PubMed Health⌕ Search

Biomedical subjects

K Son

Publications and source records attributed to K Son.

At least 19 recordsLinked to original sources
PubMed2000

Elevation of serum soluble tumour necrosis factor receptors in patients with polymyositis and dermatomyositis.

The aim of the study was, to examine the relationship between serum levels of soluble tumour necrosis factor receptors (sTNF-R) and the gene expression of two types of receptor for TNF (TNF-R), a 55 a receptor (TNF-R1) and a 75 kDa receptor (TNF-R2), bloodin peripheral mononuclear cells (PBMC) from patients with polymyositis and dermatomyositis (PM/DM). Soluble tumour necrosis factor receptor 1 (sTNF-R1) and soluble tumour necrosis factor receptor 2 (sTNF-R2) levels in sera from patients were measured by enzyme-linked immunosorbent assay. Expression of TNF-R1 and TNF-R2 mRNAs in PBMC was analysed by Northern blotting. Serum sTNF-R1 and sTNF-R2 levels were elevated significantly in 25 patients with active-stage PM/DM, compared to those in 18 patients with inactive-stage PM/DM and 32 normal controls. Serum concentrations of sTNF-R1 and sTNF-R2 were correlated with PM/DM disease activity. TNF-R1 gene expression was enhanced in freshly isolated PBMC from patients with active-stage PM/DM. In contrast, TNF-R2 mRNA was expressed constitutively in patients with active-stage PM/DM and in normal controls. The expression of TNF-R1 and TNF-R2 mRNAs in PBMC and elevation of their soluble forms in the sera of patients with active-stage PM/DM suggest increased proteolytic cleavage of cell surface TNF-R from PBMC in patients with active-stage PM/DM, and that sTNF-R may regulate TNF-alpha-mediated muscle fibre damage in PM/DM.

Adolescent↗
PubMed2000

Antinociceptive mechanisms of dipsacus saponin C administered intrathecally in mice.

Dipsacus saponin C (DSC) administered intrathecally (i.t.) showed antinociceptive effect in a dose-dependent (from 3.75 to 30 microg) manner as measured by the tail-flick assay. The antinociception induced by DSC at the dose of 30 microg reached at peak 7.5 min and almost returned to the control level after 60 min. 5-Amino-valeric acid (5-AVA, a GABA(A) receptor antagonist, from 1 to 20 microg) and SR 95531 (a GABA(B) receptor antagonist, from 0.1 to 2 ng) dose-dependently attenuated i.t. administered DSC-induced increase of the inhibition of the tail-flick response. The i.t. injection of yohimbine (an alpha(2)-adrenergic receptor antagonist, from 1 to 20 microg) and methysergide (a serotonin receptor antagonist, from 1 to 20 microg), but not naloxone (from 2 to 8 microg), significantly attenuated inhibition of the tail-flick response induced by DSC (30 microg) administered i.t. Sulfated cholecystokinin (CCK, from 0.05 to 0.5 ng) injected i.t. significantly reduced the inhibition of the tail-flick response induced by DSC (30 microg) administered i.t. Our results suggest that DSC shows an antinociceptive effect when it is administered spinally and GABA(A), GABA(B), alpha(2)-adrenergic and serotonin receptors located at the spinal cord level, but not opioid receptors, may be involved in DSC-induced antinociception. Furthermore, CCK may play an important role for the modulation of i. t. injected DSC-induced antinociception.

Adrenergic alpha-Antagonists↗
PubMed2000

Abnormal IL-1 receptor antagonist production in patients with polymyositis and dermatomyositis.

