Biomedical subjects

D W Shin

Publications and source records attributed to D W Shin.

At least 19 recordsLinked to original sources

PubMed2001

Early postoperative intraperitoneal chemotherapy with mitomycin C, 5-fluorouracil and cisplatin for advanced gastric cancer.

OBJECTIVE: The long-term survival of patients who undergo surgery for stage IV gastric cancer is poor, due to metastatic spread of the tumor. Intraperitoneal chemotherapy (IPT) as a possible treatment for peritoneal dissemination has been investigated in a number of different tumors. The aim of this study was to investigate the toxicity and impact of early postoperative IPT on the survival of patients with advanced gastric cancer. METHODS: Between 1993 and 1997, a total of 91 patients with stage IV gastric cancer who underwent potentially curative or palliative resection received intraperitoneal mitomycin C before closure of the abdominal wound. 5-Fluorouracil and cisplatin were administered intraperitoneally on postoperative days 1-4, and this was repeated at 4-week intervals. RESULTS: All patients received a median of 3 IPT perfusions. There were 24 (26.4%) postoperative complications and 1 (1.1%) mortality. The most frequent hematologic toxicity (grade 3-4) was leukopenia. The major nonhematologic toxicities (grade 3-4) were emesis and nephrotoxicity. After a median follow-up period of 26 months, 14 patients remain alive without evidence of recurrence, whereas 75 patients died due to recurrence or progression of disease. The median survival period for all 91 patients was 15.4 months. When survival according to the residual tumor was analyzed, median survival was 36.0 months in the R0 (curative resection) group, 20.6 months in the R1 group (margins of resected specimens showing microscopic residual tumor or diameter of each residual tumor less than 3 mm) and 9.0 months in the R2 group (macroscopic residual tumor larger than 3 mm) (p < 0.001). CONCLUSIONS: IPT was found to be safe, and it appears to improve the prognosis in patients with minimal residual tumors. However, complete cytoreductive surgery is mandatory for achieving the beneficial effect of IPT.

Adult↗

PubMed2001

Effects of specific monoclonal antibodies to dense granular proteins on the invasion of Toxoplasma gondii in vitro and in vivo.

Although some reports have been published on the protective effect of antibodies to Toxoplasma gondii surface membrane proteins, few address the inhibitory activity of antibodies to dense granular proteins (GRA proteins). Therefore, we performed a series of experiments to evaluate the inhibitory effects of monoclonal antibodies (mAbs) to GRA proteins (GRA2, 28 kDa; GRA6, 32 kDa) and surface membrane protein (SAG1, 30 kDa) on the invasion of T. gondii tachyzoites. Passive immunization of mice with one of three mAbs following challenge with a lethal dose of tachyzoites significantly increased survival compared with results for mice treated with control ascites. The survival times of mice challenged with tachyzoites pretreated with anti-GRA6 or anti-SAG1 mAb were significantly increased. Mice that received tachyzoites pretreated with both mAb and complement had longer survival times than those that received tachyzoites pretreated with mAb alone. Invasion of tachyzoites into fibroblasts and macrophages was significantly inhibited in the anti-GRA2, anti-GRA6 or anti-SAG1 mAb pretreated group. Pretreatment with mAb and complement inhibited invasion of tachyzoites in both fibroblasts and macrophages. These results suggest that specific antibodies to dense-granule molecules may be useful for controlling infection with T. gondii.

Animals↗

PubMed2000

The asp-rich region at the carboxyl-terminus of calsequestrin binds to Ca(2+) and interacts with triadin.

Calsequestrin (CSQ) is a high capacity Ca(2+) binding protein in the junctional sarcoplasmic reticulum of striated muscles, and has been shown to regulate the ryanodine receptor (RyR) through triadin and junctin. In order to identify the functional roles of specific regions on CSQ, several CSQ deletion mutants were prepared by molecular cloning and Escherichia coli expression. 45Ca(2+) overlay assay using a native gel system revealed that the major Ca(2+) binding motif of CSQ resides in the asp-rich region (amino acids 354-367). In an in vitro binding assay using a glutathione-S-transferase affinity column, the interaction between CSQ and triadin was found to be Ca(2+)-dependent, and the site of interaction was confined to the asp-rich region of CSQ. Our results suggest that the asp-rich region of CSQ could participate in the RyR-mediated Ca(2+) release process by offering a direct binding site to luminal Ca(2+) as well as triadin.

