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Biomedical subjects

C Park

Publications and source records attributed to C Park.

At least 181 records · Page 10Linked to original sources
PubMed1996

Differential expression and butyrate response of human alkaline phosphatase genes are mediated by upstream DNA elements.

Human placentas express high levels of the placental alkaline phosphatase (PLAP) gene and low levels of a highly related gene, germ cell AP (GCAP). Malignant transformation of the placenta is accompanied by a reversal of this pattern of expression. Three Sp1-binding GC-rich DNA elements (sites I-III) located within the first 156 base pairs upstream of the GCAP gene have been shown to direct optimal GCAP gene expression in choriocarcinoma cells. Here we show that the first 100 base pairs upstream of the GCAP gene, which contains sites I and II, constitutes a minimal GCAP promoter. The simultaneous presence of both sites I and II is necessary for GCAP expression and its induction by sodium butyrate. The PLAP promoter directs only a very low level of gene expression in choriocarcinoma cells; the expression does not respond to butyrate. The -100/-1 DNA regions between the GCAP and PLAP promoters differ by only eight base pairs. However, the GC-rich stretches in sites I and II of the GCAP promoter are disrupted in the corresponding PLAP promoter. This disruption blocks or markedly reduces the binding of choriocarcinoma nuclear factors to the PLAP promoter, leading to a reduction in expression and a loss of butyrate response. We further demonstrate that nucleotides -75 to -58 in both AP promoters, which bind a human Y-box binding protein, appear to down-regulate GCAP expression.

Alkaline Phosphatase↗
PubMed1996

A pathologic study of Hodgkin's disease in Korea and its association with Epstein-Barr virus infection.

BACKGROUND: The incidence of Hodgkin's disease (HD) in Korea and other Asian countries is much lower than in western countries and its association with the Epstein-Barr virus has not been well characterized. METHODS: We evaluated the clinical, morphologic, and immunohistochemical features of 87 patients with Hodgkin's disease and also analyzed patients for Epstein-Barr virus (EBV) using in situ hybridization for EBV DNA, RNA, and latent membrane protein (LMP1). RESULTS: There were 68 males and 19 females, with a mean age of 38 years. Mixed cellularity was the most prevalent subtype. Expression of EBV RNA (EBER:EBV-encoded RNA) was detected in 60 of 87 cases (69%): 1 of 1 (100%) with lymphocyte predominance, nodular; 4 of 7 (57%) with lymphocyte predominance, diffuse; 10 of 17 (59%) with nodular sclerosis; 38 of 51 (75%) with mixed cellularity; and 7 of 11 (64%) with lymphocyte depletion. Positivity was higher in advanced clinical stages; 4 of 7 patients (57%) with Stage I; 6 of 12 patients (50%) with Stage II: 7 of 9 patients (75%) with Stage III; and 5 of 5 patients (100%) with Stage IV HD EBV DNA was detected in 9 of 25 cases tested (36%). LMP1 was seen in 39 of 87 cases (45%). EBER and LMP1 positivity were higher in children and older adults than in adults aged between 15-50 years. Immediate early mRNAs (BHLF:Bam H-fragment, lower strand frame) was seen in a single patient. CONCLUSIONS: HD in Korea showed a high incidence of mixed cellularity subtype and a high prevalence of EBV. EBV was detected in all subtypes, including a case of nodular lymphocytic predominance, and in all age groups, and showed correlation with mixed cellularity subtype and higher clinical stage. The expression of EBER and LMP were more frequently seen in children and older adults, suggesting a lowered immune surveillance in those age groups or a different pathophysiology of HD among different age groups.

Adolescent↗
PubMed1996

Genetically probing the regions of ribose-binding protein involved in permease interaction.

