Biomedical subjects

Y B Kim

Publications and source records attributed to Y B Kim.

At least 73 records · Page 4Linked to original sources

PubMed2001

Oxidative stress is more important than acid in the pathogenesis of reflux oesophagitis in rats.

BACKGROUND: Although antisecretory medications such as histamine type II receptor antagonists or proton pump inhibitors have been used to treat reflux oesophagitis, a considerable number of patients do not achieve complete mucosal healing or suffer from either sustained symptoms or ensuing complications, suggesting other damaging factors or impaired mucosal resistance are also involved in the pathogenesis of reflux oesophagitis. AIMS: The present study was designed to evaluate oxidative stress as the major pathogenic factor of reflux oesophagitis and to determine the usefulness of antioxidants in the treatment of reflux oesophagitis. MATERIALS AND METHODS: Reflux oesophagitis was induced by insertion of a 3 mm calibre ring into the duodenum, 1 cm distal to the ligament of Treitz, in Sprague-Dawley rats. RESULTS: DA-9601, a novel antioxidant substance, significantly attenuated the gross and histopathological scores of reflux oesophagitis compared with those treated with ranitidine alone or reflux oesophagitis controls in a dose dependent manner. Only scattered erosions were observed in the antioxidant pretreated group but acid suppression by ranitidine was not effective in decreasing the severity of reflux oesophagitis. Significantly increased amounts of malondialdehyde (MDA), increased nuclear factor kappaB (NFkappaB) activation, and depletion of reduced glutathione (GSH) were observed in experimentally induced reflux oesophagitis. DA-9601 pretreatment attenuated the decrement in mucosal GSH levels and decreased MDA formation significantly. DA-9601 treatment caused significant reductions in activation of NFkappaB transcription factor, especially the p50 subunit, in accordance with the significantly higher levels of inhibitory protein of NFkappaB expression. CONCLUSION: Reflux oesophagitis caused considerable levels of oxidative stress in the oesophageal mucosa and antioxidant treatment should be considered as supplementary therapy in the prevention or treatment of reflux oesophagitis with acid suppression.

Animals↗

PubMed2001

Chronic hepatitis: in vivo proton MR spectroscopic evaluation of the liver and correlation with histopathologic findings.

PURPOSE: To correlate the in vivo hydrogen 1 ((1)H) magnetic resonance (MR) spectroscopic features of the chronic hepatitis-involved liver with the histopathologic stages of fibrosis. MATERIALS AND METHODS: Seventy-five patients with chronic hepatitis were examined with (1)H MR spectroscopy, which was performed in the right hepatic lobe. The peak areas of glutamine and glutamate complex (Glx), phosphomonoesters (PME), glycogen and glucose complex (Glyu), and lipid were measured on the liver spectra. The histopathologic features were correlated with the in vivo (1)H MR spectroscopic findings at each stage of chronic hepatitis. Fifteen healthy volunteers also were included as a control group. RESULTS: (1)H MR spectroscopy depicted Glx, PME, Glyu, and lipid in all livers. In the normal livers, the calculated mean (+/- SD) relative metabolite-to-lipid ratios of Glx, PME, and Glyu were 0.14 +/- 0.04, 0.03 +/- 0.01, and 0.21 +/- 0.04, respectively. The mean value of each metabolite-to-lipid ratio was significantly different between all stages of chronic hepatitis, and with the exception of the mean ratio at the interval between stages 0 and 1 (P > .05), the mean value increased significantly with increasing stage (P < .05). A pronounced peak was demonstrated at 3.9-4.1 ppm at (1)H MR spectroscopy of all stages of chronic hepatitis except stage 0. CONCLUSION: The increased Glx, PME, and Glyu levels relative to the lipid content with chronic hepatitis indicated the severity of fibrosis and thus were concordant with the histopathologic stages. In vivo (1)H MR spectroscopy might be a substitute for liver biopsy in the diagnosis and staging of chronic hepatitis.

Adolescent↗

PubMed2001

Hyperfractionated re-irradiation using a 3-dimensional conformal technique for locally recurrent carcinoma of the nasopharynx; preliminary results.

