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S S Park

Publications and source records attributed to S S Park.

At least 19 recordsLinked to original sources
PubMed2006

Plasma cell tumour progression in iMycEmu gene-insertion mice.

The authors have recently reported that gene-targeted iMyc(Emu) mice that carry a His(6)-tagged mouse Myc cDNA, Myc(His), just 5' of the immunoglobulin heavy-chain enhancer, Emu, are prone to 'spontaneous' neoplasms of the B-lymphocyte lineage. The present study has used histological, immunohistochemical, and molecular genetic methods to investigate a subset of these neoplasms referred to as extraosseous plasmacytomas (PCTs). It is shown that 20.8% (20/96) of tumour-bearing iMyc(Emu) mice on a mixed genetic background of segregating C57BL/6 and 129/SvJ alleles develop PCT by 500 days. The Myc(His)-induced PCTs produced monoclonal immunoglobulin and developed in the gut-associated lymphoid tissue (GALT), particularly the mesenteric node and Peyer's patches. The PCTs overexpressed Myc(His), at the expense of normal Myc, and exhibited gene expression changes on cDNA macroarrays that were consistent with Myc(His)-driven neoplasia. Surprisingly, in one of three PCT-derived cell lines, Myc(His) was 'replaced' by a naturally occurring T(12;15) translocation, which changed the mode of Myc deregulation from gene insertion (Myc(His) transgene) to chromosomal translocation (juxtaposition of normal Myc to the immunoglobulin heavy-chain locus Igh). These findings provide evidence that recreation of the mouse PCT-associated T(12;15)(Igh(Emu)-Myc) translocation by gene insertion in mice results in the predictable development of PCTs in approximately one-fifth of the tumour-bearing mice. Myc(His)-driven PCTs recapitulate aspects of human plasma cell neoplasms, for which relatively few models exist in mice. For example, PCT development in the iMyc(Emu) mice may provide a good system to study the mechanism by which human MYC facilitates the progression of plasma cell myeloma (multiple myeloma) in humans.

Animals↗
PubMed2006

Dual reporter genes enabling cell tracing with viable and reliable selection of various cell types.

Dual reporter genes driven by either a ubiquitous cytomegalovirus (CMV) or a neuro-specific tubulin alpha1 promoter (Talpha1) were constructed. The new genes, CMV (pCMV-GL) or Talpha1 promoter-driven GFP-LacZ (pTalpha1-GL), robustly expressed the fused GFP-LacZ protein reporting constitutive expressions in various cell types including CHO cells, loach and chicken embryos, and neuro-specific expression in differentiating mouse embryonic stem cells, respectively. The dual reporter genes thus provide a versatile tool for the studies of gene expression, cell lineage within the embryo and possibly the fate of stem cells in transplantation experiment, thus facilitating different analyses depending on the experimental purposes.

Animals↗
PubMed2005

Mitochondrial DNA content is decreased in autosomal dominant optic atrophy.

BACKGROUND: Autosomal dominant optic atrophy (ADOA) is the commonest form of inherited optic neuropathy. Mutations in the OPA1 gene encoding a dynamin-related mitochondrial protein underlie ADOA and may perturb the biogenesis and maintenance of mitochondria. OBJECTIVE: To investigate the mutation spectrum of the OPA1 gene and assess alterations in mitochondrial content caused by OPA1 mutations. METHODS: Sixteen Korean patients with clinically suspected ADOA were studied. The mutation spectrum of the OPA1 gene was analyzed by PCR single-strand conformation polymorphism and sequencing, and mitochondrial DNA (mtDNA) content was quantified by real-time PCR. RESULTS: Eight different mutations were found, including five novel mutations. Quantitative real-time PCR analysis showed excellent linearity and precision for the determination of mtDNA copy numbers. The number of mtDNA copies per cell in patients with OPA1 gene mutations (ages 7 to 40) was significantly lower than those in all normal control subjects (p = 0.037), particularly lower than in normal control subjects ages 10 to 39 (p = 0.022). CONCLUSION: The mutation spectrum of the OPA1 gene disclosed marked genetic heterogeneity and the mitochondrial DNA content was found to be lower in autosomal dominant optic neuropathy, which provides direct evidence for a pathogenetic role of mutations of the OPA1 gene.

