Clinical Findings of Sepsis-Associated Cholestasis in the Neonates / 소아과

PURPOSE: Bacterial endotoxins or inflammatory cytokines are known to be important causes of cholestasis in patients with systemic infections such as sepsis. This study was undertaken to investigate the clinical features of cholestasis in newborn infants with sepsis. METHODS: This study included 17 neonates with cholestasis diagnosed at the time of septicemia who had no previous history of cholestasis. Cholestasis was defined as a serum level of direct bilirubin greater than 2 mg/dL. Clinical findings such as gestational age, birth weight, onset time of cholestasis, bilirubin level, underlying sepsis and prognosis were evaluated. RESULTS: Sepsis-associated cholestasis developed in 17(14%) of the 121 cases. Sixteen(94%) of 17 patients were premature infants, 15(88%) were on parenteral nutrition (PN) at the time of septicemia, and 2(12%) of them showed hepatic dysfunction. Incidence of sepsis-associated cholestasis was significantly higher in infants with K. pneumoniae sepsis than those with other bacterial or candida sepsis(P<0.05). Sepsis and cholestasis developed at 26+/-11, 28+/-11 days of life respectively and the mean total/direct bilirubin level was 5.0/2.7 mg/dL. Two infants who no had PN at the time of septicemia had prolonged starvation and cholestasis of 7 and 15 days, respectively. The mortality rate of the patient group was similar to that of sepsis patients without cholestasis. CONCLUSION: Sepsis-associated cholestasis in neonates was commonly developed in Gram (-) infection, especially K. pneumoniae. Sepsis should be considered in the causes of cholestasis in neonates, in addition to prolonged starvation and PN.

A Case of Right Intrathoracic Kidney with Complex Cardiac Anomalies / 대한주산의학회잡지

Intrathoracic kidneys are rare developmental anomalies and represent less than 5% of all congenital kidney ectopia. Ectopic intrathoracic kidneys are usually asymptomatic and have normal renal function. This disease occurs more frequently in males and on the left side. We report a case of right intrathoracic kidney with congenital complex cardiac anomalies such as single atrium, patent ductus arteriosus and tricuspid regurgitation.

Direct Cytotoxicity of Interferon-gamma (IFN-gamma) on Renal Cell Carcinoma Cell Line / 대한비뇨기과학회지

No abstract available.

Fas-induced Apoptosis in Renal Cell Carcinoma Cell Line by Interferon-gamma (IFN-gamma) Treatment / 대한비뇨기과학회지

No abstract available.

The Change of Cytokines by Risperidone in Patients with Schizophrenia / 신경정신의학

OBJECT: This study was carried out to evaluate immunologic difference between baseline and after 4 weeks drug treatment with atypical antipsychotics (rispreidone) by measurement of serum concentration of 6 cytokines. METHODS: The subjets were composed of 25 patients who are admitted at Dajeon St's Marys hospital of psychiatry department and diagnosed as schizophrenia by DSM-IV diagnositc criteria. We measured serum IL-1beta, IL-2, IL-6, IL-12, INF-gamma, TNF-alpha concenatrations by quantitative ELISA method using ELISA kit (Endogen Inc., Woburn, MA, USA).The two psyciatrists performed PANSS examination between baseline and after 4 weeks risperidone treatments. RESULTS: The serum level of IL-12 was increased significantly after medication of 4 weeks and the serum concentration of IFN-gamma showed the tendency of decreasement but not significant. The serum level of the other cytokines showed no significant change. CONCLUSIONS: We spectulate that the increasement of IL-12 may contribute to role of activation of immune response by treatment of antipsychotic medication (risperidone). This study is first trial of IL-12 study in neuropsychiatric field and IL-12 which play important role of immune response becomes interesting subjects in immune research.

Construction of MAGE - 3 Expressing Plasmid for Development of DNA Vaccine Encoding MAGE - 3 Cancer Antigen / 대한암학회지

