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K Y Chung

Publications and source records attributed to K Y Chung.

At least 19 recordsLinked to original sources
PubMed1999

Changes in axon arrangement in the retinofugal [correction of retinofungal] pathway of mouse embryos: confocal microscopy study using single- and double-dye label.

The changes in quadrant-specific fiber order in the retinofugal pathway of the C57-pigmented mouse aged embryonic day 15 were investigated by using single- (1,1'-dioctadecyl-3,3,3',3'-tetramethyl-indocarbocyanine perchlorate; DiI) and double- (N-4-4-didecylaminostyryl-N-methylpyridinium iodide; 4Di-10ASP in addition to DiI) labeling techniques. At this earliest stage of development, before any fibers arrive at their targets, retinal axons display a distinct quadrant-specific order at the optic stalk close to the eye. This order gradually disappears along the stalk and is virtually lost at the chiasm, as shown in single-label preparations. The double-label preparations, in which the population peaks of fibers from two retinal quadrants are shown simultaneously in an image, show a fiber arrangement at the chiasm that is different from the pattern seen in the single-label preparations. A distinct and consistent preferential distribution of fibers from different retinal quadrants is shown in the chiasm. Before the midline, the central part of the cross section of the chiasm is dominated by dorsal fibers, whereas the rostral and caudal parts of the chiasm are dominated by ventral nasal and ventral temporal fibers, respectively. Moreover, the double-label preparations demonstrate a major reshuffling of fiber position after the fibers cross the midline. Fibers from ventral retina are shifted gradually to a rostral position at the threshold of the optic tract, whereas fibers from dorsal retina are shifted caudally. These changes in fiber position indicate a postmidline location in the chiasm, where fibers are re-sorted in accordance with their origins in the dorsal ventral axis of the retina, and suggest a change in axon response to guidance signals when the fibers cross the midline of the chiasm. These changes in fiber order may also be related to the re-sorting of fibers according to their ages at the postmidline chiasm.

Animals↗
PubMed1999

Nuclear factor-kappa B mediates TNF-alpha inhibitory effect on alpha 2(I) collagen (COL1A2) gene transcription in human dermal fibroblasts.

Among its plethora of activities as an inflammatory mediator, TNF-alpha has potent regulatory control on extracellular matrix production and degradation. Earlier studies have documented that TNF-alpha inhibits type I collagen gene (COL1A2) expression at the transcriptional level, but the characterization of the transcription factors involved has been elusive. In the present study, using transient cell transfection of human dermal fibroblasts with a battery of 5' end deletion/chloramphenicol acetyltransferase (CAT) reporter gene constructs, we have characterized the TNF-alpha response element of the COL1A2 promoter. The TNF-alpha response element was attributed to a specific region that comprises noncanonical activator protein-1 (AP-1) (CGAGTCA) and NF-kappa B (AGAGTTTCCC) binding sites. TNF-alpha effect was eliminated by a 2-bp substitution mutation in the NF-kappa B1 binding half site of the NF-kappa B cis element. Electrophoretic mobility shift assays (EMSA) showed that recombinant human NF-kappa B heterodimers as well as NF-kappa B1 and RelA homodimers, but not AP-1, were capable of binding this element. Further, EMSA with human fibroblast nuclear extracts demonstrated enhanced binding of a single, specific complex within 5 min of TNF-alpha stimulation, which reached a plateau by 1 h and was not affected by preincubation of cells with cycloheximide. Gel supershift assays identified the complex as the NF-kappa B (p50/p65) heterodimer, whereas Abs to nuclear factor of activated T cells (NF-AT) and Jun family members failed to recognize the complex. These data suggest that in fibroblasts TNF-alpha activates and initiates the nuclear translocation of NF-kappa B that binds a divergent NF-kappa B element and plays a critical role in the observed inhibition of alpha 2(I) collagen gene transcription.

Carrier Proteins↗
PubMed1999

Common blue naevus with satellite lesions: possible perivascular dissemination resulting in a clinical resemblance to malignant melanoma.

We report a case of common blue naevus with polymorphous guttate and linear satellite lesions, thereby mimicking peripherally spreading malignant melanoma. Histopathologic examination showed that the naevus cells are clustered around blood vessels in the primary as well as satellite lesions, suggestive of spreading of the naevus cells along the perivascular space. Such biological behaviour resulting in a clinical manifestation of a malignant melanoma-like lesion is a rarity in common blue naevus, a benign cutaneous disorder that is devoid of a malignant potential, and has not been described before.

