Biomedical subjects

S H Park

Publications and source records attributed to S H Park.

At least 19 recordsLinked to original sources

PubMed1995

Treatment with bacterial LPS renders genetically resistant C57BL/6 mice susceptible to Theiler's virus-induced demyelinating disease.

Theiler's murine encephalomyelitis virus (TMEV) induces a demyelinating disease in susceptible strains, which clinically and histopathologically resembles human multiple sclerosis. Since bacterial LPS produced by Gram-negative bacteria is known to potentiate an immune response and trigger resident central nervous system cells to produce various inflammatory cytokines, we examined the ability of LPS to affect resistance to TMEV-induced demyelinating disease (TMEV-IDD). Intraperitoneal injection of LPS, concomitant with intracerebral of genetically resistant C57BL/6 mice with TMEV, resulted in clinical symptoms in approximately 50% of the group. The increase in susceptibility following LPS treatment correlated with the enhanced levels of TMEV-specific delayed-type hypersensitivity and T cell proliferative responses. Similar treatment with LPS, however, did not accelerate the clinical course of susceptible (SJL/J) or intermediately susceptible (C3H) mice. The LPS-treated C57BL/6 mice displayed an increased viral persistence in the central nervous system when compared with nontreated control mice. Intraperitoneal administration of IL-1 beta could mimic the LPS effect in C57BL/6 mice, suggesting that the increase in susceptibility to TMEV-IDD may function via IL-1 produced following LPS stimulation.

Adjuvants, Immunologic↗

PubMed1995

Inactivation of the UAS1 of STA1 by glucose and STA10 and identification of two loci, SNS1 and MSS1, involved in STA10-dependent repression in Saccharomyces cerevisiae.

It has been reported that two upstream activation sites, UAS1 and UAS2, exist in the 5' non-coding region of the STA1 gene of Saccharomyces cerevisiae var. diastaticus. Based on studies using a UAS1STA1-CYC1-lacZ fusion, we divided UAS1 into two subsites, UAS1-1 and UAS1-2. The activation of the CYC1 promoter by UAS1STA1 was repressed by glucose in the culture medium and by the STA10 gene. The MATa/MAT alpha mating type configuration did not, however, affect UAS1STA1 activation. The UAS1STA1-CYC1-lacZ expression system was used to study STA10 repression further. A mutant insensitive to STA10-dependent repression was isolated. This sns1 mutation was not linked to STA10 and partially overcame the repressive effect of STA10 at the transcriptional level. From a genomic library constructed in the UAS1STA1-CYC1-lacZ expression vector, the MSS1 locus (multicopy suppressor of sns1) was isolated. This suppression of the sns1 mutation by multiple copies of the MSS1 locus occurred at the transcriptional level. When a gene disruption experiment was performed to examine the effect of a mss1 mutation, the sns1 mss1 double mutants produced 4 times higher levels of STA1 transcripts in the presence of STA10 than did the sns1 strain. Data presented in this paper suggest that both SNS1 and MSS1 loci are involved in STA10-dependent repression.

Cloning, Molecular↗

PubMed1995

Loss of p53 function leads to metastasis in ras+myc-initiated mouse prostate cancer.

To study the interactions between dominantly acting oncogenes and tumor suppressor genes we used p53 'knockout' mouse urogenital sinus tissue for retroviral transduction of ras and myc in the mouse prostate reconstitution (MPR) model system. Epithelial hyperplasia was observed in all wild-type p53 MPRs with one small focal cancer and no evidence of metastasis. Prostatic cancer was found in 100% of the heterozygous and homozygous p53 mutant MPRs with metastatic deposits in 95% of the mice. The pattern of metastasis was remarkably similar to that in human prostate cancer with gross metastatic deposits in the lung, lymph nodes, bone and liver of many animals. Progression of carcinomas in the ras+myc-initiated heterozygous p53 mutant MPRs was invariably associated with either complete loss, partial deletion or loss of expression of the wild-type p53 allele. Southern blotting analysis of proviral-cellular DNA junction fragments in primary carcinomas and cell lines derived from metastatic deposits revealed that metastases do not necessarily seed out from the most abundant clone in the primary carcinoma.