To evaluate the efficacy of hyperfractionated re-irradiation using a three-dimensional conformal radiotherapy (3-D CRT) technique in patients with locally recurrent carcinoma of the nasopharynx. Four patients with locally recurrent nasopharyngeal cancer were retreated with a hyperfractionated schedule using a 3-D CRT technique. Re-irradiation was delivered in 1.1-1.2 Gy fractions twice per day (BID), with interfraction intervals of more than 6 hours. The total dose ranged from 59.4 to 69.2 Gy. A 3-D CRT technique with 5- or 6-field coplanar and/or non-coplanar beams were employed during the entire treatment procedure. All four patients achieved complete remission of locally recurrent lesions, with marked improvement of subjective symptoms, immediately after re-irradiation. All are alive and well without evidence of disease after limited follow-up periods, which range from 7 to 20 months. So far, there have been no radiation-induced neurologic complications. Four patients with locally recurrent carcinoma of the nasopharynx were successfully treated by hyperfractionated re-irradiation using a 3-D CRT technique. A relatively high re-irradiation dose of more than 60 Gy may be safely delivered with no serious acute or late radiation-induced complications in patients with local recurrences and who were initially treated with doses greater than 70 Gy.

Aged↗

PubMed2001

Seroepidemiology of HBV infection in South Korea, 1995 through 1999.

BACKGROUND: We analyzed serologic data that were obtained from the Korea Association of Health from 1995 to 1999 to estimate the reliable prevalence of HBV in South Korea. METHODS: 603,375, 639,465, 621,476, 612,705 and 650,398 serum samples were annually tested for HBsAg. Of HBsAg positive persons whose serum samples were available, HBeAg positivity was checked. RESULTS: HBsAg positivities among subjects between 6 and 19 years old were 8.2%, 3.9%, 2.1%, 2.6% and 1.3%. HBsAg positivities among subjects above 20 years old were 8.9%, 6.4%, 5.9%, 5.4% and 5.4%. The positive rates of HBeAg were 39.8 to 62.9% among subjects between 6 and 19 years old, and 18.3 to 37.9% among persons above 20 years old, in each year. In both subgroups, HBsAg positivity in the latter year was significantly lower than that in the former year (p < 0.001). It also showed that HBsAg positivities among subjects between 6 and 19 years old have been significantly lower than those among subjects above 20 years old, but those of HBeAg the exact reverse of HBsAg since 1996 (p < 0.001). CONCLUSIONS: It was observed that prevalence of HBV infection in the late 1990s, especially in the group between 6 and 19 years old, was conspicuously lower than that in the past. The nationwide vaccination programme might be one of the most important contributors to this tendency in Korea.

Adolescent↗

PubMed2001

Correlation between angiogenesis, apoptosis and cell proliferation in invasive ductal carcinoma of the breast and their relation to tumor behavior.

OBJECTIVE: To investigate the relationship between angiogenesis, apoptosis and cell proliferation in invasive ductal carcinoma of the breast and their relation to tumor behavior. STUDY DESIGN: Microvessels were immunohistochemically labeled with antibody to CD34 in sections from 82 cases of invasive ductal carcinoma. Computerized image analysis was used to evaluate microvessel density (MVD). The authors measured the apoptotic index (AI) using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling technique and proliferating cell nuclear antigen labeling index (PCNA LI) by PCNA immunohistochemistry on serial sections. RESULTS: Statistical analysis revealed a significant inverse correlation between MVD and AI (r = -.313, P = .004) and failed to find a significant correlation between MVD and PCNA LI. There was a significant positive correlation between AI and PCNA LI (r = .393, P = .000). Significant differences in AI between high MVD (> or = 59.9%) and low MVD (< 59.9%) were seen (P < .001), with no appreciable differences in PCNA LI between the two groups. Histologic grade and stage were the only independent prognostic factors in both disease-free and overall survival. CONCLUSION: Angiogenesis in breast cancer may be related to the ability of tumor cells to survive rather than to their proliferative activity. Apoptosis is related to cell proliferation in breast cancer.

Adult↗

PubMed2000

Evaluation of various carbon substrates for the biosynthesis of polyhydroxyalkanoates bearing functional groups by Pseudomonas putida.

