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Biomedical subjects

B S Park

Publications and source records attributed to B S Park.

At least 19 recordsLinked to original sources
PubMed2000

Concurrence of replicative senescence and elevated expression of p16(INK4A) with subculture-induced but not calcium-induced differentiation in normal human oral keratinocytes.

Primary normal human oral keratinocytes (NHOKs) undergo differentiation in the presence of calcium concentrations higher than 0.15 mM in vitro, which is useful in investigating the mechanisms involved in the differentiation of epithelial cells. Serial subculture of NHOKs to the postmitotic stage also induces terminal differentiation. However, the detailed mechanisms of both differentiation processes remain substantially unknown. To investigate the molecular differences in these processes, NHOKs were induced to differentiate by exposure to 1.2 mM of calcium and by serial subculture to the postmitotic stage. To study whether the cells were induced to differentiate and to undergo replicative senescence, the amount of cellular involucrin and the expression of senescence-associated beta-galactosidase (SA-beta-gal) were measured respectively. The expression of replicative senescence-associated genes and the activity of telomerase from the differentiated cells were also determined. Both calcium treatment and serial subculture to the postmitotic stage notably elevated the cellular involucrin. The percentage of SA-beta-gal-positive cells was significantly elevated by the continued subculture, but such changes were not observed in keratinocytes exposed to calcium. The concentration of cellular p16(INK4A) protein was progressively increased by the continued subculture but was not changed by calcium treatment. On the other hand, the concentrations of cellular p53 were similar in both differentiation processes. However, telomerase activity was lost in NHOKs that had undergone differentiation by both calcium treatment and serial subculture. The results indicate that calcium-induced differentiation of NHOKs has similar characteristics to their serial subculture-induced differentiation, but that the differentiation processes are not identical, because calcium-induced differentiation does not concur with either replicative senescence or the gradually increased concentration of p16(INK4A).

Calcium↗
PubMed2000

Acute modulation of the extent of apoB mRNA editing and the relative rates of syntheses of apoB48 and apoB100 in cultured rat hepatocytes by osmotic and other stress stimuli.

The mRNA for apolipoprotein B (apoB) is edited by the enzyme APOBEC-1, which acts as part of a multiprotein complex or editosome. In cultured rat hepatocytes obtained from fed animals this results in the presence of edited and unedited apoB mRNA in a ratio of approximately 3:2 in the basal state. In this study we show that hyper-osmotic media, which induce cell shrinkage, resulted in an acute increase in the degree of editing of apoB mRNA (hypo-osmotic conditions had no effect). This increase was accompanied by a parallel and highly positively correlated change in the ratio of the rate of synthesis of apoB48 relative to that of apoB100. These changes occurred in the absence of any changes in the overall APOBEC-1 mRNA levels, indicating that the activation of editing occurred at a post-transcriptional level. Levels of total apoB mRNA were also unaffected by hyper-osmotic exposure of the cells indicating that changes in the relative rates of synthesis of apoB48 and apoB100 were due to post/translational events. Exposure of cells to anisomycin at concentrations (50 micrograms/ml) that inhibit protein synthesis or to the transcriptional inhibitor actinomycin D produced changes in the degree of apoB mRNA editing that were similar to those given by hyper-osmotic shock indicating that editing is able to respond acutely to transcriptional or translational inhibition. Anisomycin, at concentrations (50 ng/ml) that activate SAPK/JNK but do not inhibit protein synthesis, gave only a fraction of the effect of hyper-osmotic shock. SB203580, an inhibitor of p38 kinase, did not attenuate the effects of hyper-osmotic conditions on APOBEC-1 editing. These observations suggest that these MAPkinase pathways play a relatively minor part in the transduction of the osmotic stimulus to the editing mechanism. The hyper-osmotically-induced increase in apoB mRNA editing was also insensitive to PD98059 and wortmannin (inhibitors of MEK and PI3 kinase, respectively). These data provide evidence that apoB mRNA editing is capable of acute modulation independently of transcriptional or translational mechanisms and suggest that one or more components of the editosome may undergo post-translational activation.