OBJECTIVE: To examine the relationship between serum levels of interleukin-1 receptor antagonist (IL-1Ra) and its gene expression in peripheral blood mononuclear cells (PBMC) from patients with polymyositis and dermatomyositis (PM/DM). METHODS: IL-1Ra levels in sera from patients and supernatants of unstimulated monocyte cultures were measured by enzyme-linked immunosorbent assay. Expression of IL-1Ra mRNA was analyzed by Northern blotting, and an 86-base pair variable repeat polymorphism in intron 2 of the IL-1Ra gene was determined by polymerase chain reaction. RESULTS: Serum IL-1Ra was significantly elevated in 27 patients with active-stage PM/DM when compared with levels in 16 patients with inactive-stage PM/DM and 19 normal controls. Serum concentrations of IL-1Ra were correlated with PM/DM disease activity. IL-1Ra mRNA was detected in freshly isolated PBMC from patients with active-stage PM/DM, but not in controls. Moreover, IL-1Ra concentrations were increased significantly in unstimulated monocytes from patients with active-stage PM/DM compared with monocytes from normal controls. However, there were no significant differences in IL-1Ra allele frequencies between patients and normal controls. CONCLUSION: Elevation of both IL-1Ra mRNA and protein in sera of patients with active-stage PM/DM suggest that higher levels of serum IL-1Ra may reflect increased IL-1Ra production in myositis, and that IL-1Ra may regulate IL-1-mediated muscle fiber damage in PM/DM.

Adolescent↗
PubMed1999

The effect of N-substituted alkyl groups on anticonvulsant activities of N-Cbz-alpha-amino-N-alkylglutarimides.

In order to examine the effects of N-substituted alkyl group on the anticonvulsant activities of N-Cbz-alpha-aminoglutarimides as novel anticonvulsants with broad spectrum, a series of (R) or (S) N-Cbz-alpha-amino-N-alkylglutarimides (1 and 2) were prepared from the corresponding (R) or (S) N-Cbz-glutamic acid and evaluated for the anticonvulsant activities in the maximal electroshock seizure (MES) test and pentylenetetrazol induced seizure (PTZ) test, including the neurotoxicity. The most potent compound in the MES test was (S) N-Cbz-alpha-amino-N-methylglutarimide (ED50=36.3 mg/kg, PI=1.7). This compound was also most potent in the PTZ test (ED50=12.5 mg/kg, PI=5.0). The order of anticonvulsant activities against the MES test as evaluated from ED50 values for (R) series was N-methyl > N-H > N-ethyl > N-allyl; for the (S) series N-methyl > N-H > N-ethyl > N-allyl > N-isobutyl compound. Against the PTZ tests, the order of anticonvulsant activities showed similar pattern; for the (R) series, N-methyl > N-H > N-ethyl > N-allyl; for the (S) series N-methyl > N-H > N-ethyl > N-allyl > N-isobutyl compound. From the above results, N-substituted alkyl groups were thought to play an important role for the anticonvulsant activities of N-Cbz-alpha-amino-N-alkylglutarimides.

Animals↗
PubMed1999

[Crohn's disease with the onset resembling systemic lupus erythematosus].

We described a 37-year-old man with Crohn's disease (CD) resembling systemic lupus erythematosus (SLE) at his disease onset. He was admitted to the municiple Akiru Hospital in October 1986 by fever, aphtous oral ulcerations, sore throat and polyarthralgia. Hematologic examination showed leukocytopenia, lymphocytopenia, positive tests for antinuclear antibody, anti-DNA antibody and LE cell phenomenon. He has had episodes of convulsion and conciousness loss of unknown etiology when he was 17 years old. The diagnosis of SLE was made, and oral medication of prednisolone was started. Several weeks later, most of symptoms and autoantibodies disappeared, although the oral aphtous ulcerations and leukocytopenia remained. In May 1987, he admitted to the other hospital because of bloody vomiting. Endoscopic examination showed the esophagial ulceration, and histology of biopsied-specimen was nonspecific esophagitis. The combination of prednisolone and oral cyclophosphamide or methotrexate was employed thereafter. However, the leukocytopenia, oral aphtous ulceration and esophagial ulceration continued in spite of these treatments. All the immunosuppressive treatment was stopped at March 1992. In October 1995, he admitted to our hospital because of body weight loss and continuous diarrhea with occasional bloody stool. Barium enema and endoscopic examination of the colon revealed the findings compatible with CD. The patient responded favorably to methylprednisolone pulse therapy followed by oral sulphasalazine. This case indicated that cases with inflammatory bowel diseases like CD could show similar clinical signs and symptoms to SLE, and in some cases of CD might satisfied the classification of criteria for SLE.