Adult↗
PubMed1999

The effects of early prenatal monocular enucleation on the routing of uncrossed retinofugal axons and the cellular environment at the chiasm of mouse embryos.

Whereas it has been shown that early monocular enucleations produce a reduction in the uncrossed pathway from the surviving eye in rats and ferrets, similar evidence for binocular interactions in the development of the uncrossed component in mice is currently open to question. Using retrograde tracing, we have investigated the time course of changes in the uncrossed retinofugal pathway immediately after the early prenatal monocular enucleation in mouse embryos. Removal of one eye from C57 pigmented mice at embryonic day (E) 13 does not cause a reduction of the earliest uncrossed component from the central retina examined 1 day later at E14. However, a substantial reduction of the uncrossed pathway is seen at E15, the time when the major uncrossed projection first arises from the ventral temporal retina. This reduction is greater in E16 one-eyed embryos, indicating that most retinal axons from the ventral temporal retina rely on a binocular interaction for their turning at the chiasm. Further, early removal of one eye at E13 does not produce any obvious changes in the cytoarchitecture of RC-2-immunopositive radial glia at the chiasm, nor of the stage-specific antigen-1 (SSEA-1) -expressing neurons. This lack of changes in the cellular organization at the chiasm indicates that the reduction of the uncrossed pathway is probably produced by an elimination of binocular fibre interactions at the chiasm, rather than through a degenerative change of cellular elements at the chiasm as a consequence of the eye removal procedure.

Animals↗
PubMed1999

Laboratory evaluation of a protocol for personal sampling of airborne particles in welding and allied processes.

A new European/International Standard (ISOprEN 10882-1) on the sampling of airborne particulates generated during welding and allied processes has been proposed. The use of a number of samplers and sampling procedures is allowable within the defined protocol. The influence of these variables on welding fume exposures measured during welding and grinding of stainless and mild steel using the gas metal arc (GMA) and flux-cored arc (FCA) and GMA welding of aluminium has been examined. Results show that use of any of the samplers will not give significantly different measured exposures. The effect on exposure measurement of placing the samplers on either side of the head was variable; consequently, sampling position cannot be meaningfully defined. All samplers collected significant amounts of grinding dust. Therefore, gravimetric determination of welding fume exposure in atmospheres containing grinding dust will be inaccurate. The use of a new size selective sampler can, to some extent, be used to give a more accurate estimate of exposure. The reliability of fume analysis data of welding consumables has caused concern; and the reason for differences that existed between the material safety data sheet and the analysis of fume samples collected requires further investigation.

Air Pollutants↗
PubMed1999

Erythema dyschromicum perstans in early childhood.

Erythema dyschromicum perstans (EDP) is a rare disorder characterized by asymptomatic, slowly progressive, ash-gray macular pigmentation of the skin which usually occurs from age 5 through adult life. We have experienced two cases of EDP in children aged 2 and 3, both exceptionally younger than the previously reported cases. We therefore suggest that EDP should be included in the differential diagnosis of pigmentary disorders occurring at an early age.

Age Factors↗
PubMed1999

Regulation of type I collagen and interstitial collagenase mRNA expression in human dermal fibroblasts by colchicine and D-penicillamine.

Sclerosis is a disease process in which idiopathic hardening occurs in the skin and/or internal organs as a result of the accumulation of type I collagen, induced mainly by transforming growth factor-beta. Colchicine and D-penicillamine are widely used for its treatment. Their effects are known to be due to post-translational down-regulation of type I collagen synthesis, with colchicine also up-regulating interstitial collagenase. To determine whether or not they have any pre-translational effect on type I collagen and MMP-1, and also to observe their effects on the action of TGF-beta, cultured neonatal foreskin fibroblasts were treated with colchicine and D-penicillamine, singly and together. The amount of type I collagen and MMP-1 mRNA were quantitated by Northern blot hybridization. Colchicine suppresses the basal level of type I collagen mRNA but minimally stimulates the mRNA expression of MMP-1, whereas D-penicillamine does not have any significant effects on either. Colchicine was also able to significantly suppress the TGF-beta-induced up-regulation of type I collagen mRNA expression.