Animals↗

PubMed2000

Calcineurin regulates ryanodine receptor/Ca(2+)-release channels in rat heart.

The present study was undertaken to examine the physical and physiological interaction of protein phosphatase 2B, calcineurin, with the ryanodine receptor (RyR) in rat cardiac tissue and neonatal cardiomyocytes. The presence of calcineurin, the RyR and FK506-binding protein (FKBP)12.6 in rat cardiac sarcoplasmic reticulum (SR) was identified by Western blot analysis. The possible interactions between calcineurin, the RyR and FKBP12.6 were further studied by co-immunoprecipitation using CHAPS-solubilized cardiac-membrane fractions (CSMFs) or SR preparations. Physical interactions between the RyR and calcineurin were found in the CSMF in the presence of added 100 microM Ca(2+); however, the interactions were interrupted in the presence of 20 mM EGTA, 1 microM rapamycin or 1 microM FK506, suggesting that the interaction is Ca(2+)-dependent, and is mediated by FKBP12.6. The Ca(2+)-dependent interaction between FKBP12.6 and the RyR was also found by co-immunoprecipitation. Effects of calcineurin inhibitors were tested on neonatal-rat-heart cardiomyocytes. Treatment of neonatal cardiomyocytes with 20 microM deltamethrin, 10 microM cyclosporin A (CsA), or 10 mciroM FK506 led to Ca(2+) oscillations in originally quiescent cardiomyocytes. Preincubation of cardiomyocytes with 20 microM rapamycin which dissociates FKBP12.6 from the RyR, evoked Ca(2+) oscillations, probably due to the leakiness of the RyR. However, Ca(2+) oscillations by rapamycin were not further affected by 10 microM CsA or 10 mciroM deltamethrin, suggesting that only RyR-associated calcineurin could regulate the channel activities. In spontaneously Ca(2+)-oscillating cardiomyocytes, CsA or FK506 treatments increased the frequency of oscillations. In 10 microM ryanodine-treated cardiomyocytes, CsA failed to induce Ca(2+) oscillations. These data show evidence that calcineurin associated with the RyR could modulate Ca(2+) release in rat heart.

Animals↗

PubMed2000

Regulation of ATP-induced calcium release in COS-7 cells by calcineurin.

Experiments were conducted to examine the role of calcineurin in regulating Ca(2+) fluxes in mammalian cells. In COS-7 cells, increasing concentrations (1-10 microM) of ATP triggered intracellular Ca(2+) release in a dose-dependent manner. Treatment of the cells with calcineurin inhibitors such as cyclosporin A (CsA), deltamethrin and FK506 resulted in an enhancement of ATP-induced intracellular Ca(2+) release. Measurement of calcineurin-specific phosphatase activity in vitro demonstrated a high level of endogenous calcineurin activities in COS-7 cells, which was effectively inhibited by the addition of deltamethrin or CsA. The expression of constitutively active calcineurin (CnADeltaCaMAI) inhibited the ATP-induced increase in intracellular Ca(2+) concentration ([Ca(2+)](i)), in both the presence and the absence of extracellular Ca(2+). These results suggest that the constitutively active calcineurin prevented Ca(2+) release from the intracellular stores. In the calcineurin-transfected cells, treatment with CsA restored the calcineurin-mediated inhibition of intracellular Ca(2+) release. Protein kinase C-mediated phosphorylation of Ins(1,4,5)P(3) receptor [Ins(1,4,5)P(3)R] was partly inhibited by the extracts prepared from the vector-transfected cells and completely inhibited by those from cells co-transfected with CnADeltaCaMAI and calcineurin B. On the addition of 10 microM CsA, the inhibited phosphorylation of Ins(1,4,5)P(3)R was restored in both the vector-transfected cells and the calcineurin-transfected cells. These results show direct evidence that Ca(2+) release through Ins(1, 4,5)P(3)R in COS-7 cells is regulated by calcineurin-mediated dephosphorylation.