The ribose-binding protein (RBP) of Escherichia coli, located in the periplasm, binds to ribose and mediates transport and chemotaxis. The regions on the tertiary structure of RBP that interact with the membrane permease, an ABC transporter, were genetically probed by screening a mutation using the chimeric receptor Trz. Trz is a hybrid protein between the periplasmic domain of chemoreceptor Trg and the cytoplasmic portion of osmosensor EnvZ, which provides a system for monitoring the chemotactic interaction of RBP on MacConkey agar plates when coupled with a reporter lacZ fused to an ompC gene. The expression of ompC can be increased by an interaction of ribose-bound RBP with Trz. A transport defect, either in the binding protein or in the membrane permease, causes a signalling-constitutive Lac+ phenotype of Trz even in the absence of ribose. This appears to be due to the presence of a small amount of ribose, which is normally taken up by the high-affinity transport system. By taking advantage of this, we have designed a system for genetic screening that permits a selection for mutations in the binding protein, causing specific defects in permease interaction but not in tactic interaction. Mutant RBPs that were isolated were unable to perform normal ribose uptake and to utilize ribose as a carbon source, while other functions such as taxis and sugar-binding properties were not substantially affected. The mutational changes were repeatedly found in several residues of RBP, concentrating on three surface regions and comprising two domains of the tertiary structure. We suggest that the two regions, including residues 52 and 166, are specifically involved in the permease interaction while the third region, including residues 72, 134, and others, recognizes both the permease and the chemosensory receptor.

ATP-Binding Cassette Transporters↗
PubMed1996

Cloning and characterization of cDNA for human adenylate kinase 2A.

We have isolated and characterized a cDNA clone encoding human adenylate kinase 2A (AK2A) from cDNA libraries of fetal liver origin. The complete nucleotide sequence of the cloned 889 nucleotide cDNA fragment indicated that the deduced gene product of human AK2A is composed of 239 amino acids with a molecular weight of 26 kD. Comparison of these nucleotide and amino acid sequences with the corresponding sequences of bovine AK2A and rat AK2 revealed a high degree of conservation. It showed 91% and 98% homologies in DNA and amino acid sequences, respectively, with bovine AK2A throughout the full open reading frame. RNA blot analysis revealed that three species of mRNA were present with approximate sizes of 3.4, 2.1, and 1.0 kb. This gene was expressed in E. coli cells and the recombinant protein was enzymatically active.

Adenylate Kinase↗
PubMed1996

Isolation and characterization of 45 polymorphic microsatellites from the bovine genome.

A small-insert bovine genomic library was constructed in pBluescript II SK(+) and enriched for microsatellites by selective rescue of single-stranded pBluescript DNA carrying (CA)n/(TG)n tandem repeats. Approximately 50% of the clones in the enriched library contained (CA)n repeats or CA-rich sequences. Sequencing of clones selected for (CA)n repeats resulted in the identification and characterization of 45 (CA)n polymorphic microsatellites. Genotyping in 9 large paternal half-sib families indicated that 40 of these microsatellite markers exhibit autosomal Mendelian inheritance. The numbers of alleles range from 2 to 18, with an average of 6.3 per locus. The polymorphic microsatellite markers we have identified and characterized will contribute to the construction of a high-resolution linkage map of bovine genome.

Animals↗
PubMed1996

Immunohistochemical characteristics of colorectal carcinoma with DNA replication errors.

It has recently been shown that nearly all cancers from hereditary nonpolyposis colorectal cancer syndrome (HNPCC), as well as a subset of sporadic colorectal cancers, have DNA replication errors (RER) at repeated sequences distributed throughout their genome. These RER-positive cancers had pathological characteristics of more frequent exophytic growth, large size and poor differentiation. However, the histogenesis and immunohistochemical characteristics of these RER-positive cancers are not known. The poorly differentiated colorectal carcinomas are heterogenous group of neoplasms that differ in their histologic appearance and prognosis. We therefore examined RER from 69 sporadic colorectal carcinomas of poor differentiation and detected in 23 cases (33%). The pathological features of RER-positive cancers differed from those without RER. The RER-positive cancers had marked preponderance of proximal location (16/23, 70%, vs. 20/46, 43%, p < 0.04), no glandular differentiation with intense peritumoral immune response (12/23, 52% vs. 6/46, 13%, p < 0.001). Immunohistochemically, most of the RER-positive cancers were reactive for cytokeratin (22/23, 96%) and CEA (17/23, 74%), and negative for NSE (2/23, 9%), chromogranin (3/23, 13%) and synaptophysin (0/23, 0%). In comparison to 46 RER-negative tumors, RER-positive cancer had less frequent CEA expression (17/23, 74% vs. 44/46, 96%, p = 0.01). We conclude that the RER-positive colorectal carcinomas have histologic characteristics of predominantly solid, poorly differentiated adenocarcinomas with intense peritumoral reaction and the tumors should be distinguished from neuroendocrine carcinomas and other more aggressive non-glandular tumors of the colon.