The ability of Pseudomonas putida to synthesize polyhydroxyalkanoate (PHA) from 36 different carboxylic acids containing various functional groups was examined. This bacterium did not utilize short carboxylic acids (C(4)-C(6)) containing bromine, methoxy, ethoxy, cyclohexyl, phenoxy, and olefin groups as the sole carbon substrate. No polymer was isolated from the cells grown with carboxylic acids bearing hydroxyl, amino, para-methoxyphenoxy, and para-ethoxyphenoxy groups regardless of the carbon substrate chain lengths used even when they were cofed with nonanoic acid. Of all the carbon substrates evaluated, only 6-para-methylphenoxyhexanoic acid, 8-para-methylphenoxyoctanoic acid, 8-meta-methylphenoxyoctanoic acid, 10-undecenoic acid, and 10-undecynoic acid supported both growth and the production of PHA containing the corresponding functional groups by P. putida. The present results indicate that the carbon availability of P. putida for growth and PHA production is significantly different from that of P. oleovorans.

Carboxylic Acids↗

PubMed2000

CM1, a possible novel activation molecule on human lymphocytes.

CM1 (centrocyte/-blast marker 1) defined by a mAb developed against concanavalin-A activated PBMC, is expressed specifically on some tonsillar germinal center (GC) B cells. In single flow cytometric analysis, the bone marrow did not express these molecules nor did the PBMC or the thymocytes. The peripheral B lymphocytes showed more than 90% positive, while the peripheral T lymphocytes showed approximately 60% positive at 48 h after activation by PMA/ionomycin, respectively. A western blot analysis and an immunoprecipitation for CM1 showed a band at 70 kDa. Cross-linking of CM1 with anti-CM1 mAb induced apoptosis of the GC B cells (CD38(+)IgD(-)). Immunohistochemical staining revealed that the CM1 molecule is distributed over the entire area except the proximal dark zone of the tonsillar germinal centers. These results suggest that the CM1 molecule might be involved in differentiation of the germinal center B cells as one of the novel centrocyte markers.

ADP-ribosyl Cyclase↗

PubMed2000

Overexpression of protein-tyrosine phosphatase-1B in adipocytes inhibits insulin-stimulated phosphoinositide 3-kinase activity without altering glucose transport or Akt/Protein kinase B activation.

Previous studies suggested that protein-tyrosine phosphatase 1B (PTP1B) antagonizes insulin action by catalyzing dephosphorylation of the insulin receptor (IR) and/or other key proteins in the insulin signaling pathway. In adipose tissue and muscle of obese humans and rodents, PTP1B expression is increased, which led to the hypothesis that PTP1B plays a role in the pathogenesis of insulin resistance. Consistent with this, mice in which the PTP1B gene was disrupted exhibit increased insulin sensitivity. To test whether increased expression of PTP1B in an insulin-sensitive cell type could contribute to insulin resistance, we overexpressed wild-type PTP1B in 3T3L1 adipocytes using adenovirus-mediated gene delivery. PTP1B expression was increased approximately 3-5-fold above endogenous levels at 16 h, approximately 14-fold at 40 h, and approximately 20-fold at 72 h post-transduction. Total protein-tyrosine phosphatase activity was increased by 50% at 16 h, 3-4-fold at 40 h, and 5-6-fold at 72 h post-transduction. Compared with control cells, cells expressing high levels of PTP1B showed a 50-60% decrease in maximally insulin-stimulated tyrosyl phosphorylation of IR and insulin receptor substrate-1 (IRS-1) and phosphoinositide 3-kinase (PI3K) activity associated with IRS-1 or with phosphotyrosine. Akt phosphorylation and activity were unchanged. Phosphorylation of p42 and p44 MAP kinase (MAPK) was reduced approximately 32%. Overexpression of PTP1B had no effect on basal, submaximally or maximally (100 nm) insulin-stimulated glucose transport or on the EC(50) for transport. Our results suggest that: 1) insulin stimulation of glucose transport in adipocytes requires </=45% of maximal tyrosyl phosphorylation of IR or IRS-1 and <50% of maximal activation of PI3K, 2) a novel PI3K-independent pathway may play a role in insulin-induced glucose transport in adipocytes, and 3) overexpression of PTP1B alone in adipocytes does not impair glucose transport.