Adolescent↗
PubMed2005

Expression and prognostic implications of cell cycle regulatory molecules, p16, p21, p27, p14 and p53 in germinal centre and non-germinal centre B-like diffuse large B-cell lymphomas.

AIMS: To evaluate the different expression patterns and the prognostic significance of cell cycle regulatory molecules in diffuse large B-cell lymphomas (DLBCLs) of germinal centre (GC) and non-GC phenotypes. METHODS AND RESULTS: Tissue microarray slides composed of 126 extranodal and 88 nodal DLBCLs were immunostained for p16, p21, p27, p14 and p53. DLBCLs were classified into GC and non-GC phenotype according to the immunohistochemical expression of bcl-6, CD10, and MUM1. Aberrant expression of p53 was more frequent in the GC phenotype in nodal cases (P = 0.038), and the loss of p16, p21 and p14 expression was significantly more common in the non-GC phenotype (P = 0.004, P = 0.001, P < 0.001). Concurrent disruptions of the p16-Rb and p14-p53 pathways as represented by the immunoprofile of p16/p14/p53 (-/-/+) were associated with a poor prognosis in the GC phenotype [mean survival 31 months in the p16/p14/p53 (-/-/+) group versus 62 months in the other groups, P =0.0485]. CONCLUSIONS: The expression and prognostic implications of cell cycle regulatory molecules differ between GC and non-GC phenotypes in DLBCLs. The immunoprofile of p16/p14/p53 (-/-/+) within the GC phenotype of DLBCLs can be defined as a poor prognostic subgroup.

Adolescent↗
PubMed2002

Lymphoid preponderance and the absence of basophilia and splenomegaly are frequent in m-bcr-positive chronic myelogenous leukemia.

Chronic myelogenous leukemia (CML) with a minor bcr-abl transcript is a rare entity. We describe a 66-year-old female who was diagnosed with CML in the chronic phase. Molecular analysis of her Philadelphia chromosome using the reverse transcriptase polymerase chain reaction and subsequent sequencing revealed a minor bcr-abl transcript. Monocytosis resembling chronic myelomonocytic leukemia was observed without splenomegaly and basophilia. Her clinical course was indolent and maintained the chronic phase of CML for nearly 3 years under hydroxyurea treatment. A review of the 23 cases of m-bcr CML including this case showed the presence of monocytosis and the absence of basophilia and splenomegaly in 55.0%, 55.0%, and 70.0% of patients, respectively. The absence of basophilia was a significant finding in patients without monocytosis ( P=0.01). Although the hematological features or clinical outcomes were variable in m-bcr CML cases, all three cases at the onset of the blastic phase showed lymphoid crisis, implying an increased lymphoid leukemogenicity of minor bcr-abl transcripts.

Aged↗
PubMed2002

Mutation analysis of the PIG-A gene in Korean patients with paroxysmal nocturnal haemoglobinuria.

AIM: Paroxysmal nocturnal haemoglobinuria (PNH) is caused by deficient biosynthesis of the glycosylphosphatidylinositol (GPI) anchor in haemopoietic stem cells. Mutation of the phosphatidylinositol glycan class A (PIG-A) gene, an X linked gene that participates in the first step of GPI anchor biosynthesis, is responsible for PNH. The characteristics of somatic mutation of the PIG-A gene in Korean patients with PNH were studied. METHODS: Twenty four patients with PNH were selected. Ham tests and sucrose haemolysis tests were carried out on all patients. The expression of CD59 in erythrocytes and granulocytes was investigated in 14 and five patients, respectively, to confirm the diagnosis. Dideoxy fingerprinting (ddF) was used to screen mutations, and direct sequencing of DNA was performed to characterise the mutations. RESULTS: Gene mutation was detected in 12 of the 24 patients. The other 12 patients were negative in ddF screening. Ten new mutations and two known mutations were detected. The mutations consisted of five deletions, six substitutions, and one insertion. These mutations resulted in six premature terminations, three abnormal splicings, one missense mutation in exon 2, and two nonsense mutations. Two patients with venous thrombosis showed mutations in exon 3 only. Substitution mutations were seen in six patients and frameshift mutations in the other six. CONCLUSIONS: There were 10 new mutations among the 12 mutations in the Korean patients with PNH and the characteristics of the mutations varied, with no significant hot spots in sites or types.