Adenosine Triphosphate↗

PubMed2000

Identification of cytoskeletal markers for the different microvilli and cell types of the rat vomeronasal sensory epithelium.

The vomeronasal organ (VNO) of the mammal nose is specialized to detect pheromones. The presumed site of the chemosensory signal transduction of pheromones is the vomeronasal brush border of the VNO sensory epithelium, which has been shown to contain two different sets of microvilli: (i) the tall microvilli of supporting cells and (ii) the short microvilli of the chemoreceptive VNO neurons that branch and intermingle with the basal portions of the longer supporting cell microvilli. A key problem when studying the subcellular distribution of possible VNO signal transduction molecules at the light microscope level is the clear discrimination of immunosignals derived from dendritic microvilli of the VNO neurons and surrounding supporting cell structures. In the present study we therefore looked for cytoskeletal marker proteins, that might help to distinguish at the light microscope level between the two sets of microvilli. By immunostaining we found that the VNO dendritic microvilli can be selectively labelled with antibodies to the calcium-sensitive actin filament-bundling protein villin, whereas supporting cell microvilli contain the actin filament cross-linking protein fimbrin, but not villin. Useful cytoplasmic marker molecules for cellular discrimination were cytokeratin 18 for supporting cells and beta-tubulin for dendrites of VNO neurons. A further finding was that the non-sensory epithelium of the rat VNO contains brush cells, a cell type that appears to be involved in certain aspects of chemoreception in the gut. Brush cells or other structures of the vomeronasal brush border did not contain alpha-gustducin.

Actins↗

PubMed2000

Recurrence following curative resection for gastric carcinoma.

BACKGROUND: The diagnosis and treatment of recurrent gastric cancer remains difficult. The aim of this study was to determine the risk factors for recurrence of gastric cancer and the prognosis for these patients. METHODS: Of 2328 patients who underwent curative resection for gastric cancer from 1987 to 1995, 508 whose recurrence was confirmed by clinical examination or reoperation were studied retrospectively. The risk factors that determined the recurrence patterns and timing were investigated by univariate and multivariate analysis. RESULTS: The mean time to recurrence was 21.8 months and peritoneal recurrence was the most frequent (45.9 per cent). Logistic regression analysis showed that serosal invasion and lymph node metastasis were risk factors for all recurrence patterns and early recurrence (at 24 months or less). In addition, independent risk factors involved in each recurrence pattern included younger age, infiltrative or diffuse type, undifferentiated tumour and total gastrectomy for peritoneal recurrence; older age and larger tumour size for disseminated, haematogenous recurrence; and older age, larger tumour size, infiltrative or diffuse type, proximally located tumour and subtotal gastrectomy for locoregional recurrence. Other risk factors for early recurrence were infiltrative or diffuse type and total gastrectomy. Reoperation for cure was possible in only 19 patients and the mean survival time after conservative treatment or palliative operation was less than 12 months. CONCLUSION: The risk factors for each recurrence pattern and timing of gastric cancer can be predicted by the clinicopathological features of the primary tumour. Since the results of treatment remain dismal, studies of perioperative adjuvant therapy in an attempt to reduce recurrence are warranted.

Female↗

PubMed2000

Sequential analysis of cell differentials and IFN-gamma production of splenocytes from mice infected with Toxoplasma gondii.

To assess the relationship between the changes of cellular components and the production of Th1 cytokine in the immune tissue, inbred C57BL/6 mice were orally infected with 40 cysts of 76K strain of Toxoplasma gondii. The sequential change of cell differentials and IFN-gamma production of splenocytes were analyzed by Diff-Quik stain and RT-PCR. There were no significant proportional changes of cellular components of splenocytes until day 4 postinfection (PI) as compared to those of day 0, and the relative percentage of macrophages and neutrophils/eosinophils increased significantly (p < 0.01) thereafter. The expression of IFN-gamma mRNA of CD3- cells was observed from day 1 PI at a low level. However, IFN-gamma production of CD3+ cells increased significantly from day 4 PI (p < 0.01) which progressively increased thereafter. These findings provide the relative percentages of granulocytes and macrophages were increased in conjunction with increase of total number of splenocytes after oral infection with T. gondii in the susceptible murine hosts, and lymphocytes were the major cellular components and the important source of IFN-gamma.