Administration, Oral↗
PubMed1998

Analysis of exploratory eye movement in a patient with lupus psychosis.

The psychiatric and cognitive condition of a patient with lupus psychosis was evaluated. Using a device that detects the corneal reflection of infrared light, the patterns of eye tracking movements were recorded before the onset of lupus psychosis, after remission, and again 1 year later. Electroencephalographic findings and cerebrospinal fluid levels of both interferon alpha and interleukin-6 were also obtained longitudinally. Electroencephalographic findings and clinical signs were correlated to the levels of interferon alpha in cerebrospinal fluid. Analysis of exploratory eye movements revealed marked decreases in the number of eye fixation, mean eye-scanning length and total eye-scanning length. Even though the lupus psychosis resolved and the electroencephalographic findings became normal, the eye movement patterns showed remaining deterioration. It was concluded that analysis of exploratory eye movements in patients with systemic lupus erythematosus may be useful in diagnosing lupus psychosis, and may also present a diagnostic clue to subclinical lupus psychosis.

Adult↗
PubMed1998

Inhibition of protein synthesis by nitric oxide correlates with cytostatic activity: nitric oxide induces phosphorylation of initiation factor eIF-2 alpha.

BACKGROUND: Nitric oxide (NO) is cytostatic for proliferating cells, inhibits microbial growth, and down-regulates the synthesis of specific proteins. Studies were undertaken to determine the mechanism by which NO inhibits total protein synthesis and whether the inhibition correlates with established cytostatic activities of NO. MATERIALS AND METHODS: In in vitro experiments, various cell types were exposed to NO using either donors or expression of inducible NO synthase (iNOS). The capacity of NO to suppress total protein synthesis, measured by incorporation of 35S-methionine into protein, was correlated with the capacity of NO to suppress cell proliferation, viral replication, or iNOS expression. Phosphorylation of eIF-2 alpha was examined as a possible mechanism for the suppressed protein synthesis by NO. RESULTS: Both NO donors and expression of the iNOS suppressed total protein synthesis in L929 cells and A2008 human ovarian tumor cells in parallel with decreased cell proliferation. Suppressed protein synthesis was also shown to correlate with decreased vaccinia virus proliferation in murine peritoneal macrophages in an iNOS-dependent manner. Furthermore, iNOS expression in pancreatic islets or RAW264.7 cells almost completely inhibited total protein synthesis, suggesting that nonspecific inhibition of protein synthesis may be the mechanism by which NO inhibited the synthesis of specific proteins such as insulin or iNOS itself. This possibility was confirmed in RAW264.7 cells where the inhibition of total protein synthesis correlated with the decreased iNOS protein. The decrease in protein levels occurred without changes in iNOS mRNA levels, implicating an inhibition of translation. Mechanistic studies revealed that iNOS expression in RAW264.7 cells resulted in the phosphorylation of eIF-2 alpha and inhibition of the 80S ribosomal complex formation. CONCLUSIONS: These results suggest that NO suppresses protein synthesis by stimulating the phosphorylation of eIF-2 alpha. Furthermore, our observations indicate that nonspecific inhibition of protein synthesis may be a generalized response of cells exposed to high levels of NO and that inhibition of protein synthesis may contribute to many of the described cytostatic actions of NO.

Animals↗
PubMed1998

The effect of N-alkyloxycarbonyl group on the anticonvulsant activities of N-alkyloxycarbonyl-alpha-amino-N-methylsuccinimides.