Adult↗
PubMed2001

Molecular analysis of Spinocerebellar ataxias in Koreans: frequencies and reference ranges of SCA1, SCA2, SCA3, SCA6, and SCA7.

Spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative disorders. CAG repeat expansions in the causative genes have been identified as the basic cause of several types of SCAs, and have been used for the diagnoses and classifications of patients with ataxia. In order to assess the frequency and CAG repeat size ranges of SCAs, and to establish an effective strategy for molecular diagnosis, we performed a molecular analysis of SCA1, SCA2, SCA3, SCA6, and SCA7 in 76 patients. These patients were as follows: 32 with dominant inheritance, 39 sporadic cases, and 5 with unknown family histories. The normal and affected CAG repeat size ranges were established at five SCA loci in Koreans, which was consistent with previous reports. The total prevalence of the five types of SCAs was 39.5% in the 76 patients with ataxia, regardless of their family history. It was 75.0% in the 32 families with a dominant inheritance. The most frequent type was SCA3 (15.8%), followed by SCA2 (14.5%). Both types combined formed 76.7% of the 30 patients with CAG expansions. SCA1, SCA6, and SCA7 were less frequent, affecting 3.9%, 2.6%, and 2.6% of the cases, respectively. This mutation spectrum is quite different from a previous report concerning Koreans, but is similar to the distributions that are seen in several ethnic populations worldwide. For a correct and effective diagnosis of SCAs, we suggest that a molecular diagnosis be undertaken, even in patients without a family history, as well as those with a family history. A stepwise approach is also recommended. Patients with ataxia should be tested for SCA2 and SCA3. Individuals testing negative should be tested for SCA1, SCA6, and SCA7.

Ataxin-1↗
PubMed2001

Cloning and characterization of a type II integral transmembrane protein gene, Itm2c, that is highly expressed in the mouse brain.

An Itm2C cDNA encoding a member of the mouse type II integral transmembrane protein (Itm2) was cloned from a mouse 13.5 days' post-coitum (dpc) embryonic head cDNA library. The nucleotide sequence and protein prediction analyses indicate that the membrane topology of the mouse Itm2c is a type II integral transmembrane protein with the N-terminus being intracellular and C-terminus, which is considered as either an extracellular or a luminal organelle domain. The predicted protein consists of 269 amino acids with a calculated Mr of 30,482 and a theoretical pI of 8.83. A putative N-glycosylation site was identified at amino acid 171, Asn. The single N-glycosylation site is conserved in the three members of the family in both mice and humans. The amino acid sequence of Itm2C is 41 and 49% identical to those of mouse Itm2A and Itm2B, respectively. A single approximately 2.1 kb transcript was detected with different levels in all of the tissues examined by Northern blot analysis. The Itm2c was highly expressed in both adult and postimplantation embryonic brains, although weak or moderate signals were also detected in other adult tissues. Among the tissues examined, RT-PCR analyses in various adult tissue shows that the Itm2c expression is highest in the adult brain. The results from this study suggest that the cloned Itm2c is a member of the Itm2 family that is specifically expressed in adult brains, unlike other members.

Amino Acid Sequence↗
PubMed2001

Induction of cytochrome P450-dependent monooxygenase in mouse liver and kidney by rutaecarpine, an alkaloid of the herbal drug Evodia rutaecarpa.

Rutaecarpine is one of the main alkaloids of an herbal remedy, Evodia rutaecarpa, which has been used for the treatment of gastrointestinal disorder and headache. Effects of rutaecarpine on hepatic and renal cytochrome P450 (CYP)-dependent monooxygenase were studied in C57BL/6J mice. Treatment of mice with rutaecarpine by gastrogavage at 50 mg/kg/day for three days resulted in 57%, 41%, 6-, and 6-fold increases of hepatic microsomal benzo(a)pyrene hydroxylation, 7-ethoxycoumarin O-deethylation, 7-ethoxyresorufin O-deethylation, and 7-methoxyresorufin O-demethylation activities, respectively. However, the treatment had no effects on hepatic oxidation activities toward benzphetamine, N-nitrosodimethylamine, nifedipine, and erythromycin. In the kidney, rutaecarpine-treatment resulted in 2-fold and 42% increases of microsomal benzo(a)pyrene hydroxylation and 7-ethoxycoumarin O-deethylation activities, respectively. The treatment also increased renal 7-ethoxyresorufin O-deethylation activity to a detectable level. Immunoblot analysis of microsomal proteins showed that rutaecarpine-treatment increased the protein levels of CYP1A1 and CYP1A2 in the liver, whereas hepatic level of CYP3A-immunoreacted protein was not affected by rutaecarpine. These CYPs were not detectable in the immunoblot analyses of control and rutaecarpine-treated mouse kidney microsomes. These results indicated that rutaecarpine was a CYP1A inducer and showed potent inductive effects on both CYP1A1 and CYP1A2 in the liver.