APOBEC-1 Deaminase↗
PubMed2000

A switch in the direction of the effect of insulin on the partitioning of hepatic fatty acids for the formation of secreted triacylglycerol occurs in vivo, as predicted from studies with perfused livers.

The direct effects of insulin on hepatic triacylglycerol secretion are important because they may determine the degree of postprandial hyperlipidaemia, a known risk factor for the development of atherosclerotic lesions. Previous work from this laboratory, conducted on isolated perfused rat livers [Zammit, V.A., Lankester, D.J., Brown, A.M. & Park, B.S. (1999) Eur. J. Biochem. 263, 859-864], has indicated that the effect of insulin on hepatic triacylglycerol secretion is dependent on the prior physiological state of the donor animals. In this paper, we demonstrate that a switch in the direction of insulin action on hepatic partitioning of fatty acyl moieties towards triacylglycerol secretion also occurs in vivo between the fed, normoinsulinaemic state and the fasted or severely insulin-deficient states. The partitioning of fatty acids in the liver of awake, unstressed rats was studied using selective labelling of hepatic fatty acids during hyperinsulinaemic-euglycaemic clamps achieved through the use of hepatocyte-targeted liposome-encapsulated insulin preparations. The data show that, whereas in the fed, normoinsulinaemic state, insulinization of the liver raises the proportion of fatty acids directed towards secreted triacylglycerol, in the fasted or insulin-deficient states, insulin inhibits the partitioning of acyl moieties into secreted triacylglycerol. These data show that observations on the direction of insulin action on hepatic triacylglycerol secretion obtained using isolated perfused rat livers are reflected in the effects of the hormone on hepatic fatty acid partitioning in vivo. They offer an explanation for the positive relationship between chronic hyperinsulinaemia, hepatic VLDL-triacylglycerol secretion and hypertriglyceridaemia observed previously in insulin-resistant states.

Animals↗
PubMed2000

Murine bone marrow-derived mast cells exhibit evidence of both apoptosis and oncosis after IL-3 deprivation.

IL-3 deprivation has been reported to induce apoptosis of bone marrow-derived mast cells. In order to evaluate this type of cell death further, we employed trypan blue and propidium iodide stainings, photometric enzyme immunoassay, fluorescence measurement of caspase-3, DNA electrophoresis, flow cytometry and transmission electron microscopy. In this experiment, although several evidences supporting apoptosis were demonstrated some findings were not consistent with typical apoptosis. On the other hand, electron microscopical observation demonstrated that most cells from all the time phases after IL-3 deprivation showed the morphology of typical oncosis, i.e. cell swelling, disintegration of ultrastructure and subsequent karyolysis. Only a small number of cells from the later time phases showed apoptotic morphology. We here suggest that BMMCs undergo both apoptosis and oncosis after IL-3 deprivation and that the dominant type of prelethal change is oncosis in all time phases, although apoptosis also plays a partial role in the late time phases.

Animals↗
PubMed2000

Importance of valine at position 152 for the substrate transport and 2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane binding of dopamine transporter.

Human and bovine dopamine transporters (DAT) demonstrate discrete functional differences in dopamine (DA), 1-methyl-4-phenylpyridium (MPP(+)) transport, and cocaine analog binding. In a previous study, the functional analyses on the chimeras of human and bovine DAT have revealed that the region from residues 133 through 186 (encompassing the third transmembrane domain) is responsible for the substrate transport and cocaine analog binding. The present study has been carried out to determine the specific amino acid(s) conferring DAT functions by interchanging the amino acid residues in the corresponding region between human and bovine DAT. As described previously, the DA, MPP(+) transport, and 2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane (CFT) binding almost disappeared in chimera hb3 in which the region from residues 133 through 186 of bovine DAT was substituted into human DAT. Replacement of isoleucine, residue 152 of chimera hb3 (bovine DAT sequence), with valine, the human DAT residue at the identical position, remarkably restored the substrate transport and CFT binding to 76% to 98% of the human DAT values. Similarly, substitution of isoleucine for valine at position 152 in the human DAT reduced the substrate transport and CFT binding by 57% to 97%. Among other amino acids tested at position 152 of the chimera hb3, only alanine resulted in small but significant increases in the DAT functions ranging from 16 to 34%. Thus, valine at position 152 plays a crucial role for molecular mechanisms underlying the interactions of DA, MPP(+), and CFT with human DAT.