Alleles↗

PubMed1995

Mesenchymal-epithelial interactions and transforming growth factor-beta 1 expression during normal and abnormal prostatic growth.

Mesenchymal-epithelial interactions are associated with growth and morphogenesis of the prostate. We have detected three isoforms of transforming growth factor beta (TGF-beta) in the developing mouse prostate that may mediate some of these interactions. Separation of the fetal urogenital sinus (UGS) tissue into mesenchymal and epithelial components indicated that mRNA expression of TGF-beta 1, 2, and 3 was more abundant in the mesenchyme compared to the epithelium. Immunohistochemical analysis revealed accumulation of TGF-beta 1 in the mesenchyme surrounding ductules in the UGS and neonatal prostate. Further analysis of TGF-beta 1 localization in surgically removed adult human prostate tissues revealed more intense staining associated with regions of abnormal growth compared to normally appearing tissue. The percent of the total stained area with extracellular accumulation of TGF-beta 1 was 59% in prostate cancer, 26% in benign prostatic hyperplasia (BPH), and 8.6% in normal tissue. In additional immunohistochemical studies we observed that intracellular TGF-beta 1 was predominantly associated with the epithelial cells in prostate cancer (epithelial cells = 33.5% of the total stained area, stromal cells = 13.3%, and unstained = 53.2%), whereas in BPH intracellular TGF-beta 1 was predominantly associated with stromal cells (stromal cells = 32.2% of the total stained area, epithelial cells = 12.3%, and unstained = 55.5%). Although additional experimental and clinical studies are needed to better understand the relationships between TGF-beta 1 and abnormal prostatic growth, our observations thus far suggest a role for TGF-beta 1 in the development of benign and malignant growth abnormalities in the prostate. One approach to establishing the pathobiological significance of TGF-beta 1 accumulation in the prostate is by introducing and overexpressing the TGF-beta 1 cDNA in prostate tissue using the mouse prostate reconstitution model system. We discuss applicability of transgenic animal and organ reconstitution models for experimental studies concerning TGF-beta-induced prostate growth abnormalities.

Animals↗

PubMed1995

Effects of genetic background on tumorigenesis in p53-deficient mice.

Mice with disrupted germline p53 alleles have been engineered by us and others and have been shown to have enhanced susceptibility to spontaneous tumors of various types. We monitored a large number of p53-deficient mice (p53+/- and p53-/-) and their wild-type littermates (p53+/+) of two different genetic backgrounds (129/Sv and mixed C57BL/6 x 129/Sv) up to 2 yr of age. p53+/- and p53-/- 129/Sv mice show accelerated tumorigenesis rates compared with their p53-deficient counterparts of mixed C57BL/6 x 129/Sv genetic background. The tumor spectra of the two strains of mice are similar except that almost half of 129/Sv p53-/- males develop malignant teratomas, whereas these tumors are rarely observed in C57BL/6 x 129/Sv mice and never in 129/Sv p53+/- males. In the study reported here, we further characterized the lymphomas that arose in the p53-nullizygous mice and found that over three-quarters of the lymphomas were of thymic origin and contained primarily immature (CD4+/CD8+) T-cells, whereas the remainder originated in the spleen and peripheral lymph nodes and were of B-cell type. The high incidence of early-onset lymphomas in the nullizygous mice makes these animals a good lymphoma model, whereas the heterozygous mice may be a useful model for Li-Fraumeni syndrome, a human inherited cancer predisposition.

Alleles↗

PubMed1995

Heterogeneity, polyploidy, aneusomy, and 9p deletion in human glioblastoma multiforme.