Administration, Oral↗
PubMed2001

Inducible mutagenesis in TEPC 2372, a mouse plasmacytoma cell line that harbors the transgenic shuttle vector lambdaLIZ.

The plasmacytoma cell line, TEPC 2372, was derived from a malignant plasma cell tumor that developed in the peritoneal cavity of a BALB/c mouse that harbored the transgenic shuttle vector for the assessment of mutagenesis in vivo, lambdaLIZ. TEPC 2372 was found to display the typical features of a BALB/c plasmacytoma. It consisted of pleomorphic plasma cells that secreted a monoclonal immunoglobulin (IgG2b/lambda), was initially dependent on the presence of IL-6 to grow in cell culture, contained a hyperdiploid chromosome complement with a tendency to undergo tetraploidization, and harbored a constitutively active c-myc gene by virtue of a T(6;15) chromosomal translocation. TEPC 2372 was further characterized by the ability to respond to in vitro exposure with 4-NQO (4-nitroquinoline-1-oxide), an oxidative model mutagen, with a vigorous dose-dependent increase in mutagenesis that peaked at a 7.85-fold elevation of mutant rates in lambdaLIZ when compared to background mutant rates in untreated controls. Cotreatment with 4-NQO and BSO (buthionine sulfoximine), a glutathione-depleting compound that causes endogenous oxidative stress, resulted in a 9.03-fold increase in the mutant frequency in lambdaLIZ. These results demonstrated that TEPC 2372, the malignant plasma cell counterpart of the lambdaLIZ-based in vivo mutagenesis assay, may be useful as an in vitro reference point for the further elucidation of oxidative mutagenesis in lymphoid tissues.

Animals↗
PubMed2001

Translocation remodeling in the primary BALB/c plasmacytoma TEPC 3610.

Myc-activating chromosomal 12;15 translocations, the hallmark mutations of inflammation-induced BALB/c plasmacytomas, have recently been shown to undergo remodeling by isotype switch-like genetic recombinations that remove approximately 180 kb of immunoglobulin heavy-chain sequence in the vicinity of the rearranged, expressed Myc gene. Here we combine cytogenetic data on the 12;15 translocation (SKY and FISH) with the molecular analysis of key junction sites (long-range PCR followed by DNA sequencing) to demonstrate that translocation remodeling occurred as an infrequent, stepwise, and disomic tumor progression event in the tetraploid, fully transformed, and transplantable plasmacytoma TEPC 3610. This result was used, in conjunction with previously obtained molecular data on five other primary plasmacytomas, to devise a hypothesis that predicts that the selective pressure to undergo translocation remodeling may be predetermined by the location of the break site in Myc. The pressure may be low if the break occurs 5' of the normal promoter region of Myc, but it may be considerably stronger if the break occurs 3' of the Myc promoter. Published 2001 Wiley-Liss, Inc.

Animals↗
PubMed2001

Comprehensive resource: Skeletal gene database.

The Skeletal Gene Database (SGD) is an integrated resource that provides comprehensive information about bone-related genes, mRNA, and proteins expressed in human and mouse, with rich links to numerous other electronic tools. SGD contains expressed sequence tag (EST) data from all the skeletal-related cDNA libraries that are available to the public. It supplies the query/data access analytic tools for users to search and compare each gene expressed in skeletal tissue(s). The results derived from EST tissue expression profiling will allow users to get the data on the mRNA copy numbers of each gene expressed in each tissue and its normalized value. From the SGD, researchers can obtain information regarding the name, symbol, size, exon/intron number, chromosomal location, LocusLink, and related disease (if any is known) of each gene. This electronic compendium also furnishes information on the protein of the corresponding gene including the protein size (amino acid number and molecular weight). It provides swift and ready access to other useful databases including OMIM, UniGene and PUBMED. The data will be updated regularly in step with current and future research, thereby providing what we hope will serve as a highly useful source of information and a powerful analytic tool to the scientific community.