Animals↗

PubMed2000

Seroepidemiological study of Toxoplasma gondii infection in the rural area Okcheon-gun, Korea.

There have been some reports about the prevalence of anti-Toxoplasma gondii antibody among Koreans, and most of all data were taken from patients visiting hospitals. However, the epidemiological data of the community-based study in Korea are rare. This study was performed to evaluate the seroprevalence of toxoplasmosis among the inhabitants of the rural area Okcheon-gun, Korea. A total of 1,109 serum samples (499 males, 610 females) were examined for the IgG antibodies by ELISA. To set up the cut-off point for ELISA, we used a commercial latex agglutination (LA) kit. The sensitivity and specificity of ELISA against LA test were 89.5%, and 98.6% respectively. Among 1,109 sera, 6.9% showed seropositivity by ELISA. The positive rates of males and females were 6.0% and 7.2%, respectively. However, there were no significant differences between sexes. Comparing the age groups, the highest seropositive rate showed in the seventies or higher, and their rates had a tendency to increase with age (0.05 < p < 0.3). These results revealed that the seroprevalence of toxoplasmosis in rural inhabitants is similar to previous reports in Korea; however we need further investigation to clarify the prevalence of toxoplasmosis in the general population.

Adult↗

PubMed2000

[History of medical ethics in Korea: focused on analysis of medical codes and covenants].

This article deals with the emergence of the codes of medical ethics and their change in Korean history. The modernized medical codes or covenants by the group of medical doctors has been made from the mid-twentieth century, although Korea has a long tradition of medical ethics, so called the Confucian medical ethics, Insul or Uido which were taken on very strong paternalistic characters. The history of the codes of medical ethics in contemporary Korea showed several revisions in 1961, 1965, 1979, and 1997 since the first establishment in 1955. Changes of political circumstances, the cultural level of the people, medical care system, and medical power leaded to the revisions. Throughout the revisions the codes or covenants of medical ethics in Korea has changed from simple translations of the codes by the World Medical Association and the American Medical Association to the reflexes of domestic medical situations; from the ones based on paternalistic doctor-patient relationship to more democratic ones; from the ones that only medical ethics were expressed to the ones that bioethics was expressed too.

Ethics, Medical↗

PubMed1999

Functional and quantitative analysis of splenic T cell immune responses following oral toxoplasma gondii infection in mice.

Functional and quantitative analysis of splenic T cell immune responses following oral Toxoplasma gondii infection in mice. Experimental Parasitology 91, 212-221. Immunity to Toxoplasma gondii is mediated primarily by the host T cell response. Although there is considerable information regarding host immunity following intraperitoneal infection with tachyzoites, little information is available regarding naturally acquired infection following peroral infection with bradyzoites. In this study, a sequential quantitative analysis of the cell-mediated immune response was performed at the single cell level. To assess the kinetics of this response and parasitic loads, inbred mice were orally infected with the 76K strain bradyzoites of T. gondii. Within 24 h of infection, follicular hyperplasia followed by infiltration with histiocytes, macrophages, and apoptotic bodies was observed in the spleens of infected mice. T. gondii were detected from day 1, and counts increased gradually during the experimental period. Splenocyte DNA synthesis to antigen and mitogen was severely suppressed at days 7 and 10. The percentages of NK1.1(+) or delta gamma T cells were increased from day 1, whereas CD4(+) and CD8alpha+ T cells were signficantly increased after day 7 postinfection. CD25 expression and intracellular IFN-gamma production increased in NK1.1(+) cells on day 1 and by all other T cell subsets after day 4. Intracellular IL-4 did not increase until day 7, and IL-10 production was increased in all T cell subsets after day 4. Together, these findings indicate that oral infection with T. gondii stimulates a strong cellular immune response that appears to polarize toward an early Th1 response. However, within 7 days, a strong immune Th2 regulatory response as well as high parasitic loads can be observed, with a reduction in lymphoproliferation to mitogen stimulation, increased production of IL-4 and IL-10, and evidence of T cell apoptosis in the splenic immune compartment.