Amino Acid Sequence↗
PubMed1999

Insulin stimulates triacylglycerol secretion by perfused livers from fed rats but inhibits it in livers from fasted or insulin-deficient rats implications for the relationship between hyperinsulinaemia and hypertriglyceridaemia.

We determined whether the direction of the acute effect of insulin on hepatic triacylglycerol secretion is dependent on the prior physiological state or on the in vitro experimental system used. The effect of insulin on triacylglycerol secretion was studied using perfused livers isolated from rats under three metabolic conditions: fed normo-insulinaemic, 24-h fasted and fed, streptozotocin-diabetic (insulin-deficient). Insulin acutely activated triacylglycerol secretion (by 43%) in organs from fed, normo-insulinaemic animals, whereas it inhibited triacylglycerol secretion in livers isolated from fasted or insulin-deficient rats (by 30 and 33%, respectively). By contrast, in 24-h-cultured hepatocytes insulin invariably acutely inhibited triacylglycerol secretion irrespective of the metabolic state of the donor animals. It is concluded that the use of perfused livers enables the observation of a switch in the direction of insulin action on hepatic triacylglycerol secretion from stimulatory, in the normo-insulinaemic state, to inhibitory in the fasting or insulin-deficient state. The possible implications of this switch for the relationship between hyperinsulinaemia, increased hepatic very-low-density lipoprotein-triacylglycerol secretion and hypertriglyceridaemia observed in vivo are discussed.

Animals↗
PubMed1999

Vitamin D receptor polymorphism is associated with psoriasis.

Vitamin D receptor is a trans-acting transcriptional factor that mediates 1alpha,25-dihydroxyvitamin D3 action in the regulation of target gene expression. Recent studies have shown that clinical response of psoriasis to 1alpha,25-dihydroxyvitamin D3 is correlated with the vitamin D receptor mRNA expression level, which may be influenced by the genotype of the vitamin D receptor. In this study, we have explored a possible association between psoriasis and the polymorphism in the gene encoding the vitamin D receptor. We examined the allelic frequencies of the vitamin D receptor in psoriasis patients (n = 104) and in healthy controls (n = 104) by analyzing the restriction pattern of the polymerase chain reaction products. A significant increase in the frequency of the A allele (absence of the restriction site at intron 8) by ApaI restriction fragment length polymorphism was observed in psoriasis patients compared with that of the control group, and the tendency was more accentuated in early onset psoriasis. Odds ratios (95% confidence interval) for psoriasis of AA and Aa genotypes were 5.0 (1.3-19.1) and 2.4 (1.3-4.3), and odds ratios for early onset of AA and Aa genotypes were 6.4 (1.6-25.0) and 3.1 (1.7-5.9), respectively. Allele frequencies for A and a alleles were 0.317 and 0.683 in the psoriasis group and 0.168 and 0.832 in the control group (p = 0.001). A significant association between vitamin D receptor genotypes and the mean age at onset was observed (p < 0.05). Our findings suggest that allelic variance in the vitamin D receptor gene itself or other genes in linkage disequilibrium with this gene, could predispose to the development of psoriasis.

Adolescent↗
PubMed1999

Characterization of early and late onset psoriasis in the Korean population.

It has been proposed that two types of psoriasis can be characterized based upon age of onset. The purpose of our study was to investigate the characteristics of early and late onset psoriasis in the Korean population. A total of 986 psoriasis patients were included in this study, and the age of onset frequency proved to be bimodal. Family history in the first-degree relatives was significantly higher in the early onset group (< 40 years old) when compared with the late onset group (> or = 40 years old). A series of statistical analyses concerning the correlation between the extent of involvement and age of onset showed that earlier onset is related to more extensive involvement. A questionnaire survey concerning the influence of various external factors upon their psoriasis was given to a subgroup of 800 psoriasis patients. Multiple logistic regression analysis, controlled for confounding factors such as current age, sex and extent of involvement, revealed that early onset psoriasis patients showed significantly increased tendencies to worsen at times of psychological stress and in winter, and to improve in summer, compared with late onset psoriasis patients. In conclusion, distribution of the age of onset revealed two peaks in Korean psoriasis patients, and psoriasis with an onset prior to the age of 40 years was associated with increased inheritability, greater susceptibility to seasonal changes and more psychological stress than psoriasis with later onset.