PURPOSE: The spectrum of melanoma antigen gene (MAGE)-expressing tumor is very wide and the gene of MAGE express antigens that are targets for specific recognition by cytotoxic T lymphocytes derived from tumor-bearing patients. All of these characteristics represent MAGE as tumor vaccine can be useful for cancer prevention or treatment. Here, we detected MAGE-3 gene expression in cancer cell lines and evaluated recombinant MAGE-3 protein producibility of MAGE plasmid to develope MAGE DNA vaccine. MATERIALS AND METHODS: MAGE-3 gene expression of cancer cell lines was evaluated by reverse transcription-polymerase chanin reaction (RT-PCR). Two kinds of MAGE-3 expressing plasmids were constructed and their MAGE-3 protein producibility was evaluated by immunohistochemistry and immunoblotting using monoclonal anti-MAGE-3 antibody. RESULTS: Among 13 cell lines, SNU484, AMC-HN-3, AMC-HN-4, AMC-HN-7, HeLa, NCI H1703 and HT29 expressed MAGE-3 mRNA. In order to make MAGE plasmid, cDNA that showed 100% DNA homology with MAGE-3 gene was cloned into pcDNA 3 plasmid and pSecTag plasmid. Intracytoplasmic and secretory recombinant MAGE-3 was produced by MAGE-3 containing pcDNA 3 plasmid and pSecTag plasmid, respectively. CONCLUSION: In this study, we showed high expression frequency of MAGE-3 in cancer cell line, and established two kinds of plasmid that produce recombinant MAGE-3 in cell lines. We expect these plasmids will be used in cancer treatment or MAGE-3 function study in future.

Induction of Humoral Immue Response in Mice by Wild and Mutant Type HBV Core DNA Vaccination / 대한면역학회지

No abstract available.

Applicability of Genes of Cancer-associated Testis Antigens in Diagnosis of Cancer / 대한면역학회지

Genes of cancer-associated testis antigens (CTAs) are expressed in various cancer tissues. In order to use CTAs as cancer diagnosis marker, we developed molecular method for detection of CTAs transcripts in tissue. In order to know the applicability of DNA of cancer-associated testis antigens (CTAs) on cancer diagnosis, molecular diagnostic methods for detection of gene expression of melanoma antigen gene (MAGE), GAGE, and B melanoma antigen (BAGE) was studied. After comparing DNA sequences of CTAs, S1/AS1 and S2/AS2, GAGE-S/ GAGE-AS, and BAGE-S/BAGE-AS primers were designed for the detection of MAGEs, GAGEs and BAGEs, respectively. The gene expression of CTAs in cancer cell lines, head and neck cancer tissues, ovary cancer tissue, and peritoneal cells of gastric cancer patients were investigated by reverse transcription-polymerase chain reaction (RT-PCR) using these primers. The MAGEs, GAGEs and BAGE genes were expressed in 8/8 (100%), 5/8 (62.5%) and 1/8 (12.5%) of head and neck cancer tissues, respectively. The gene expression of MAGEs were also detected in 8/10 (80%) of ovary cancer tissues and in 9/10 (90%) of peritoneal cells of gastric cancer patients in RT-PCR test using S1/AS1 primers. The results of this study suggest that molecular diagnosis method using CTAs genes, especially RT-PCR using S1/AS1 primer combination, is useful for diagnosis of cancer and it will be used for the prediction of cancer progression or regression and metastasis in future.

LPS-induced Chemokine Gene Expression in Mesangial Cell / 대한신장학회잡지

This study was designed to investigate the mole- cular mechanism of chemokine induction by lipopoly-saccharide(LPS) of E. coli. Chemokine gene expression was evaluated by the reverse transcriptase-polymerase chain reaction(RT-PCR) assay using RNAs isolated either from kidneys of LPS-injected inice or from the mesangial cells stimulated with LPS, IFN-r or TNF-a. LPS was shown to induce interferon gamma(IFN- 7 ) inducible protein 10 (IP-10) and monokine induced by interferon gamma (MIG) in kidney. IP-10 gene expression was induced by LPS and IFN-r, but MIG gene expression was induced by IFN-r in mesangial cell. Chemokines induced by LPS increased splenocyte migration. Sodium salicylate, wortmanin and piperazine blocked LPS mediated chemokine induction suggesting the activation of nuclear factor-a B pathway. It is concluded from this study that mesangial cells are the target of LPS in the renal failure resulting from the systemic infections. LPS induces chemokines directly and/or indirectly in the mesan- gial cells, and these chemokines may associated with renal inflammation.

DNA-mediated immunization of mice with plasmid encoding HBs antigen

In order to develop an experimental DNA vaccine for the prevention and treatment of hepatitis B virus infection, hepatitis B virus surface antigen (HBsAg) DNA was subcloned into an E. coli-eukaryotic cell shuttle vector and was expressed in the Baculovirus expression system. Intramuscular, intradermal, and intraperitoneal injections of 30 microg of the plasmid DNA expressing HBsAg induced humoral and cellular immune responses in ICR mice. The first IgG antibodies were detected after ten days and specific IgG antibody titers peaked after two months of a single intramuscular DNA injection. Anti-HBs antibody titers gradually increased and peaked at four months following intradermal DNA injection, and in case of intraperitoneal injection they peaked at seven months. Generation of HBs-specific helper T lymphocytes was also investigated through the production of interleukin-2 by T helper cells. Boosting effects of HBs DNA were investigated without much results. In general, DNA-mediated HBs immunization induced humoral and cellular immune responses in mice that appears to simulate immune responses in human during the course of HBV vaccination.