Animals↗

PubMed1999

Crystallization and preliminary X-ray crystallographic studies of the D2 region of the skeletal muscle ryanodine receptor.

The N-terminal portion (amino acids 1303-1367) of the type 1 ryanodine receptor D2 region is thought to be critical for excitation-contraction coupling in skeletal muscle. A segment of the D2 region (amino acids 1317-1355) was expressed as a glutathione S-transferase fusion protein (GST-D2) and then crystallized at room temperature using ammonium sulfate as precipitant. Using a newly developed cryo-soaking method, complete native data sets were measured to a resolution of 2.2 A using synchrotron radiation. The crystal was found to be hexagonal, belonging to space group P6(3)22, with unit-cell parameters a = b = 116.1, c = 77.9 A.

Animals↗

PubMed1999

Clinicopathologic characteristics of mucinous gastric adenocarcinoma.

There has been considerable controversy over the prognosis of mucinous gastric adenocarcinoma (MGC). In this study we analyzed the clinicopathologic differences between MGC and non-mucinous gastric carcinoma (NMGC). In addition, the relationship between mucin content and other clinicopathologic variables, including prognosis in MGC, was also investigated. We reviewed 2118 patients with pathologically-confirmed gastric cancer who underwent gastrectomy at the Department of Surgery, Yonsei University College of Medicine, during the period between Jan. 1987 and Dec. 1993. Among them, 130 patients had gastric carcinoma with extracellular mucin (MGC) and 1988 patients had gastric carcinoma without extracellular mucin (NMGC). We placed the MGC patients into two groups according to mucin content: mucin content involving over 50% of the tumor (dominant type, n = 94) and mucin content involving less than 50% of the tumor area (partial type, n = 36). The results were as follows: MGC was more common in males than NMGC. The size of the tumor in MGC (mean 5.3 cm) was larger than that of NMGC (mean 4.4 cm). The patients with MGC had a higher incidence of Borrmann type IV (MGC: 16.1%, NMGC: 9.9%), more frequent serosal invasion (MGC: 75.4%, NMGC: 48.6%), lymph-node metastasis (MGC: 75.4%, NMGC: 50.7%), and peritoneal metastasis (MGC: 10.0%, NMGC: 3.5%) than patients with NMGC. The patients with MGC were more advanced in stage at the time of diagnosis and had a worse overall 10-year survival rate (44.9%) than patients with NMGC (54.7%). However, the 10-year survival rate according to the stage of MGC was similar to that of NMGC. There were no significant differences between the mucin content and other pathologic variables, including prognosis, i.e. similar biologic behavior between dominant type MGC and partial type MGC. In conclusion, we suggest that MGC was more frequently diagnosed in advanced stage than NMGC with a poorer prognosis and that it is reasonable to consider the carcinoma with mucin content involving more than 30% of the tumor area as MGC.

Adenocarcinoma↗

PubMed1998

Cerebral perfusion impairment in a patient with toluene abuse.

We report the case of a 17-yr-old man diagnosed as a toluene abuser. He had an 8-mo history of toluene inhalation exposure and was admitted to this hospital with symptoms of auditory and visual hallucination. Magnetic resonance imaging (MRI) revealed no structural abnormalities both on T1- and T2-weighted images, whereas SPECT using 99mTc-ethyl cysteinate dimer (ECD) showed multifocally decreased perfusion in the cerebral cortex, basal ganglia and thalami. Our case indicates that SPECT detects early central nervous system injury from toluene inhalation even when neurological examination and neuroanatomic imaging such as MRI are normal.

Adolescent↗

PubMed1998

A generalized estimating equations approach for testing ordered group effects with repeated measurements.