Adolescent↗
PubMed1998

Cloning and expression of a novel gene encoding a new antibacterial peptide from silkworm, Bombyx mori.

We differentially screened a novel gene encoding a new antibacterial peptide from the immunized Bombyx mori cDNA library. The gene showed a similar structure to that of cecropin-family, encoding 59 amino acids including a putative leader peptide and mature peptide. The deduced peptide, named Enbocin, had conserved amino acid residues which have been known to play an important role in the antibacterial activities. Enbocin genomic sequence revealed that the transcription unit of Enbocin gene was about 1.2 kb, and the coding sequence was interrupted by an intron of 660 bases. Recombinant Enbocin, expressed under the control of the baculovirus polyhedrin promoter, demonstrated a broad range of antibacterial activities against gram positive and gram negative bacteria.

Amino Acid Sequence↗
PubMed1998

Factors influencing psoriasis: an analysis based upon the extent of involvement and clinical type.

A variety of external stimuli are accepted as important in modifying the severity of psoriasis. We sought to determine whether there is any difference in the influence of external factors on psoriasis in relation to extent of involvement or clinical type. A total of 870 psoriasis patients seen between 1982 and 1995 were categorized as mild, moderate, or severe on the basis of extent of the disease, and as guttate, nummular/plaque, or exfoliative/generalized pustular according to clinical type. We then performed a questionnaire survey concerning the influence of external factors such as seasonal changes, sunlight, stress, and pregnancy. These data sets were combined and analysed. The majority of patients stated favorable effects of summer, sunlight, and pregnancy and adverse effects of winter and stress. A statistically significant correlation was noted between the extent of psoriasis and the proportion of patients stating that their disease worsened at times of psychological stress (p < 0.01). We confirmed that psoriasis patients with more extensive involvement experience greater fluctuations in their condition, notice these changes, and therefore relate them to psychological stress.

Adolescent↗
PubMed1998

Dermal dendrocytes participate in the cellular pathology of experimental acute graft-versus-host disease.

In a well established murine model relevant to human disease, graft-versus-host disease results from recognition of recipient minor histocompatibility antigens by donor bone marrow-derived T lymphocytes. Previous studies suggest that factor XIIIa-positive dermal dendrocytes may be involved in the pathogenesis of disorders involving antigen presentation to T cells and dermal fibrosis. This study was undertaken to determine (i) whether normal murine skin contains factor XIIIa-positive dermal dendrocytes, and (ii) whether such cells participate in the pathophysiology of acute graft-versus-host disease. Graft-versus-host disease was produced using B10.BR CD8+ donor T cells administered to CBA recipients. Skin samples were collected weekly for a 5-week period and evaluated by immunohistochemistry and electron microscopy. Our data indicate that normal murine dermis contains factor XIIIa-positive cells localized primarily around deep dermal microvessels. Ultrastructural analyses reveal these cells to have long processes, pinocytotic vesicles, fibronexuses, and intimate associations with mast cells. During graft-versus-host disease, factor XIIIa-positive dendrocytes appeared within the superficial dermis. By ultrastructure, the dendrocytes were hypertrophic and highly branched, and demonstrated an intimate relationship with neighboring cells. In conclusion, factor XIIIa-positive dendrocytes comprise a normal component of the murine dermis and undergo alterations in experimental acute graft-versus-host disease consistent with participation in disease pathophysiology.

Acute Disease↗
PubMed1997

Promoter sequences of two homologous pectin esterase genes from Chinese cabbage (Brassica campestris L. ssp. pekinensis) and pollen-specific expression of the GUS gene driven by a promoter in tobacco plants.