Cells, Cultured↗
PubMed1998

Changes in morphology and behaviour of retinal growth cones before and after crossing the midline of the mouse chiasm - a confocal microscopy study.

The growth of retinal axons was investigated in different regions of the optic chiasm in C57 pigmented mouse embryos aged embryonic day 13 (E13) to E15. Individual retinal axons and their growth cones were labelled anterogradely by DiI and imaged using a confocal imaging system. In aldehyde-fixed embryos, retinal growth cones display a simple form in the optic nerve and become more complex in morphology in the chiasm. The complex form is particularly prominent in those axons that turn to the ipsilateral tract in the premidline region of chiasm. Moreover, complex growth cones are also commonly found in axons in the postmidline chiasm, which are markedly different in morphology from those axons in the premidline region, suggesting that the postmidline chiasm contains a novel environment for the pathfinding of retinal axons. In another experiment, the dynamic growth of retinal axons is studied in a brain slice preparation of the living retinofugal pathway. Retinal axons show an intermittent growth across the premidline and postmidline chiasm. Extensive remodelling of growth cone form followed by a shift in growth direction is commonly seen during the pause periods, indicating that signals that guide axon growth across the chiasm are not restricted to the midline, but are laid down throughout the chiasm. Moreover, dramatic changes in axon trajectory are noted first at the premidline chiasm where the uncrossed axons segregate from the crossed axons, and second at the postmidline chiasm where specific sorting of retinal axons according to their position in the dorsal ventral retinal axis and their ages are known to take place. These results show that there are two distinct environments, separated by the midline in the chiasm, where axons show different responses to local guidance cues and develop the distinct fibre orders.

Animals↗
PubMed1997

A GT-rich sequence binding the transcription factor Sp1 is crucial for high expression of the human type VII collagen gene (COL7A1) in fibroblasts and keratinocytes.

Type VII collagen is the major component of anchoring fibrils, structural elements that stabilize the attachment of the basement membrane to the underlying dermis. In this study, we have dissected the human type VII collagen gene (COL7A1) promoter to characterize the cis-elements responsible for the expression of the gene in cultured fibroblasts and keratinocytes. Using transient cell transfections with various 5' end deletion COL7A1 promoter/chloramphenicol acetyltransferase reporter gene plasmid constructs, we determined that the region between nucleotides -524 and -456, relative to the transcription start site, is critical for high promoter activity in both cell types studied. Gel mobility shift assays using several DNA fragments spanning this region identified a GT-rich sequence between residues -512 and -505, necessary for the binding of nuclear proteins to this region of the promoter. Point mutations abolished the binding of nuclear proteins in gel shift assays and drastically diminished the activity of the promoter in transient cell transfections. Supershift assays with antibodies against various transcription factors including Sp1, Sp3, c-Jun/AP-1, and AP-2, and competition experiments with oligonucleotides containing consensus sequences for Sp1 and AP-1 binding identified Sp1 as the transcription factor binding to this region of the COL7A1 promoter. Indeed, recombinant human Sp1 was shown to bind the COL7A1 promoter GT-rich element but not its mutated form in gel mobility shift assays. In addition, co-transfection of pPacSp1, an expression vector for Sp1, together with the COL7A1 promoter/chloramphenicol acetyltransferase construct into Sp1-deficient Drosophila Schneider SL2 cells unequivocally demonstrated that Sp1 is essential for high expression of the COL7A1 gene. These data represent the first in-depth analysis of the human COL7A1 promoter transcriptional control.

Collagen↗
PubMed1997

Correlation between K-ras gene mutation and prognosis of patients with nonsmall cell lung carcinoma.

BACKGROUND: Mutations at codons 12, 13, and 61 of the three ras genes, H-ras, K-ras, and N-ras, convert these genes into active oncogenes. It appears that ras gene mutations can be found in a variety of tumor types. The purpose of this study was to evaluate the clinical significance of K-ras gene mutation in nonsmall cell lung carcinoma (NSCLC). METHODS: The authors analyzed 58 NSCLC patients for mutations at codons 12, 13, and 61 of the K-ras gene and correlated the findings with the tumor stage and patient survival. Polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) and the direct nucleotide sequencing method were used to detect mutations after amplification of ras specific sequences by PCR. RESULTS: Fourteen mutations (24%) of ras genes were found, all at codon 12 of the K-ras gene. GGT to GAT transition was the predominant mutational pattern. There was a significant association between K-ras mutation and the tumor stage (i.e., the higher the stage, the higher the mutation rate) (P = 0.014). Using univariate analysis, the presence of K-ras mutation in paraffin embedded tissue from patients who received treatment with curative intent was associated with a shorter survival (P = 0.039). The median survival duration for patients with or without K-ras mutation was 9 and 30 months, respectively. The Cox proportional hazards model also predicted a higher risk for patients with K-ras mutations (P = 0.047). CONCLUSIONS: K-ras mutations, present in a subset of NSCLC, are associated with tumor progression and shortened patient survival.