The short arm of chromosome 9 is frequently deleted in malignant gliomas. We used locus-specific probes for interferon-A (IFNA) and D9S3 in combination with a chromosome 9 centromeric probe to detect genetic aberrations on a cell-by-cell basis in touch preparations of 30 glioblastomas by fluorescence in situ hybridization. Seven (23%) of 30 tumors had deletions in > 70% of cells; the IFNA locus was deleted in all seven, but the D9S3 locus was deleted in only five of the seven. The latter data confirm that a tumor suppressor gene on 9p relevant to glioblastoma multiforme lies between D9S3 and IFNA. Eleven tumors had deletions in 20-40% of cells, more than three standard deviations above the level in control tissues. The remaining tumors had deletions in < 20% of cells. The seven tumors with the lowest percentage of deleted cells each had more than one genetically abnormal population of cells. In total, 10 cases were of this type (i.e., aneusomic for chromosome 9). Three of these 10 tumors had hybridization patterns consistent with polyploidy.

Adult↗

PubMed1995

Nuclear magnetic resonance study of complexes between CRP and its 22- and 28-base-pair operators.

The binding of the cAMP receptor protein (CRP) to the portion of the lac promoter comprising the core of the CRP recognition sequence has been investigated. The effect of the binding of CRP to the symmetrical 22- and 28-base-pair operators was investigated by 1H NMR. The binding of cAMP*CRP to the 22mer DNA did not bring about any changes in the chemical shift values of the imino proton resonances of the DNA, but did cause selective line broadening of the imino proton resonances of specific base pairs (TA 4, GC 5). These base pairs are contained in the motif 5'(TGTGA)3', which is thought to be the region crucial to interaction with the CRP. The binding of cAMP*CRP to the 28mer DNA brought about large changes in the imino proton resonances that seem to be induced by DNA bending. Therefore it seems likely that CRP requires DNA longer than a 22mer to bend it. We also used a C-terminal protease-digested CRP (CRPcy) in a DNA-binding experiment. The binding of cAMP*CRPcy to the 28mer DNA did not induce bending. These results indicate that the C-terminal region of CRP participates in DNA binding and is important for DNA bending.

Base Composition↗

PubMed1995

A comparison of the relaxation responses of isolated cavernosal smooth muscles by endothelium-independent and endothelium-dependent vasodilators in diabetic men with impotence.

This study was intended to explore the effects of endothelium-independent, direct smooth muscle relaxants(papaverine, verapamil) and endothelium-dependent vasodilators(acetylcholine, bradykinin, adenosine) on the isolated cavernosal smooth muscle strips taken from diabetic men with impotence. When smooth muscle contraction was evoked with norepinephrine for the study of relaxation to these vasodilators, the tension induced was similar in diabetic and non-diabetic men with importance. Papaverine showed the strongest relaxation response followed by verapamil, acetylcholine, bradykinin and adenosine both in non-diabetic and in diabetic men. Relaxation of the cavernosal tissues to endothelium-independent vasodilators was similar in non-diabetic and diabetic men. However, the relaxation response of the tissues to endothelium-dependent vasodilators was significantly reduced in the diabetic group compared with that in the non-diabetic group (p < 0.05). In conclusion, the impairment of endothelium-mediated relaxation of cavernosal smooth muscle seems to play a more important role in the pathogenesis of diabetogenic impotence rather than the problem of smooth muscle itself. This finding forms a rational basis for the use of intracavernosal injections of vasodilators to induce endothelium-independent relaxation of the cavernosal smooth muscle in the patients with diabetogenic impotence.

Adult↗

PubMed1995

Dysphagia due to mediastinal tuberculous lymphadenitis presenting as an esophageal submucosal tumor: a case report.