Biomarkers, Tumor↗
PubMed1996

Peritoneoscopic liver biopsy findings in asymptomatic chronic HBsAg carriers with normal liver function tests and no hepatomegaly.

Asymptomatic chronic HBsAg carriers with normal liver function tests are, in general regarded as having no liver pathology. Most of the histologic findings in asymptomatic chronic carriers have been reported from areas with low incidence of Hepatitis B virus (HBV) infection, such as North America and Western Europe. It is well known that there are many differences in HBV infection between low and high endemic areas, but there have been few reports on the histologic findings of asymptomatic chronic HBsAg carriers from endemic areas. The present study was undertaken in Korea which is one of the endemic areas for HBV infection and was designed to assess the prevalence of chronic liver disease by peritoneoscopic liver biopsy among asymptomatic chronic HBsAg carriers and to make a basis for the follow-up of asymptomatic chronic HBsAg carriers according to the results obtained. One hundred and ten asymptomatic HBsAg-positive carriers with normal liver function tests and no hepatomegaly were included in the study. Final diagnosis by peritoneoscopic liver biopsy revealed that of the 110 asymptomatic carriers only 27 (24.5%) had a histologically normal liver, while 51 (46.4%) had chronic liver diseases, and the remaining 32 (29.1%) had nonspecific histologic abnormalities (nonspecific reactive changes in 18 cases, cholestasis in 6 cases, and fatty change in 8 cases). Of the 51 patients with chronic liver diseases, 3 had liver cirrhosis, 4 chronic active hepatitis with cirrhosis, 11 chronic active hepatitis and 33 chronic persistent hepatitis. The frequency of liver cirrhosis and chronic active hepatitis with cirrhosis was significantly high in the over 30 years of age group (12.1%) than in the under 30 years of age group (0%; p = 0.011 by Fisher's exact test). In conclusion, 46.4% of the Korean asymptomatic chronic HBsAg carriers with normal liver function tests and no hepatomegaly had chronic liver disease. This finding contrasted with reports from low incidence areas of HBV infection. Our results suggest that in endemic areas, a liver biopsy should be considered to assess the status of liver disease in asymptomatic chronic HBsAg carriers even if liver function tests are normal and hepatomegaly is absent, and the result can be used as a basis for the follow-up of each asymptomatic chronic HBsAg carriers.

Adolescent↗
PubMed1996

Expression of NF2 gene product merlin in arachnoid villi and meningiomas.

Neurofibromatosis type 2 (NF2) gene encodes a novel 595 amino acid protein named merlin. Recently, Ruttledge et al demonstrated inactivation of NF2 gene in approximately 60% of sporadically occurring meningiomas. Merlin is thought to physiologically exist beneath the cell membrane, and to form a part of modulation in signal transduction, for example, information concerning contact inhibition. In NF2-related tumors, it is supposed that the mutation of merlin results in loss of this signal transduction leading to tumorigenesis. In this paper, we investigated the expression of NF2 gene product merlin in arachnoid villi and meningiomas. The immunohistochemical staining of merlin showed a striking contrast between arachnoid villi and meningiomas. In arachnoid cells, merlin was labeled in the whole cytoplasm, but not within the nuclei. In contrast, in meningiomas, immunoreactivity of merlin was mainly seen in the nuclei. These results suggest that arachnoid cells with normal merlin are capable of normal signal transduction, whereas meningioma cells with mutated merlin show impairment of signal transduction which may lead to tumorigenesis.

Arachnoid↗
PubMed1995

Effect of folding on the export of ribose-binding protein studied with the genetically isolated suppressors for the signal sequence mutation.