The promoter regions of two genomic clones, GBAN215-6 and GBAN215-12 from Chinese cabbage (Brassica campestris L. ssp. pekinensis), were sequenced. The nucleotide sequences of their promoter regions were compared with that of the Bp19 pollen-specific gene of Brassca napus. High nucleotide sequence homologies were observed among these three genes in the region between 210 bp upstream and the putative transcription start site. A sequence motif TGTGGTG, which is similar to that of the PB core motif (TGTGGTT) of two tomato pollen-specific genes, LAT52 and LAT56, was present in these two cloned genes. To determine regulatory sequences responsible for the anther-specific expression of the gene BAN215-6, two recombinant plasmids, pBPE3 (-274- + 109) and pBPE4 (-816- + 109) containing different lengths of the promoter fused with the GUS gene, were constructed and introduced into tobacco plants by Agrobacterium-mediated transformation. The result showed that the 383 bp (-274- + 109) of the BAN215-6 promoter region was sufficient for the anther-specific expression of the GUS gene. The GUS expression in a tobacco plants transformed with these constructs was first detected in uninucleate microspores and persisted at in vitro germinated pollen tubes. The expression level was increased during anther development, reaching the highest level in mature pollens.

Brassica↗
PubMed1997

Planar gradient coil design by scaling the spatial frequencies of minimum-inductance current density.

Gradient coil inductance has been remarkably reduced by the minimum-inductance design technique, which minimizes the magnetic energy stored by the gradient coil. The planar gradient coil designed by this technique, however, often has poor magnetic field linearity. Scaling the spatial frequencies of the current density function derived by this method, the magnetic field linearity of the planar gradient coil can be greatly improved with a small sacrifice of gradient coil inductance. A figure of merit of the planar gradient coil has been found to be improved by scaling the spatial frequencies.

Equipment Design↗
PubMed1997

Malignant proliferating trichilemmal tumor showing distant metastases.

We describe a case of malignant proliferating trichilemmal tumor showing multiple distant metastases. For 10 years, the patient had had a round mass in the occiput, which recurred twice after wide excisions, and later metastasized to the cervical lymph nodes, periparotid area, and chest. Each time the lesions were excised, histologic specimens demonstrated a proliferating trichilemmal tumor with increasing nuclear atypia. Serial specimens showed increasing Ki-67 positivity as the extent of the tumor advanced.

Adult↗
PubMed1997

Disseminated superficial porokeratosis in a patient with chronic liver disease.

A 55-year-old male suffering from liver cirrhosis presented with diffuse annular hyperkeratotic papules of abrupt onset on the trunk and extremities. Histopathologic examination revealed cornoid lamella and eosinophilic spongiosis. He did not receive any medications other than cephalosporin for spontaneous bacterial peritonitis. A review of the literature revealed that three cases developed porokeratosis when their liver function declined and that, in one case, the porokeratosis disappeared spontaneously with liver transplantation. Although the precise mechanism is unclear, there is evidence demonstrating immunoincompetence in cirrhosis. Even though we did not perform immunologic studies or exclude the possibility of drug-induced porokeratosis in our case, it is conceivable that porokeratosis can be triggered by immunosuppression due to liver cirrhosis per se.

Humans↗
PubMed1997

Photoprotective effect of calcipotriol upon skin photoreaction to UVA and UVB.

It has been shown that 1,25-dihydroxyvitamin D3 has a photoprotective effect against UVB injury in mouse skin and cultured rat keratinocytes by induction of metallothionein (MT). Calcipotriol is a synthetic analogue of 1,25-dihydroxyvitamin D3 with equipotent cell regulating properties, but with a lower risk of calcium-related side effects. The aim of the present study was to see whether calcipotriol has a photoprotective property both in vitro and in vivo. We examined the effect of calcipotriol on UV-induced damage of cultured human keratinocytes through a cell viability assay, and measurement of DNA synthesis by cultured keratinocytes, on UV-induced damage of mouse skin and on minimal erythema dose (MED). We found that calcipotriol was protective against UVB-induced reduction in DNA synthetic activity of cultured keratinocytes in relatively low doses (20 and 40 mJ/cm2) of UVB. With phototesting following application of calcipotriol, five subjects among 10 healthy volunteers and three among six psoriasis patients showed an increase in MED compared with the vehicle-treated site. These findings imply that calcipotriol may be photoprotective and that more extensive studies with various doses of UV irradiation and modes of calcipotriol delivery are required.

Administration, Cutaneous↗