Mediastinal tuberculous lymphadenitis is rare in adults, and it is even rarer for dysphagia to be the presenting symptom of mediastinal tuberculous lymphadenitis. Mediastinal tuberculous lymphadenitis with esophageal symptoms has been presented as esophageal ulceration, mucosal or submucosal mass with ulceration, fistula or sinus formation, extrinsic compression, or displacement of the esophagus. An exaggerated form of extrinsic compression may be presented as a submucosal tumor, radiologically or endoscopically. A barium esophagography of a 34 year-old woman with painful dysphagia revealed a large submucosal tumor-like mass on the mid-esophagus. The symptom was spontaneously improved over a 3-week period together with reduction of the mass size. A computed tomography of the chest disclosed an enlarged subcarinal lymph node and histologic examination of the specimen obtained by thoracoscopic biopsy brought about a diagnosis of tuberculosis. We herein report a case of mediastinal tuberculosis with unusual manifestations.

Adult↗

PubMed1995

TNFB gene polymorphism in patients with systemic lupus erythematosus in Korean.

OBJECTIVES: To elucidate the gene frequency of TNFB Ncol polymorphism and its association with HLA class II antigen in patients with systemic lupus erythematosus(SLE) in Korea. METHODS: We investigated the gene frequency of the TNFB alleles using DNA obtained from peripheral mononuclar cells in 141 healthy controls and in 58 patients with SLE. The polymorphisms of TNFB gene (735 bp) were studied by Ncol PCR-RELP. A portion of TNFB gene(735 bp) was amplified by PCR and its products were digested with Ncol restriction enzyme. The digested samples of amplified DNA were analyzed by agarose gel electrophoresis. TNFB*1 and TNFB*2 alleles were identified according to polymorphic fragments on Ncol restriction site in the first intron of the TNFB gene. The generic types of HLA-DRBI were also determined by PCR with sequence specific primers(SSP) using genomic DNA from the same subjects. RESULTS: The genotypic frequency of TNFB*2 homozygote was significantly increased in patients with SLE compared with controls(RR = 2.36, P = 0.011). The frequency of HLA-DRBI*15 was also significantly increased in patients (RR = 2.27, P = 0.029). However, the increased frequency of TNFB*2 homozygote was apparently increased in nephritis group (RR = 2.79, P = 0.035), whereas the significance of TNFB*2 homozygote was weakend in non-nephritis group. CONCLUSIONS: Our results suggest that genetic predisposition of TNFB*2 homozygote is another risk factor in Korean SLE, especially in DR2 negative patients. In addition, TNFB*2 homozygote could have a tendency for the development of nephritis in patients with SLE.

Base Sequence↗

PubMed1995

The origin of submicron polyethylene wear debris in total hip arthroplasty.

The microscopic morphology of worn polyethylene surfaces was compared with that of the associated polyethylene particles for acetabular cups tested in a wear simulator and for cups worn in vivo, using scanning electron microscopy. In the absence of significant third-body abrasive damage, the articulation of the ball in the cup produced a visually polished surface on the polyethylene. On a micron scale, the morphology of the worn polyethylene from in vitro and in vivo wear included nodules and fibrils consistent with adhesive, abrasive, and microfatigue wear mechanisms. Larger wear features, such as deep scratches or pits measuring in 10s of microns, that were seen in the in vivo cups were attributed to third-body wear. The polyethylene particles isolated from the serum lubricants of the wear tests and from the periprosthetic tissues were primarily submicron in size, were either rounded or elongated, and were consistent with the submicron wear features seen on the cup surfaces. It is the submicron particles that are associated with inflammatory periprosthetic bone loss in total hip replacement. Although the mean dimensions of the particles generated in vitro were slightly smaller than those of the in vivo particles, the overall morphologies were very comparable, suggesting that the same lubrication and wear processes were acting in the simulator as in vivo.

Foreign Bodies↗

PubMed1994

Histogenetic consideration of ovarian sex cord-stromal tumors analyzed by expression pattern of cytokeratins, vimentin, and laminin. Correlation studies with human gonads.

