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Biomedical subjects

K Park

Publications and source records attributed to K Park.

At least 307 records · Page 17Linked to original sources
PubMed1995

Overexpression of TGF-beta 1 in the central nervous system of transgenic mice results in hydrocephalus.

Transforming growth factor beta (TGF-beta) has been proposed to play a number of roles in central nervous system (CNS) development and response to injury. To test these proposals, transgenic mice were generated which overproduce TGF-beta 1 in the CNS. Surprisingly, these mice developed severe hydrocephalus and died between birth and 3 weeks of age. Ovary transplantation from an affected female founder has permitted perpetuation of one of the lines as a hydrocephalus model whose genetic defect is known. These results also demonstrate that the developing CNS is highly sensitive to TGF-beta, and suggest a role for aberrant expression of TGF-beta in the pathogenesis of developmental disease of the CNS.

Animals↗
PubMed1995

Intracellular pH modulates the activity of chloride channels in isolated lacrimal gland acinar cells.

The effects of intracellular pH (pHi) on Ca(2+)-activated Cl- currents in rat lacrimal gland acinar cells were examined. Cl- currents were recorded by conventional whole cell patch-clamp methods using K(+)-free and Na(+)-free solutions. pHi was varied by using electrode solutions with pH at 6.8, 7.3, or 7.8, and Ca2+ activity was buffered at 100 nM with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid. Increasing pH from 6.8 to 7.8 was found to increase whole cell currents. The currents observed exhibited time-dependent activation at depolarizing potentials and time-dependent inactivation at hyperpolarizing potentials (pH 7.8). This behavior is characteristic of Ca(2+)-activated Cl- channels in lacrimal gland cells. The selectivity of the current was examined at pH 7.8 by removing Cl- from the bath solution. This maneuver caused a positive shift in the reversal potential, as expected for a Cl(-)-selective current. Thus increasing pHi appears to activate Ca(2+)-activated Cl- channels. The possibility that an increase in pHi may help sustain Cl- channel activity during secretory activity is discussed.

Acetylcholine↗
PubMed1995

Targeted expression of transforming growth factor-beta 1 in intracardiac grafts promotes vascular endothelial cell DNA synthesis.

Intracardiac grafts comprised of genetically modified skeletal myoblasts were assessed for their ability to effect long-term delivery of recombinant transforming growth factor-beta (TGF-beta) to the heart. C2C12 myoblasts were stably transfected with a construct comprised of an inducible metallothionein promoter fused to a modified TGF-beta 1 cDNA. When cultured in medium supplemented with zinc sulfate, cells carrying this transgene constitutively secrete active TGF-beta 1. These genetically modified myoblasts were used to produce intracardiac grafts in syngeneic C3Heb/FeJ hosts. Viable grafts were observed as long as three months after implantation, and immunohistological analyses of mice maintained on water supplemented with zinc sulfate revealed the presence of grafted cells which stably expressed TGF-beta 1. Regions of apparent neovascularization, as evidenced by tritiated thymidine incorporation into vascular endothelial cells, were observed in the myocardium which bordered grafts expressing TGF-beta 1. The extent of vascular endothelial cell DNA synthesis could be modulated by altering dietary zinc. Similar effects on the vascular endothelial cells were not seen in mice with grafts comprised of nontransfected cells. This study indicates that genetically modified skeletal myoblast grafts can be used to effect the local, long-term delivery of recombinant molecules to the heart.

Animals↗
PubMed1995

Early loss of pit and fissure sealant: a clinical and SEM study.

The rate of early loss of preventive resin restoration and single application of pit and fissure sealant was determined by a clinical survey. The rate of partial and complete sealant loss on the observed surfaces was 14.4% (43/299) at the 3-month recall, with a further loss of 7.0% (12/171) between the 3- and 6-month recalls. Typically, a complete loss of sealant was observed on maxillary molars and on the buccal surface of mandibular molars, while partial loss caused on the occlusal surface of mandibular molars. Scanning electron microscopic observation of in vivo tooth replicas revealed partial gap formations and small fractures of sealant indicating failure or degradation of adhesion. The presence of unetched areas after routine cleaning and acid etching, especially in and around pits and fissures could be a major cause of early sealant loss.