Animals↗
PubMed2001

Auricular reconstruction.

Auricular defects occur from a variety of different causes and a wide array of reconstructive options are often necessary. This article presents a general algorithm for approaching the reconstruction of auricular defects. The spectrum of problems ranges from simple lacerations to superficial cutaneous defects to total avulsions. There are small tips that can help improve results with adjacent flaps as well as guidelines for total auricular reconstruction.

Cartilage↗
PubMed2001

Isolation of neuronal precursors from differentiating P19 embryonal carcinoma cells by neuronal T alpha 1-promoter-driven GFP.

The induction of pluripotent P19 embryonal carcinoma (EC) cells with retinoic acid results in their differentiation into cells that resemble neurons, glia, and fibroblasts. To isolate and enrich the developing neurons from heterogeneously differentiating P19 EC cells, we used a recently introduced protocol combining the expression of green fluorescent protein (GFP) driven by a tissue-specific promoter and fluorescence-activated cell sorting. Cells were transfected with the gene for GFP, which is under the control of the neuronal T alpha 1 tubulin promoter. After four days of retinoic acid treatment, GFP was specifically detected in cells undergoing neuronal differentiation. Sorting of fluorescent differentiating P19 EC transfectants yielded populations highly enriched in neuronal precursors and neurons. Immunoreactivity for nestin and neurofilament was observed in 80 and 25% of the sorted cell population, respectively. These results demonstrate that differentiated neuronal precursor cells can be efficiently isolated from differentiating pluripotent embryonic cells in vitro, suggesting that this method can reproducibly provide homogeneous materials for further studies on neurogenesis.

Antineoplastic Agents↗
PubMed2001

Acute funisitis of preterm but not term placentas is associated with severe fetal inflammatory response.

Acute funisitis, whose basic pathologic feature is umbilical vasculitis, constitutes a type of fetal inflammatory response to intrauterine infection. In the present study, a comparative analysis was performed between the clinicopathologic profiles of acute funisitis in term and preterm placentas along with measurement of fetal plasma interleukin 6 (IL-6) levels by specific immunoassay to assess the different biologic implications for the fetus. Acute funisitis in preterm placentas showed a significantly higher incidence of umbilical arteritis (P <.000001), higher fetal plasma IL-6 level (P <.0001), and higher prevalence of major perinatal morbidities (P <.0001). To assess the possible variation in fetal cell response to infectious agents according to gestational age, amnion cells and placental villous tissues obtained at different gestational ages were treated with bacterial lipopolysaccharides, and the IL-6 level of the culture media was assayed. Amnion cells and placental villous tissues from preterm placenta showed a more pronounced cytokine response than those from term placenta. The findings of this study indicate that the clinicopathologic significance of acute funisitis in term placentas is different from that of preterm placentas. Furthermore, they indicate that the robust inflammatory response of the fetus associated with elevated fetal plasma IL-6 level may reflect the biologic needs of the premature fetus to escape from the hostile intrauterine environment.

Amnion↗
PubMed2001

Scar revision via resurfacing.

Numerous techniques exist to treat noticeable facial scars. Techniques range from surgical excision to resurfacing. In this review of dermabrasion and laser resurfacing, we address the clinical considerations, techniques, adjuncts, and peri-operative management of scar resurfacing. Dermabrasion offers the advantage of being a tried-and-true technique familiar to surgeons. Recent advances in laser technology have resulted in the increased use of pulsed-dye lasers (PDLs), erbium:yttrium-aluminum-garnet (YAG) lasers, and CO(2) lasers. PDLs are effective for hypertrophic scars and show lower rates of recurrence compared with erbium:YAG and CO2 lasers. In contrast, erbium:YAG and CO(2) lasers are well suited to treating atrophic and acne scars. Chemical peels play a minor role in scar resurfacing and function primarily as an adjunct. Scar resurfacing is an integral part of scar camouflage and is often used in conjunction with excision and irregularization techniques.

Acne Vulgaris↗