Detection of Chemokine Gene Expression Induced by IL-12/IL-2 in Renca Tumor / 대한면역학회지

In order to evaluate antitumor rnechanisms of interleukin (IL)-12/IL-2 that has been shown significant tumor suppressive activity on established primary and metastatic Renca tumor, we studied chemokine gene expression induced by direct action of IL- 12/IL-2 or cytokine cascade. IL-12/IL-2 induced gene expression of interferon gamma (IFN-r) and granulocyte monocyte-colony stimulating factor (GM-CSF) in splenocytes, and it induced gene expression of monokine induced by IFN-r (Mig), interferon inducible protein 10 (IP- 10), SDF-1, macrophage inflammatory protein (MIP)-1a, MIP-1B, MIP-2, monocyte chemotactic protein (MCP)-1, and Rantes in tumor mass. However IL-12/IL-2 could not induce these chemokines in tumor mass of GKO mice and Renca cell in vitro. IL- 12 also did not increased chemokine gene expression in Renca cell in vitro, but IFN-r induced gene expression of Mig, IP-10, MCP-1 in Renca cell in vitro. In the chemotaxis assay, culture supernatant of Renca cell stimulated with IFN-r increased splenocyte migration in vitro. All these data suggest IL-12/IL-2 can induce IFN-r-chemokine cascade in tumor mass, and Mig, IP-10, MCP-1 produced from tumor cell may play an important role for initial immune cell migration into tumor mass.

Induction of Dendritic Cell and Cytokine Gene Expression by In situ Delivery of Flt3 Ligand Plasmid / 대한면역학회지

Dendritic cell (DC)s are protessional antigen presenting cells and they have been used for antitumor immunotherapy or cell vaccines. However therapy using DC is restricted because the number of DC available from tissue is very low. Flt3 ligand (FL) has been known as a hematopoietic growth factor that increases proliferation of hematopoietic stem cells and progenitor cells, and recently it showed inducibility of dendritic cell (DC)s and signiticant antitumor effects in vivo. Thus FL will be frequently used for DC induction and antitumor immunotherapy in future. Here we constructed FL plasmid and studied its in vivo effect. FL plasmids were made by cloning of partial FL cDNA into pcDNA3 plasmid, and gene expression and protein producibility of FL plasmid were confirmed in Renca cells transfected with FL plasmid. Mice were injected with FL plasmid (100ug/mouse) three times and 20 days later mouse spleens were harvested for staining and RT-PCR. There were lots of blastogenic cells in the spleen of mice treated with FL plasmid. FL plasmid also induced DEC205, IL-12 and GM-CSF gene expression in mouse splenocyte. All these data suggest FL plasmid may be used for induction of DC and antitumor therapy as DNA adjuvant.

Study on the Production and Function of Macrophage Migration Inhibitory Factor ( MIF ) : Effect of Recombinant MIF and MIF cDNA on the Induction of Cytokine mRNA / 대한면역학회지

In order to study the functions of migration inhibitory factor (MIF) as macrophage activating cytokine and to investigate the possibility of MIF cDNA as gene therapeutic agent or adjuvant, we produced recombinant MIF (rMIF), anti-MIF antibody and pcDNA I plasmid containing mMIF cDNA (mMIF plasmid). We have investigated the effects of recombinant mMIF or mMIF plasmid on the expression of immune response-related gene in the mouse peritoneal macrophage or splenocyte. Recombinant mMIF produced by Baculovirus expression system was biologically active; it increased mRNA expression of tumor necrosis factor (TNF)-a, Interleukin (IL)-1, IL-6, granulocyte monocyte-colony stimulating factor (GM-CSF), nitric oxide synthase (NOS), Fas and Bcl-x when applied to the cultures of mouse peritoneal macrophage. Anti-mMIF antibody blocked these effects of mMIF on macrophage. Plasmid DNA carrying MIF cDNA inoculated into mouse peritoneal cavity also increased mRNA transcriptions from TNF, IL-1, IL-6, IL-12, GM-CSF, NOS genes of peritoneal macrophage. It enhanced proliferation of splenocyte stimulated with phorbol myristate acetate and IL-2 mRNA expression of splenocytes. Frorn these results, we conclude that rMIF is a strong macrophage activating factor and especially MIF plasmid can be used as an immune potentiating DNA drug in gene therapy for cancer or DNA adjuvant in vaccination in future.