A total of 30 sex cord-stromal tumors including 9 adult type and 5 juvenile type granulosa cell tumors (GCTs), 4 Sertoli-Leydig cell tumors (SLTs), 1 gynandroblastoma, 5 thecomas, 2 fibromas and 3 sclerosing stromal tumors were immunohistochemically evaluated by means of cytokeratins of different molecular weight, vimentin and laminin with regard to the histogenesis of these tumors and to the embryogenesis of the sex cord and stroma of developing gonads. For comparison, 7 embryonic gonads, 9 fetal and 9 adult ovaries, 14 fetal and 5 postnatal testes, and 1 gonadoblastoma were also examined. The coelomic epithelium of all gonads were positive for both cytokeratins (CAM 5.2 and AE1) and vimentin. In fetal ovaries, the granulosa cells of primordial follicles express low molecular weight cytokeratins only and those cells of more maturing follicles did not express any cytokeratin or vimentin. In adult ovaries, the granulosa cells of primordial follicles coexpressed low molecular weight cytokeratins and vimentin, but those cells of more maturing follicles expressed vimentin only. In fetal testes before 20 weeks gestational age, the Sertoli and Leydig cells did not express any cytokeratins and vimentin. After that time, both cells expressed vimentin only throughout life. The rete ovarii and rete testis from fetal to adult life coexpressed both low molecular weight cytokeratins and vimentin. The rete ovarii in all ages and rete testis in prenatal and childhood ages were surrounded by the laminin-positive basement membrane, however, the rete testis in adult were not. In neoplasia, the GCTs, thecomas, fibromas, and sclerosing stromal tumors expressed vimentin only.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1992

Ras-induced hyperplasia occurs with mutation of p53, but activated ras and myc together can induce carcinoma without p53 mutation.

Using a reconstituted mouse prostate organ, the effects on endogenous p53 expression of the ras oncogene or of the ras + myc oncogenes were investigated. In this system the ras gene alone causes mild hyperplasia, but the combination of ras and myc leads to the formation of carcinomas. Surprisingly, while p53 mutations were found in cells derived from the reconstituted organs containing ras alone, no such mutations were found in the ras + myc-transformed cells. Their growth, unlike that of the cells containing ras alone, was not inhibited by transfection with plasmids encoding wild-type human p53. We suggest that expression of both activated ras and myc genes bypasses the need for p53 mutation by neutralizing the tumor suppressor activity of normal p53.

Animals↗

PubMed1992

Chromogranin-A expression in gastric and colon cancer tissues.

UNLABELLED: We studied the expression of chromogranin A (CgA) in human gastric (n = 17) and colorectal (n = 18) adenocarcinomas by nucleic acid hybridization and immunohistochemical analyses using a specific monoclonal antibody (MAb) to human chromogranin A (CgA). Some corresponding adjacent non-malignant mucosal tissues were also examined. RESULTS: (1) Northern blotting: of 3 normal gastric mucosas examined, 2 (67%) had an easily detected signal for expression of CgA. Only one of 14 gastric carcinomas (7%) and one of 18 colorectal carcinomas (6%) had easily detected RNA signals. (2) Immunohistochemical staining: all non-malignant samples of gastric and colonic mucosa contained CgA-positive neuroendocrine (NE) cells. Two of 17 (12%) gastric adenocarcinomas, and 3 of 18 (17%) of colorectal adenocarcinomas contained CgA-positive tumor cells. Interestingly, the positive cases detected by immunohistochemistry included both cases detected by Northern blotting. Of the 5 cases detected by immunohistochemistry, 2 gastric cancers and 1 rectal carcinoma contained many diffusely scattered positive cells, occurring singly or in small clusters, while 2 colorectal carcinomas contained only occasional single CgA-positive tumor cells. In one of the positive gastric cases, a well-differentiated adenocarcinoma arising in a tubular adenoma, both the adenomatous and the carcinomatous elements contained positively staining cells. Our specific assays for CgA indicate that (1) a NE cell component, either diffusely scattered or occasional, occurs in about 15% of gastric and colorectal tumors; (2) there is no correlation between the presence of NE cells and degree of tumor differentiation; and (3) because only a minority of the tumor cells in positive cases stain for CgA, immunohistochemistry is a more sensitive method than Northern blotting.