Bicuspid↗
PubMed1995

Retroperitoneal endoscopic live donor nephrectomy: report of 3 cases.

In a variation of laparoscopic surgery we performed retroperitoneal surgery using endoscopy and a special retractor in 3 cases of live donor nephrectomy. The procedure using retroperitoneal endoscopy offers several advantages compared to conventional live donor nephrectomy. With the development of retractors to obtain operating space and the further development of surgical techniques retroperitoneal endoscopic live donor nephrectomy can be established as an alternative surgical method for harvesting donated kidneys.

Adult↗
PubMed1995

Induction of cell death by myristylated death domain of p55 TNF receptor is not abolished by Iprcg-like point mutation in death domain.

We transiently expressed the intracellular domains of p55 TNF receptor (TNFR1) as either a cytosolic- or a membrane-associated form and examined their effects on the endogenous receptor-mediated gene expression as well as on cell viability. We found that gene expression as measured by luciferase activity under NF-kappa B-controlling elements was blocked by all forms of the intracellular domain of TNFR1. The blockade of reporter gene expression was due to the cell death induced by the intracellular domain of TNFR1 per se. The killing mechanism of the intracellular domain peptides appeared to be apoptotic. Interestingly, myristylated form of the intracellular domain, consisting of mainly death domain showed the most potent cell-killing activity. Moreover, this myristylated death domain could still induce cell death even if lprcg-like point mutation (Leu351 to Ala), which has been reported to abrogate TNF-induced cytotoxicity, was introduced. This result suggests that the myristylated death domain activates an additional death signaling pathway which is not involved in TNF-induced cell death.

Apoptosis↗
PubMed1994

The E1A oncogene induces resistance to the effects of 1,25-dihydroxyvitamin D3 on inhibition of growth of mouse keratinocytes.

1,25-Dihydroxyvitamin D3 [1,25-(OH)2D3] inhibited DNA synthesis in transformed mouse keratinocytes (Pam212) in a time- and dose-dependent manner as measured by [3H]thymidine incorporation. To investigate the mechanism through which 1,25-(OH)2D3 acts, we examined its effects on Pam212 cells further transformed with the E1A oncogene. Here, we show that transformation of the cells with the E1A oncogene induced resistance to the effects of 1,25-(OH)2D3 on inhibition of growth of Pam212 cells. While 1,25-(OH)2D3 treatment increased the level of expression of vitamin D receptor mRNA 20-fold in parental cells, the E1A-transformed cells failed to express vitamin D receptor mRNA even after treatment with 1,25-(OH)2D3. Transfection of the E1A-transformed cell line with an expression construct encoding the vitamin D receptor restored receptor expression as well as the inhibition of growth by 1,25-(OH)2D3. These results suggest that one of the mechanisms for acquisition of 1,25-(OH)2D3 resistance induced by E1A may involve loss of vitamin D receptor inducibility by 1,25-(OH)2D3.

Adenovirus E1A Proteins↗
PubMed1994

Genetic changes in the transforming growth factor beta (TGF-beta) type II receptor gene in human gastric cancer cells: correlation with sensitivity to growth inhibition by TGF-beta.

We have found several genetic changes in the TGF-beta-type II receptor gene in human gastric cancer cell lines resistant to the growth inhibitory effect of TGF-beta. Southern blot analysis showed deletion of the type II receptor gene in two of eight cell lines and amplification in another two lines. The single cell line we studied that is sensitive to growth inhibition by TGF-beta showed no structural abnormalities of the type II receptor gene. Some of the gastric cancer cells resistant to the growth inhibitory effect of TGF-beta express either truncated or no detectable TGF-beta type II receptor mRNAs, whereas the one that retains responsiveness to the growth inhibitory effect of TGF-beta expresses a full-size type II receptor mRNA. Immunoprecipitation followed by Western blot analysis showed parallel changes in TGF-beta type II receptor expression. Our results suggest that one of the possible mechanisms of escape from autocrine or paracrine growth control by TGF-beta during carcinogenesis could involve genetic changes in the TGF-beta type II receptor gene itself or altered expression of its mRNA.