In connection with the development of new anticonvulsant agents with a broad spectrum, we found that N-Cbz-alpha-amino-N-alkylsuccinimides showed significant anticonvulsant activities, and the pharmacological activities of these compounds were dependent on their stereochemistry and N-substituted alkyl group. These results prompted us to define the effects of other functional group on the anticonvulsant activities of these compounds. Therefore a series of N-alkoxycarbonyl-alpha-amino-N-methylsuccinimide were prepared from N-Cbz-aspartic acid and were evaluated with their anticonvulsant activities against the MES and PTZ tests, in order to define the effect of N-substituted alkoxy carbonyl group with the anticonvulsant activities. From these studies, it was found that all the tested N-alkoxycarbonyl-alpha-amino-N-methylsuccinimides exhibited significant anticonvulsant activities in the PTZ test and were not active in the MES test. The most active compound in the PTZ test was (S) N-ethoxycarbonyl-alpha-amino-N-methyl-succinimide. We found that the pharmacological activities in the PTZ test were dependent on their N-alkoxycarbonyl groups. They follow as such; The order of anticonvulsant activities for (R) series as evaluated by ED50 was N-phenoxycarbonyl = N-4-nitrobenzyloxycarbonyl > N-ethoxycarbonyl > N-allyloxycarbonyl > N-tert. butoxycarbonyl compound; For the (S) series N-ethoxycarbonyl > N-phenoxycarbonyl > N-allyloxycarbonyl compound. From the above results, it was conceivable that N-substituted alkoxycarbonyl group had certain effects on the anticonvulsant activities of N-alkoxycarbonyl-alpha-amino-N-methylsuccinimides.

Animals↗
PubMed1998

The effect of N-alkyloxycarbonyl group on the anticonvulsant activities of N-alkyloxycarbonyl-alpha-aminoglutarimides.

In connection with the development of new anticonvulsant agents with a broad spectrum, we reported that N-Cbz-alpha-aminoglutarimides, combining common structures of other anticonvulsants such as N-CO-C-N and cyclic imides in a single molecule, showed significant anticonvulsant activities in the MES (maximal electroshock seizure) and PTZ (pentylenetetrazole induced seizure) tests. In these studies, a series of (R) and (S) N-alkyloxycarbonyl-alpha-aminoglutarimides 7a-7e and 8a-8e, which were substituted with various alkyloxycarbonyl group instead of Cbz group, were prepared from the corresponding (R) and (S) N-Cbz-glutamic acid 3 and 4, and were evaluated with their anticonvulsant activities against the MES and PTZ tests, including neurotoxicity, in order to define the effect of N-alkyloxycarbonyl group on the anticonvulsant activities of N-alkyloxycarbonyl-alpha-aminoglutarimides. Among them, (S) N-4-nitrobenzyloxycarbonyl-alpha-amino-N-methylglutarimide 8e was the most active in MES (ED50 = 35.6 mg/kg, PI = 2.7) and PTZ tests (ED50 = 15.6, PI = 6.1). Interestingly, (R) and (S) N-4-nitrobenzyloxycarbonyl-alpha-amino-N-methylglutarimide 7e and 8e and (R) N-phenoxycarbonyl-alpha-amino-N-methylglutrimide 7d showed significant anticonvulsant activities in both the MES and PTZ tests and other compounds showed anticonvulsant activities in only the PTZ test. In addition, it was found that their anticonvulsant activities were dependent on their stereochemistries and N-substituted alkyloxycarbonyl groups.

Animals↗
PubMed1996

A nitric oxide production bioassay for interferon-gamma.