3T3 Cells↗

PubMed2000

Endogenous interleukin-18 modulates immune escape of murine melanoma cells by regulating the expression of Fas ligand and reactive oxygen intermediates.

It has been known that melanoma cells can suppress the immune system by the Fas ligand. The present study investigated whether interleukin (IL)-18, which can enhance Fas ligand expression, is produced by B16F10 melanoma cells and is involved in immune escape of tumor cells. Immunohistology, reverse transcription-PCR, intracellular fluorescence-activated cell-sorting analysis, and immunoblotting demonstrated that melanoma cells express IL-18. C57BL/6 splenocytes cultured with culture supernatants of B16F10 melanoma cells enhanced IFN-gamma production, which was blocked by anti-IL-18 antibody, indicating that IL-18 in the culture supernatants is functional. In addition to IL-18, the IL-18 receptor was also detected in B16F10 melanoma cells, suggesting a role of this cytokine in regulating the functions of B16F10 melanoma cells. The functional effect of IL-18 on B16F10 melanoma cells was shown by reduction of Fas ligand expression in cells treated with anti-IL-18 antibody or transfected with IL-18 antisense cDNA. In addition, the same treatments decreased intracellular reactive oxygen intermediate levels in B16F10 melanoma cells, indicating that IL-18 regulates reactive oxygen intermediate production, which is involved in Fas ligand expression. Furthermore, transfection of IL-18 antisense cDNA into melanoma cells increased the susceptibility of tumor cells to natural killer cells in vitro. When IL-18 antisense transfectants were implanted into syngeneic mice, severe reduction of tumor cell growth was observed with concomitant infiltrated natural killer cells in the tumor area. Taken together, these results demonstrate that IL-18 has a critical role as a survival factor for B16F10 melanoma cells.

Animals↗

PubMed2000

The effects of N-methyl-N-nitrosourea and azoxymethane on focal cerebral infarction and the expression of p53, p21 proteins.

If the activity of pro-apoptotic genes can be down-regulated by certain chemicals, cells may be protected from apoptosis. To test this hypothesis in a cerebral infarction model, we used N-methyl-N-nitrosourea (MNU) and azoxymethane (AOM), which were approved gene-modulating chemicals. A focal cerebral infarction was created by coagulation of the right middle cerebral artery and ipsilateral common carotid artery (CCA) and simultaneous transient occlusion of the contralateral CCA for 30 min in 25 adult Sprague-Dawley rats that were sacrificed 24 h later. In one group (n=7), MNU (5 mg/kg) was injected intravenously 30 min before initiation of ischemia. In another group (n=7), AOM (15 mg/kg) was administered intraperitoneally before 24 h of ischemia. The infarction volumes were checked and the brains were stained for p53 and p21 proteins. The width in micrometers of the peri-infarct area containing p53 or p21 protein-positive cells, and the number of p53 or p21 protein-positive cells (cells/HPF) were measured at an adjacent peri-infarct area. The AOM-treated group showed a significantly reduced infarction volume (by 42.5%, p<0.001), a significantly greater number of p53 positive cells (by 12.0%, p<0. 05), and a significantly wider p53 protein-positive area (by 15.6%, p<0.01) than the untreated group. AOM did not show any influence on the expression pattern of the p21 protein. MNU had no effect in the expression of p53 or p21 proteins. As a result, we concluded that AOM revealed a protective effect in ischemia by suppressing the pro-apoptotic activity of the p53 gene. Safer chemicals that can modulate apoptotic genes, if any, will provide a new therapeutic modality for cerebral infarction.

Animals↗

PubMed2000

Ligation of ICAM-1 molecules inhibits target cell-induced granule exocytosis of IL-12-activated natural killer cells.