APUD Cells↗

PubMed1992

The contribution of residue ion pairs to the helical stability of a model peptide.

Comparative CD measurements were made on the model helical peptides acetylYEAAAKEAXAKEAAAKAamide and acetylYEAAAEKAXAKEAAAKAamide in which X represents a nonaromatic nonionic residue. The former peptide contains three potential i, i + 4 complementary ion pairs at neutral pH, while the latter peptide contains one potential complementary and two potential antagonistic i, i + 4 ion pairs. The effect of pH and ionic strength on the mean residue ellipticity of these peptides was measured at 222 nm and 0 degrees C. These measurements were analyzed assuming a common two-state helix/coil transition and only i, i, + 4 ion-pair interactions. The analyses suggest that the central ion pairs do modulate helical content while the peripheral ion pairs do not, presumably due to the location of the peripheral ion pairs in the frayed ends of the helix. The complementary central ion pair stabilizes the helix by about 0.4 kcal/mole and the antagonistic central ion pair destabilizes the helix by about 0.2 kcal/mole.

Amino Acid Sequence↗

PubMed1992

Transforming growth factor beta 1 as a biomarker for prostate cancer.

Using the mouse prostate reconstitution (MPR) model system, under conditions where the ras and myc oncogenes are introduced via a recombinant retrovirus into both the mesenchymal and epithelial compartments of the urogenital sinus, poorly differentiated prostate cancer is produced with high frequency (> 90%) using inbred C57BL/6 mice. Northern blotting and immunohistochemical analysis showed that the transition from benign prostatic hyperplasia (BPH) to prostate cancer is invariably associated with the induction of elevated transforming growth factor-beta 1 (TGF-beta 1) expression. Similar analysis of TGF-beta 1 in human BPH and prostate cancer is consistent with our MPR results and indicates that the accumulation of extracellular TGF-beta 1 is significantly more intense in prostate cancer compared to normal or benign prostate tissues. Interestingly, where benign pathologies are observed in the prostatic stroma in the presence of benign prostatic epithelium, extracellular TGF-beta 1 is seen predominantly in the stromal compartment. Experimental studies clearly demonstrate that mRNA levels of TGF-beta 1 and other growth related genes are regulated by androgens in prostate cancer cells. Overall, our results suggest that elevated TGF-beta 1 is involved in the development of prostate cancer. Direct determination of TGF-beta 1 levels and distribution as well as analysis of localized and systemic effects produced by TGF-beta 1 may serve as useful biomarkers for prostate cancer.

Animals↗

PubMed1992

Marchiafava-Bignami disease: serial changes in corpus callosum on MRI.

Serial MRI findings of changes in corpus callosum lesions in two cases of Marchiafava-Bignami disease are presented. In both, MRI displayed diffuse swelling of the corpus callosum in the acute stage, thought to represent oedema and demyelination. In the chronic stage, in addition to atrophy of the corpus callosum with presumed focal necrosis, previously undescribed focal hypointensity on T2-weighted images, of unknown cause, was observed in the corpus callosum.

Alcoholism↗

PubMed1992

HLA-DR expression in human fetal thymocytes.

We analyzed the expression of MHC class I (W6/32) and class II (HLA-DR) antigens on human fetal and postnatal thymocytes by fluorescence-activated cell sorting. Less than 5% of prenatal thymocytes expressed HLA-DR before week 12 of gestation. However, the number of HLA-DR-positive cells significantly increased during the late second and third trimester of gestation, when greater than 50% of prenatal thymocytes expressed HLA-DR. Such high-level expressions of HLA-DR in fetal thymocytes were also demonstrated by Northern-blot analysis and immunohistochemistry. After birth, the percentage of HLA-DR-positive cells in thymocytes decreased gradually. A high-level expression of class I antigen was also observed in thymocytes from the early stages of gestation, but, in contrast to MHC class II, a majority of postnatal thymocytes maintained high levels of class I antigen after birth.

Cell Separation↗