Adult↗
PubMed1997

Intravascular lymphomatosis of the T cell type presenting as interstitial lung disease--a case report.

Intravascular lymphomatosis (IL) is a rare and generally fatal disease characterized by proliferation of large lymphoma cells almost exclusively within the lumen of small blood vessels. The skin and central nervous systems are typically affected, but involvement of other organs, such as lung, has been described. Predominant lung involvement without cutaneous and neurologic manifestation is very rare and difficult to diagnose. Originally considered as an endothelial disorder, IL has recently been reclassified as lymphoma. Most of the cases reported are of B cell lineage with a few cases of T cell type. We describe a case of the T-cell type IL manifested clinically as an interstitial lung disease without involvement of skin and central nervous systems. Immunohistochemical studies showed the T-cell nature of the neoplastic cells in open lung biopsy sample.

Blood Vessels↗
PubMed1996

Cell-specific induction of distinct oncogenes of the Jun family is responsible for differential regulation of collagenase gene expression by transforming growth factor-beta in fibroblasts and keratinocytes.

Transforming growth factor-beta (TGF-beta) plays a major role in regulating connective tissue deposition by controlling both extracellular matrix production and degradation. In this study, we show that TGF-beta transcriptionally represses both basal and tumor necrosis factor-alpha-induced collagenase (matrix metalloprotease-1) gene expression in dermal fibroblasts in culture, whereas it activates its expression in epidermal keratinocytes. We demonstrate that this differential effect of TGF-beta on collagenase gene expression is due to a cell type-specific induction of distinct oncogenes of the Jun family, which participate in the formation of AP-1 complexes with different trans-activating properties. Specifically, our data indicate that the inhibitory effect of TGF-beta in fibroblasts is likely to be mediated by jun-B, based on the following observations: (a) TGF-beta induces high levels of jun-B expression and (b) over-expression of jun-B mimics TGF-beta effect in inhibiting basal collagenase promoter activity and preventing tumor necrosis factor-alpha-induced trans-activation of the collagenase promoter. In contrast, TGF-beta induction of collagenase gene expression in keratinocytes is preceded by transient elevation of c-jun proto-oncogene expression. Over-expression of c-jun leads to trans-activation of the collagenase promoter in both cell types, suggesting that c-jun is a ubiquitous inducer of collagenase gene expression. Transfection of keratinocytes with an antisense c-jun construct together with a collagenase promoter/reporter gene construct inhibits basal and TGF-beta-induced up-regulation of the collagenase promoter activity, implying that c-jun mediates TGF-beta effect in this cell type. Collectively, our data suggest differential signaling pathways for TGF-beta in dermal fibroblasts and epidermal keratinocytes, leading to cell type-specific induction of two AP-1 components with opposite transcriptional activities.

3T3 Cells↗
PubMed1996

An AP-1 binding sequence is essential for regulation of the human alpha2(I) collagen (COL1A2) promoter activity by transforming growth factor-beta.

Previous studies have shown that transforming growth factor-beta (TGF-be ta) and tumor necrosis factor-alpha (TNF-alpha) modulate type I collagen gene expression in fibroblasts. To fine-map the corresponding response elements in the human alpha2(I) collagen (COL1A2) promoter, we have generated a series of 5' deletion promoter/chloramphenicol acetyltransferase (CAT) reporter gene constructs. Transient cell transfection assays using human dermal fibroblasts and stable transfection experiments using NIH 3T3 fibroblasts identified the region located between residues -265 and -241, as critical for TGF-beta response. Specifically, we demonstrate that this 25-base pair region mediates the up-regulatory effect of TGF-beta on COL1A2 promoter activity and allows antagonistic activity of TNF-alpha on the TGF-beta effect. Gel mobility shift assays indicate that nuclear factor binding to this 25-base pair region of COL1A2 promoter is competed by AP-1, but not NF-1 or NF-kappaB, oligonucleotides. Transient cell transfection experiments with plasmid constructs in which the potential AP-1-binding site located within this short region of promoter was modified by site-directed mutagenesis indicated that this element plays a significant role in the basal activity of the promoter. Furthermore, this sequence is essential for TGF-beta response and does not require the presence of the three Sp-1-binding sites located further upstream, between nucleotides -273 and -304. In addition, overexpression of c-jun in co-transfection experiments with COL1A2 promoter/CAT constructs blocks the TGF- beta response, further implicating AP-1 in the regulation of COL1A2 gene expression. Our results clarify the molecular mechanisms involved in the regulation of type I collagen gene expression and further emphasize the importance of AP-1 in mediating some of the TGF-beta effects on gene transcription.