The importance of cell adhesion molecules such as ICAM-1 is emphasized in cell-to-cell interactions that are critical in the generation of effective immune reactions. In this study, the involvement of ICAM-1 in natural killer (NK) cell activities was characterized in IL-12-activated human NK cells. To address the question of whether ligation of ICAM-1 molecules can modulate NK cell cytolytic activities, a 4-h (51)Cr-release assay was performed after pretreatment of NK cells with R6.5 mAb (anti-human ICAM-1 mAb). Ligation of membrane ICAM-1 molecules significantly inhibited IL-12-enhanced NK cytotoxicity against K562, and the pretreatment of neutralizing soluble ICAM-1 with R6.5 mAb blocked this inhibitory effect. The involvement of Ca(2+)-dependent granular exocytosis was evaluated. BLT esterase assay demonstrated that the ligation of ICAM-1 molecules inhibited granular exocytosis of NK cells. Additionally, the ICAM-1-mediated inhibition of Ca(2+) flux in NK cells was detected using Fluo-3AM, while the pretreatment of NK cells with R6.5 mAb did not affect conjugate formation between NK and K562 cells. Collectively, these results suggest that the signals transduced from ICAM-1 molecules might be sufficient to induce inhibitory effects on NK cells.

Antibodies, Monoclonal↗

PubMed2000

Usefulness of triphasic perfusion computed tomography for intravenous thrombolysis with tissue-type plasminogen activator in acute ischemic stroke.

BACKGROUND: Intravenous thrombolysis for acute ischemic stroke has been investigated in several clinical trials without enough information on collateral blood flow and perfusion deficit in the ischemic areas. The therapeutic time window varies from patient to patient depending on these factors. Triphasic perfusion computed tomography (TPCT) can provide this information as reliably as conventional angiography. OBJECTIVE: To assess the safety and efficacy of thrombolysis within 3 or 7 hours of stroke onset according to the extent of perfusion deficit on TPCT. METHODS: In 46 patients with acute middle cerebral artery (MCA) territory stroke, TPCT was performed with power injector-controlled, intravenous administration of contrast media after taking precontrast CT scans. Sequential scans of early, middle, and late phases were performed. The entire procedure took 5 minutes. Depending on collateral blood flow, the perfusion deficit on TPCT was graded as "severe perfusion deficit" or "moderate perfusion deficit." Twenty-nine patients were excluded based on clinical, laboratory, and TPCT findings. Seventeen patients were treated with an intravenous recombinant tissue-type plasminogen activator, 0.9 mg/kg. The 17 treated patients were divided into 2 groups: group 1 with small severe perfusion deficit (</=33% of the presumed MCA territory) and group 2 with medium-sized severe perfusion deficit (>33% but </=50% of the presumed MCA territory). The 13 patients in group 1 were treated within 7 hours of onset and the 4 patients in group 2 were treated within 3 hours. RESULTS: Initial mean National Institutes of Health Stroke Scale score was 12.1 (range, 6.0-20.0) in group 1 and 19.0 (range, 18.0-21. 0) in group 2. The initial score correlated better with the total extent of moderate perfusion deficit and severe perfusion deficit than that of severe perfusion deficit alone. Mean time lapse to thrombolysis was 4.2 hours (range, 1.5-7.0 hours) in group 1 and 2.2 hours (range, 1.9-2.5 hours) in group 2. Eight patients (47%), 7 from group 1 and 1 from group 2, improved by 4 points or more from baseline Stroke Scale score within 24 hours of thrombolysis. Patients with moderate perfusion deficit of 50% or more of MCA territory (n = 4) had a better chance of early improvement than did those (n = 13) with moderate perfusion deficit of less than 50% (4 of 4 vs 4 of 13). No fatal hemorrhage occurred. Only 1 patient (6%) had symptomatic small basal ganglia hemorrhage after thrombolysis. CONCLUSIONS: Thrombolysis can be safely performed within 3 or 7 hours of stroke onset according to the extent of severe perfusion deficit on TPCT. A larger extent of moderate perfusion deficit on TPCT may predict early improvement after thrombolysis.

Adult↗

PubMed2000

Molecular cloning, gene structure, and expression pattern of pig immunoreceptor DAP12.