In repeated measures studies, we are often interested in comparing group effects in which groups are associated with a certain order relation. We propose testing procedures for ordered group effects using the generalized estimating equations (GEE) approach of Liang and Zeger (1986, Biometrika 73, 13-22). The order-constrained GEE estimators of group effects are approximated by the isotonic regression of the unconstrained GEE estimators. Based on these constrained estimators, we construct test statistics for detecting ordered group effects. The limiting distributions of the test statistics are mixtures of chi-square distributions. A Monte Carlo experiment shows improved performances of the proposed tests over the usual chi-square tests in detecting ordered group effects. The proposed test procedures are illustrated by familial polyposis supplementation trial data.

Adenomatous Polyposis Coli↗

PubMed1997

Extralobar pulmonary sequestration with an associated cyst of mixed bronchogenic and esophageal type--a case report.

We report an unusual case of extralobar pulmonary sequestration (ELS) with an associated cyst of mixed bronchogenic and esophageal type. A 58-year-old woman was incidentally found to have a 6 x 6 x 5 cm sized mass in the right superior mediastinum. The mass consisted of sequestrated pulmonary tissue and an unilocular cyst with a direct communication. The cyst could not be easily classified because it was lined by squamous or respiratory epithelium with two distinct muscle layers and bronchial glands. Bronchial cartilage was present in close proximity to the ELS. This unusual combination of ELS with a foregut cyst might be a part of bronchopulmonary foregut malformation, attributed to a common embryologic pathogenesis.

Bronchogenic Cyst↗

PubMed1997

[Immunological properties of the 30 kDa antigen of toxoplasma gondii].

The molecular weight 30 kDa membrane protein of Toxoplasma gondii (Toxoplasma 30 kDa) apparently conserved in most strains of T. gondii and sera of infected hosts. The present study aimed to elucidate Toxoplasma 30 kDa as a useful diagnostic antigen for serodiagnosis of toxoplasmosis by ELISA and for induction of protective immunity. Murine spleen cells immunized with the membrane antigen of T. gondii were fused with mouse Sp2/O-Ag14 myeloma cells. Out of 8 clones selected, five were IgG2b, the others belonged to IgG1 and IgG2a. The 30 kDa antigen was distributed mainly on the surface membrane of tachyzoites by indirect fluorescence method. Murine peritoneal macrophages which were activated by 30 kDa antigen produced more amounts of NO2 compared with crude antigen-treated group, however there were no significant differences in toxoplamacidal activity between the two groups. Higher specificity of Toxoplasma 30 kDa antigen was recognized for serodiagnosis of toxoplasmosis than the crude antigen. From these results, Toxoplasma 30 kDa antigen enhances the cytotoxic effect of macrophages as well as a more reliable means for the serodiagnosis of toxoplasmosis by ELISA.

Animals↗

PubMed1995

[Detection of Toxoplasma antigens and antibodies in mice infected with different strains of Toxoplasma gondii].

This study aims to assess the possible strain-dependent variations in detection of Toxoplasma antigens and antibodies. The virulent RH strain or avirulent Beverley strain of T. gondii were injected into mice, intraperitoneally, and their antigens, antibodies and parasites were identified from the blood or tissues; liver, brain and spleen by ELISA, Western blot and PCR. In mice infected with RH strain, circulating antigens and parasitemia were first detected from 2 days after infection, and Toxoplasma DNA were found in the blood, liver, brain and spleen from 3 days after infection. It was impossible to detect specific IgM and IgG antibodies to T. gondii, and any specific band was not found by Western blot. In mice infected with Beverley strain, circulating antigens were detected between day 10 and day 35. The Toxoplasma DNA was found in the blood and liver from day 15 until day 60, and in the brain from day 20. But Toxoplasma DNA in the spleen were mainly detected between day 10 and day 30. The IgM antibodies were first appeared on day 10 post-infection, and were noted obviously increased between day 15 and 25. The IgG antibodies were first detected on day 15, and showed progressively increased titers. The antibody binding bands were specific according to infection period. Sera from mice infected with Beverley strain reacted mainly with the antigen of 27.5-kDa and 32.5-kDa. In conclusion, mice infected with RH strain revealed Toxoplasma antigens strongly, but not antibodies. However, mice infected with Beverley strain revealed both the Toxoplasma antigens and antibodies. The present results showed that immune responses are different between avirulent and virulent T. gondii.

Animals↗