mediated inhibition of TNF-alpha secretion from primary astrocytes by PTAE. Treatment of PTAE to astrocytes stimulated with both LPS and SP decreased IL-1 secretion to the level observed with LPS alone. Moreover, incubation of astrocytes with IL-1 antibody abolished the synergistic co-operative effect of LPS and SP. These results suggest that PTAE may inhibit TNF-alpha secretion by inhibiting IL-1 secretion and that PTAE has an anti-inflammatory activity on the central nervous system curing some pathological disease states.

Animals↗