Natural killer (NK) cells express receptors for MHC class I that contain immunoreceptor tyrosine-based inhibitory motif (ITIM) sequences in their cytoplasmic domain. Whereas these receptors inhibit NK cell cytotoxicity, certain isoforms of these NK receptors (e.g., KIR2DS, CD94/NKG2C, and Ly49D) do not have ITIMs, but associate with DAP12 and activate NK cell function. We cloned pig DAP12 cDNA from a pig peripheral blood lymphocyte (PBL) cDNA library using human DAP12 cDNA as a probe. The length of the pig DAP12 cDNA is 526 bp and contains an open reading frame of 324 bp. It has 79% identity with the human DAP12 cDNA sequence in the coding region and 73% identity with mouse DAP12 cDNA. The predicted polypeptide sequence of pig DAP12 is 108 amino acids, being composed of a 23-amino acid leader, a 14-amino acid extracellular domain, a 24-amino acid transmembrane segment, and a 47-amino acid cytoplasmic region. The amino acid sequence of pig DAP12 has 74% and 71% sequence identity with human DAP12 and mouse DAP12, respectively. Pig DAP12 has a conserved aspartic acid in the transmembrane region, and two conserved cysteine residues in the extracellular domain. It also contains an immunoreceptor tyrosine-based activation motif sequence in the cytoplasmic region. Genomic organization reveals that pig DAP12 consists of five exons and four introns. Southern blot analysis of pig genomic DNA revealed that DAP12 is a single-copy gene. In Northern blot analysis, DAP12 transcripts were detected in spleen, liver, thymus, and lymph node. DAP12 transcripts are expressed not only in PBLs, but also in granulocytes, macrophages, and monocytes.

Adaptor Proteins, Signal Transducing↗

PubMed2000

A comparison of different lead biomarkers in their associations with lead-related symptoms.

OBJECTIVES: To evaluate whether dimercaptosuccinic acid (DMSA) -chelatable lead, an estimate of current bioavailable lead stores, is a better predictor of lead-related symptoms than are other commonly used lead biomarkers. METHODS: A total of 95 male lead workers from three lead industries (one secondary lead smelting facility, one polyvinyl chloridestabilizer manufacturing plant, and one lead-acid storage battery factory), and 13 workers without occupational lead exposure recruited from an occupational health institute, were studied. Blood lead, blood zinc protoporphyrin (ZPP), 4 h DMSA-chelatable lead (after oral administration of 10 mg/kg DMSA), urine lead, and urinary delta-aminolevulinic acid levels were evaluated as predictors of 15 lead-related symptoms, assessed by self-administered questionnaire, with linear and logistic regression controlling for covariates. Total symptoms and symptoms in three categories (gastrointestinal, neuromuscular, and general) were evaluated. RESULTS: The mean (SD) 4 h DMSA-chelatable lead level was 288.7 (167.7) microg, with a range from 32.4 to 789 microg in the 95 lead workers. The mean (SD) in the non-exposed subjects was 23.7 (11.5) microg with a range from 10.5 to 43.5 microg. Blood lead, blood ZPP, and spot urine lead levels ranged from 21.4 to 78.4 microg/dl, 40 to 331 microg/l, and 7.5 to 153.0 micro/l, respectively, in the lead workers, and from 4.0 to 7.2 micro/dl, 27 to 52 microg/l, and 2.9 to 15.5 microg/l in the non-exposed controls, respectively. The overall mean symptom score (SD), derived as the sum of 0 or 1 point for absence or presence of 15 symptoms, of the lead workers was 3.7 (2.0), compared to 1.2 (1.5) for the non-exposed workers. DMSA-chelatable lead was the best predictor of symptom scores in both crude and adjusted analyses, compared with the other biomarkers. Lead workers with DMSA-chelatable lead values greater than the median (260.5 microg) were 6.2 times more likely to have frequent tingling or numbness of the arms or legs and 3.3 times more likely to have muscle pain than subjects with lower chelatable lead values. Three symptoms (tingling or numbness of arm or leg, muscle pain, and feeling irritation at the slightest disturbance) evidenced a dose-dependent relationship with DMSA-chelatable lead levels. CONCLUSIONS: DMSA-chelatable lead was found to be the best predictor of lead-related symptoms, particularly of both total symptom scores and neuromuscular symptoms, than were the other other lead biomarkers.

Adult↗

PubMed2000

Dehydroepiandrosterone and melatonin prevent Bacillus anthracis lethal toxin-induced TNF production in macrophages.