Carcinoma↗
PubMed1994

The human retinoblastoma susceptibility gene promoter is positively autoregulated by its own product.

The product of the retinoblastoma susceptibility gene is a 105-kDa protein that has properties of a cell cycle regulatory factor. Previous reports indicated that two distinct DNA-binding factors, RBF-1 and ATF, play an important part in the transcription of the human retinoblastoma gene (Rb). Recently, we demonstrated that pRb activates expression of the human transforming growth factor-beta 2 gene through ATF-2. Since the human Rb gene promoter also contains an ATF-2-like binding site, we examined whether pRb can regulate its own expression through ATF-2. Here we report that overexpression of Rb stimulates Rb promoter activity through the ATF binding site in a variety of different cell types. Mutation of the ATF binding site of the Rb promoter abolishes the Rb autoinduction. We have also determined that the carboxyl-terminal domain of pRb is responsible for the Rb autoinduction through ATF-2. Rb autoinduction may be important for maintaining the action of pRb during cell growth, and loss of autoinductibility may contribute to retinoblastoma.

Activating Transcription Factors↗
PubMed1994

Nerve growth factor induces transcription of transforming growth factor-beta 1 through a specific promoter element in PC12 cells.

Nerve growth factor (NGF) stimulates the differentiation of PC12 pheochromocytoma cells to those resembling sympathetic neurons. We have investigated whether NGF regulates transforming growth factor (TGF)-beta gene expression and protein secretion in PC12 cells. These cells constitutively express TGF-beta 1 mRNA, whereas TGF-beta 2 and -beta 3 mRNAs are expressed at very low levels. TGF-beta 1 gene expression was stimulated greater than 10-fold when PC12 cells were treated with NGF. Sequences between -119 and -98 in the TGF-beta 1 promoter, homologous to an Egr-1 binding site, were shown to be important for both basal and NGF-induced promoter activity. We also found that a factor(s) present in nuclear extracts from PC12 cells interacted with the sequences between -119 and -98 and that expression of this factor was induced by NGF treatment. Moreover, specific binding to TGF-beta 1 promoter fragments between -119 and -98 was seen using the bacterially expressed transcription factor Egr-1. These results indicate that activation of TGF-beta 1 expression is one of the cellular responses of PC12 cells to NGF and suggest that TGF-beta may play a role in the differentiation of sympathetic neurons.

Adrenal Gland Neoplasms↗
PubMed1994

Inhibition of protein phosphatases activates P4 promoter of the human insulin-like growth factor II gene through the specific promoter element.

To understand the transcriptional regulation of the human insulin-like growth factor II (IGF-II) gene, we examined the effects of okadaic acid, a potent in vitro inhibitor of protein phosphatases, on the activation of human IGF-II gene expression. Treatment of A-549 human lung adenocarcinoma cells with okadaic acid increased expression of the IGF-II mRNAs. Since the 4.8-kb mRNA is transcribed under the control of human IGF-II P4 promoter, we examined the P4 promoter element responsible for the okadaic acid-mediated transcriptional activation. Transfection of IGF-II P4 promoter-chloramphenicol acetyltransferase constructs demonstrated that the effects of okadaic acid on the induction of IGF-II gene expression are mediated through multiple promoter elements, including an Egr-1 consensus element. We have also shown that okadaic acid induced the expression of the transcription factor Egr-1. Moreover, by using a GAL4-Egr-1 fusion protein, we have directly demonstrated that okadaic acid positively regulates Egr-1 transcriptional activity in vivo. These results indicate that protein phosphatases play an important role in the transcriptional regulation of the IGF-II.

Adenocarcinoma↗