Base Sequence↗
PubMed1996

Cyclin D1 protein expression in lung cancer.

Cyclin D1, a G1 cyclin, has been implicated in the oncogenesis of various types of malignancies via deregulation of cell cycles. Amplification of cyclin D1 as a part of 11q13 amplicon has been reported in lung cancer as well as a subset of carcinomas arising from various organs including breast, head and neck, and esophagus. In addition to its role as an oncogene, several recent studies have suggested that amplification is indicative of poor prognosis. In this study we examined the cyclin D1 protein expression in 102 consecutive cases of lung cancers using the microwave enhanced immunohistochemical staining method and correlated the data with the histologic subtype and grade, Ki-67 (MIB-1) labeling index, and survival. Nuclear positive staining was observed in 18 cases (18 %) of lung cancers. Although squamous cell carcinoma demonstrated a higher rate of expression (12 /58, 21%), three of 33 adenocarcinomas (9%) revealed overexpression and both adenocarcinoma and squamous cell carcinoma components within the adenosquamous carcinoma showed nuclear staining. There was no correlation between cyclin D1 overexpression and histologic grade, Ki-67 (MIB-1) labeling index, and survival. These observations indicate that cyclin D1 protein overexpression might be implicated in the oncogenesis of the various histologic types of non-small cell lung carcinomas but it has no usefulness as a prognostic marker.

Cyclin D1↗
PubMed1995

Memory T lymphocytes' adherence to interferon gamma-activated human dermal microvascular endothelial cells via E-selectin.

The regulation of leukocytes-endothelial cells binding by biological response modifiers have an important role in determining the progression of acute and chronic inflammatory responses. In order to define the influence of E-selectin on the binding of T lymphocytes to human dermal microvascular endothelial cells (HDMEC), we examined the cell surface expression of E-selectin on HDMEC and the regulation of the binding of T lymphocytes to HDMEC by IFN-gamma. We have demonstrated that stimulation of HDMEC with IL-1 alpha or TNF alpha leads to transient E-selectin induction which disappears after 48 h, but stimulation of HDMEC with IFN-gamma resulted in delayed E-selectin induction which was seen at 48 h of incubation and persisted until 72 h after stimulation. However, stimulation with IFN-gamma failed to induce E-selectin expression on human umbilical vein endothelial cells. The delayed E-selectin expression on HDMEC by IFN-gamma coincided with the increases in T lymphocyte binding to IFN-gamma-activated HDMEC. The binding of memory T lymphocytes to IFN-gamma-activated HDMEC was greater than that of naive T lymphocytes. Anti-E-selectin antibody partially inhibited memory T lymphocyte binding to HDMEC after 48 h of stimulation with IFN-gamma. These data show that E-selectin expressions by IFN-gamma on endothelial cells are regulated in a tissue-specific fashion and that E-selectin may be important in vivo in the preferential migration of memory T lymphocytes into inflammatory sites in the skin.

Antibodies, Monoclonal↗
PubMed1995

Disseminated eruptive nevocellular nevi.

A 13-year-old boy suddenly developed about 2,000 dark brown to black colored papules on his face and neck and about 500 lesions on his trunk and upper extremities during a six month period. Histopathologic features were compatible with junctional nevus. The results of alpha melanocyte stimulating hormone (MSH), proliferating cell nuclear antigen (PCNA), and epidermal growth factor receptor (EGF/R) studies are presented. To the best of our knowledge, this report represents an outbreak of the highest number of nevocellular nevi in a short period without any malignant nature or evident triggering factor.

Adolescent↗