The lethal toxin of Bacillus anthracis, which is composed of two separate proteinaceous exotoxins, namely protective antigen and lethal factor, is central to the pathogenesis of anthrax. Low levels of this toxin are known to induce release of cytokines such as tumor necrosis factor alpha (TNF-alpha). In the present study we investigated the effect of dehydroepiandrosterone (DHEA), melatonin (MLT), or DHEA + MLT on production of lethal toxin-induced TNF-alpha in mouse peritoneal macrophages. We found that treatment with DHEA significantly inhibited the TNF-alpha production caused by anthrax lethal toxin. Exposure of MLT to anthrax lethal toxin-treated macrophages also decreased the release of TNF-alpha to the extracellular medium as compared to the control. However, combined use of DHEA and MLT also inhibited TNF-alpha release, but not more than single therapies. These results suggest that DHEA and MLT may have a therapeutic role in reducing the increased cytokine production induced by anthrax lethal toxin.

Adjuvants, Immunologic↗

PubMed2000

Intracellular calcium antagonist protects cultured peritoneal macrophages against anthrax lethal toxin-induced cytotoxicity.

The lethal toxin of Bacillus anthracis is central to the pathogenesis of anthrax. Using primary cultures of mouse peritoneal macrophages, we have demonstrated that intracellular calcium release inhibitors protect against anthrax lethal toxin-induced cytotoxicity. The cytolytic effect of anthrax lethal toxin was markedly reduced by dantrolene, an inhibitor of calcium release from intracellular calcium stores. Pretreatment of macrophages with cyclosporin A, which has been shown to be a potent inhibitor of calcium release from mitochondria, also protected cells against cytotoxicity. These results indicate that calcium release from intracellular store may be an essential step for the propagation of anthrax lethal toxin-induced cell damage in macrophages. Thus our findings suggest that dantrolene, cyclosporin A, and possibly other drugs affecting intracellular calcium pools might be effectively preventing the toxicity from anthrax lethal toxin.

Animals↗

PubMed2000

Overexpression of c-H-ras p21 is correlated with vascular endothelial growth factor expression and neovascularization in advanced gastric carcinoma.

BACKGROUND AND AIMS: ras Gene and its product (p21) have been reported to be associated with vascular endothelial growth factor (VEGF), which is one of the most important angiogenic factors, and tumor-associated angiogenesis. We tried to evaluate the correlation between the expression of c-H-ras gene product p21 and angiogenesis in advanced gastric carcinoma. METHODS: Immunohistochemical expression of c-H-ras p21 and VEGF was examined in 49 advanced gastric adenocarcinomas. In addition, double immunohistochemical staining was performed using anti-CD34 and anti-Ki-67 antibodies, and the intratumoral microvessel densities and their endothelial proliferative labeling indices were then counted to evaluate the degree of angiogenesis. RESULTS: The expression of c-H-ras p21 was demonstrated in 43 out of 49 gastric adenocarcinomas (87.8%). It did not correlate with histologic type, depth of invasion or metastasis. However, the degree of c-H-ras p21 expression was correlated with VEGF. In addition, the degree of c-H-ras p21 expression was correlated with increased intratumoral microvascular density and endothelial proliferative activity. CONCLUSIONS: We suggest that c-H-ras oncogene product p21 contributes to the upregulation of tumor-associated angiogenesis by the increased production of VEGF in advanced gastric carcinomas. Therefore, treatment involving the targeting of ras oncogene could inhibit solid tumor growth by suppressing tumor-associated angiogenesis.

Adenocarcinoma↗

PubMed2000

Ciliated foregut cyst of the gallbladder: a case report and review of the literature.

A case is presented of a ciliated cyst of the gallbladder in a 36-year-old Korean woman which was incidentally found on ultrasonographic study. A cystic mass measuring 1.5 x 1 x 1 cm was found in the fundus of the gallbladder. The cyst was unilocular and intramural without communication to the lumen. Microscopically, the cyst wall was lined by a single layer of pseudostratified, ciliated, columnar epithelium and goblet cells with underlying smooth muscle layers. This was considered to be the cyst arising from the embryonic foregut and showing differentiation toward respiratory structures. The term 'ciliated foregut cyst of the gallbladder' is suggested here.

Adult↗