Interferon-gamma (IFN-gamma), produced by stimulated T lymphocytes and natural killer cells, has an antitumor and antiviral activity by inhibition of cell growth, immunomodulation, and/or activation of macrophages. Although several IFN-gamma assays have been used, there are no simple, inexpensive, and specific assays. We have developed a new bioassay for IFN-gamma which measures the concentration of nitric oxide (NO) generated by a macrophage cell line RAW264.7 stimulated with IFN-gamma. NO production, determined by nitrite (NO2-) accumulation in culture medium, was linear at IFN-gamma concentrations between 0 and 10 U/ml and logarithmically linear between 2 and 100 U/ml, when RAW cells (1 x 10(5) cells/200 microliters/well in 96 well plate) were incubated with murine recombinant IFN-gamma for 24 h. The new assay has a high sensitivity with the detection limit of 0.1-0.2 ng/ml IFN-gamma, which is similar to that of the enzyme-linked immunosorbent assay (ELISA) and antiviral assays. Other cytokines such as IFN-alpha, IFN-beta, tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1 beta, IL-2, and IL-6, either alone or in combination did not produce NO from RAW264.7. Exogenous NO2-, NO3- or NO2- plus NO3- did not interfere with the IFN-gamma-induced NO formation as well as NO2- measurement. The IFN-gamma bioactivity, measured by the RAW264.7 bioassay, expressed from the transfected human ovarian tumor cells was closely correlated with the levels of IFN-gamma protein concentration measured by the ELISA. Therefore, our new method can be applicable for monitoring IFN-gamma gene expression and accumulation in culture medium for IFN-gamma therapy.

Animals↗
PubMed1996

Restriction fragment length polymorphism analysis in the HLA class III genes of patients with diffuse panbronchiolitis.

Although diffuse panbronchiolitis (DPB) is known to be positively associated with certain major histocompatibility complex (MHC) class I antigens, e.g., HLA-B54 in Japanese patients, it is not clear whether the MHC genes predispose to the disease or are markers for other disease susceptibility gene(s). Because the HLA class III genes such as tumor necrosis factor (TNF) or the fourth component of complement (C4) are localized in the proximity of the HLA-B locus, one or more of these genes might be responsible for susceptibility to DPB. To analyze the role of HLA class III genes in DPB patients, we first evaluated the HLA-B54 association in 32 patients with DPB, and subsequently, studied the restriction fragment length polymorphism (RFLP) of the TNF-alpha and -beta (TNF-alpha/beta) genes as well as the C4A and B (C4A/B) genes in DPB patients and normal individuals. The HLA-B54 antigen was significantly more frequent in DPB patients than in normal individuals (40.3% vs 13.0%, p < 0.001), however, we did not detect a significant association between DPB and gene polymorphisms of either TNF-alpha/beta or C4A/B. Furthermore, there was no evidence of C4A gene deletion in patients with DPB. These results suggest that the HLA-B54 antigen itself might be directly involved in the pathogenesis of DPB.

Bronchiolitis↗
PubMed1996

Factors influencing the drug sensitization of human tumor cells for in situ lipofection.

The cisplatin induced enhancement of in situ lipofection was optimized by considering the factors that can increase the degree of sensitization. Two other anticancer drugs, mechlorethamine (nitrogen mustard) and taxol, enhanced CAT gene expression but the degree of sensitization was not as great as cisplatin. Besides human 2008 ovarian cancer cells we also found that human lung (A549) and head and neck cancer cells (SCC 25) were transiently sensitized by cisplatin. The transfectability of the two commercially available cationic liposomes, Lipofectin and LipofectAmine, was either weak or not consistent among tumors tested. In vivo transfection efficiency of 2008 cells was the highest at 1 microgram DNA per nmol or microgram liposome with all three cationic liposomes. In vitro transfection efficiency of 2008 cells at 1:1 (microgram of DNA:nmole of DC-chol/DOPE liposome) increased in a dose-dependent manner while at 1:10, an optimal ratio for in vitro lipofection, rapidly decreased with an increase in dose. This result indicated that there was a correlation between in vivo and in vitro lipofection at 1:1 ratio for delivering liposomal DNA. Most of the DNA injected into the tumor was concentrated in the tumor and in the skin above the tumor whether cisplatin was preinjected or liposomes were used as carriers.

Animals↗
PubMed1995

In vivo cisplatin-exposed macrophages increase immunostimulant-induced nitric oxide synthesis for tumor cell killing.