Ribose-binding protein (RBP) has a bilobate structure and functions in the periplasm of Escherichia coli. Mutations that affect the folding of RBP were isolated as intragenic suppressors for the export-defective signal sequence mutation. Of 13 different mutational changes found in the mature region, 12 were located in the several peptides forming the N-domain, and one in the C-domain. Translocation kinetics of mutant proteins were analyzed by pulse-labeling and chase experiments, showing the recovery of precursor processing in the range of 42 to 70%. Folding properties of seven mutant RBPs purified were investigated in vitro by means of tyrosine fluorescence. The stability of the mutant proteins, estimated by equilibrium analysis in the presence of denaturant, were reduced by 2.1 to 5.1 kcal/mol of changes in free energy of unfolding. All the mutant proteins showed retardation in folding rate by 4.4 to 63-fold compared to wild-type while unfolding was little affected. The only exception was the L129Q that has a change in the C-domain resulting in unstability due to faster unfolding. Our approach took advantage of an involvement of the folding process in protein export, which was genetically employed to dissect the folding pathway of RBP. As a result, amino acid residues that are specifically involved in the folding pathway of RBP were identified. Most of them are concentrated in one of the subdomains, suggesting that the folding event in the N-domain of RBP is crucial in the rate-determining step.

Calorimetry↗
PubMed1995

Genetic mapping of F13A to BTA23 by sperm typing: difference in recombination rate between bulls in the DYA-PRL interval.

Our objective was to extend the linkage and comparative maps of BTA23 by determining whether the structural gene for the A subunit of blood coagulation factor XIII (F13A) is linked to BoLA-DYA, a centromeric marker, or the distally located gene encoding prolactin (PRL). Bovine F13A was mapped relative to DYA and PRL in an experiment that examined segregation of alleles in 176 sperm. Genotyping was performed by PCR-RFLP for all loci, following amplification of the haploid genome by primer extension preamplification. F13A was found to be linked to PRL (theta = 0.314 +/- 0.038). The most likely order is DYA-PRL-F13A (odds > 10(4):1). This result demonstrates conservation of synteny between BTA23 and most of HSA6p. Surprisingly, theta DYA-PRL was 0.310 +/- 0.039, 83.4% greater (P < 0.02) than we found for another bull (Van Eijk et al., Mamm. Genome 4: 113, 1993). The difference in recombination rate in the DYA-PRL interval provides further evidence for an unusual recombination hot spot between the bovine Mhc class IIa and class IIb subregions and suggests that bull-specific maps may be necessary for marker-assisted selection.

Animals↗
PubMed1995

Induced premature G2/M-phase transition in pachytene spermatocytes includes events unique to meiosis.

Little is known about the control of events ending the lengthy prophase of meiosis I and leading to the G2/M-phase transition in mammalian spermatocytes, primarily because the relevant late pachytene, diplotene, and MI cells are present in low numbers in the testis and it is not possible to isolate them in significant numbers. We have utilized short-term cultures of pachytene spermatocytes from the mouse to study events of the G2/M cell-cycle transition induced by the protein phosphatase inhibitor okadaic acid (OA). Treatment of cultured pachytene spermatocytes with OA induced a rapid and premature onset of events leading to the M phase, visualized cytologically by nuclear envelope breakdown and chromosome condensation. After OA treatment, condensed chromosomes were seen as bivalents, not as univalents. Treatment with OA induced disassembly of synaptonemal complexes and resolution of crossovers as cytologically visible chiasmata. Chiasmata counts were similar in treated cells and control cells. Thus, surprisingly, even though the treated cells were in the pachytene substage of meiotic prophase, events of recombination were apparently completed to the point of chiasma formation in the majority of these cells. The sex chromosomes, forming the sex body of the pachytene spermatocyte, lagged behind the autosomal chromosomes in their condensation and progression toward the M phase. Treatment with OA induced an increase in histone H1 kinase activity, generally used as an indicator of metaphase-promoting factor (MPF) activity; furthermore, the OA-induced cell-cycle transition does not require new protein synthesis. These results suggest that OA treatment overrides a cell-cycle checkpoint control that normally keeps pachytene spermatocytes in a lengthy prophase and that this control may be exerted by regulation of protein phosphorylation status.

Animals↗
PubMed1995

Benchmark Dose Workshop: criteria for use of a benchmark dose to estimate a reference dose.