Mice pre-exposed to cisplatin increased their production of nitric oxide (NO) when treated with lipopolysaccharide (LPS). Peritoneal macrophages, isolated from mice 11 days after cisplatin treatment and cultured with LPS plus IFN-gamma, increased NO production, whereas the macrophages isolated 2 days after cisplatin treatment decreased it. In both cases, NO was not produced without immunostimulant(s). Northern and Western Blot analysis showed that macrophages exposed to cisplatin for 11 days increased production of mRNA and protein expression of inducible nitric oxide synthase (iNOS). THis result indicated that macrophages became more sensitive to LPS and IFN-gamma when they were exposed to cisplatin in vivo. Peritoneal macrophages, when activated with LPS plus IFN-gamma and then cocultured with several tumor cells, exhibited cytotoxic activity against both cisplatin-sensitive and cisplatin-resistant tumor cells. There was no difference in cytotoxicity between the paired cells. Under the same experimental condition, macrophages that were exposed to cisplatin for 11 days had significantly increased their cytotoxicity to the tumor cells. This cytotoxic activity was inhibited by the NOS inhibitor NG-monomethyl-L-arginine, indicating that NO is a major effector for macrophage-mediated tumor cell killing. Treatment of tumor cells with S-nitroso-N-acetylpenicillamine, a NO-generating compound, showed the similar tumoricidal effect. These data demonstrated that injection of cisplatin into the mice can enhance the sensitivity of macrophages to the subsequent treatment of immunostimulant(s) for effective tumor cell killing through enhanced NO production.

Animals↗
PubMed1994

Exposure of human ovarian carcinoma to cisplatin transiently sensitizes the tumor cells for liposome-mediated gene transfer.

Human ovarian carcinoma cells (line 2008) grown as subcutaneous solid tumor in the severe combined immunodeficient mouse can be transfected by directly injecting a plasmid DNA-liposome complex into the tumor (in situ lipofection). The level of reporter gene expression in the tumor cells was significantly elevated if the animal received a single i.p. injection of cisplatin 1 week before the lipofection. Sensitization of the tumor for lipofection peaked 1 week after cisplatin injection and declined thereafter. Cells exposed to low concentration of cisplatin in vitro for four to five doubling times also showed elevated sensitivity for lipofection in vitro. Cisplatin was the only anticancer drug tested that exhibited this activity. These results suggest a sequential combinational gene therapy protocol with cisplatin for the ovarian carcinoma.

Animals↗
PubMed1994

Cationic liposomes for direct gene transfer in therapy of cancer and other diseases.

Cationic liposomes can mediate efficient delivery of DNA and DNA/protein complex to mammalian cells in vitro and in vivo. Cationic cholesterol derivatives mixed with phosphatidylethanolamine and sonicated to form small unilamellar vesicles can complex with DNA and mediate the entry into the cytosol from the endosome compartment. One of the liposome formulations, DC-Chol liposomes, is used in a gene therapy clinical trial for melanoma. Recently, we exploited these cationic liposomes for the delivery of trans-activating protein factors to regulate and control the expression of delivered transgenes in a protein dose-dependent manner. Bacteriophage T7 RNA polymerase was co-delivered with a reporter gene under the control of T7 promoter to allow cytoplasmic expression of the gene. Human immunodeficiency virus-1 transactivating protein was also codelivered with a reporter gene under the control of HIV-1 long terminal repeat. Finally, human tumor cells selected for cis-platin resistance or isolated from patients who have failed cis-platin therapy are highly transfectable with cationic liposomes. These results suggest a serial therapy protocol with cis-platin and gene therapy for malignancy.

Animals↗
PubMed1994

Isolation of a fibronectin-binding tryptic peptide from the antigen 85A protein of Mycobacterium bovis BCG.

Antigen 85A, a major secreted mycobacterial fibronectin-binding protein, was isolated from culture fluids of the Tice substrain BCG vaccine. Tryptic digestion of this protein and passage of the digest through a fibronectin affinity chromatographic column resulted in the identification of a polypeptide fragment of molecular weight < or = 6.5 kD, which had marked fibronectin-binding activity. The identity of a 62-residue polypeptide was deduced from the amino-terminal sequence, indicating that the primary structure may define the integrin-binding capability.

Amino Acid Sequence↗