The purpose of the Benchmark Dose Workshop was to assess the feasibility and implications of replacing the no observed adverse effect level (NOAEL) with a benchmark dose (BMD) when deriving reference doses and concentrations (RfDs and RfCs). The workshop participants supported the use of the BMD method to remove many of the limitations inherent in using the NOAEL approach. Participants endorsed in general the use of a BMD for all quantal noncancer health effects and endorsed in particular the BMD for assessing developmental toxicity based on data presented at the workshop. The discussions of implementation recognized the need to demonstrate that changing from a NOAEL to a BMD gives the risk manager more certain information on which to base decisions. Most participants agreed that the current NOAEL-derived RfDs and RfCs are sufficiently protective and should only be changed as data become available for estimating a BMD. It was recognized that to achieve general acceptance of the BMD approach, it will have to be applied to a variety of endpoints.

Animals↗
PubMed1995

Selective targeting of trabecular meshwork cells: in vitro studies of pulsed and CW laser interactions.

The purpose of the present study was to selectively target pigmented trabecular meshwork cells without producing collateral damage to adjacent non-pigmented cells or structures. The ability to selectively target trabecular meshwork cells without coagulation, while preserving the structural integrity of the meshwork, could be a useful approach to study whether the biological response of non-coagulative damage to the trabecular meshwork and trabecular meshwork cells is similar to that seen with coagulative damage to the trabecular meshwork which occurs with argon laser trabeculoplasty. This approach also may be useful to non-invasively deplete trabecular meshwork cells while preserving the structural integrity of the trabecular meshwork in an animal model. A mixed cell culture of pigmented and non-pigmented trabecular meshwork cells were irradiated with Q-switched Nd-YAG and frequency-doubled Nd-YAG lasers, microsound pulsed dye-lasers, and an argon ion laser in order to define a regime where laser absorption would be confined to pigmented trabecular meshwork cells, thereby permitting selective targeting of these cells without producing collateral thermal damage to adjacent non-pigmented cells. Pulse durations ranged from 10 nsec to 0.1 sec. A fluorescent viability/cytotoxicity assay was used to evaluate laser effects and threshold energies, and cells were examined morphologically by light and TEM. Selective targeting of pigmented trabecular meshwork cells was achieved with pulse durations between 10 nsec and 1 microsec and 1 microsec without producing collateral thermal or structural damage to adjacent non-pigmented trabecular meshworks cells when examined by light and transmission electron microscopy. Pulse durations greater than 1 microsec resulted in non-selective killing of non-pigmented trabecular meshwork cells. Threshold radiant exposures were as low as 18 mJ cm-2, and increased at longer wavelengths, longer pulse durations and lower melanin contents within the cells. It is concluded that selective targeting of pigmented trabecular meshwork cells can be achieved using pulsed lasers with low threshold radiant exposures avoiding collateral thermal damage to adjacent non-pigmented trabecular meshwork cells. This approach can be readily applied in vivo.

Cell Survival↗
PubMed1995

Oxygen desaturation on swallowing as a potential marker of aspiration in acute stroke.

We have assessed the measurement of oxygen saturation (SaO2) as a means of detecting aspiration in patients with stroke. For 10 weeks all acute stroke [AS] admissions were seen within 48 hours. Basal SaO2 was measured by pulse oximetry. Patients swallowed 10ml water while sitting up and SaO2 was noted for 2 minutes. Two control groups [young, fit (YF) and inpatient age- and sex-matched, non-neurological disease (IP)] underwent the same assessment. AS subjects underwent independent assessment of swallowing by a speech and language therapist (SLT). Exclusion criteria comprised impaired consciousness, other neurological disease and chest infection. Forty-nine AS subjects [20 men; aged 46-93 (mean 71) years], 55 YF [26 men; aged 18-55 (mean 32) years] and 65 IP [28 men; aged 53-96 (mean 71) years] were studied. Mean (SD) SaO2 fall in AS subjects [2.6 (2.9)%)] was significantly more than in YF [1.1 (0.8)%] or IP [1.1 (0.9)%]. The lower 95% confidence limit for variation in SaO2 did not differ between YF and IP (3.0% 'fall'); 19 (39%) AS subjects desaturated below this 95% lower confidence limit. Mean (SD) SaO2 fall was significantly more in SLT-graded 'aspirators' [4.6 (2.7)%] than 'nonaspirators' [1.4 (1.0)%]. We conclude that (1) a fall in SaO2 on swallowing fluid is common in patients with acute stroke; (2) the presence or absence of desaturation agrees statistically with SLT assessment of aspiration; (3) SaO2 measures may aid bedside assessment of swallowing.

Adolescent↗